Arianna G. Cassidy et al.
Assessment of Adverse Reactions, Antibody Patterns, and 12-month Outcomes in the Mother-Infant Dyad After COVID-19 mRNA Vaccination in Pregnancy
JAMA, July 2023; doi:10.1001/jamanetworkopen.2023.23405
Abstract
Importance Longitudinal data on COVID-19 messenger RNA (mRNA) vaccine reactogenicity and immunogenicity in pregnancy and for the mother-infant dyad are needed.
Objective To examine COVID-19 mRNA vaccine reactogenicity and immunogenicity in pregnancy and observe longitudinal maternal and infant outcomes.
Design, Setting, and Participants This prospective cohort study of pregnant individuals enrolled in the COVID-19 Vaccination in Pregnancy and Lactation study from December 1, 2020, through December 31, 2021, with follow-up through March 31, 2022, was conducted at a large academic medical center in an urban metropolitan area in California. Pregnant individuals receiving COVID-19 mRNA vaccines (mRNA-1273 [Moderna] and BNT162b2 [Pfizer-BioNTech]) were eligible. Of 81 participants enrolled, 5 were excluded after enrollment: 1 terminated pregnancy, 1 received the third vaccine dose prior to delivery, and 3 delivered prior to completing the initial vaccine series.
Exposure COVID-19 mRNA vaccination at any time during pregnancy.
Main Outcomes and Measures The primary outcomes were vaccine response as measured by blood Immunoglobulin G (IgG) titers after each vaccine dose and self-reported postvaccination symptoms. Patients’ IgG titers were measured in cord blood and in infant blood at intervals up to 1 year of life; IgG and IgA titers were measured in maternal milk. Clinical outcomes were collected from medical records.
Results Of 76 pregnant individuals included in final analyses (median [IQR] maternal age, 35 [29-41] years; 51 [67.1%] White; 28 [36.8%] primigravid; 37 [48.7%] nulliparous), 42 (55.3%) received BNT162b2 and 34 (44.7%) received mRNA-1237. There were no significant differences in maternal characteristics between the 2 vaccine groups. Systemic symptoms were more common after receipt of the second vaccine dose than after the first dose (42 of 59 [71.2%] vs 26 of 59 [44.1%]; P = .007) and after mRNA-1237 than after BNT162b2 (25 of 27 [92.6%] vs 17 of 32 53.1%; P = .001). Systemic symptoms were associated with 65.6% higher median IgG titers than no symptoms after the second vaccine dose (median [IQR], 2596 [1840-4455] vs 1568 [1114-4518] RFU; P = .007); mean cord titers in individuals with local or systemic symptoms were 6.3-fold higher than in individuals without symptoms. Vaccination in all trimesters elicited a robust maternal IgG response. The IgG transfer ratio was highest among individuals vaccinated in the second trimester. Anti-SARS-CoV-2 IgG was detectable in cord blood regardless of vaccination trimester. In milk, IgG and IgA titers remained above the positive cutoff for at least 5-6 months after birth, and infants of mothers vaccinated in the second and third trimesters had positive IgG titers for at least 5 to 6 months of life. There were no vaccine-attributable adverse perinatal outcomes.
Conclusions and Relevance The findings of this cohort study suggest that mRNA COVID-19 vaccination in pregnancy provokes a robust IgG response for the mother-infant dyad for approximately 6 months after birth. Postvaccination symptoms may indicate a more robust immune response, without adverse maternal, fetal, or neonatal outcomes.
Margaret M Cortese et al
Surveillance for Multisystem Inflammatory Syndrome in US Children Aged 5–11 Years Who Received Pfizer-BioNTech COVID-19 Vaccine, November 2021 through March 2022
Academic.oup ; February 2023; doi.org/10.1093/infdis/jiad051
Abstract
Multisystem inflammatory syndrome in children (MIS-C) is a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; in the United States, reporting of MIS-C after coronavirus disease 2019 (COVID-19) vaccination is required for vaccine safety monitoring. Pfizer-BioNTech COVID-19 vaccine was authorized for children aged 5−11 years on 29 October 2021. Covering a period when approximately 7 million children received vaccine, surveillance for MIS-C ≤ 90 days postvaccination using passive systems identified 58 children with MIS-C and laboratory evidence of past/recent SARS-CoV-2 infection, and 4 without evidence. During a period with extensive SARS-CoV-2 circulation, MIS-C illness in children after COVID-19 vaccination who lacked evidence of SARS-CoV-2 infection was rare (<1 per million vaccinated children).
Daniel D’Souza et al.
Incidence of Diabetes in Children and Adolescents During the COVID-19 Pandemic
A Systematic Review and Meta-Analysis
JAMA, June 2023 ; doi:10.1001/jamanetworkopen.2023.21281
Abstract
Importance There are reports of increasing incidence of pediatric diabetes since the onset of the COVID-19 pandemic. Given the limitations of individual studies that examine this association, it is important to synthesize estimates of changes in incidence rates.
Objective To compare the incidence rates of pediatric diabetes during and before the COVID-19 pandemic.
Data Sources In this systematic review and meta-analysis, electronic databases, including Medline, Embase, the Cochrane database, Scopus, and Web of Science, and the gray literature were searched between January 1, 2020, and March 28, 2023, using subject headings and text word terms related to COVID-19, diabetes, and diabetic ketoacidosis (DKA).
Study Selection Studies were independently assessed by 2 reviewers and included if they reported differences in incident diabetes cases during vs before the pandemic in youths younger than 19 years, had a minimum observation period of 12 months during and 12 months before the pandemic, and were published in English.
Data Extraction and Synthesis From records that underwent full-text review, 2 reviewers independently abstracted data and assessed the risk of bias. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline was followed. Eligible studies were included in the meta-analysis and analyzed with a common and random-effects analysis. Studies not included in the meta-analysis were summarized descriptively.
Main Outcomes and Measures The primary outcome was change in the incidence rate of pediatric diabetes during vs before the COVID-19 pandemic. The secondary outcome was change in the incidence rate of DKA among youths with new-onset diabetes during the pandemic.
Results Forty-two studies including 102 984 incident diabetes cases were included in the systematic review. The meta-analysis of type 1 diabetes incidence rates included 17 studies of 38 149 youths and showed a higher incidence rate during the first year of the pandemic compared with the prepandemic period (incidence rate ratio [IRR], 1.14; 95% CI, 1.08-1.21). There was an increased incidence of diabetes during months 13 to 24 of the pandemic compared with the prepandemic period (IRR, 1.27; 95% CI, 1.18-1.37). Ten studies (23.8%) reported incident type 2 diabetes cases in both periods. These studies did not report incidence rates, so results were not pooled. Fifteen studies (35.7%) reported DKA incidence and found a higher rate during the pandemic compared with before the pandemic (IRR, 1.26; 95% CI, 1.17-1.36).
Conclusions and Relevance This study found that incidence rates of type 1 diabetes and DKA at diabetes onset in children and adolescents were higher after the start of the COVID-19 pandemic than before the pandemic. Increased resources and support may be needed for the growing number of children and adolescents with diabetes. Future studies are needed to assess whether this trend persists and may help elucidate possible underlying mechanisms to explain temporal changes
Dan-Yu Lin et al.
Effects of COVID-19 vaccination and previous SARS-CoV-2 infection on omicron infection and severe outcomes in children under 12 years of age in the USA: an observational cohort study
The Lancet, July 2023 ; doi.org/10.1016/S1473-3099(23)00272-4
Abstract
Data on the protection conferred by COVID-19 vaccination and previous SARS-CoV-2 infection against omicron (B.1.1.529) infection in young children are scarce. We aimed to estimate the time-varying effects of primary and booster COVID-19 vaccination and previous SARS-CoV-2 infection on subsequent omicron infection and severe illness (hospital admission or death) in children younger than 12 years of age.
Methods
In this observational cohort study, we obtained individual-level records on vaccination with the BNT162b2 and mRNA-1273 vaccines and clinical outcomes from the North Carolina COVID-19 Surveillance System and the COVID-19 Vaccine Management System for 1 368 721 North Carolina residents aged 11 years or younger from Oct 29, 2021 (Oct 29, 2021 for children aged 5–11 years and June 17, 2022 for children aged 0–4 years), to Jan 6, 2023. We used Cox regression to estimate the time-varying effects of primary and booster vaccination and previous infection on the risks of omicron infection, hospital admission, and death.
Findings
For children 5–11 years of age, the effectiveness of primary vaccination against infection, compared with being unvaccinated, was 59·9% (95% CI 58·5–61·2) at 1 month, 33·7% (32·6–34·8) at 4 months, and 14·9% (95% CI 12·3–17·5) at 10 months after the first dose. Compared with primary vaccination only, the effectiveness of a monovalent booster dose after 1 month was 24·4% (14·4–33·2) and that of a bivalent booster dose was 76·7% (45·7–90·0). The effectiveness of omicron infection against reinfection was 79·9% (78·8–80·9) after 3 months and 53·9% (52·3–55·5) after 6 months. For children 0–4 years of age, the effectiveness of primary vaccination against infection, compared with being unvaccinated, was 63·8% (57·0–69·5) at 2 months and 58·1% (48·3–66·1) at 5 months after the first dose, and the effectiveness of omicron infection against reinfection was 77·3% (75·9–78·6) after 3 months and 64·7% (63·3–66·1) after 6 months. For both age groups, vaccination and previous infection had better effectiveness against severe illness as measured by hospital admission or death as a composite endpoint than against infection.
Interpretation
The BNT162b2 and mRNA-1273 vaccines were effective against omicron infection and severe outcomes in children younger than 12 years, although the effectiveness decreased over time. Bivalent boosters were more effective than monovalent boosters. Immunity acquired via omicron infection was high and waned gradually over time. These findings can be used to develop effective prevention strategies against COVID-19 in children younger than 12 years.
Prof Tao Huang et al
Safety and immunogenicity of heterologous boosting with orally aerosolised or intramuscular Ad5-nCoV vaccine and homologous boosting with inactivated vaccines (BBIBP-CorV or CoronaVac) in children and adolescents: a randomised, open-label, parallel-controlled, non-inferiority, single-centre study
The Lancet, May 2023; doi.org/10.1016/S2213-2600(23)00129-7
Abstract
Heterologous booster immunisation with orally administered aerosolised Ad5-nCoV vaccine (AAd5) has been shown to be safe and highly immunogenic in adults. Here, we aimed to assess the safety and immunogenicity of heterologous booster immunisation with orally administered AAd5 in children and adolescents aged 6–17 years who had received two doses of inactivated vaccine (BBIBP-CorV or CoronaVac).
Methods
We did a randomised, open-label, parallel-controlled, non-inferiority study to assess the safety and immunogenicity of heterologous booster immunisation with AAd5 (0·1 mL) or intramuscular Ad5-nCoV vaccine (IMAd5; 0·3 mL) and homologous booster immunisation with inactivated vaccine (BBIBP-CorV or CoronaVac; 0·5 mL) in children (aged 6–12 years) and adolescents (aged 13–17 years) who had received two doses of inactivated vaccine at least 3 months earlier in Hunan, China. Children and adolescents who were previously immunised with two-dose BBIBP-CorV or CoronaVac were recruited for eligibility screening at least 3 months after the second dose. A stratified block method was used for randomisation, and participants were stratified by age and randomly assigned (3:1:1) to receive AAd5, IMAd5, or inactivated vaccine. The study staff and participants were not masked to treatment allocation. Laboratory and statistical staff were masked during the study. In this interim analysis, adverse events within 14 days and geometric mean titre (GMT) of serum neutralising antibodies on day 28 after the booster vaccination, based on the per-protocol population, were used as the primary outcomes. The analysis of non-inferiority was based on comparison using a one-sided 97·5% CI with a non-inferiority margin of 0·67. This study was registered at ClinicalTrials.gov, NCT05330871, and is ongoing.
Findings
Between April 17 and May 28, 2022, 436 participants were screened and 360 were enrolled: 220 received AAd5, 70 received IMAd5, and 70 received inactivated vaccine. Within 14 days after booster vaccination, vaccine-related adverse reactions were reported: 35 adverse events (in 13 [12%] of 110 children and 22 [20%] of 110 adolescents) in 220 individuals in the AAd5 group, 35 (in 18 [51%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 13 (in five [14%] of 35 children and eight [23%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. Solicited adverse reactions were also reported: 34 (13 [12%] of 110 children and 21 [10%] of 110 adolescents) in 220 individuals in the AAd5 group, 34 (17 [49%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 12 (five [14%] of 35 children and seven [20%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. The GMTs of neutralising antibodies against ancestral SARS-CoV-2 Wuhan-Hu-1 (Pango lineage B) in the AAd5 group were significantly higher than the GMTs in the inactivated vaccine group (adjusted GMT ratio 10·2 [95% CI 8·0–13·1]; p<0·0001).
Interpretation
Our study shows that a heterologous booster with AAd5 is safe and highly immunogenic against ancestral SARS-CoV-2 Wuhan-Hu-1 in children and adolescents.
Siân Harrison et al
The impact of the Covid-19 pandemic on postnatal depression: analysis of three population-based national maternity surveys in England (2014–2020)
The Lancet, May 2023; doi.org/10.1016/j.lanepe.2023.100654
Abstract
Few studies have evaluated postnatal depression before and during the Covid-19 pandemic using comparable data across time. We used data from three national maternity surveys in England to compare prevalence and risk factors for postnatal depression before and during the pandemic.
Methods
Analysis was conducted using population-based surveys carried out in 2014 (n = 4571), 2018 (n = 4509), and 2020 (n = 4611). Weighted prevalence estimates for postnatal depression (EPDS score ≥13) were compared across surveys. Modified Poisson regression was used to estimate adjusted risk ratios (aRR) for the association between sociodemographic, pregnancy- and birth-related, and biopsychosocial factors, and postnatal depression.
Findings
Prevalence of postnatal depression increased from 10.3% in 2014 to 16.0% in 2018 (difference = +5.7% (95% CI: 4.0–7.4); RR = 1.55 (95% CI: 1.36–1.77)) and to 23.9% in 2020 (difference = +7.9% (95% CI: 5.9–9.9); RR = 1.49 (95% CI: 1.34–1.66)). Having a long-term mental health problem (aRR range = 1.48–2.02), antenatal anxiety (aRR range = 1.73–2.12) and antenatal depression (aRR range = 1.44–2.24) were associated with increased risk of postnatal depression, whereas satisfaction with birth (aRR range = 0.89–0.92) and social support (aRR range = 0.73–0.78) were associated with decreased risk before and during the pandemic.
Interpretation
This analysis indicates that Covid-19 had an important negative impact on postnatal women's mental health and may have accelerated an existing trend of increasing prevalence of postnatal depression. Risk factors for postnatal depression were consistent before and during the pandemic. Timely identification, intervention and follow-up are key to supporting women at risk, and it is essential that mechanisms to support women are strengthened during times of heightened risk such as the pandemic.
HarsitaPatel et al.
Evaluation of Autoantibody Binding to Cardiac Tissue in Multisystem Inflammatory Syndrome in Children and COVID-19 Vaccination–Induced Myocarditis
JAMA, May 2023; doi:10.1001/jamanetworkopen.2023.14291
Abstract
Importance Cardiac dysfunction and myocarditis have emerged as serious complications of multisystem inflammatory syndrome in children (MIS-C) and vaccines against SARS-CoV-2. Understanding the role of autoantibodies in these conditions is essential for guiding MIS-C management and vaccination strategies in children.
Objective To investigate the presence of anticardiac autoantibodies in MIS-C or COVID-19 vaccine-induced myocarditis.
Design, Setting, and Participants This diagnostic study included children with acute MIS-C or acute vaccine myocarditis, adults with myocarditis or inflammatory cardiomyopathy, healthy children prior to the COVID-19 pandemic, and healthy COVID-19 vaccinated adults. Participants were recruited into research studies in the US, United Kingdom, and Austria starting January 2021. Immunoglobulin G (IgG), IgM, and IgA anticardiac autoantibodies were identified with immunofluorescence staining of left ventricular myocardial tissue from 2 human donors treated with sera from patients and controls. Secondary antibodies were fluorescein isothiocyanate–conjugated antihuman IgG, IgM, and IgA. Images were taken for detection of specific IgG, IgM, and IgA deposits and measurement of fluorescein isothiocyanate fluorescence intensity. Data were analyzed through March 10, 2023.
Main Outcomes and Measures IgG, IgM and IgA antibody binding to cardiac tissue.
Results By cohort, there were a total of 10 children with MIS-C (median [IQR] age, 10 [13-14] years; 6 male), 10 with vaccine myocarditis (median age, 15 [14-16] years; 10 male), 8 adults with myocarditis or inflammatory cardiomyopathy (median age, 55 [46-63] years; 6 male), 10 healthy pediatric controls (median age, 8 [13-14] years; 5 male), and 10 healthy vaccinated adults (all older than 21 years, 5 male). No antibody binding above background was observed in human cardiac tissue treated with sera from pediatric patients with MIS-C or vaccine myocarditis. One of the 8 adult patients with myocarditis or cardiomyopathy had positive IgG staining with raised fluorescence intensity (median [IQR] intensity, 11 060 [10 223-11 858] AU). There were no significant differences in median fluorescence intensity in all other patient cohorts compared with controls for IgG (MIS-C, 6033 [5834-6756] AU; vaccine myocarditis, 6392 [5710-6836] AU; adult myocarditis or inflammatory cardiomyopathy, 5688 [5277-5990] AU; healthy pediatric controls, 6235 [5924-6708] AU; healthy vaccinated adults, 7000 [6423-7739] AU), IgM (MIS-C, 3354 [3110-4043] AU; vaccine myocarditis, 3843 [3288-4748] AU; healthy pediatric controls, 3436 [3313-4237] AU; healthy vaccinated adults, 3543 [2997-4607] AU) and IgA (MIS-C, 3559 [2788-4466] AU; vaccine myocarditis, 4389 [2393-4780] AU; healthy pediatric controls, 3436 [2425-4077] AU; healthy vaccinated adults, 4561 [3164-6309] AU).
Conclusions and Relevance This etiological diagnostic study found no evidence of antibodies from MIS-C and COVID-19 vaccine myocarditis serum binding cardiac tissue, suggesting that the cardiac pathology in both conditions is unlikely to be driven by direct anticardiac antibody–mediated mechanisms.
Elyse O. Kharbanda et al.
