Covid19-Sources

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Genome wide screen of RNAi molecules against SARS-CoV-2 creates a broadly potent prophylaxis
Genome wide screen of RNAi molecules against SARS-CoV-2 creates a broadly potent prophylaxis
Expanding the arsenal of prophylactic approaches against SARS-CoV-2 is of utmost importance, specifically those strategies that are resistant to antigenic drift in Spike. Here, we conducted a screen with over 16,000 RNAi triggers against the SARS-CoV-2 genome using a massively parallel assay to identify hyper-potent siRNAs. We selected 10 candidates for in vitro validation and found five siRNAs that exhibited hyper-potent activity with IC50
·biorxiv.org·
Genome wide screen of RNAi molecules against SARS-CoV-2 creates a broadly potent prophylaxis
Covid-19 deaths in Africa: prospective systematic postmortem surveillance study
Covid-19 deaths in Africa: prospective systematic postmortem surveillance study
Objective To directly measure the fatal impact of coronavirus disease 2019 (covid-19) in an urban African population. Design Prospective systematic postmortem surveillance study. Setting Zambia’s largest tertiary care referral hospital. Participants Deceased people of all ages at the University Teaching Hospital morgue in Lusaka, Zambia, enrolled within 48 hours of death. Main outcome measure Postmortem nasopharyngeal swabs were tested via reverse transcriptase quantitative polymerase chain reaction (PCR) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Deaths were stratified by covis-19 status, location, age, sex, and underlying risk factors. Results 372 participants were enrolled between June and September 2020; PCR results were available for 364 (97.8%). SARS-CoV-2 was detected in 58/364 (15.9%) according to the recommended cycle threshold value of
·bmj.com·
Covid-19 deaths in Africa: prospective systematic postmortem surveillance study
Emanuel Wyler on Twitter
Emanuel Wyler on Twitter
#CoronaInfo – Die seit Anfang Januar dominierende Omikron-Variante von SARS-CoV-2 macht die Menschen seltener schwer krank als die Delta-Variante davor. Das ist vor allem von Krankenhauseinweisungen bekannt, aber wie sind die Unterschiede bei milderen Verläufen? … (1/8)— Emanuel Wyler (@ewyler) April 19, 2022
·twitter.com·
Emanuel Wyler on Twitter
Safety, Immunogenicity and Antibody Persistence of a Bivalent Beta-Containing Booster Vaccine
Safety, Immunogenicity and Antibody Persistence of a Bivalent Beta-Containing Booster Vaccine
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants have caused multiple waves of infection globally. This phase 2/3 study evaluated the safety and immunogenicity of the bivalent vaccine candidate mRNA-1273.211 (equal mRNA amounts of ancestral SARS-CoV-2 and Beta variant spik...
·researchsquare.com·
Safety, Immunogenicity and Antibody Persistence of a Bivalent Beta-Containing Booster Vaccine
Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study
Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study
Adolescents who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but had a higher prevalence of single and, particularly, multiple symptoms at the time of PCR testing and 3 months later. Clinicians should consider multiple symptoms that affect functioning and recognise different clusters of symptoms. The multiple and varied symptoms show that a multicomponent intervention will be required, and that mental and physical health symptoms occur concurrently, reflecting their close relationship.
·thelancet.com·
Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study
Comparing aerosol number and mass exhalation rates from children and adults during breathing, speaking and singing | Interface Focus
Comparing aerosol number and mass exhalation rates from children and adults during breathing, speaking and singing | Interface Focus
Aerosol particles of respirable size are exhaled when individuals breathe, speak and sing and can transmit respiratory pathogens between infected and susceptible individuals. The COVID-19 pandemic has brought into focus the need to improve the ...
·royalsocietypublishing.org·
Comparing aerosol number and mass exhalation rates from children and adults during breathing, speaking and singing | Interface Focus
Anthony J Leonardi, PhD, MS on Twitter
Anthony J Leonardi, PhD, MS on Twitter
To normalize the level of death at this frequency you must normalize the pathogenSars cov 2 hyperstimulates and behaves like a SARS even on reinfectionIt creates unprecedented levels of autoimmunity that persistIt is intrinsically virulenthttps://t.co/mx2nqxLHr0 pic.twitter.com/1XegF1THIb— Anthony J Leonardi, PhD, MS (@fitterhappierAJ) April 15, 2022
·twitter.com·
Anthony J Leonardi, PhD, MS on Twitter
Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study
Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study
Objective To quantify the risk of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19. Design Self-controlled case series and matched cohort study. Setting National registries in Sweden. Participants 1 057 174 people who tested positive for SARS-CoV-2 between 1 February 2020 and 25 May 2021 in Sweden, matched on age, sex, and county of residence to 4 076 342 control participants. Main outcomes measures Self-controlled case series and conditional Poisson regression were used to determine the incidence rate ratio and risk ratio with corresponding 95% confidence intervals for a first deep vein thrombosis, pulmonary embolism, or bleeding event. In the self-controlled case series, the incidence rate ratios for first time outcomes after covid-19 were determined using set time intervals and the spline model. The risk ratios for first time and all events were determined during days 1-30 after covid-19 or index date using the matched cohort study, and adjusting for potential confounders (comorbidities, cancer, surgery, long term anticoagulation treatment, previous venous thromboembolism, or previous bleeding event). Results Compared with the control period, incidence rate ratios were significantly increased 70 days after covid-19 for deep vein thrombosis, 110 days for pulmonary embolism, and 60 days for bleeding. In particular, incidence rate ratios for a first pulmonary embolism were 36.17 (95% confidence interval 31.55 to 41.47) during the first week after covid-19 and 46.40 (40.61 to 53.02) during the second week. Incidence rate ratios during days 1-30 after covid-19 were 5.90 (5.12 to 6.80) for deep vein thrombosis, 31.59 (27.99 to 35.63) for pulmonary embolism, and 2.48 (2.30 to 2.68) for bleeding. Similarly, the risk ratios during days 1-30 after covid-19 were 4.98 (4.96 to 5.01) for deep vein thrombosis, 33.05 (32.8 to 33.3) for pulmonary embolism, and 1.88 (1.71 to 2.07) for bleeding, after adjusting for the effect of potential confounders. The rate ratios were highest in patients with critical covid-19 and highest during the first pandemic wave in Sweden compared with the second and third waves. In the same period, the absolute risk among patients with covid-19 was 0.039% (401 events) for deep vein thrombosis, 0.17% (1761 events) for pulmonary embolism, and 0.101% (1002 events) for bleeding. Conclusions The findings of this study suggest that covid-19 is a risk factor for deep vein thrombosis, pulmonary embolism, and bleeding. These results could impact recommendations on diagnostic and prophylactic strategies against venous thromboembolism after covid-19. The study protocol (R script) for the SCCS and matched cohort study are available on request from the corresponding author. The study used secondary registry data, which is regulated by the Public Access to Information and Secrecy Act (2009:400) and is protected by strict confidentiality. However, for the purpose of research, after formal application to access personal data, the responsible authority can grant access to data, although this is contingent on vetting by the Ethical Review Authority of Sweden, according to the Act (2003:460) concerning the Ethical Review of Research Involving Humans. Synthetic (ie, depersonalised and jittered) data can be provided on request from the corresponding author.