COVID-19 Booster Vaccination in Early Pregnancy and Surveillance for Spontaneous Abortion
JAMA, May 2023; doi:10.1001/jamanetworkopen.2023.14350
Abstract
Importance Adherence to COVID-19 booster vaccine recommendations has lagged in pregnant and nonpregnant adult populations. One barrier to booster vaccination is uncertainty regarding the safety of booster doses among pregnant people.
Objective To evaluate whether there is an association between COVID-19 booster vaccination during pregnancy and spontaneous abortion.
Design, Setting, and Participants This observational, case-control, surveillance study evaluated people aged 16 to 49 years with pregnancies at 6 to 19 weeks’ gestation at 8 health systems in the Vaccine Safety Datalink from November 1, 2021, to June 12, 2022. Spontaneous abortion cases and ongoing pregnancy controls were evaluated during consecutive surveillance periods, defined by calendar time.
Exposure Primary exposure was receipt of a third messenger RNA (mRNA) COVID-19 vaccine dose within 28 days before spontaneous abortion or index date (midpoint of surveillance period in ongoing pregnancy controls). Secondary exposures were third mRNA vaccine doses in a 42-day window or any COVID-19 booster in 28- and 42-day windows.
Main Outcomes and Measures Spontaneous abortion cases and ongoing pregnancy controls were identified from electronic health data using a validated algorithm. Cases were assigned to a single surveillance period based on pregnancy outcome date. Eligible ongoing pregnancy time was assigned to 1 or more surveillance periods as an ongoing pregnancy-period control. Generalized estimating equations were used to estimate adjusted odds ratios (AOR) with gestational age, maternal age, antenatal visits, race and ethnicity, site, and surveillance period as covariates and robust variance estimates to account for inclusion of multiple pregnancy periods per unique pregnancy.
Results Among 112 718 unique pregnancies included in the study, the mean (SD) maternal age was 30.6 (5.5) years. Pregnant individuals were Asian, non-Hispanic (15.1%); Black, non-Hispanic (7.5%); Hispanic (35.6%); White, non-Hispanic (31.2%); and of other or unknown (10.6%); and 100% were female. Across eight 28-day surveillance periods, among 270 853 ongoing pregnancy-period controls, 11 095 (4.1%) had received a third mRNA COVID-19 vaccine in a 28-day window; among 14 226 cases, 553 (3.9%) had received a third mRNA COVID-19 vaccine within 28 days of the spontaneous abortion. Receipt of a third mRNA COVID-19 vaccine was not associated with spontaneous abortion in a 28-day window (AOR, 0.94; 95% CI, 0.86-1.03). Results were consistent when using a 42-day window (AOR, 0.97; 95% CI, 0.90-1.05) and for any COVID-19 booster in a 28-day (AOR, 0.94; 95% CI, 0.86-1.02) or 42-day (AOR, 0.96; 95% CI, 0.89-1.04) exposure window.
Conclusions and Relevance In this case-control surveillance study, COVID-19 booster vaccination in pregnancy was not associated with spontaneous abortion. These findings support the safety of recommendations for COVID-19 booster vaccination, including in pregnant populations.
Meagan C. Fitzpatrick et al
Estimated US Pediatric Hospitalizations and School Absenteeism Associated With Accelerated COVID-19 Bivalent Booster Vaccination
JAMA, May 2023; doi:10.1001/jamanetworkopen.2023.13586
Abstract
Importance Adverse outcomes of COVID-19 in the pediatric population include disease and hospitalization, leading to school absenteeism. Booster vaccination for eligible individuals across all ages may promote health and school attendance.
Objective To assess whether accelerating COVID-19 bivalent booster vaccination uptake across the general population would be associated with reduced pediatric hospitalizations and school absenteeism.
Design, Setting, and Participants In this decision analytical model, a simulation model of COVID-19 transmission was fitted to reported incidence data from October 1, 2020, to September 30, 2022, with outcomes simulated from October 1, 2022, to March 31, 2023. The transmission model included the entire age-stratified US population, and the outcome model included children younger than 18 years.
Interventions Simulated scenarios of accelerated bivalent COVID-19 booster campaigns to achieve uptake that was either one-half of or similar to the age-specific uptake observed for 2020 to 2021 seasonal influenza vaccination in the eligible population across all age groups.
Main Outcomes and Measures The main outcomes were estimated hospitalizations, intensive care unit admissions, and isolation days of symptomatic infection averted among children aged 0 to 17 years and estimated days of school absenteeism averted among children aged 5 to 17 years under the accelerated bivalent booster campaign simulated scenarios.
Results Among children aged 5 to 17 years, a COVID-19 bivalent booster campaign achieving age-specific coverage similar to influenza vaccination could have averted an estimated 5 448 694 (95% credible interval [CrI], 4 936 933-5 957 507) days of school absenteeism due to COVID-19 illness. In addition, the booster campaign could have prevented an estimated 10 019 (95% CrI, 8756-11 278) hospitalizations among the pediatric population aged 0 to 17 years, of which 2645 (95% CrI, 2152-3147) were estimated to require intensive care. A less ambitious booster campaign with only 50% of the age-specific uptake of influenza vaccination among eligible individuals could have averted an estimated 2 875 926 (95% CrI, 2 524 351-3 332 783) days of school absenteeism among children aged 5 to 17 years and an estimated 5791 (95% CrI, 4391-6932) hospitalizations among children aged 0 to 17 years, of which 1397 (95% CrI, 846-1948) were estimated to require intensive care.
Conclusions and Relevance In this decision analytical model, increased uptake of bivalent booster vaccination among eligible age groups was associated with decreased hospitalizations and school absenteeism in the pediatric population. These findings suggest that although COVID-19 prevention strategies often focus on older populations, the benefits of booster campaigns for children may be substantial.
Paul L. Aronson et al.
Prevalence of Urinary Tract Infection, Bacteremia, and Meningitis Among Febrile Infants Aged 8 to 60 Days With SARS-CoV-2
JAMA, May 2023; doi:10.1001/jamanetworkopen.2023.13354
Abstract
Importance The prevalence of urinary tract infection (UTI), bacteremia, and bacterial meningitis in febrile infants with SARS-CoV-2 is largely unknown. Knowledge of the prevalence of these bacterial infections among febrile infants with SARS-CoV-2 can inform clinical decision-making.
Objective To describe the prevalence of UTI, bacteremia, and bacterial meningitis among febrile infants aged 8 to 60 days with SARS-CoV-2 vs without SARS-CoV-2.
Design, Setting, and Participants Thismulticenter cross-sectional study was conducted as part of a quality improvement initiative at 106 hospitals in the US and Canada. Participants included full-term, previously healthy, well-appearing infants aged 8 to 60 days without bronchiolitis and with a temperature of at least 38 °C who underwent SARS-CoV-2 testing in the emergency department or hospital between November 1, 2020, and October 31, 2022. Statistical analysis was performed from September 2022 to March 2023.
Exposures SARS-CoV-2 positivity and, for SARS-CoV-2–positive infants, the presence of normal vs abnormal inflammatory marker (IM) levels.
Main Outcomes and Measures Outcomes were ascertained by medical record review and included the prevalence of UTI, bacteremia without meningitis, and bacterial meningitis. The proportion of infants who were SARS-CoV-2 positive vs negative was calculated for each infection type, and stratified by age group and normal vs abnormal IMs.
Results Among 14 402 febrile infants with SARS-CoV-2 testing, 8413 (58.4%) were aged 29 to 60 days; 8143 (56.5%) were male; and 3753 (26.1%) tested positive. Compared with infants who tested negative, a lower proportion of infants who tested positive for SARS-CoV-2 had UTI (0.8% [95% CI, 0.5%-1.1%]) vs 7.6% [95% CI, 7.1%-8.1%]), bacteremia without meningitis (0.2% [95% CI, 0.1%-0.3%] vs 2.1% [95% CI, 1.8%-2.4%]), and bacterial meningitis (<0.1% [95% CI, 0%-0.2%] vs 0.5% [95% CI, 0.4%-0.6%]). Among infants aged 29 to 60 days who tested positive for SARS-CoV-2, 0.4% (95% CI, 0.2%-0.7%) had UTI, less than 0.1% (95% CI, 0%-0.2%) had bacteremia, and less than 0.1% (95% CI, 0%-0.1%) had meningitis. Among SARS-CoV-2–positive infants, a lower proportion of those with normal IMs had bacteremia and/or bacterial meningitis compared with those with abnormal IMs (<0.1% [0%-0.2%] vs 1.8% [0.6%-3.1%]).
Conclusions and Relevance The prevalence of UTI, bacteremia, and bacterial meningitis was lower for febrile infants who tested positive for SARS-CoV-2, particularly infants aged 29 to 60 days and those with normal IMs. These findings may help inform management of certain febrile infants who test positive for SARS-CoV-2.
Nina UrkeErtesvåg et al.
Post COVID-19 condition after delta infection and omicron reinfection in children and adolescents
eBioMedicne, May 2023; doi.org/10.1016/j.ebiom.2023.104599
Abstract
The burden of COVID-19 in children and adolescents has increased during the delta and omicron waves, necessitating studies of long-term symptoms such as fatigue, dyspnoea and cognitive problems. Furthermore, immune responses in relation to persisting symptoms in younger people have not been well characterised. In this cohort study, we investigated the role of antibodies, vaccination and omicron reinfection upon persisting and long-term symptoms up to 8 months post-delta infection.
Methods
SARS-CoV-2 RT-PCR positive participants (n = 276, aged 10–20 years) were prospectively recruited in August 2021. We recorded the major symptoms of post COVID-19 condition and collected serum samples 3- and 8-months post delta infection. Binding antibodies were measured by spike IgG ELISA, and surrogate neutralising antibodies against Wuhan and delta variants by the hemagglutination test (HAT).
Findings
After delta infection, persisting symptoms at 3 months were significantly associated with higher delta antibody titres (OR 2.97, 95% CI 1.57–6.04, p = 0.001). Asymptomatic acute infection compared to symptomatic infection lowered the risk of persisting (OR 0.13, 95% CI 0.02–0.55, p = 0.013) and long-term (OR 0.28 95% CI 0.11–0.66, p = 0.005) symptoms at 3 and 8 months, respectively. Adolescents (16–20 years) were more likely to have long-term symptoms compared to children (10–15 years) (OR 2.44, 95% CI 1.37–4.41, p = 0.003).
Interpretation
This clinical and serological study compares long-term symptoms after delta infection between children and adolescents. The association between high antibody titres and persisting symptoms suggest the involvement of an immune mechanism. Similarly to adults, the dominant long-term symptoms in children are fatigue, dyspnoea and cognitive problems.
SheriMadigan et al.
Changes in Depression and Anxiety Among Children and Adolescents From Before to During the COVID-19 Pandemic
A Systematic Review and Meta-analysis
JAMA, May 2023; https://doi:10.1001/jamapediatrics.2023.0846
Abstract
Importance There is a growing body of high-quality cohort-based research that has examined changes in child and adolescent mental health during the COVID-19 pandemic vs before the pandemic. Some studies have found that child and adolescent depression and anxiety symptoms have increased, while others have found these symptoms to have remained stable or decreased.
Objective To synthesize the available longitudinal cohort-based research evidence to estimate the direction and magnitude of changes in depression and anxiety symptoms in children and adolescents assessed before and during the pandemic.
Data Sources Medline, Embase, and PsycInfo were searched for studies published between January 1, 2020, and May 17, 2022.
Study Selection Included studies reported on depression and/or anxiety symptoms, had cohort data comparing prepandemic to pandemic estimates, included a sample of children and/or adolescents younger than 19 years, and were published in English in a peer-reviewed journal.
Data Extraction and Synthesis In total, 53 longitudinal cohort studies from 12 countries with 87 study estimates representing 40 807 children and adolescents were included.
Main Outcomes and Measures Standardized mean changes (SMC) in depression and anxiety symptoms from before to during the pandemic.
Results The analysis included 40 807 children and adolescents represented in pre–COVID-19 studies and 33 682 represented in during–COVID-19 studies. There was good evidence of an increase in depression symptoms (SMC, 0.26; 95% CI, 0.19 to 0.33). Changes in depression symptoms were most conclusive for study estimates among female individuals (SMC, 0.32; 95% CI, 0.21 to 0.42), study estimates with mid to high income (SMC, 0.35; 95% CI, 0.07 to 0.63), and study estimates sourced from North America (SMC, 0.25; 95% CI, 0.15 to 0.36) and Europe (SMC, 0.35; 95% CI, 0.17 to 0.53). There was strong evidence that anxiety symptoms increased slightly during the pandemic (SMC, 0.10; 95% CI, 0.04 to 0.16), and there was some evidence of an increase in study estimates with mid to high income.
Conclusions This systematic review and meta-analysis of longitudinal studies including children and adolescents found an increase in depression symptoms during the COVID-19 pandemic, particularly among female individuals and those from relatively higher-income backgrounds Alane Izu et al.
All-cause and pathogen-specific lower respiratory tract infection hospital admissions in children younger than 5 years during the COVID-19 pandemic (2020–22) compared with the pre-pandemic period (2015–19) in South Africa: an observational study
The Lancet, May 2023; doi.org/10.1016/S1473-3099(23)00200-1
Abstract
Non-pharmaceutical interventions affected the circulation of and illness due to endemic respiratory pathogens during the COVID-19 pandemic. We investigated the incidence of admissions to hospital for overall and specific pathogen-associated lower respiratory tract infection (LRTI) during the COVID-19 pandemic compared with incidence in the pre-pandemic period.
Methods
In this observational study, we analysed surveillance data for children younger than 5 years from two public hospitals in Soweto, South Africa, for all-cause LRTI, respiratory syncytial virus (RSV), influenza, human metapneumovirus, and Bordetella pertussis from Jan 1, 2015 to Dec 31, 2022. Data were obtained from an electronic database that includes information for all admissions to the general paediatric wards at the two hospitals, automatically identified by a computer program. We excluded children admitted to hospital with incidental SARS-CoV-2 infection or COVID-19 without LRTI diagnosis. Incidence during COVID-19 pandemic years (2020, 2021, and 2022) were compared with pre-pandemic rates (2015–19).
Findings
Overall, there were 42 068 all-cause hospital admissions, including 18 303 all-cause LRTI hospital admissions, from Jan 1, 2015, to Dec 31, 2022, 17 822 (42·4%) of whom were female, 23 893 (57·0%) were male, and 353 (0·8%) had missing data. All-cause LRTI incidence risk ratio (IRR) was 30% lower in 2020 (IRR 0·70, 95% CI 0·67–0·74) and 13% lower in 2021 (0·87, 0·83–0·91), but 16% higher in 2022 (1·16, 1·11–1·21) compared with the pre-pandemic period. Furthermore, compared with the pre-pandemic period, incidence of RSV-associated LRTI (0·52, 0·45–0·58), influenza-associated LRTI (0·05, 0·02–0·11), and pulmonary tuberculosis (0·52, 0·41–0·65) were lower in 2020, with similar trends observed for human-metapneumovirus-associated LRTI, pertussis, and invasive pneumococcal disease (IPD). Compared with the pre-pandemic period, by 2022, RSV-associated LRTI incidence was similar (1·04, 0·95–1·14) and influenza-associated LRTI showed a non-significant increase (1·14, 0·92–1·39), whereas incidence remained lower for tuberculosis (0·79, 0·65–0·94) and IPD (0·51, 0·24–0·99). In 2022, the incidence of COVID-19-associated LRTI hospital admission (65 per 100 000 children younger than 5 years) was lower than pre-pandemic RSV-associated LRTI (0·23, 0·19–0·27) but higher than pre-pandemic influenza-associated LRTI (1·19, 0·97–1·45), although the difference was not significant. All-cause LRTI death in 2022 (57 per 100 000 children younger than 5 years) was 28% higher than in the pre-pandemic period (1·28, 1·03–1·58).
Interpretation
The higher incidence of all-cause LRTI admissions to hospital in 2022 compared with the pre-pandemic period is partly due to ongoing COVID-19 admission to hospital, and could worsen if other endemic respiratory pathogens revert to pre-pandemic incidence. Interventions, including the introduction of vaccines for people who are pregnant that aim to prevent RSV and possibly COVID-19 in young children, are warranted.
Iulia G Ionescu et al.
BNT162b2 Effectiveness Against Delta and Omicron Variants of Severe Acute Respiratory Syndrome Coronavirus 2 in Adolescents Aged 12–17 Years, by Dosing Interval and Duration
Academic, January 2023; doi.org/10.1093/infdis/jiad006
Abstract
Two- and 3-dose BNT162b2 vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, including Delta and Omicron variants, was assessed among adolescents in Canada, where first and second doses were spaced longer than the manufacturer-specified 3-week interval.
Conclusions
In adolescents, 2 BNT162b2 doses provided strong and sustained protection against Delta but reduced and rapidly waning VE against Omicron. A longer interval between first and second doses and a third dose marginally improved Omicron protection.
Alejandro Jara et al.
Effectiveness of an inactivated SARS-CoV-2 vaccine in children and adolescents: a large-scale observational study
The Lancet, April 20223doi.org/10.1016/j.lana.2023.100487
Abstract
Policymakers urgently need evidence to adequately balance the costs and benefits of mass vaccination against COVID-19 across all age groups, including children and adolescents. In this study, we aim to assess the effectiveness of CoronaVac's primary series among children and adolescents in Chile.
Interpretation
Our results suggest that a complete primary immunization schedule with the inactivated SARS-CoV-2 vaccine provides effective protection against severe COVID-19 disease for children 6–16 years.
ConstanzeHeinzel et al.
Saliva and Plasma Antibody Levels in Children and Adolescents After Primary Infection With Omicron Variants of SARS-CoV-2 Infection in Germany
JAMA, April 2023; doi:10.1001/jamapediatrics.2023.0631
Abstract
Omicron is escaping neutralization by antibodies induced by prior infections and vaccination.1 Little information is available on antibody prevalence attributable to a primary Omicron infection; a challenging investigation as many individuals are already vaccinated and/or have had pre-Omicron SARS-CoV-2 infections. Antibodies in saliva may contribute to protection against recurrent SARS-CoV-2 infection.2 Since summer 2020, we have been monitoring 1850 children and adolescents for exposure to SARS-CoV-2 in Tübingen, Germany, to investigate antibody response after primary Omicron infection on a large scale.
Methods
This cross-sectional study is part of the longitudinal prospective observational study approved by the ethics committee of the University Hospital Tübingen.3 This report follows the STROBE reporting guideline. Participants or their legal representatives gave written informed consent. Individuals with a prior SARS-CoV-2 infection as documented by a certified laboratory test (polymerase chain reaction or antigen) were included. Enzyme-linked immunosorbent assays were performed to quantify IgG reactive to SARS-CoV-2 receptor binding domain of the index (RBD-WT) and Omicron variants (RBD-BA.1, RBD-BA.2), to the spike trimer of the index (Tri-WT) and Omicron (Tri-BA.1), and to nucleocapsid-protein (NCP-BA.1) in saliva4 and in plasma5,6 (eMethods in Supplement 1).
Discussion
SARS-CoV-2 Omicron reinfections within short periods are increasingly reported.7 Our data suggest that this might be explained by a weak humoral immune response to Omicron. In contrast to pre-Omicron variants, a primary Omicron infection elicited only a poor IgG antibody response, possibly resulting in insufficient infection prevention by salivary IgG. The observed neutralization escape of recurrent Omicron variants may be due to the absence of antibodies rather than reduced binding affinity. As a result, first-time SARS-CoV-2 infections with the Omicron variant may remain also largely undetected by seroprevalence studies. Further work on cellular immune responses and viral loads is needed to draw conclusions on the immunogenicity of Omicron and to test whether the results of this study are generalizable a larger population, including adults.
Brian W. McCrindle et al.
SARS-CoV-2 Variants and Multisystem Inflammatory Syndrome in Children
NEJM, April 2023; DOI: 10.1056/NEJMc2215074
Abstract
Multisystem inflammatory syndrome in children (MIS-C), a delayed hyperinflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is an important cause of illness in children. Changes in the prevalent variant throughout the coronavirus disease 2019 pandemic have influenced the transmissibility and incidence of disease, but their association with clinical presentation and outcomes of MIS-C is incompletely known.1,2
We used data from the International Kawasaki Disease Registry (IKDR) to identify patients who had been hospitalized with SARS-CoV-2 infection during the period from April 2020 through June 2022 and met the criteria for MIS-C according to the Centers for Disease Control and Prevention.
The features of MIS-C at presentation were more often similar to the features of Kawasaki’s disease among patients hospitalized with SARS-CoV-2 infection during the more recent variant periods than among those during the earlier periods; however, without a definitive diagnostic test for either condition, it remains to be determined whether this represents a true change in phenotype or an increase in the number of patients with Kawasaki’s disease who meet the criteria for MIS-C through concurrent but unrelated SARS-CoV-2 infection. Although we acknowledge the limitations of the ecologic study design and the inherent risk of misclassification of variant at the patient level, our data support observations that the severity of MIS-C has decreased with each subsequent SARS-CoV-2 variant. Nevertheless, critical illness in patients hospitalized with MIS-C remains prevalent.
Brittany J. Raffa et al.
Ingestion of Illicit Substances by Young Children Before and During the COVID-19 Pandemic
JAMA, April 2023; doi:10.1001/jamanetworkopen.2023.9549
Abstract
Importance Information about the trend in illicit substance ingestions among young children during the pandemic is limited.
Objectives To assess immediate and sustained changes in overall illicit substance ingestion rates among children younger than 6 years before and during the COVID-19 pandemic and to examine changes by substance type (amphetamines, benzodiazepines, cannabis, cocaine, ethanol, and opioids) while controlling for differing statewide medicinal and recreational cannabis legalization policies.
Design, Setting, and Participants Retrospective cross-sectional study using an interrupted time series at 46 tertiary care children’s hospitals within the Pediatric Health Information System (PHIS). Participants were children younger than 6 years who presented to a PHIS hospital for an illicit substance(s) ingestion between January 1, 2017, and December 31, 2021. Data were analyzed in February 2023.
Exposure Absence or presence of the COVID-19 pandemic.
Main Outcome(s) and Measure(s) The primary outcome was the monthly rate of encounters for illicit substance ingestions among children younger than 6 years defined by International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code(s) for poisoning by amphetamines, benzodiazepines, cannabis, cocaine, ethanol, and opioids. The secondary outcomes were the monthly rate of encounters for individual substances.
Results Among 7659 children presenting with ingestions, the mean (SD) age was 2.2 (1.3) years and 5825 (76.0%) were Medicaid insured/self-pay. There was a 25.6% (95% CI, 13.2%-39.4%) immediate increase in overall ingestions at the onset of the pandemic compared with the prepandemic period, which was attributed to cannabis, opioid, and ethanol ingestions. There was a 1.8% (95% CI, 1.1%-2.4%) sustained monthly relative increase compared with prepandemic trends in overall ingestions which was due to opioids. There was no association between medicinal or recreational cannabis legalization and the rate of cannabis ingestion encounters.
Conclusions and Relevance In this study of illicit substance ingestions in young children before and during the COVID-19 pandemic, there was an immediate and sustained increase in illicit substance ingestions during the pandemic. Additional studies are needed to contextualize these findings in the setting of pandemic-related stress and to identify interventions to prevent ingestions in face of such stress, such as improved parental mental health and substance treatment services, accessible childcare, and increased substance storage education.
Rosa Morello et al.
Risk factors for post-COVID-19 condition (Long Covid) in children: a prospective cohort study
The Lancet, April 2023; doi.org/10.1016/j.eclinm.2023.101961
Abstract
Adults and children can develop post-Covid-19 condition (PCC) (also referred to as Long Covid). However, existing evidence is scarce, partly due to a lack of a standardised case definition, short follow up duration, and heterogenous study designs, resulting in wide variation of reported outcomes. The primary aim of this study was to characterise risk factors for PCC and longitudinal rates of recovery in a cohort of children and young people using a standardised protocol.
Methods
We performed a prospective “disease-based” cohort study between 01/02/2020 to 31/10/2022 including children aged 0–18 years old, with a previous diagnosis of Covid-19. Children with microbiologically confirmed SARS-CoV-2 infection, were invited for an in-clinic follow-up assessment at a paediatric post-covid clinic in Rome, Italy, at serial intervals (3-, 6-, 12- and 18-months post-onset). PCC was defined as persistence of otherwise unexplained symptoms for at least three months after initial infection. The statistical association between categorical variables was obtained by Chi-squared tests or Fisher's exact tests. Multivariable logistic regressions are presented using odds ratios (OR) and 95% confidence interval (CI). Survival analysis was conducted using the Kaplan–Meier method.
Findings
1243 children were included, median age: 7.5 (4–10.3) years old; 575 (46.3%) were females. Of these, 23% (294/1243) were diagnosed with PCC at three months post-onset. Among the study population, 143 patients remained symptomatic at six months, 38 at 12 months, and 15 at 18 months follow up evaluation. The following risk factors were associated with PCC: >10 years of age (OR 1.23; 95% CI 1.18–1.28), comorbidities (OR 1.68; 95% CI 1.14–2.50), and hospitalisation during the acute phase (OR 4.80; 95%CI 1.91–12.1). Using multivariable logistic regression, compared to the Omicron variant, all other variants were significantly associated with PCC at 3 and 6 months. At least one dose of vaccine was associated with a reduced, but not statistically significant risk of developing PCC.
Interpretation
In our study, acute-phase hospitalisation, pre-existing comorbidity, being infected with pre-Omicron variants and older age were associated with a higher risk of developing PCC. Most children recovered over time, but one-in-twenty of those with PCC at three months reported persistent symptoms 18 months post-Sars-CoV-2 infection. Omicron infection was associated with shorter recovery times. We did not find a strong protective effect of vaccination on PCC development. Although our cohort cannot be translated to all Italian children with PCC as more nationwide studies are needed, our findings highlight the need of new strategies to prevent and treat pediatric PCC are needed.
Madeleine Otto et al.
COVID-19 related ICU admissions in paediatric and young adult patients in Australia: a national case series 2020–2022
The Lancet, April 2023; doi.org/10.1016/j.lanwpc.2023.100763
Abstract
COVID-19 pandemic research efforts have focused on disease phenotypes in adults. A distinct spectrum of illness has been documented in paediatric populations. We aimed to review paediatric intensive care unit (ICU) admissions in Australia, across differing variant predominant phases of the pandemic.
Interpretation
This study demonstrated an appreciable burden of COVID-19 in paediatric patients. Adolescent patients presented phenotypically similar to young adults, however, illness severity was lower in younger cohorts. The Omicron phase of the pandemic demonstrated an increased age-specific population incidence of COVID-19 ICU admissions, albeit a reduced incidence when based on SARS-CoV-2 notifications.
M Edwards, Kathleen M Neuzi
Developing Mucosal Vaccines for Severe Acute Respiratory Syndrome Coronavirus 2: What Will It Take?
CID, December2022; doi.org/10.1093/cid/ciac935
Abstract
Initial efficacy results from the randomized clinical trials of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA vaccines were impressive. Vaccine efficacy against laboratory-confirmed coronavirus disease 2019 (COVID-19) approached 95% after 2 doses of vaccine [1, 2]. We were pleased by these findings and encouraged that the vaccines would also reduce infection and subsequent transmission. However, the outbreak of COVID-19 in a largely vaccinated group of adults in July 2021 in Barnstable County, Massachusetts, highlighted that prevention of infection and subsequent transmission with parenteral vaccines was a daunting task [3]. Subsequent population-based studies have confirmed the limitations of vaccines and prior infection in conferring sterilizing immunity. While binding and neutralizing antibody responses and systemic cellular responses have been standard measures of infection and vaccine-induced immunity, mucosal antibody or cellular responses in tissue-resident lymphocytes have been less well studied. Since SARS-CoV-2 infection is initiated at the mucosal surfaces in the respiratory tract, generation of robust adaptive immunity at respiratory mucosal sites has the potential to prevent infection and subsequent transmission, in addition to protecting against disease.
The work presented by Cohen and his colleagues at the National Institutes of Health (NIH) in this issue of Clinical Infectious Diseases provides some understanding of the challenges of using parenteral vaccines to stimulate mucosal immunity [4]. They measured antibody levels to the SAR-CoV-2 spike and nucleocapsid proteins in the plasma, nose, and saliva of vaccine recipients and infected persons who were employees at the NIH in Bethesda, Maryland. After vaccination, anti-spike antibody levels in the plasma were higher and declined more slowly than antibody levels in the nose and saliva. In addition, vaccination of previously infected persons boosted anti-spike antibody levels more in the plasma than in the nose or saliva. Both nasal and saliva anti-spike antibody levels correlated significantly with plasma antibody, suggesting that mucosal antibodies were derived from transudation from the blood rather than local production. The authors concluded, “these observations indicate the need for development of mucosal vaccines to induce potent immune responses at sites where SARS-CoV-2 infection occurs.”
Mucosal vaccines with the potential to generate effective local immunity to SARS-CoV-2 in the respiratory tract would be attractive options, although historically mucosal vaccines have posed unique challenges. Currently, there are 5 prototype mucosal vaccines licensed for human use, with 4 administered orally and only 1 vaccine licensed for intranasal administration, live attenuated influenza vaccine (LAIV). As another example of the challenges with intranasal vaccines, the first licensed mucosal vaccine in Europe, an intranasal inactivated influenza vaccine with a unique adjuvant, was associated with Bell's palsy in a significant number of vaccine recipients and led to the removal of that mucosal vaccine from the European market [8]. Thus, live mucosal vaccines represent a delicate balance between “overattenuation,” generating poorly immunogenic responses, and “underattenuation,” leading to increased rates of local and systemic adverse events after vaccine receipt. In addition, as shown with the intranasal inactivated vaccine with the adjuvant, such vaccines may pose unique risks associated with their route of administration.
Despite the previous challenges with mucosal vaccines for respiratory infections, there are many mucosal vaccines in preclinical studies for SAR-CoV-2.
Few human studies have been conducted with mucosal vaccines.
How will these mucosal vaccines be evaluated to determine their efficacy? One approach used in the human studies thus far is to simply compare the immune responses both locally and systemically between the mucosal and the parenteral vaccines. However, this poses challenges because the level of antibody needed to prevent infection or disease has not been precisely determined. Another approach would be to conduct large efficacy studies, such as the study being conducted by Codagenix and the Serum Institute of India where the efficacy will be determined by comparing the number of laboratory-confirmed cases in the vaccine and the placebo groups, like the pivotal trials of the parenteral vaccines. However, this approach poses challenges as well since many people are already vaccinated, and thus the population is not generalizable. The selection of an appropriate and generalizable vaccinated population may likewise be difficult. The ethics of a placebo-controlled trial in susceptible individuals when effective vaccines exist raises additional concerns. One potential option to study the impact of the vaccines on infectivity would be to use human challenge models; some of these studies are ongoing. Like the animal studies, the challenge model could more precisely determine the impact of the vaccine on infectivity. However, human challenge studies have only been performed with the original Wuhan strain; how earlier findings would extrapolate to the evolving variants has not been determined.
Overall, we agree with Cohen et al that mucosal vaccines for SARS-CoV-2 need to be pursued. However, there are significant hurdles to mucosal vaccine development, including incomplete knowledge of the nature of protective mucosal immune response, ensuring the safety and efficacy of new mucosal adjuvants that might be needed to provide a robust immune response, and the most effective ways to test the effectiveness of the vaccines for prevention of infection in a largely vaccinated and/or previously infected population.This is further complicated by the continued circulation of evolved SARS-CoV-2 viruses that cause human infections. We propose that the best path to success is the coordinated, multidisciplinary effort that was used to accelerate the development of the initial parenteral SARS-CoV-2 vaccines. Such an approach will require a public investment of funds to ensure the best scientific and strategic path forward for development of mucosal vaccines.
KojiMatsuo et al.
Severe Maternal Morbidity and Mortality of Pregnant Patients With COVID-19 Infection During the Early Pandemic Period in the US
JAMA, April 2023; doi:10.1001/jamanetworkopen.2023.7149
Abstract
From the beginning of the COVID-19 pandemic in mid-March, 2020, through mid-February 2023, nearly 103 million cases and 1.1 million deaths were reported in the United States.1 Increasing evidence suggests that pregnant patients with COVID-19 infection are at high risk for adverse pregnancy outcomes.2-4
Several studies have examined outcomes before and during the pandemic periods.2-4 National-level data comparing pregnancy outcomes with and without COVID-19-infection are limited but are clinically compelling. The objective of this study was to examine the patient characteristics and maternal outcomes associated with COVID-19 infection among pregnant patients at delivery during the early pandemic period in the United States.
Discussion
This national-level analysis found substantial adverse maternal outcomes among pregnant patients with COVID-19 infection at delivery during the early pandemic in the US. Specifically, the odds of severe respiratory complications were increased among pregnant patients with COVID-19 infection at delivery. Greater than 10-fold increased maternal mortality risk associated with COVID-19 infection validates prior investigations with national-level data6; moreover, increased failure-to-rescue risk following severe maternal morbidity among patients with COVID-19 adds important information.
Key limitations included lack of information on COVID-19 infection status (eg, severity and treatment), neonatal outcomes, delivery indication, and cause of death. Despite these limitations, the evaluation of the initial pandemic period in this study demonstrates the substantial morbidity and mortality of COVID-19 in pregnant patients and highlights the importance of prevention of COVID-19 in this population. Further investigation to assess the generalizability in the subsequent vaccine era is warranted.
Peijun Wen et al.
Proper use of light environments for mitigating the effects of COVID-19 and other prospective public health emergency lockdowns on sleep quality and fatigue in adolescents
Cell, March 2023; doi.org/10.1016/j.heliyon.2023.e14627
Abstract
Coronavirus disease 2019 (COVID-19) remains a public health emergency of international concern, and some countries still implement strict regional lockdowns. Further, the upcoming 2023 Asian Games and World University Games will implement a closed-loop management system. Quarantine can harm mental and physical health, to which adolescents are more vulnerable compared with adults. Previous studies indicated that light can affect our psychology and physiology, and adolescents were exposed to the artificial light environment in the evening during the lockdown. Thus, this study aimed to establish and assess appropriate residential light environments to mitigate the effects of lockdowns on sleep quality and fatigue in adolescents. The participants were 66 adolescents (12.15 ± 2.45 years of age) in a closed-loop management environment, who participated in a 28-day (7-day baseline, 21-day light intervention) randomized controlled trial of a light-emitting diode (LED) light intervention. The adolescents were exposed to different correlated color temperature (CCT) LED light environments (2000 K or 8000 K) for 1 h each evening. The results for self-reported daily sleep quality indicated that the low CCT LED light environment significantly improved sleep quality (p < 0.05), and the blood test results for serum urea and hemoglobin indicated that this environment also significantly reduced fatigue (p < 0.05) and moderately increased performance, compared to the high CCT LED light environment. These findings can serve as a springboard for further research that aims to develop interventions to reduce the effects of public health emergency lockdowns on mental and physical health in adolescents, and provide a reference for participants in the upcoming Asian Games and World University Games.
Andrea G. Edlow et al.
Sex-Specific Neurodevelopmental Outcomes Among Offspring of Mothers With SARS-CoV-2 Infection During Pregnancy
JAMA, March 2023; doi:10.1001/jamanetworkopen.2023.4415
Abstract
Importance Prior studies using large registries have suggested a modest increase in risk for neurodevelopmental diagnoses among children of mothers with immune activation during pregnancy, and such risk may be sex-specific.
Objective To determine whether in utero exposure to SARS-CoV-2 is associated with sex-specific risk for neurodevelopmental disorders up to 18 months after birth, compared with unexposed offspring born during or prior to the COVID-19 pandemic period.
Design, Setting, and Participants This retrospective cohort study included the live offspring of all mothers who delivered between January 1 and December 31, 2018 (born and followed up before the COVID-19 pandemic), between March 1 and December 31, 2019 (born before and followed up during the COVID-19 pandemic), and between March 1, 2020, and May 31, 2021 (born and followed up during the COVID-19 pandemic). Offspring were born at any of 8 hospitals across 2 health systems in Massachusetts.
Exposures Polymerase chain reaction evidence of maternal SARS-CoV-2 infection during pregnancy.
Main Outcomes and Measures Electronic health record documentation of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes corresponding to neurodevelopmental disorders.
Conclusions and Relevance In this cohort study of offspring with SARS-CoV-2 exposure in utero, such exposure was associated with greater magnitude of risk for neurodevelopmental diagnoses among male offspring at 12 months following birth. As with prior studies of maternal infection, substantially larger cohorts and longer follow-up will be required to reliably estimate or refute risk.
Tumaini R. Coker et al.
Addressing the Long-term Effects of the COVID-19 Pandemic on Children and Families
A Report From the National Academies of Sciences, Engineering, and Medicine
JAMA, March 2023; doi:10.1001/jama.2023.4371
Abstract
My mom lost her business…we were trying to maintain everything but the bills just kept piling up. Food prices went up, rent, everything went up.…We didn’t know if we were gonna get food the next day, if we were even going to have our place.…It got to the point where I wasn’t able to sleep properly anymore or eat properly anymore, and I did gain a lot of anxiety and depression.
This is just one of many stories from children and youth who experienced the worst pandemic in US history. Although the COVID-19 Public Health Emergency is set to end on May 11, 2023, it is clear it has, and will continue to have, deleterious effects on the children and youth who experienced the pandemic during sensitive periods of their development.
The National Academies of Sciences, Engineering, and Medicine (NASEM) released a consensus report that reviews the impact of COVID-19 on the health and well-being of children and families thus far, and what needs to be done to attenuate longer-term negative effects.1
The NASEM committee for this report was intentionally designed to address areas most relevant to children and families (education, social and emotional development, physical and mental health, economic well-being), and to focus on the groups who bore the brunt of the pandemic: those from racial and ethnic minoritized groups and low-income families.
In its multidisciplinary review of the literature, the committee found that across almost every outcome of well-being—education, social, emotional, physical, mental, and economic—low-income children and families in racially and ethnically minoritized communities have experienced a disproportionately high burden from the pandemic, which is rooted in structural racism, creating long-standing and pervasive inequities.
In the US more than 265 000 children have lost a parent or caregiver to COVID-19.2 The number of bereaved US children is high overall but there are important differences: 1 in 753 White children lost a parent or caregiver to COVID-19, but rates for Black (1 in 310), Latino (1 in 412), and Native American (1 in 168) children are even higher, and portend a cascade of negative effects that can follow if appropriate supports are not ensured for these children and their families throughout their continued development.3
Early in the pandemic, schools closed, parents lost jobs, and children lost learning opportunities, stabilizing routines, and social and emotional supports. While these initial stressors resulted in immediate effects on children and families, the long-term impact remains unknown. There were drops in enrollment in early childhood programs, elementary through high school, and colleges. Students at all levels missed learning, though the greatest losses were among students without access to in-person schooling, children from minoritized populations, and those from low-income households.4
Maternal mortality rates increased during the pandemic, with the largest increases among Black and Latina women5; childhood obesity and food insecurity increased, as did the number of fentanyl-related substance overdose deaths, with the highest rates among Native American youth.6 Although the US started the pandemic already in a child mental health crisis, in which 1 in 5 children had a mental health condition, and just half of those received treatment, rates of depression and anxiety symptoms in children have continue to rise.7
The federal response to the pandemic was swift and effective, but those federal provisions have largely ended. Low-income families will require ongoing action at the state and federal level. The Child Tax Credit (CTC), for example, was expanded, increased, and delivered in monthly allotments during part of the pandemic, which resulted in a reduction of food insecurity and household and child poverty. The expansion of the CTC, continuous eligibility for Medicaid enrollees, and other effective pandemic-era federal provisions that buffered negative health and economic effects on children and families, including stimulus payments and expanded SNAP (Supplemental Nutrition Assistance Program) benefits, have been discontinued or are ending.
The NASEM committee makes recommendations that provide a roadmap to providing essential supports to children and families to recover from the pandemic’s effects and to rectify the preexisting inequities that created a disproportionate burden on minoritized and low-income children and families. The committee’s recommendations1 are as follows.
Ousseny Zerbo et al.
Maternal SARS-CoV-2 vaccination and infant protection against SARS-CoV-2 during the first six months of life
Nature, February 2023; doi.org/10.1038/s41467-023-36547-4
Abstract
We examined the effectiveness of maternal vaccination against SARS-CoV-2 infection in 30,311 infants born at Kaiser Permanente Northern California from December 15, 2020, to May 31, 2022. Using Cox regression, the effectiveness of ≥2 doses of COVID-19 vaccine received during pregnancy was 84% (95% confidence interval [CI]: 66, 93), 62% (CI: 39, 77) and 56% (CI: 34,71) during months 0–2, 0–4 and 0- 6 of a child’s life, respectively, in the Delta variant period. In the Omicron variant period, the effectiveness of maternal vaccination in these three age intervals was 21% (CI: −21,48), 14% (CI: −9,32) and 13% (CI: −3,26), respectively. Over the entire study period, the incidence of hospitalization for COVID-19 was lower during the first 6 months of life among infants of vaccinated mothers compared with infants of unvaccinated mothers (21/100,000 person-years vs. 100/100,000 person-years). Maternal vaccination was protective, but protection was lower during Omicron than during Delta. Protection during both periods decreased as infants aged.
Lyndsay A. Avalos et al.
Association of the COVID-19 Pandemic With Unstable and/or Unsafe Living Situations and Intimate Partner Violence Among Pregnant Individuals
JAMA, February 2023; doi:10.1001/jamanetworkopen.2023.0172
Abstract
Importance The social, behavioral, and economic consequences of the COVID-19 pandemic may be associated with unstable and/or unsafe living situations and intimate partner violence (IPV) among pregnant individuals.
Objective To investigate trends in unstable and/or unsafe living situations and IPV among pregnant individuals prior to and during the COVID-19 pandemic.
Design, Setting, and Participants A cross-sectional population-based interrupted time-series analysis was conducted among Kaiser Permanente Northern California members who were pregnant and screened for unstable and/or unsafe living situation and IPV as part of standard prenatal care between January 1, 2019, and December 31, 2020.
Exposures COVID-19 pandemic (prepandemic period: January 1, 2019, to March 31, 2020; during pandemic period: April 1 to December 31, 2020).
Main Outcomes and Measures The 2 outcomes were unstable and/or unsafe living situations and IPV. Data were extracted from electronic health records. Interrupted time-series models were fit and adjusted for age and race and ethnicity.
Conclusions and Relevance This cross-sectional study noted an overall increase in unstable and/or unsafe living situations and IPV over the 24-month period, with a temporary increase associated with the COVID-19 pandemic. It may be useful for emergency response plans to include IPV safeguards for future pandemics. These findings suggest the need for prenatal screening for unsafe and/or unstable living situations and IPV coupled with referral to appropriate support services and preventive interventions.
Yael Travis-Lumer et al.
Rates of Spontaneous Abortion in Israel Before and During the COVID-19 Pandemic
JAMA, february 2023; doi:10.1001/jamanetworkopen.2023.0233
Abstract
Spontaneous abortion (SA) (pregnancy loss before 20 weeks’ gestation) affects between 11% and 20% of pregnancies.1 Studies of the SA rate during the COVID-19 pandemic focus mainly on vaccine safety.2 However, exposure to the prolonged biopsychosocial adversities of the pandemic may have cumulated in a perfect storm of risk factors (eg, infection and stress during pregnancy)3,4 associated with an increased SA rate. Alternatively, as found for other pregnancy-related outcomes, COVID-19 attenuation strategies may have been associated with reduced stress and, hence, SA. However, these possibilities are unexamined.
Discussion
The results showed that the RRs of SA rates during 3 pandemic waves did not differ from rates during the 3 prepandemic years. Forecast models suggested that the SA incidence will increase slightly compared with prepandemic levels, even assuming an absence of an association of the pandemic with SA rates. However, pandemic changes may offset our forecasts. This result may reflect ongoing socioeconomic disruptions and COVID-19 anxiety.
This study has some limitations. Due to imprecise timing in our data, we could not examine the association of vaccination or cases of COVID-19 infection with SA rates. Truncation bias seems modest, as data are available until February 2022, which allowed us to estimate all pregnancies until April 2021. Nonetheless, pregnancy is estimated in this study, and so may contain error. We lacked information on repeated pregnancies, socioeconomic status, and other potential confounders, making residual confounding plausible. However, the results, based on interrupted time series analysis, remained null in 10 rigorous sensitivity analyses.
This study suggests that trends in the monthly SA incidence rates in Israel observed before and during the COVID-19 pandemic did not differ. However, forecasting models indicate an anticipated increase, which underscores the need for enhanced public health monitoring for SA prevention.
Dagan N. et. al
Effectiveness of the BNT162b2 mRNA COVID-19 vaccine in pregnancy
Nature medicine, https://www.nature.com/articles/s41591-021-01490-8.pdf
CONTENUTO : Studio osservazionale di coorte condotto in Israele (20/12/20-3/06/21), su una popolazione di 10.861 donne che rispettavano i criteri di elegibilità : gravidanza in corso all’inizio del follow-up, appartenenza al Clalit Health services per almeno un anno completo, età maggiore di 16 anni, nessuna precedente infezione da Sars-CoV2, non residenti in strutture di lungodegenza, non in isolamento domiciliare per motivi di salute, non impiegato nel sistema sanitario e senza interazioni con ambienti del sistema sanitario nei due giorni precedenti l’inizio dello studio. Tale popolazione, vaccinata per Sars-CoV2 in corso di gravidanza, è stata confrontata con una popolazione di controllo di egual numero di gravide non vaccinate, includendo come outcomes infezioni accertate per Sars-CoV2, infezioni sintomatiche, ospedalizzazione COVID relata, malattia severa e decesso. Durante il follow-up a 77 giorni sono state documentate 131 infezioni nel gruppo delle vaccinate. Vs. 235 infezioni nel gruppo di controllo. L’efficacia del vaccino per infezioni documentate è stata del 96% tra la 7° e la 56°giornata dopo la seconda somministrazione, del 97% per infezioni sintomatiche e dell’89% per l’ospedalizzazione, dati sovrapponibili a quelli della popolazione generale rispetto alle varianti presenti in Israele al momento dello studio.
COMMENTO : I dati suggeriscono che le donne in gravidanza sono ugualmente protette dal vaccino Cominarty ( Pfizer BionTech) quanto le non gravide e la popolazione generale. Lo studio è però limitato alle 10 settimene di gravidanza, non prende in considerazione la questione degli aborti spontanei ( alquanto dibattuta in letteratura) e sopratutto non dice nulla della safety del vaccino in gravidanza. Limiti piuttosto notevoli.
Welzel T. et al.
Methylprednisolone versus intravenous immunoglobulins in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): an open-label, multicentre, randomised trial
The Lancet, February 2023; doi.org/10.1016/S2352-4642(23)00020-2
Abstract
Background
The emergence of paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) led to the widespread use of anti-inflammatory treatments in the absence of evidence from randomised controlled trials (RCTs). We aimed to assess the effectiveness of intravenous methylprednisolone compared with intravenous immunoglobulins.
Methods
This is an open-label, multicentre, two-arm RCT done at ten hospitals in Switzerland in children younger than 18 years hospitalised with PIMS-TS (defined as age <18 years; fever and biochemical evidence of inflammation, and single or multiorgan dysfunction; microbiologically proven or putative contact with SARS-CoV-2; and exclusion of any other probable disease). Patients were randomly assigned 1:1 to intravenous methylprednisolone (10 mg/kg per day for 3 days) or intravenous immunoglobulins (2 g/kg as a single dose). The primary outcome was length of hospital stay censored at day 28, death, or discharge. Secondary outcomes included proportion and duration of organ support. Analyses were done by intention-to-treat. The study was registered with Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588).
Findings
Between May 21, 2021, and April 15, 2022, 75 patients with a median age of 9·1 years (IQR 6·2–12·2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulins group). The median length of hospital stay was 6·0 days (IQR 4·0–8·0) in the methylprednisolone group and 6·0 days (IQR 5·0–8·8) in the intravenous immunoglobulins group (estimated effect size –0·037 of the log10 transformed times, 95% CI –0·13 to 0·065, p=0·42). Fewer patients in the methylprednisolone group (ten [27%] of 37) required respiratory support compared with the intravenous immunoglobulin group (21 [55%] of 38, p=0·025). Need and duration of inotropes, admission to intensive care units, cardiac events after baseline, and major bleeding and thrombotic events were not significantly different between the study groups.
Interpretation
In this RCT, treatment with methylprednisolone in children with PIMS-TS did not significantly affect the length of hospital stay compared with intravenous immunoglobulins. Intravenous methylprednisolone could be an acceptable first-line treatment in children with PIMS-TS.
Fatnic E. et al.
Outcome predictors and patient progress following delivery in pregnant and postpartum patients with severe COVID-19 pneumonitis in intensive care units in Israel (OB-COVICU): a nationwide cohort study
The Lancet, February 2023; doi.org/10.1016/S2213-2600(22)00491-X
Abstract
Background
A key unresolved controversy in severe COVID-19 pneumonitis in pregnancy is the optimum timing of delivery and whether delivery improves or worsens maternal outcomes. We aimed to assess clinical data on every intensive care unit (ICU) day for pregnant and postpartum women admitted to the ICU with COVID-19, with a particular focus on the days preceding and following delivery.
Methods
In this multicentre, nationwide, prospective and retrospective cohort study, we evaluated all pregnant women who were admitted to an ICU in Israel with severe COVID-19 pneumonitis from the 13th week of gestation to the 1st week postpartum. We excluded pregnant patients in which the ICU admission was unrelated to severe COVID-19 pneumonitis. We assessed maternal and neonatal outcomes and longitudinal clinical and laboratory ICU data. The primary overall outcome was maternal outcome (worst of the following: no invasive positive pressure ventilation [IPPV], use of IPPV, use of extracorporeal membrane oxygenation [ECMO], or death). The primary longitudinal outcome was Sequential Organ Failure Assessment (SOFA) score, and the secondary longitudinal outcome was the novel PORCH (positive end-expiratory pressure [PEEP], oxygenation, respiratory support, chest x-ray, haemodynamic support) score. Patients were classified into four groups: no-delivery (pregnant at admission and no delivery during the ICU stay), postpartum (ICU admission ≥1 day after delivery), delivery-critical (pregnant at admission and receiving or at high risk of requiring IPPV at the time of delivery), or delivery-non-critical (pregnant at admission and not critically ill at the time of delivery).
Findings
From Feb 1, 2020, to Jan 31, 2022, 84 patients were analysed: 34 patients in the no-delivery group, four in postpartum, 32 in delivery-critical, and 14 in delivery-non-critical. The delivery-critical and postpartum groups had worse outcomes than the other groups: 26 (81%) of 32 patients in the delivery-critical group and four (100%) of four patients in the postpartum group required IPPV; 12 (38%) and three (75%) patients required ECMO, and one (3%) and two (50%) patients died, respectively. The delivery-non-critical and no-delivery groups had far better outcomes than other groups: six (18%) of 34 patients and two (14%) of 14 patients required IPPV, respectively; no patients required ECMO or died. Oxygen saturation (SpO2), SpO2 to fraction of inspired oxygen (FiO2) ratio (S/F ratio), partial pressure of arterial oxygen to FiO2 ratio (P/F ratio), ROX index (S/F ratio divided by respiratory rate), and SOFA and PORCH scores were all highly predictive for adverse maternal outcome (p<0·0001). The delivery-critical group deteriorated on the day of delivery, continued to deteriorate throughout the ICU stay, and took longer to recover (ICU duration, Mantel-Cox p<0·0001), whereas the delivery-non-critical group improved rapidly following delivery. The day of delivery was a significant covariate for PORCH (p<0·0001) but not SOFA (p=0·09) scores.
Interpretation
In patients who underwent delivery during their ICU stay, maternal outcome deteriorated following delivery among those defined as critical compared with non-critical patients, who improved following delivery. Interventional delivery should be considered for maternal indications before patients deteriorate and require mechanical ventilation.
Watanabe A. et al.
Assessment of Efficacy and Safety of mRNA COVID-19 Vaccines in Children Aged 5 to 11 Years
A Systematic Review and Meta-analysis
JAMA, January 2023; doi:10.1001/jamapediatrics.2022.6243
Abstract
Importance Evidence of the efficacy and safety of messenger RNA (mRNA) COVID-19 vaccines in children aged 5 to 11 years has been emerging. Collecting these data will inform clinicians, families, and policy makers.
Objective To evaluate the efficacy and safety of mRNA COVID-19 vaccines in children aged 5 to 11 years in a systematic review and meta-analysis.
Data Sources PubMed and Embase databases were searched on September 29, 2022, without language restrictions.
Study Selection Randomized clinical trials and observational studies comparing vaccinated vs unvaccinated children aged 5 to 11 years and reporting efficacy or safety outcomes were included. Studies reporting safety outcomes in vaccinated children only (ie, no control group) were also included.
Main Outcomes and Measures The primary outcome was SARS-CoV-2 infections with or without symptoms. The secondary outcomes included symptomatic SARS-CoV-2 infections, hospitalizations, and multisystem inflammatory syndrome in children. The incidences of each AE following vaccination were also evaluated.
Conclusions and Relevance In this systematic review and meta-analysis, COVID-19 mRNA vaccines among children aged 5 to 11 years were associated with measures of efficacy in preventing SARS-CoV-2 infection and severe COVID-19–related illnesses. While most children developed local AEs, severe AEs were rare, and most of AEs resolved within several days. These data provide evidence for future recommendations.
Kienast P. et al.
SARS-CoV-2 variant-related abnormalities detected by prenatal MRI: a prospective case–control study
Sciencedirect, January 2023; doi.org/10.1016/j.lanepe.2023.100587
Abstract
Background
There are known complications for fetuses after infection with SARS-CoV-2 during pregnancy. However, previous studies of SARS-CoV-2 in pregnancy have largely been limited to histopathologic studies of placentas and prenatal studies on the effects of different SARS-CoV-2 variants are scarce to date. To examine the effects of SARS-CoV-2 variants on the placenta and fetus, we investigated fetal and extra-fetal structures using prenatal MRI.
Methods
For this prospective case–control study, two obstetric centers consecutively referred pregnant women for prenatal MRI after confirmed SARS-CoV-2 infection. Thirty-eight prenatal MRI examinations were included after confirmed infection with SARS-CoV-2 and matched 1:1 with 38 control cases with respect to sex, MRI field strength, and gestational age (average deviation 1.76 ± 1.65, median 1.5 days). Where available, the pathohistological examination and vaccination status of the placenta was included in the analysis. In prenatal MRI, the shape and thickness of the placenta, possible lobulation, and vascular lesions were quantified. Fetuses were scanned for organ or brain abnormalities.
Findings
Of the 38 included cases after SARS-CoV-2 infection, 20/38 (52.6%) were infected with pre-Omicron variants and 18/38 (47.4%) with Omicron. Prenatal MRIs were performed on an average of 83 days (±42.9, median 80) days after the first positive PCR test. Both pre-Omicron (P = .008) and Omicron (P = .016) groups showed abnormalities in form of a globular placenta compared to control cases. In addition, placentas in the pre-Omicron group were significantly thickened (6.35, 95% CI .02–12.65, P = .048), and showed significantly more frequent lobules (P = .046), and hemorrhages (P = .002). Fetal growth restriction (FGR) was observed in 25% (n = 5/20, P = .017) in the pre-Omicron group.
Interpretation
SARS-CoV-2 infections in pregnancy can lead to placental lesions based on vascular events, which can be well visualized on prenatal MRI. Pre-Omicron variants cause greater damage than Omicron sub-lineages in this regard.
Eun Jung Jang et al.
BNT162b2 Vaccine Effectiveness Against the SARS-CoV-2 Omicron Variant in Children Aged 5 to 11 Years
JAMA, january 2023; doi:10.1001/jamapediatrics.2022.5221
Abstract
A rapid increase in COVID-19 cases due to the SARS-CoV-2 Omicron variant among children has raised concerns.1 We estimated the effectiveness associated with the BNT162b2 messenger RNA vaccine (Pfizer BioNTech) against SARS-CoV-2 infection and critical infection among children aged 5 to 11 years during an Omicron-dominant period in South Korea.
Discussion
Our findings indicate that vaccine effectiveness against all infection caused by the SARS-CoV-2 Omicron variant was 41.2% at 61 to 90 days after the second-dose vaccination in children in Korea, which is similar to Israeli data.2 Previous studies from Italy and the United States reported that, in the setting of Omicron, the effectiveness against SARS-CoV-2 infection was 30% to 40%.3,4 Nonetheless, our data also suggested that the effectiveness against critical infection remained high throughout the observed period, which is consistent with data from Singapore, with effectiveness against hospitalization of 82.7%.5 The observation period for this analysis coincided with a high incidence of SARS-CoV-2 infection in children in Korea.
The estimated effectiveness against critical infection should be interpreted with caution given the small number of critical cases. Other unmeasured bias might have occurred, including risk and behavioral differences between vaccinated and unvaccinated children. Further studies are needed about bivalent vaccine effectiveness because the present data are from a program using a monovalent vaccine.
The vaccine effectiveness described in this report for the BNT162b2 vaccine against the Omicron variant reinforces previous findings that the vaccination provides a preventive benefit in children. COVID-19 vaccination, even with moderate effectiveness against all infection, can substantially prevent the risk of serious consequences of SARS-CoV-2 infection among children.
Otero S et al.
Maternal Antibody Response and Transplacental Transfer Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection or Vaccination in Pregnancy
CID, November 2022; doi.org/10.1093/cid/ciac793
Abstract
Background
Pregnant persons are at increased risk of severe coronavirus disease 2019 (COVID-19) and adverse obstetric outcomes. Understanding maternal antibody response, duration, and transplacental transfer after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 vaccination is important to inform public health recommendations.
Methods
This prospective observational cohort study included 351 pregnant people who had SARS-CoV-2 infection or COVID-19 vaccination during pregnancy. Immunoglobulin (Ig) G and IgM to SARS-CoV-2 S1 receptor binding domain were measured in maternal and cord blood. Antibody levels and transplacental transfer ratios were compared across (1) disease severity for those with SARS-CoV-2 infection and (2) infection versus vaccination.
Results
There were 252 individuals with SARS-CoV-2 infection and 99 who received COVID-19 vaccination during pregnancy. Birthing people with more severe SARS-CoV-2 infection had higher maternal and cord blood IgG levels (P = .0001, P = .0001). Median IgG transfer ratio was 0.87–1.2. Maternal and cord blood IgG were higher after vaccination than infection (P = .001, P = .001). Transfer ratio was higher after 90 days in the vaccinated group (P < .001). Modeling showed higher amplitude and half-life of maternal IgG following vaccination (P < .0001). There were no significant differences by fetal sex.
Conclusions
COVID-19 vaccination in pregnancy leads to higher and longer lasting maternal IgG levels, higher cord blood IgG, and higher transfer ratio after 90 days compared with SARS-CoV-2 infection. Greater infection severity leads to higher maternal and cord blood antibodies. Maternal IgG decreases over time following both vaccination and infection, reinforcing the importance of vaccination, even after infection, and vaccine boosters for pregnant patients.
Anita Slomski
Moderna COVID-19 Vaccine Safe and Effective for Children 6 Months to 5 Years
JAMA; December 2022; doi:10.1001/jama.2022.20056
Abstract
Atrial found that two 25-μg doses of the mRNA-1273 (Moderna) vaccine were safe for children aged 6 months to 5 years and elicited immune responses consistent with those seen in older children, adolescents, and adults who had received higher doses of the vaccine.
The estimated vaccine efficacy against COVID-19 was 36.8% among 2- to 5-year-olds and 50.6% among 6- to 23-month-olds at a time when the Omicron variant was the predominant circulating variant. Reduced vaccine effectiveness against the Omicron variant has also been observed among adults and adolescents. The long-term effectiveness of mRNA-1273 will continue to be assessed in the trial.
Garneau W.M. et al.
Analysis of Clinical Outcomes of Pregnant Patients Treated With Nirmatrelvir and Ritonavir for Acute SARS-CoV-2 Infection
JAMA; November 2022; doi:10.1001/jamanetworkopen.2022.44141
Abstract
Importance Pregnant people are at increased risk of poor outcomes due to infection with SARS-CoV-2, and there are limited therapeutic options available.
Objective To evaluate the clinical outcomes associated with nirmatrelvir and ritonavir used to treat SARS-CoV-2 infection in pregnant patients.
Design, Setting, and Participants This case series included pregnant patients who were diagnosed with SARS-CoV-2 infection, received nirmatrelvir and ritonavir, and delivered their offspring within the Johns Hopkins Health System between December 22, 2021, and August 20, 2022.
Exposures Treatment with nirmatrelvir and ritonavir for SARS-CoV-2 infection during pregnancy.
Main Outcomes and Measures Clinical characteristics and outcomes were ascertained through manual record review.
Conclusions and Relevance In this case series, pregnant patients who were treated with nirmatrelvir and ritonavir tolerated treatment well, although there was an unexpectedly high rate of cesarean deliveries. The lack of an increase in serious adverse effects affecting pregnant patients or offspring suggests that clinicians can use this drug combination to treat pregnant patients with SARS-CoV-2 infection.
Amit Bahl et al.
Severe COVID-19 outcomes in pediatrics: An observational cohort analysis comparing Alpha, Delta, and Omicron variants
Lancet, December 2022; doi.org/10.1016/j.lana.2022.100405
Abstract
Objective
COVID-19 can rarely lead to severe illness in pediatric patients. The aim of this study was to determine if severe outcomes in pediatric COVID-19 have changed over the course of the pandemic.
Conclusions
While Omicron cases had the highest admission frequency, severe illness was lower than Delta and Alpha variants. Coinfection with respiratory viruses increased the risk of severe outcomes and impacted infants more than older children.
Florentino PTV et al.
Effectiveness of BNT162b2 booster after CoronaVac primary regimen in pregnant people during omicron period in Brazil
The Lancet, December 2022; doi.org/10.1016/S1473-3099(22)00728-9
Abstract
Infection with SARS-CoV-2 during pregnancy increases the risk of severe negative maternal and foetal clinical outcomes.1 In the general population, the SARS-CoV-2 B.1.1.529 (omicron) variant can evade both natural and vaccine-induced protection,2 highlighting the importance of booster doses.3 However, little is known about the vaccine effectiveness of a booster dose against COVID-19 in pregnant people, and no data have been published for those with a primary series of CoronaVac (inactivated-virus vaccine).4, 5 In this study, we investigated the vaccine effectiveness in pregnant people who received two doses of CoronaVac to estimate the additional protection provided by a booster dose with BNT162b2 (mRNA vaccine) during the omicron period.
Our findings strongly support the importance of a booster dose for pregnant people, because they provide additional maternal protection against mild and severe COVID-19 during the omicron period. Further studies are needed to assess the protection afforded by a booster dose in preventing negative foetal outcomes of COVID-19 for BNT162b2 and other COVID-19 vaccine regimens.
Powell A.A. et al
Protection against symptomatic infection with delta (B.1.617.2) and omicron (B.1.1.529) BA.1and BA.2 SARS-CoV-2 variants after previous infection and vaccination in adolescents in England, August, 2021–March, 2022: a national, observational, test-negative, case-control study
The Lancet, November 2022; doi.org/10.1016/S1473-3099(22)00729-0
Abstract
Background
Little is known about protection against SARS-CoV-2 infection following previous infection with specific individual SARS-CoV-2 variants, COVID-19 vaccination, and a combination of previous infection and vaccination (hybrid immunity) in adolescents. We aimed to estimate protection against symptomatic PCR-confirmed infection with the delta (B.1.617.2) and omicron (B.1.1.529) variants in adolescents with previous infection, mRNA vaccination, and hybrid immunity.
Interpretation
Previous infection with any SARS-CoV-2 variant provided some protection against symptomatic reinfection, and vaccination added to this protection. Vaccination provides low-to-moderate protection against symptomatic omicron infection, with waning protection after each dose, while hybrid immunity provided the most robust protection. Although more data are needed to investigate longer-term protection and protection against infection with new variants, these data question the need for additional booster vaccine doses for adolescents in populations with already high protection against SARS-CoV-2 infection.
Lei Wang et al.
Safety and immunogenicity following a homologous booster dose of CoronaVac in children and adolescents
Nature, November 2022; doi.org/10.1038/s41467-022-34280-y
Abstract
Data on safety and immunity elicited by a third booster dose of inactivated COVID-19 vaccine in children and adolescents are scarce. Here we conducted a study based on a double-blind, randomised, placebo-controlled phase 2 clinical trial (NCT04551547) to assess the safety and immunogenicity of a third dose of CoronaVac. In this study, 384 participants in the vaccine group were assigned to two cohorts. One received the third dose at a 10-months interval (cohort 1) and the other one at a 12-months interval (cohort 2). The primary endpoint is safety and immunogenicity following a third dose of CoronaVac. The secondary endpoint is antibody persistence following the primary two-dose schedule. Severities of local and systemic adverse reactions reported within 28 days after dose 3 were mild and moderate in both cohorts. A third dose of CoronaVac increased GMTs to 681.0 (95%CI: 545.2–850.7) in cohort 1 and 745.2 (95%CI: 577.0–962.3) in cohort 2. Seropositivity rates against the prototype were 100% on day 28 after dose 3. Seropositivity rates against the Omicron variant were 90.6% (cohort 1) and 91.5% (cohort 2). A homologous booster dose of CoronaVac is safe and induces a significant neutralising antibody levels increase in children and adolescents.
Flannery D.D. et al
Comparison of Maternal and Neonatal Antibody Levels After COVID-19 Vaccination vs SARSCoV-2 Infection
JAMA, November 2022; doi:10.1001/jamanetworkopen.2022.40993
Abstract
Importance: Pregnant persons are at an increased risk of severe COVID-19 from SARS-CoV-2 infection, and COVID-19 vaccination is currently recommended during pregnancy. Objective: To ascertain the association of vaccine type, time from vaccination, gestational age at delivery, and pregnancy complications with placental transfer of antibodies to SARS-CoV-2. Design, Setting, and Participants This cohort study was conducted in Pennsylvania Hospital in Philadelphia, Pennsylvania, and included births at the study site between August 9, 2020, and April 25, 2021. Maternal and cord blood serum samples were available for antibody level measurements for maternal-neonatal dyads. Exposures: SARS-CoV-2 infection vs COVID-19 vaccination. Main Outcomes and Measures IgG antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein were measured by quantitative enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were measured after SARS-CoV-2 infection or receipt of COVID-19 vaccines. Results: A total of 585 maternal-newborn dyads (median [IQR] maternal age, 31 [26-35] years; median [IQR] gestational age, 39 [38-40] weeks) with maternal IgG antibodies to SARS-CoV-2 detected at the time of delivery were included. IgG was detected in cord blood from 557 of 585 newborns (95.2%). Among 169 vaccinated persons without SARS-CoV-2 infection, the interval from first dose of vaccine to delivery ranged from 12 to 122 days. The geometric mean IgG level among 169 vaccine recipients was significantly higher than that measured in 408 persons after infection (33.88 [95% CI, 27.64-41.53] arbitrary U/mL vs 2.80 [95% CI, 2.50-3.13] arbitrary U/mL). Geometric mean IgG levels were higher after vaccination with the mRNA-1273 (Moderna) vaccine compared with the BNT162b2 (Pfizer/BioNTech) vaccine (53.74 [95% CI, 40.49-71.33] arbitrary U/mL vs 25.45 [95% CI, 19.17-33.79] arbitrary U/mL; P.001). Placental transfer ratios were lower after vaccination compared with after infection (0.80 [95% CI, 0.68-0.93] vs 1.06 [95% CI, 0.98-1.14]; P < .001) but were similar between the mRNA vaccines (mRNA-1273: 0.70 [95% CI, 0.55-0.90]; BNT162b2: 0.85 [95% CI, 0.69-1.06]; P = .25). Time from infection or vaccination to delivery was associated with transfer ratio in models that included gestational age at delivery and maternal hypertensive disorders, diabetes, and obesity. Placental antibody transfer was detectable as early as 26 weeks’gestation. Transfer ratio that was higher than 1.0 was present for 48 of 51 (94.1%) births at 36weeks’ gestation or later by 8 weeks after vaccination.
Conclusions and Relevance: This study found that maternal and cord blood IgG antibody levels were higher after COVID-19 vaccination compared with after SARS-CoV-2 infection, with slightly lower placental transfer ratios after vaccination than after infection. The findings suggest that time from infection or vaccination to delivery was the most important factor in transfer efficiency.
Chemaitelly H et al.
Covid-19 Vaccine Protection among Children and Adolescents in Qatar
NEJM, November 2022; DOI: 10.1056/NEJMoa2210058
Abstract
BACKGROUND
The BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) has been authorized for use in children 5 to 11 years of age and adolescents 12 to 17 years of age but in different antigen doses.
METHODS
We assessed the real-world effectiveness of the BNT162b2 vaccine against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children and adolescents in Qatar. To compare the incidence of SARS-CoV-2 infection in the national cohort of vaccinated participants with the incidence in the national cohort of unvaccinated participants, we conducted three matched, retrospective, target-trial, cohort studies — one assessing data obtained from children 5 to 11 years of age after the B.1.1.529 (omicron) variant became prevalent and two assessing data from adolescents 12 to 17 years of age before the emergence of the omicron variant (pre-omicron study) and after the omicron variant became prevalent. Associations were estimated with the use of Cox proportional-hazards regression models.
CONCLUSIONS
Vaccination in children was associated with modest, rapidly waning protection against omicron infection. Vaccination in adolescents was associated with stronger, more durable protection, perhaps because of the larger antigen dose. (Funded by Weill Cornell Medicine–Qatar and others.)
Hessami K. et al.
COVID-19 Pandemic and Infant Neurodevelopmental Impairment
JAMA, October 2022; doi:10.1001/jamanetworkopen.2022.38941
Abstract
In this review and meta-analysis examining the association between COVID-19 pandemic and the risk of NDI, findings suggest that overall neurodevelopment in the first year of life was not changed by either being born or raised during the SARS-CoV-2 pandemic or by gestational exposure to SARS-CoV-2.
Lavallée A., Dumitriu D.
Low Risk of Neurodevelopmental Impairment in the COVID-19 Generation Should Not Make Researchers Complacent
JAMA, October 2022; doi:10.1001/jamanetworkopen.2022.38958
Abstract
The authors evaluated the risk of neurodevelopmental impairments in 6-month to 12-month-old infants exposed in utero to maternal SARS-CoV-2 infection or screened during the pandemic regardless of their exposure status.
Ellington S.& Olson C.K
Safety of mRNA COVID-19 vaccines during pregnancy
Lancet, August 2022; doi.org/10.1016/S1473-3099(22)00443-1
Abstract
Pregnant people with COVID-19 are at increased risk of severe illness and death compared with non-pregnant females of reproductive age (aged 15–49 years).COVID-19 during pregnancy is associated with increased risk for adverse pregnancy outcomes, such as preterm birth and stillbirth.
Public health researchers have been assessing the safety and effectiveness of COVID-19 vaccines during pregnancy.
Schwartz D.A. et al.
SARS-CoV-2 Placentitis, Stillbirth and Maternal COVID-19 Vaccination: Clinical- Pathological Correlations
AJOG, October 2022;doi.org/10.1016/j.ajog.2022.10.001
Abstract
Stillbirth is a recognized complication of COVID-19 in pregnant women. Global studies have found that the placental pathology present in cases of stillbirth consists of a combination of concurrent destructive findings that include increased fibrin deposition that typically reaches the level of massive perivillous fibrin deposition, chronic histiocytic intervillositis, and trophoblast necrosis. This article discusses clinical and pathologic aspects of the relationship between maternal COVID-19 vaccination, SARS-CoV-2 placentitisand perinatal death.
E.J. Anderson et al.
Evaluation of mRNA-1273 Vaccine in Children 6 Months to 5 Years of Age
The New England J of Medicine, October 2022; doi:10.1056/NEJMoa2209367
Abstract
The authors evaluated the safety, reactogenicity, immunogenicity, and efficacy of the mRNA-1273 coronavirus disease 2019 (Covid-19) vaccine in young children.
G. Witberg et al.
Myocarditis after BNT162b2 Vaccination in Israeli Adolescents
New England J of Medicine, October 2022; doi:10.1056/NEJMc2207270
Abstract
The aim of the authors was to provide further evidence regarding the incidence of myocarditis after vaccination among adolescents and data regarding follow-up of 6 months or more.
S.J. Schrag et al.
Estimation of Covid-19 Mrna vaccine effectiveness against medically attended Covid-19 in pregnancy during periods of delta and omicron variant predominance in the United States
JAMA Network Open, September 2022; doi:10.1001/jamanetworkopen.2022.33273
Abstract
During the Covid-19 pandemia pregnant women are at high risk for severe COVID-19 but were excluded from mRNA vaccine trials. Data on the COVID-19 vaccine effectiveness (VE) are needed. In this study, maternal vaccination, including booster dose, was associated with protection against serious COVID-19 during pregnancy.
M. N. Hanna et al.
Detection of Messenger RNA COVID-19 Vaccines in Human Breast
JAMA Pediatrics, September 2022; doi:10.1001/jamapediatrics.2022.3581
Abstract
The US Food and Drug Administration deferred the decision to authorize COVID-19 mRNA vaccines for infantsyoungerthan 6 monthsuntil more data are availablebecause of the potential priming of the children’s immune responsesthatmay alter theirimmunity. The Centers for Disease Control and Preventionrecommendsoffering the COVID-19 mRNA vaccines to breastfeedingindividuals, although the possiblepassage of vaccine mRNAs in breastmilkresulting in infants’ exposureatyoungerthan 6 monthswasnotinvestigated. This study investigatedwhether the COVID-19 vaccine mRNA can be detected in the expressedbreastmilk (EBM) of lactatingindividualsreceiving the vaccinationwithin 6 months after delivery.
C. J. Chiew et al.
Effectiveness of primaryseries and booster vaccinationagainst SARS-CoV-2 infection and hospitalisationamongadolescentsaged 12–17 years in Singapore: a national cohort study.
Lancet InfectiousDiseases, September 2022; doi.org/10.1016/S1473-3099(22)00573-4
Abstract
Singapore offered the BNT162b2 vaccine (tozinameran; Pfizer-BioNTech) to adolescentsaged 12–17 years in May 18, 2021, and extended booster vaccines to this group in Jan 21, 2022. Literature on the effectiveness of primaryseries and booster vaccinationamongadolescentsisscarceoutside of Europe and North America. The authors to determine primaryseries and booster vaccine effectivenessagainst SARS-CoV-2 infection and hospitalisationamongadolescents in Singapore.
N.H. Birkebaek et al.
Impact of the COVID-19 pandemic on long-term trends in the prevalence of diabeticketoacidosisatdiagnosis of paediatrictype 1 diabetes: an international multicentre study based on data from 13 national diabetesregistries.
Lancet DiabetesEndocrinology, October 2022; doi.org/10.1016/ S2213-8587(22)00246-7
Abstract
An increasedprevalence of diabeticketoacidosisatdiagnosis of type 1 diabetes in childrenwasobserved in variousdiabetes centres worldwideduring the COVID-19 pandemic. The study aimed to evaluate trends in the prevalence of diabeticketoacidosisatdiagnosis of paediatrictype 1 diabetesbefore and during the COVID-19 pandemic, and to identifypotentialpredictors of changes in diabeticketoacidosisprevalenceduring the pandemic.
E.K. Kendall et al.
Association of SARS-CoV-2 infection with new-onset type 1 diabetes among pediatricpatients from 2020 to 2021
JAMA Network Open, September 2022; doi:10.1001/jamanetworkopen.2022.33014
Abstract
Incidence of new-onset type 1 diabetes (T1D) increased during the COVID-19 pandemic, and this increase has been associated with SARS-CoV-2 infection. The US Centers for Disease Control and Prevention reported that pediatric patients with COVID-19 were more likely to be diagnosed with diabetes after infection, although types 1 and 2 were not separated. This cohort study assessed whether there was an increase in new diagnoses of T1D among pediatric patients after COVID-19.
A. Haddad et al.
Long COVID symptoms in exposed and infected children, adolescents and their parents one year after SARS-CoV-2 infection: A prospective observational cohort study
eBioMedicine, October 2022;doi.org/10.1016/j. ebiom.2022.104245
Abstract
Long COVID in children and adolescents remains poorly understood due to a lack of well-controlled studies with long-term follow-up. In particular, the impact of the family context on persistent symptoms following SARS-CoV-2 infection remains unknown. The authors examined long COVID symptoms in a cohort of infected children, adolescents, and adults and their exposed but non-infected household members approximately 1 year after infection and investigated clustering of persistent symptoms within households.
L. Dan-Yu et al.
Effects of Vaccination and Previous Infection on Omicron Infections in Children
The New England J of Medicine, September 2022; doi: 10.1056/NEJMc2209371
Abstract
Recent case–control studies have shown modest short-term effectiveness of the BNT162b2 vaccine in children 5 to 11 years of age during the early phase of the period when the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was spreading. This is a large cohort study over a 6-month period when the omicron variant was dominant. The authors report on the protection conferred by the BNT162b2 vaccine and by previous SARS-CoV-2 infection against infection and coronavirus disease 2019 (Covid-19)–related hospitalization and death in children 5 to 11 years of age.
O. Amir et al.
Initial protection against SARS-CoV-2 omicron lineage infection in children and adolescents by BNT162b2 in Israel: an observational study
Lancet Infectious Diseases, September 2022; doi.org/10.1016/ S1473-3099(22)00527-8
Abstract
The BNT162b2 (Pfizer-BioNTech) two-dose vaccine regiment for children and the BNT162b2 third dose for adolescents were approved shortly before the SARS-CoV-2 omicron (B.1.1.529) outbreak in Israel. The authors aimed to estimate the effects of these vaccines on the rates of confirmed infection against the omicron variant in children and adolescents.
M. Ohashi et al.
Amelioration of prevalence of threatened preterm labor during the COVID-19 pandemic: nationwide database analysis in Japan
Scientific Reports, September 2022; doi.org/10.1038/s41598-022-19423-x
Abstract
The authors aimed to evaluate the changes in maternal and neonatal complications such as threatened preterm labor (TPL) and preterm birth before and during the coronavirus disease 2019 (COVID-19) pandemic using large-scale real-world data in Japan. The study suggests that the COVID-19 pandemic has ameliorated TPL and consequently reduced the number of preterm births.
S. A. Irving et al.
COVID-19 vaccination protects children and adolescents
Lancet Infectious Diseases, September 2022; doi: 10.1016/S1473-3099(22)00575-8
Abstract
By February 2022, European and US agencies recommended use of the BNT162b2 mRNA COVID-19 vaccine (Pfizer–BioNTech) as a primary two-dose series in children aged 5–11 years and as a booster dose in adolescents aged 12–15 years. Since then, some real-world BNT162b2 vaccine effectiveness data among children and adolescents have generally showed moderate protection against symptomatic infection,with better protection against COVID-19-associated serious outcomes especially in the weeks immediately after vaccination.
During the study the authors found substantially lower rates of confirmed SARS-CoV-2 infection among vaccinated children and among boosted adolescents compared with unvaccinated children and adolescents.
K. M. Vadrevu et al.
Immunogenicity and reactogenicity of an inactivated SARS-CoV-2 vaccine (BBV152) in children aged 2–18 years: interim data from an open-label, non-randomised, age de-escalation phase 2/3 study
Lancet Infect Dis, September 2022; doi: 10.1016/S1473-3099(22)00307-3
Abstract
Despite having milder symptoms than adults, children are still susceptible to and can transmit SARS-CoV-2. Vaccination across all age groups is therefore necessary to curtail the pandemic. Among the available COVID-19 vaccine platforms, an inactivated vaccine platform has the advantage of excellent safety profile across all age groups; hence, we conducted an age de-escalation study to assess the safety, reactogenicity, and immunogenicity of an inactivated COVID-19 vaccine, BBV152 (COVAXIN; Bharat Biotech International, Hyderabad, India), in children aged 2-18 years.
BBV152 was well tolerated in children aged 2-18 years, and induced higher neutralising antibody responses than those observed in adults, in whom the efficacy (ie, the prevention or decrease in the severity of COVID-19 infection) has been demonstrated.
S. Hall
Should parents delay kids’ second COVID vaccine? Here’s what the research says
Nature news, August 2022; doi.org/10.1038/d41586-022-02159-z
Abstract
Increasing the interval between the first two mRNA-vaccine doses might boost children’s immunity, but it is a gamble as a new variant sweeps the globe. More than two years into the pandemic, the United States and Canada have become the first nations to approve two mRNA vaccines for children as young as six months. But the vaccines, made by Pfizer–BioNTech and Moderna, have proven less effective against the Omicron variant. So some parents are considering extending the interval between initial doses — a trick that might make the vaccines more potent.
A. V. Ballering et al.
Persistence of somatic symptoms after COVID-19 in the Netherlands: an observational cohort study
Lancet, August 2022; doi: 10.1016/S0140-6736(22)01214-4
Abstract
Background: Patients often report various symptoms after recovery from acute COVID-19. Previous studies on post-COVID-19 condition have not corrected for the prevalence and severity of these common symptoms before COVID-19 and in populations without SARS-CoV-2 infection. We aimed to analyse the nature, prevalence, and severity of long-term symptoms related to COVID-19, while correcting for symptoms present before SARS-CoV-2 infection and controlling for the symptom dynamics in the population without infection.
Methods: This study is based on data collected within Lifelines, a multidisciplinary, prospective, population-based, observational cohort study examining the health and health-related behaviours of people living in the north of the Netherlands. All Lifelines participants aged 18 years or older received invitations to digital COVID-19 questionnaires. Longitudinal dynamics of 23 somatic symptoms surrounding COVID-19 diagnoses (due to SARS-CoV-2 alpha [B.1.1.7] variant or previous variants) were assessed using 24 repeated measurements between March 31, 2020, and Aug 2, 2021. Participants with COVID-19 (a positive SARS-CoV-2 test or a physician's diagnosis of COVID-19) were matched by age, sex, and time to COVID-19-negative controls. We recorded symptom severity before and after COVID-19 in participants with COVID-19 and compared that with matched controls.
Findings: 76 422 participants (mean age 53·7 years [SD 12·9], 46 329 [60·8%] were female) completed a total of 883 973 questionnaires. Of these, 4231 (5·5%) participants had COVID-19 and were matched to 8462 controls. Persistent symptoms in COVID-19-positive participants at 90-150 days after COVID-19 compared with before COVID-19 and compared with matched controls included chest pain, difficulties with breathing, pain when breathing, painful muscles, ageusia or anosmia, tingling extremities, lump in throat, feeling hot and cold alternately, heavy arms or legs, and general tiredness. In 12·7% of patients, these symptoms could be attributed to COVID-19, as 381 (21·4%) of 1782 COVID-19-positive participants versus 361 (8·7%) of 4130 COVID-19-negative controls had at least one of these core symptoms substantially increased to at least moderate severity at 90-150 days after COVID-19 diagnosis or matched timepoint.
Interpretation: To our knowledge, this is the first study to report the nature and prevalence of post-COVID-19 condition, while correcting for individual symptoms present before COVID-19 and the symptom dynamics in the population without SARS-CoV-2 infection during the pandemic. Further research that distinguishes potential mechanisms driving post-COVID-19-related symptomatology is required.
G. Guglielmi
Pandemic drives largest drop in childhood vaccinations in 30 years
Nature News, July 2022; https://www.nature.com/articles/d41586-022-02051-w
Abstract
Data collected by the World Health Organization (WHO) and the United Nations children’s charity UNICEF show that the percentage of children who received three doses of the vaccine against diphtheria, tetanus and whooping cough (DTP3) decreased by 5 percentage points between 2019 and 2021, to 81% worldwide (see ‘Childhood immunizations decline’). DTP3 is considered to be a marker of vaccine coverage; if children miss these jabs, they’re probably also missing out on crucial vaccinations for many other diseases.
S. Zilberman-Itskovich et al.
Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial
Nature Scientific Reports, July 2022; doi: 10.1038/s41598-022-15565-0
Abstract
Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. The mechanism can be related to brain tissue pathology caused by virus invasion or indirectly by neuroinflammation and hypercoagulability. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT or HBO2 therapy) on post-COVID-19 patients with ongoing symptoms for at least 3 months after confirmed infection. Seventy-three patients were randomized to receive daily 40 session of HBOT (n = 37) or sham (n = 36). Follow-up assessments were performed at baseline and 1-3 weeks after the last treatment session. Following HBOT, there was a significant group-by-time interaction in global cognitive function, attention and executive function (d = 0.495, p = 0.038; d = 0.477, p = 0.04 and d = 0.463, p = 0.05 respectively). Significant improvement was also demonstrated in the energy domain (d = 0.522, p = 0.029), sleep (d = - 0.48, p = 0.042), psychiatric symptoms (d = 0.636, p = 0.008), and pain interference (d = 0.737, p = 0.001). Clinical outcomes were associated with significant improvement in brain MRI perfusion and microstructural changes in the supramarginal gyrus, left supplementary motor area, right insula, left frontal precentral gyrus, right middle frontal gyrus, and superior corona radiate. These results indicate that HBOT can induce neuroplasticity and improve cognitive, psychiatric, fatigue, sleep and pain symptoms of patients suffering from post-COVID-19 condition. HBOT's beneficial effect may be attributed to increased brain perfusion and neuroplasticity in regions associated with cognitive and emotional roles.
S. Rodin et al.
Risk factors for multisystem inflammatory syndrome in children – A population-based cohort study of over 2 million children
The Lancet Regional Health - Europe; August 2022; doi.org/10.1016/j.lanepe.2022.100443
Abstract
Background
Although severe acute COVID-19 is rare in children, SARS-CoV-2 infection can trigger the novel post-infectious condition multisystem inflammatory syndrome in children (MIS-C). Increased knowledge on risk factors for MIS-C could improve our understanding of the pathogenesis of the condition and better guide targeted public health interventions. The aim of the study was to assess risk factors for MIS-C with the aim to identify vulnerable children.
Methods
A register-based cohort study including all children and adolescents <19 years born in Sweden between March 1, 2001- December 31, 2020 was performed. Data on sociodemographic risk factors and comorbidities (sex, age, parental region of birth, parental education, asthma, autoimmune disease, chromosomal anomalies, chronic heart disease, chronic lung disease, obesity, life-limiting condition) were retrieved from national health and population registers. The outcome was MIS-C diagnosis according to the Swedish Pediatric Rheumatology Quality Register during March 1, 2020 – December 8, 2021.
Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression analysis. Incidence rates per 100 000 person-years were calculated assuming a Poisson distribution.
Findings
Among 2 117 443 children included in the study, 253 children developed MIS-C, corresponding to an incidence rate of 6·8 (95% CI: 6·0-7·6) per 100 000 person-years. Male sex (HR 1·65, 95% CI: 1·28-2·14), age 5-11 years (adjusted HR 1·44, 95% CI: 1·06-1·95 using children 0-4 years as reference), foreign-born parents (HR 2·53, 95% CI: 1·93-3·34), asthma (aHR 1·49, 95% CI: 1·00-2·20), obesity (aHR 2·15, 95% CI: 1·09-4·25) and life-limiting conditions (aHR 3·10, 95% CI: 1·80-5·33) were associated with MIS-C. Children 16-18 years had a reduced risk for MIS-C (aHR 0·45, 95% CI: 0·24-0·85).
R.T. Souza et al.
The COVID-19 pandemic in Brazilian pregnant and postpartum women: results from the REBRACO prospective cohort study
Nature Scientific Reports, July 2022; doi.org/10.1038/s41598-022-15647-z
Abstract
Brazil presented a very high number of maternal deaths and evident delays in healthcare. We aimed at evaluating the characteristics of SARS-CoV-2 infection and associated outcomes in the obstetric population. We conducted a prospective cohort study in 15 Brazilian centers including symptomatic pregnant or postpartum women with suspected COVID-19 from Feb/2020 to Feb/2021. Women were followed from suspected infection until the end of pregnancy. We analyzed maternal characteristics and pregnancy outcomes associated with confirmed COVID-19 infection and SARS, determining unadjusted risk ratios. In total, 729 symptomatic women with suspected COVID-19 were initially included. Among those investigated for COVID-19, 51.3% (n = 289) were confirmed COVID-19 and 48% (n = 270) were negative. Initially (before May 15th), only 52.9% of the suspected cases were tested and it was the period with the highest proportion of ICU admission and maternal deaths. Non-white ethnicity (RR 1.78 [1.04–3.04]), primary schooling or less (RR 2.16 [1.21–3.87]), being overweight (RR 4.34 [1.04–19.01]) or obese (RR 6.55 [1.57–27.37]), having public prenatal care (RR 2.16 [1.01–4.68]), planned pregnancies (RR 2.09 [1.15–3.78]), onset of infection in postpartum period (RR 6.00 [1.37–26.26]), chronic hypertension (RR 2.15 [1.37–4.10]), pre-existing diabetes (RR 3.20 [1.37–7.46]), asthma (RR 2.22 [1.14–4.34]), and anaemia (RR 3.15 [1.14–8.71]) were associated with higher risk for SARS. The availability of tests and maternal outcomes varied throughout the pandemic period of the study; the beginning was the most challenging period, with worse outcomes. Socially vulnerable, postpartum and previously ill women were more likely to present SARS related to COVID-19.
E. Colosi et al.
Screening and vaccination against COVID-19 to minimise school closure: a modelling study
The Lancet Infectious Diseases, April 2022; doi.org/10.1016/S1473-3099(22)00138-4
Abstract
Background Schools were closed extensively in 2020–21 to counter SARS-CoV-2 spread, impacting students’ education and wellbeing. With highly contagious variants expanding in Europe, safe options to maintain schools open are urgently needed. By estimating school-specific transmissibility, our study evaluates costs and benefits of different protocols for SARS-CoV-2 control at school.
Methods We developed an agent-based model of SARS-CoV-2 transmission in schools. We used empirical contact data in a primary and a secondary school and data from pilot screenings in 683 schools during the alpha variant (B.1.1.7) wave in March–June, 2021, in France. We fitted the model to observed school prevalence to estimate the schoolspecific effective reproductive number for the alpha (Ralpha) and delta (B.1.617.2; Rdelta) variants and performed a cost– benefit analysis examining different intervention protocols.
Findings We estimated Ralpha to be 1·40 (95% CI 1·35–1·45) in the primary school and 1·46 (1·41–1·51) in the secondary school during the spring wave, higher than the time-varying reproductive number estimated from community surveillance. Considering the delta variant and vaccination coverage in Europe as of mid-September, 2021, we estimated Rdelta to be 1·66 (1·60–1·71) in primary schools and 1·10 (1·06–1·14) in secondary schools. Under these conditions, weekly testing of 75% of unvaccinated students (PCR tests on saliva samples in primary schools and lateral flow tests in secondary schools), in addition to symptom-based testing, would reduce cases by 34% (95% CI 32–36) in primary schools and 36% (35–39) in secondary schools compared with symptom-based testing alone. Insufficient adherence was recorded in pilot screening (median ≤53%). Regular testing would also reduce studentdays lost up to 80% compared with reactive class closures. Moderate vaccination coverage in students would still benefit from regular testing for additional control—ie, weekly testing 75% of unvaccinated students would reduce cases compared with symptom-based testing only, by 23% in primary schools when 50% of children are vaccinated.
Interpretation The COVID-19 pandemic will probably continue to pose a risk to the safe and normal functioning of schools. Extending vaccination coverage in students, complemented by regular testing with good adherence, are essential steps to keep schools open when highly transmissible variants are circulating.
S. Kikkenborg Berg et al.
Long COVID symptoms in SARS-CoV-2-positive children aged 0–14 years and matched controls in Denmark (LongCOVIDKidsDK): a national, cross-sectional study
The Lancet, June 2022; doi.org/10.1016/ S2352-4642(22)00154-7
Abstract
Background After the acute phase of SARS-CoV-2 infection, children can develop long COVID symptoms. We aimed to investigate the prevalence of long-lasting symptoms, the duration and intensity of symptoms, quality of life, number of sick days and absences from daycare or school, and psychological and social outcomes in children aged 0–14 years who had been infected with SARS-CoV-2 relative to controls with no history of SARS-CoV-2 infection.
Methods A nationwide cross-sectional study was conducted including children with a confirmed SARS-CoV-2-positive PCR test (cases) and matched controls from Danish national registers. A survey was sent to mothers (proxy reporting) of children aged 0–14 years who had had a positive SARS-CoV-2 test between Jan 1, 2020, and July 12, 2021, and a control group matched (1:4) by age and sex. The survey included the Pediatric Quality of Life Inventory (PedsQL) and the Children’s Somatic Symptoms Inventory-24 (CSSI-24) to capture current overall health and wellbeing, and ancillary questions about the 23 most common long COVID symptoms. Descriptive statistics and logistic regression analysis were used. Clinically relevant differences were defined as those with a Hedges’ g score greater than 0·2. This study is registered at ClinicalTrials.gov (NCT04786353).
Findings Responses to the survey were received from 10997 (28·8%) of 38152 cases and 33016 (22·4%) of 147212 controls between July 20, 2021, and Sept 15, 2021. Median age was 10·2 years (IQR 6·6–12·8) in cases and 10·6 years (6·9–12·9) in controls. 5267 (48·2%) cases and 15777 (48·3%) controls were female, and 5658 (51·8%) cases and 16870 (51·7%) controls were male. Cases had higher odds of reporting at least one symptom lasting more than 2 months than did controls in the 0–3 years age group (478 [40·0%] of 1194 vs 1049 [27·2%] of 3855; OR 1·78 [95% CI 1·55–2·04], p0·2).
Interpretation Compared with controls, children aged 0–14 years who had a SARS-CoV-2 infection had more prevalent long-lasting symptoms. There was a tendency towards better quality-of-life scores related to emotional and social functioning in cases than in controls in older children. The burden of symptoms among children in the control group requires attention. Long COVID must be recognised and multi-disciplinary long COVID clinics for children might be beneficial.
C. Sacco et al.
Effectiveness of BNT162b2 vaccine against SARS-CoV-2 infection and severe COVID-19 in children aged 5–11 years in Italy: a retrospective analysis of January–April, 2022
Lancet, June 2022; doi.org/10.1016/ S0140-6736(22)01185-0
Abstract
Background
By April 13, 2022, more than 4 months after the approval of BNT162b2 (Pfizer–BioNTech) for children, less than 40% of 5–11-year-olds in Italy had been vaccinated against COVID-19. Estimating how effective vaccination is in 5–11-year-olds in the current epidemiological context dominated by the omicron variant (B.1.1.529) is important to inform public health bodies in defining vaccination policies and strategies.
Methods
In this retrospective population analysis, we assessed vaccine effectiveness against SARS-CoV-2 infection and severe COVID-19, defined as an infection leading to hospitalisation or death, by linking the national COVID-19 surveillance system and the national vaccination registry. All Italian children aged 5–11 years without a previous diagnosis of infection were eligible for inclusion and were followed up from Jan 17 to April 13, 2022. All children with inconsistent vaccination data, diagnosed with SARS-CoV-2 infection before the start date of the study or without information on the municipality of residence were excluded from the analysis. With unvaccinated children as the reference group, we estimated vaccine effectiveness in those who were partly vaccinated (one dose) and those who were fully vaccinated (two doses).
Findings
By April 13, 2022, 1 063 035 (35·8%) of the 2 965 918 children aged 5–11 years included in the study had received two doses of the vaccine, 134 386 (4·5%) children had received one dose only, and 1 768 497 (59·6%) were unvaccinated. During the study period, 766 756 cases of SARS-CoV-2 infection and 644 cases of severe COVID-19 (627 hospitalisations, 15 admissions to intensive care units, and two deaths) were notified. Overall, vaccine effectiveness in the fully vaccinated group was 29·4% (95% CI 28·5–30·2) against SARS-CoV-2 infection and 41·1% (22·2–55·4) against severe COVID-19, whereas vaccine effectiveness in the partly vaccinated group was 27·4% (26·4–28·4) against SARS-CoV-2 infection and 38·1% (20·9–51·5) against severe COVID-19. Vaccine effectiveness against infection peaked at 38·7% (37·7–39·7) at 0–14 days after full vaccination and decreased to 21·2% (19·7–22·7) at 43–84 days after full vaccination.
Interpretation
Vaccination against COVID-19 in children aged 5–11 years in Italy showed a lower effectiveness in preventing SARS-CoV-2 infection and severe COVID-19 than in individuals aged 12 years and older. Effectiveness against infection appears to decrease after completion of the current primary vaccination cycle.
J.C. Cohen-Stavi et al.
BNT162b2 Vaccine Effectiveness against Omicron in Children 5 to 11 Years of Age
N Engl J Med July 2022; doi: 10.1056/NEJMoa2205011
Abstract
BACKGROUND
Limited evidence is available on the real-world effectiveness of the BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) and specifically against infection with the omicron variant among children 5 to 11 years of age.
METHODS
Using data from the largest health care organization in Israel, we identified a cohort of children 5 to 11 years of age who were vaccinated on or after November 23, 2021, and matched them with unvaccinated controls to estimate the vaccine effectiveness of BNT162b2 among newly vaccinated children during the omicron wave. Vaccine effectiveness against documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and symptomatic Covid-19 was estimated after the first and second vaccine doses. The cumulative incidence of each outcome in the two study groups through January 7, 2022, was estimated with the use of the Kaplan–Meier estimator, and vaccine effectiveness was calculated as 1 minus the risk ratio. Vaccine effectiveness was also estimated in age subgroups.
RESULTS
Among 136,127 eligible children who had been vaccinated during the study period, 94,728 were matched with unvaccinated controls. The estimated vaccine effectiveness against documented infection was 17% (95% confidence interval [CI], 7 to 25) at 14 to 27 days after the first dose and 51% (95% CI, 39 to 61) at 7 to 21 days after the second dose. The absolute risk difference between the study groups at days 7 to 21 after the second dose was 1905 events per 100,000 persons (95% CI, 1294 to 2440) for documented infection and 599 events per 100,000 persons (95% CI, 296 to 897) for symptomatic Covid-19. The estimated vaccine effectiveness against symptomatic Covid-19 was 18% (95% CI, −2 to 34) at 14 to 27 days after the first dose and 48% (95% CI, 29 to 63) at 7 to 21 days after the second dose. We observed a trend toward higher vaccine effectiveness in the youngest age group (5 or 6 years of age) than in the oldest age group (10 or 11 years of age).
CONCLUSIONS
Our findings suggest that as omicron was becoming the dominant variant, two doses of the BNT162b2 messenger RNA vaccine provided moderate protection against documented SARS-CoV-2 infection and symptomatic Covid-19 in children 5 to 11 years of age. (Funded by the European Union through the VERDI project and others.)
T. Patalon et al.
Naturally-acquired Immunity Dynamics against SARS-CoV-2 in Children and Adolescents
medRxiv, June 2022; doi.org/10.1101/2022.06.20.22276650
Abstract
Objectives: There are paucity of studies examining naturally acquired immunity against SARS-CoV-2 in children and adolescents, though they are generally the last group to be afforded the vaccine, and a significant portion of them are still unvaccinated. This study examined the duration of protection conferred by a previous SARS-CoV-2 infection amongst children and adolescents.
Design: A retrospective study, applying two complementary approaches: a matched test-negative case control design and a retrospective cohort design.
Setting: Nationally centralized database of Maccabi Healthcare Services, an Israeli national health fund that covers 2.5 million people.
Participants: The study population included between 293,743 and 458,959 individuals (depending on the model), 5-18 years of age, who were unvaccinated SARS-CoV-2 naive persons or unvaccinated convalescent patients.
Main outcomes and measures: Analyses focused on the period of July 1 to December 13, 2021, a Delta-dominant period in Israel. We evaluated three SARS-CoV-2-related outcomes: (1) documented PCR confirmed infection or reinfection, (2) COVID-19 and (3) severe COVID-19.
Results: Overall, children and adolescents who were previously infected acquired durable protection against reinfection (symptomatic or not) with SARS-CoV-2 for at least 18 months. Importantly, no COVID-19 related deaths were recorded in either the SARS-CoV-2 naive group or the previously infected group. Effectiveness of naturally-acquired immunity against a recurrent infection reached 89.2% (95% CI: 84.7%-92.4%) three to six months after first infection, mildly declining to 82.5% (95% CI, 79.1%-85.3%) nine months to one year after infection, then remaining rather steady for children and adolescents for up to 18 months, with a slight non-significant waning trend. Additionally, we found that ages 5-11 exhibited no significant waning of naturally acquired protection throughout the outcome period, whereas waning protection in the 12-18 age group was more prominent, but still mild.
Conclusions: Children and adolescents who were previously infected with SARS-CoV-2 remain protected against reinfection to a high degree for 18 months. Policy decision makers should consider when and if convalescent children and adolescents should be vaccinated. Nonetheless, further research is needed to examine naturally acquired immunity against emerging variants, including the Omicron.
N.B. Halasa et al.
Maternal Vaccination and Risk of Hospitalization for Covid-19 among Infants
The New England Journal of Medicine, June 2022; doi: 10.1056/NEJMoa2204399
Abstract
BACKGROUND Infants younger than 6 months of age are at high risk for complications of coronavirus disease 2019 (Covid-19) and are not eligible for vaccination. Transplacental transfer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after maternal Covid-19 vaccination may confer protection against Covid-19 in infants.
METHODS We used a case–control test-negative design to assess the effectiveness of maternal vaccination during pregnancy against hospitalization for Covid-19 among infants younger than 6 months of age. Between July 1, 2021, and March 8, 2022, we enrolled infants hospitalized for Covid-19 (case infants) and infants hospitalized without Covid-19 (control infants) at 30 hospitals in 22 states. We estimated vaccine effectiveness by comparing the odds of full maternal vaccination (two doses of mRNA vaccine) among case infants and control infants during circulation of the B.1.617.2 (delta) variant (July 1, 2021, to December 18, 2021) and the B.1.1.259 (omicron) variant (December 19, 2021, to March 8, 2022).
RESULTS A total of 537 case infants (181 of whom had been admitted to a hospital during the delta period and 356 during the omicron period; median age, 2 months) and 512 control infants were enrolled and included in the analyses; 16% of the case infants and 29% of the control infants had been born to mothers who had been fully vaccinated against Covid-19 during pregnancy. Among the case infants, 113 (21%) received intensive care (64 [12%] received mechanical ventilation or vasoactive infusions). Two case infants died from Covid-19; neither infant’s mother had been vaccinated during pregnancy. The effectiveness of maternal vaccination against hospitalization for Covid-19 among infants was 52% (95% confidence interval [CI], 33 to 65) overall, 80% (95% CI, 60 to 90) during the delta period, and 38% (95% CI, 8 to 58) during the omicron period. Effectiveness was 69% (95% CI, 50 to 80) when maternal vaccination occurred after 20 weeks of pregnancy and 38% (95% CI, 3 to 60) during the first 20 weeks of pregnancy.
CONCLUSIONS Maternal vaccination with two doses of mRNA vaccine was associated with a reduced risk of hospitalization for Covid-19, including for critical illness, among infants younger than 6 months of age.
De Silva et al.
Evaluation of Acute Adverse Events after Covid-19 Vaccination during Pregnancy
The New England Journal of Medicine, June 2022; doi: 10.1056/NEJMc2205276
Abstract
Pregnant women with symptomatic coronavirus disease 2019 (Covid-19) have a higher risk of adverse outcomes than do women who are not pregnant. In part because of these findings, Covid-19 vaccination has been recommended for pregnant women. However, uptake has been lower in pregnant women than among women who are not pregnant. The concern of many women regarding safety remains a barrier to maternal vaccination.
We performed a retrospective, observational, matched-cohort study involving pregnant women between the ages of 16 and 49 years at eight Vaccine Safety Datalink sites from December 15, 2020, through July 1, 2021. We matched each dose of a Food and Drug Administration–authorized Covid-19 vaccine received by a pregnant woman to an unvaccinated pregnant woman, according to study site and pregnancy start date. Included in the pregnancy cohort were women who were subsequently found to be pregnant within 28 days after receiving the vaccine. Vaccinations were captured through electronic health records, claims data, and bidirectional linkages with state and local immunization registries
M.J. Heilskov Rytter et al.
Difficult questions about long COVID in children
Lancet, June 2022 ; doi.org/10.1016/ S2352-4642(22)00167-5
Abstract
The COVID-19 pandemic is likely to leave long-lasting marks on a generation of children and young people, mainly from indirect effects, including those of school closures, social isolation, and a so-called immunity debt resulting from 2 years with reduced exposure to common pathogens. A small proportion of children have had serious sequelae of SARS-CoV-2 infection itself, with the most dramatic being multisystem inflammatory syndrome in children (MIS-C). Furthermore, a less well defined entity, termed long COVID or post-COVID-19 condition, has been suggested, referring to children with long-lasting symptoms after SARS-CoV-2 infection that are not explained by another disease. In contrast to MIS-C, the symptoms attributed to long COVID are non-specific and occur frequently in otherwise healthy children; headache, mood swings, abdominal pain, and fatigue are all common, and, although they can be symptoms of a disease, they often are not. Accordingly, the occurrence of these symptoms after infection with SARS-CoV-2 does not necessarily mean that they are caused by the infection. Paediatricians frequently meet children with non specific symptoms. Since the pandemic started, parents have occasionally considered whether a child’s symptoms could be caused by COVID-19 occurring in the preceding months. Therefore, Selina Kikkenborg Berg and colleagues should be applauded for their study, published in The Lancet Child & Adolescent Health, assessing whether non-specific symptoms are more frequent in children after infection with SARS-CoV-2 than in children who have never had the infection.
K.E. Fleming-Dutra et al.
Association of prior bnt162b2 covid-19 vaccination with symptomatic Sars-Cov-2 infection in children and adolescents during omicron predominance
JAMA, June 2022; doi:10.1001/jama.2022.7493
Abstract
Importance Efficacy of 2 doses of the BNT162b2 COVID-19 vaccine (Pfizer-BioNTech) against COVID-19 was high in pediatric trials conducted before the SARS-CoV-2 Omicron variant emerged. Among adults, estimated vaccine effectiveness (VE) of 2 BNT162b2 doses against symptomatic Omicron infection was reduced compared with prior variants, waned rapidly, and increased with a booster.
Objective To evaluate the association of symptomatic infection with prior vaccination with BNT162b2 to estimate VE among children and adolescents during Omicron variant predominance.
Design, Setting, and Participants A test-negative, case-control analysis was conducted using data from 6897 pharmacy-based, drive-through SARS-CoV-2 testing sites across the US from a single pharmacy chain in the Increasing Community Access to Testing platform. This analysis included 74 208 tests from children 5 to 11 years of age and 47 744 tests from adolescents 12 to 15 years of age with COVID-19–like illness who underwent SARS-CoV-2 nucleic acid amplification testing from December 26, 2021, to February 21, 2022.
Exposures Two BNT162b2 doses 2 weeks or more before SARS-CoV-2 testing vs no vaccination for children; 2 or 3 doses 2 weeks or more before testing vs no vaccination for adolescents (who are recommended to receive a booster dose).
Main Outcomes and Measures Symptomatic infection. The adjusted odds ratio (OR) for the association of prior vaccination and symptomatic SARS-CoV-2 infection was used to estimate VE: VE = (1 − OR) × 100%.
Results A total of 30 999 test-positive cases and 43 209 test-negative controls were included from children 5 to 11 years of age, as well as 22 273 test-positive cases and 25 471 test-negative controls from adolescents 12 to 15 years of age. The median age among those with included tests was 10 years (IQR, 7-13); 61 189 (50.2%) were female, 75 758 (70.1%) were White, and 29 034 (25.7%) were Hispanic/Latino. At 2 to 4 weeks after dose 2, among children, the adjusted OR was 0.40 (95% CI, 0.35-0.45; estimated VE, 60.1% [95% CI, 54.7%-64.8%]) and among adolescents, the OR was 0.40 (95% CI, 0.29-0.56; estimated VE, 59.5% [95% CI, 44.3%-70.6%]). During month 2 after dose 2, among children, the OR was 0.71 (95% CI, 0.67-0.76; estimated VE, 28.9% [95% CI, 24.5%-33.1%]) and among adolescents, the OR was 0.83 (95% CI, 0.76-0.92; estimated VE, 16.6% [95% CI, 8.1%-24.3%]). Among adolescents, the booster dose OR 2 to 6.5 weeks after the dose was 0.29 (95% CI, 0.24-0.35; estimated VE, 71.1% [95% CI, 65.5%-75.7%]).
Conclusions and Relevance Among children and adolescents, estimated VE for 2 doses of BNT162b2 against symptomatic infection was modest and decreased rapidly. Among adolescents, the estimated effectiveness increased after a booster dose.
K.E. Fleming-Dutra et al.
Association of Prior BNT162b2 COVID-19 Vaccination With Symptomatic SARS-CoV-2 Infection in Children and Adolescents During Omicron Predominance
JAMA, May 2022; doi:10.1001/jama.2022.7493
Abstract
Importance Efficacy of 2 doses of the BNT162b2 COVID-19 vaccine (Pfizer-BioNTech) against COVID-19 was high in pediatric trials conducted before the SARS-CoV-2 Omicron variant emerged. Among adults, estimated vaccine effectiveness (VE) of 2 BNT162b2 doses against symptomatic Omicron infection was reduced compared with prior variants, waned rapidly, and increased with a booster.
Objective To evaluate the association of symptomatic infection with prior vaccination with BNT162b2 to estimate VE among children and adolescents during Omicron variant predominance.
Design, Setting, and Participants A test-negative, case-control analysis was conducted using data from 6897 pharmacy-based, drive-through SARS-CoV-2 testing sites across the US from a single pharmacy chain in the Increasing Community Access to Testing platform. This analysis included 74 208 tests from children 5 to 11 years of age and 47 744 tests from adolescents 12 to 15 years of age with COVID-19–like illness who underwent SARS-CoV-2 nucleic acid amplification testing from December 26, 2021, to February 21, 2022.
Exposures Two BNT162b2 doses 2 weeks or more before SARS-CoV-2 testing vs no vaccination for children; 2 or 3 doses 2 weeks or more before testing vs no vaccination for adolescents (who are recommended to receive a booster dose).
Main Outcomes and Measures Symptomatic infection. The adjusted odds ratio (OR) for the association of prior vaccination and symptomatic SARS-CoV-2 infection was used to estimate VE: VE = (1 − OR) × 100%.
Results A total of 30 999 test-positive cases and 43 209 test-negative controls were included from children 5 to 11 years of age, as well as 22 273 test-positive cases and 25 471 test-negative controls from adolescents 12 to 15 years of age. The median age among those with included tests was 10 years (IQR, 7-13); 61 189 (50.2%) were female, 75 758 (70.1%) were White, and 29 034 (25.7%) were Hispanic/Latino. At 2 to 4 weeks after dose 2, among children, the adjusted OR was 0.40 (95% CI, 0.35-0.45; estimated VE, 60.1% [95% CI, 54.7%-64.8%]) and among adolescents, the OR was 0.40 (95% CI, 0.29-0.56; estimated VE, 59.5% [95% CI, 44.3%-70.6%]). During month 2 after dose 2, among children, the OR was 0.71 (95% CI, 0.67-0.76; estimated VE, 28.9% [95% CI, 24.5%-33.1%]) and among adolescents, the OR was 0.83 (95% CI, 0.76-0.92; estimated VE, 16.6% [95% CI, 8.1%-24.3%]). Among adolescents, the booster dose OR 2 to 6.5 weeks after the dose was 0.29 (95% CI, 0.24-0.35; estimated VE, 71.1% [95% CI, 65.5%-75.7%]).
Conclusions and Relevance Among children and adolescents, estimated VE for 2 doses of BNT162b2 against symptomatic infection was modest and decreased rapidly. Among adolescents, the estimated effectiveness increased after a booster dose.
S. Della Paolera et al.
Case Report: Use of Anakinra in Multisystem Inflammatory Syndrome During COVID-19 Pandemic
Frontiers in Pediatrics, February 2021; doi.org/10.3389/fped.2020.624248
Abstract
During COVID-19 outbreak, a large number of children with severe inflammatory disease has been reported. This condition, named Pediatric Multi-inflammatory Syndrome temporally associated with COVID-19 (PIMS-TS) or Multisystem Inflammatory Syndrome associated with Coronavirus Disease 2019 (MIS-C), shares some clinical features with Kawasaki disease and is frequently complicated by myocarditis or shock. It has been suggested that MIS-C belongs to the group of cytokine storm syndromes triggered by SARS-CoV-2 infection. So far, intravenous immunoglobulin (IVIG) and systemic glucocorticoids are the most common therapeutic approaches reported in this group of patients. However, the use of anakinra in patients with severe forms of COVID-19 is showing promising results. Here we reported two patients with multisystem inflammatory syndrome complicated with shock. Both the patients presented a poor response to IVIG and systemic glucocorticoids and received anakinra. Treatment with IL-1 receptor antagonist showed a rapid improvement of clinical conditions and biochemical analysis in both patients and demonstrated a good safety profile. Thus, we look forward for future controlled clinical trials with the aim to demonstrate the effectiveness of anakinra in patients with MIS-C and established precise criteria for its use.
Maza-Arnedo et al.
Maternal mortality linked to COVID-19 in Latin America: Results from a multi-country collaborative database of 447 deaths
Lancet Regional Health Americas, August 2022;doi: 10.1016/j.lana.2022.100269
Abstract
Background: This study aimed to describe the clinical characteristics of maternal deaths associated with COVID-19 registered in a collaborative Latin-American multi-country database.
Methods: This was an observational study implemented from March 1st 2020 to November 29th 2021 in eight Latin American countries. Information was based on the Perinatal Information System from the Latin American Center for Perinatology, Women and Reproductive Health. We summarized categorical variables as frequencies and percentages and continuous variables into median with interquartile ranges.
Findings: We identified a total of 447 deaths. The median maternal age was 31 years. 86·4% of women were infected antepartum, with most of the cases (60·3%) detected in the third trimester of pregnancy. The most frequent symptoms at first consultation and admission were dyspnea (73·0%), fever (69·0%), and cough (59·0%). Organ dysfunction was reported in 90·4% of women during admission. A total of 64·8% women were admitted to critical care for a median length of eight days. In most cases, the death occurred during the puerperium, with a median of seven days between delivery and death. Preterm delivery was the most common perinatal complication (76·9%) and 59·9% were low birth weight.
Interpretation: This study describes the characteristics of maternal deaths in a comprehensive multi-country database in Latin America during the COVID-19 pandemic. Barriers faced by Latin American pregnant women to access intensive care services when required were also revealed. Decision-makers should strengthen severity awareness, and referral strategies to avoid potential delays.
J.B. Moore
COVID-19, childhood obesity, and NAFLD: colliding pandemics
The Lancet.com, June 2022; doi.org/10.1016/S2468-1253(22)00100-5
Abstract
The COVID-19 pandemic drastically affected the lives of children and young people worldwide in 2020 and 2021. Public health measures to reduce community transmission of SARS-CoV-2 included unprecedented school closures and stay-at-home orders. In the UK, national lockdown measures in March, 2020, closed nurseries, primary and secondary schools, and universities for most students through the remainder of the school year. In 2021, primary and secondary schools were again closed in the UK from January to early March. Alongside these school closures were varying levels of restrictions on outdoor recreation, social gatherings, and economic activities. Although the role of social inequalities in exacerbating the negative effects of lockdown on the health and wellbeing of children was evident after the first wave of COVID-19,stark new data highlight the effects of the pandemic and socioeconomic deprivation on childhood obesity rates.
Victoria Male et al.
SARS- CoV-2 infection and COVID-19 vaccination in pregnancy
Nature Reviews Immunology, https://www.nature.com/articles/s41577-022-00703-6.pdf
CONTENUTO E COMMENTO: In questa review vengono illustrati i recenti sviluppi scientifici nella comprensione dei rischi dell'infezione da SARS-CoV-2 specifici della gravidanza per la donna e per il feto, e come la vaccinazione può ridurli in modo sicuro.
Ferrara A et al.
Perinatal Complications in Individuals in California With or Without SARS-CoV-2 Infection During Pregnancy
JAMA Intern Med, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2790318
CONTENTUO E COMMENTO: Studio retrospettivo di popolazione condotto in California su una coorte di 43886 donne in gravidanza, di cui 1332 (3%) con tampone molecolare positivo per SARS-CoV-2. In questo studio viene dimostrato che l’infezione da SARS-CoV-2 in gravidanza è associata ad un aumentato rischio di patologie gestazionali gravi (tra cui infarto del miocardio, insufficienza renale acuta e sepsi), parto pretermine e tromboembolismo venoso. Oltre a fornire informazioni sul rischio di complicanze perinatali associate all’infezione da SARS-CoV-2 durante la gravidanza, lo studio supporta la vaccinazione delle donne in gravidanza e in coloro che programmano una gravidanza.
Allotey J et al
SARS-CoV-2 positivity in offspring and timing of mother-to-child transmission: living systematic review and meta-analysis
The BMJ, https://www.bmj.com/content/376/bmj-2021-067696
CONTENUTO E COMMENTO: Ampia revisione sistematica di quasi 500 lavori sulla trasmissione verticale di SARS-CoV-2 dalla madre al feto, oppure al neonato durante il parto o in epoca perinatale; il fenomeno è descritto in tutti e tre i casi, ma appare estremamente raro e associato alla gravità dell’infezione materna.
Coma, E.; et al.
Unravelling the role of the mandatory use of face covering masks for the control of SARS-CoV-2 in schools: A quasi-experimental study nested in a population-based cohort in Catalonia (Spain)
SSRN.com, file:///C:/Users/00122705/Downloads/SSRN-id4046809.pdf
CONTENUTO E COMMENTO: Studio spagnolo ancora non peer-reviewed sull’efficacia delle mascherine obbligatorie nelle scuole come misura di prevenzione dell’infezione da SARS-CoV-2 nel periodo in cui era prevalente la variante Delta.
Nello studio vengono confrontate classi di scuola dell’infanzia e di scuola primaria.
L’uso della mascherina in questo studio non sembra essere associata ad una minore incidenza o trasmissione di SARS-CoV-2. Al contrario l'età sembra essere la variabile più importante per spiegare la diversa circolazione/trasmissione del virus tra i bambini (l'incidenza di SARS-CoV-2 era significativamente più bassa in bambini di età prescolare che non avevano obbligo di mascherina rispetto a quelli del primo anno di scuola primaria che l’avevano). Questi risultati potrebbero essere correlati anche alla tendenza al cambiamento nella risposta immunitaria innata che si verifica nell’età scolare con uno shift verso un modello di risposta immunologica più simile a quella dell'adulto con un conseguente maggiore rischio di infezione.
Olson S. M. et al.
Effectiveness of BNT162b2 Vaccine against Critical Covid-19 in Adolescents
NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2117995
CONTENUTO E COMMENTO : studio caso controllo, a design test-negativo per valutare l’efficacia della vaccinazione contro SARS-coV2 nella popolazione adolescente su ospedalizzazione, ammissione in rianimazione e procedure di supporto vitale valutando gli odds di precedente vaccinazione nei casi confermati da laboratorio e controlli ospedalizzati senza COVID19. Sono stati screenati adolescenti tra i 12 e i 18 anni ospedalizzati nel CVC-funded Overcoming COVID19 Network nel periodo tra maggio e ottobre 2021. Sono stati comparati 445 casi vs 777 controlli. Nonostante l’eleggibilità per vaccinazione, il 96% di coloro ospedalizzati per COVID e 99% di quelli che hanno ricevuto supporto vitale non sono stati vaccinati. La vaccinazione con due dosi di BNT162b2 ha ridotto il rischio di ospedalizzazione del 94% negli adolescenti. Dei 13 adolescenti che hanno ricevuto ECMO e 7 che sono deceduti, nessuno era vaccinato. I dati sono quindi compatibili con una riduzione del rischio del 94% in questa coorte di ospedalizzazione per COVID19 e del 98% per rianimazione, nonostante le differenze con gli adolescenti vaccinati nei trial registrativi (maggiore prevalenza di obesità e condizioni mediche sottostanti nella coorte in studio) e un periodo di follow-up dello studio maggiore (90 giorni). Solo il 39% dei controlli erano vaccinati.
LIMITAZIONI: non disponibili dati di sequenziamento, anche se la maggior parte delle varianti circolanti nel periodo di arruolamento era delta (96%); multicentrico ma non facilmente generalizzabile a contesti non urbani; 56% proveniente dal sud degli USA, dove la circolazione del virus era molto alta nel periodo in studio; non analizzata la protezione derivante da una sola dose vaccinale o da altri tipi di schedula vaccinale; non analizzabile la durata di protezione.
Taytard J. et Al.
Leibowitz R. et Al
Walter E. B. et al.
More on BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age Correspondence
NEJM, https://www.nejm.org/doi/pdf/10.1056/NEJMc2201556
CONTENUTO E COMMENTO : in risposta allo studio pubblicato in gennaio di Walter et al, che riporta l’efficacia e sicurezza della vaccinazione nei bambini tra i 5 e gli 11 anni, Taytard et al presenta i dati proveniente dall’unità pneumologica in cui lavora, in cui i bambini ospedalizzati per COVID sono raddoppiati nel passaggio temporale tra prevalenza delta a prevalenza omicron, con caratteristiche diverse: i bambini attualmente ricoverati presentano meno comorbidita’ e presentazione clinica differente (riduzione della dispnea, maggiore coriza, febbre e deterioramento delle condizioni cliniche generali). Nessuno dei bambini ricoverati attualmente e’ stato sottoposto a un ciclo vaccinale completo.
Leibowitz R. et al. contestano il fatto che Walter et al. non abbiano riportato gli effetti avversi noti sottomessi presso la FDA, specialmente gli effetti avversi non severi, con dei cutoff al follow-up a un mese dalla seconda dose e non a settembre 2021, come il resto dei dati. Questo, sottolineano, porterà a una maggiore difficoltà nel creare metanalisi a partire da quei dati. I dati sembrano suggerire infatti un’incidenza dello 0.2% di effetti non seri nei bimbi vaccinati, che può avere importanti conseguenze nel momento di una campagna vaccinale di massa in questa popolazione.
Walter E. B. et al. rispondono che i dati di sicurezza sono stati presentati come da endpoint definiti da protocollo, ossia la valutazione dalla prima dose a dopo un mese dalla seconda dose per gli effetti avversi e dalla prima dose a 6 mesi dopo la somministrazione della seconda per gli effetti avversi severi (un periodo maggiore di quello del documento FDA riportato).
Kotiloglu-Karaa E et al
SARS-CoV-2 placental infection is associated with massive perivillous fibrin deposition at the maternal-fetal interface: a preliminary study
Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac173/6540910
CONTENUTO E COMMENTO : In questo studio gli autori hanno osservato un’aumentata frequenza di deposizione massiva di fibrina perivillare (MPFD) nella placenta durante la seconda ondata pandemica di COVID-19 dominata dalla variante alfa. Hanno quindi ricercato tramite RT-PCR la variante alfa in tutti i campioni di placenta che potevano essere sequenziati, trovando un’associazione del 100% tra MPFD e positività della RT-PCR per la variante alfa di SARS-CoV-2.
Questi risultati suggeriscono che SARS-CoV-2 possa causare MPFD, ed in particolar modo la variante alfa determini un aumentato rischio di MPFD. Sono tuttavia necessari ulteriori studi che includano dei campioni di controllo da pazienti SARS-CoV-2 negative e campioni di placenta da pazienti infettate con diverse varianti del virus.
Encinosa W et al
Severity of Hospitalizations from SARS-CoV-2 vs Influenza and Respiratory Syncytial Virus Infection in Children Aged 5 to 11 Years in 11 US States
JAMA, https://jamanetwork.com/journals/jamapediatrics/fullarticle/2789353
CONTENUTO E COMMENTO : Confronto fra le ospedalizzazioni infantili (5-11 anni) per MIS-C nel periodo gennaio-maggio 2021 per SARS-CoV-2 e quelle per MIS-C da influenza e virus respiratorio sinciziale in un periodo precedente: su quasi 3000 bambini osservati si è verificato 1 caso di MIS-C ogni 100 ricoveri per SARS-CoV-2 circa, il che rende questa complicanza meno rara di quanto inizialmente stimato.
Torri D. Metzet al
Association of SARS-CoV-2 Infection With Serious Maternal Morbidity and Mortality From Obstetric Complications
JAMA, https://jamanetwork.com/journals/jama/fullarticle/2788985
CONTENUTO E COMMENTIO : Studio retrospettivo di coorte su 14,104 donne in gravidanza e puerpere, con l’obiettivo di valutare l’associazione tra infezione da SARS-CoV-2 e morbidità e mortalità materne dovute a comuni complicanze ostetriche.
I risultati mostrano che le pazienti con infezione da SARS-CoV-2 moderato-severa hanno un rischio maggiore di morte materna e di malattie gravi correlate al parto, quali disordini ipertensivi, emorragia post-partum o infezioni diverse da SARS-CoV-2. Hanno inoltre un aumentato rischio di parto cesareo. Questa associazione non è stata dimostrata per le pazienti con infezione da SARS-CoV-2 lieve o asintomatica.
Garcia-Flores V et al
Maternal-fetal immune responses in pregnant women infected with SARS-CoV-2
Nature Communications, https://www.nature.com/articles/s41467-021-27745-z.pdf
CONTENUTO E COMMENTO : Studio osservazionale su 15 donne in gravidanza con infezione da SARS-CoV-2, nelle quali si osserva come il virus induca una risposta immunitaria prevalentemente cellulo-mediata nella madre, in assenza di elevati titoli anticorpali nel sangue cordonale. Il virus non è stato rinvenuto in nessun caso nella placenta, confermando il dato che l’infezione transplacentare non sia una evenienza significativa.
Stephanie E. Perez, BS et al.
Human Milk SARS-CoV-2 Antibodies up to 6 Months After Vaccination
Pediatrics,
https://publications.aap.org/pediatrics/article/doi/10.1542/peds.2021-054260/184351/Human-Milk-SARS-CoV-2-Antibodies-up-to-6-Months?searchresult=1
CONTENUTO E COMMENTO: Studio prospettico longitudinale condotto su 30 donne in gravidanza o in allattamento con l’obiettivo di analizzare la presenza nel latte materno degli anticorpi anti-SARS-Cov-2 e la loro capacità neutralizzante confrontando i livelli nel periodo pre- e nei mesi successivi alla vaccinazione. I risultati hanno evidenziato che nel latte materno sono stati rilevati anticorpi specifici anti-SARS-Cov-2 fino a 6 settimane dopo la vaccinazione materna.
Jean B. Nachega et al.
Assessment of Clinical Outcomes Among Children and Adolescents Hospitalized With COVID-19 in 6 Sub-Saharan African Countries
JAMA Pediatr, https://jamanetwork.com/journals/jamapediatrics/fullarticle/2788373
CONTENUTO E COMMENTO: In questo studio di coorte condotto su circa 460 bambini e adolescenti ricoverati con COVID-19 in 6 paesi dell'Africa sub-sahariana, sono stati registrati tassi di morbilità e mortalità notevolmente superiori a quelli riportati dagli altri Paesi non appartenenti al continente Africano. Morbilità e mortalità inoltre sono indipendentemente associate a età < 1 anno e alla presenza di comorbidità, fra cui ipertensione, patologie respiratorie croniche e ematologiche. I risultati di questo studio possono avere implicazioni per la pratica clinica e la politica sanitaria in materia di COVID-19 pediatrico nei Paesi Africani; dato il loro alto rischio di outcomes negativi, la vaccinazione e le cure per l’infezione da Sars-CoV2 sono necessarie per i bambini e gli adolescenti africani.
Shoji K et al
Clinical characteristics and outcomes of COVID-19 in pregnant women: a propensity score matched analysis of the data from the COVID-19 Registry Japan
Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac028/6509063
CONTENUTO E COMMENTO : Studio retrospettivo di coorte condotto utilizzando i dati del registro COVID-19 nazionale giapponese in cui 187 donne in gravidanza sono state matchate per gravità con 935 donne non in gravidanza per valutare i fattori di rischio di sviluppare malattia moderato-severa nelle donne in gravidanza.
I risultati hanno dimostrato che la gravidanza in sè rappresenta un fattore di rischio per forme moderato-severe e che nelle donne in gravidanza la presenza di comorbidità e le fasi avanzate di gravidanza (secondo e terzo trimestre) rappresentano fattori di rischio per forme moderato-severe di COVID-19.