·bmj.com·
Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study
Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine
Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine
We examined antibody and memory B cell responses longitudinally for ∼9-10 months after primary 2-dose SARS-CoV-2 mRNA vaccination and 3 months after a 3rd dose. Antibody decay stabilized between 6 to 9 months and antibody quality continued to improve for at least 9 months after 2-dose vaccination. Spike- and RBD-specific memory B cells remained durable over time, and 40-50% of RBD-specific memory B cells simultaneously bound the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells were efficiently re-activated by a 3rd dose of wild-type vaccine and correlated with the corresponding increase in neutralizing antibody titers. In contrast, pre-3rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit the added protection afforded by repeat short interval boosting. These data provide insight into the quantity and quality of mRNA vaccine-induced immunity over time through 3 or more antigen exposures.
·cell.com·
Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine
CHANGES IN LIFE EXPECTANCY BETWEEN 2019 AND 2021: UNITED STATES AND 19 PEER COUNTRIES
CHANGES IN LIFE EXPECTANCY BETWEEN 2019 AND 2021: UNITED STATES AND 19 PEER COUNTRIES
BACKGROUND Prior studies reported large decreases in US life expectancy during 2020 as a result of the COVID-19 pandemic, disproportionately affecting Hispanic and Black populations and vastly exceeding the average change in life expectancy in other high-income countries. Life expectancy estimates for 2021 have not been reported. This study estimated changes in life expectancy during 2019-2021 in the US population, in three US racial/ethnic groups, and in 19 peer countries. METHODS US and peer country death data for 2019-2021 were obtained from the National Center for Health Statistics, the Human Mortality Database, and overseas statistical agencies. The 19 peer countries included Austria, Belgium, Denmark, England and Wales, Finland, France, Germany, Israel, Italy, Netherlands, New Zealand, Northern Ireland, Norway, Portugal, Scotland, South Korea, Spain, Sweden, and Switzerland. Life expectancy was calculated for 2019 and 2020 and estimated for 2021 using a previously validated modeling method. RESULTS US life expectancy decreased from 78.86 years in 2019 to 76.99 years in 2020 and 76.60 years in 2021, a net loss of 2.26 years. In contrast, peer countries averaged a smaller decrease in life expectancy between 2019 and 2020 (0.57 years) and a 0.28-year increase between 2020 and 2021, widening the gap in life expectancy between the United States and peer countries to more than five years. The decrease in US life expectancy was highly racialized: whereas the largest decreases in 2020 occurred among Hispanic and non-Hispanic Black populations, in 2021 only the non-Hispanic White population experienced a decrease in life expectancy. DISCUSSION The US mortality experience during 2020 and 2021 was more severe than in peer countries, deepening a US disadvantage in health and survival that has been building for decades. Over the two-year period between 2019 and 2021, US Hispanic and non-Hispanic Black populations experienced the largest losses in life expectancy, reflecting the legacy of systemic racism and inadequacies in the US handling of the pandemic. Reasons for the crossover in racialized outcomes between 2020 and 2021, in which life expectancy decreased only in the non-Hispanic White population, could have multiple explanations. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Dr. Masters received support from the University of Colorado Population Center grant from the Eunice Kennedy Shriver Institute of Child Health and Human Development (CUPC project 2P2CHD066613-06). Dr. Woolf received partial funding from grant UL1TR002649 from the National Center for Advancing Translational Sciences. There was no specific funding for this study. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript.
·medrxiv.org·
CHANGES IN LIFE EXPECTANCY BETWEEN 2019 AND 2021: UNITED STATES AND 19 PEER COUNTRIES
Use of face masks did not impact COVID-19 incidence among 10–12-year-olds in Finland
Use of face masks did not impact COVID-19 incidence among 10–12-year-olds in Finland
In fall 2021 in Finland, the recommendation to use face masks in schools for pupils ages 12 years and above was in place nationwide. Some cities recommended face masks for younger pupils as well. Our aim was to compare COVID- 19 incidence among 10–12-year-olds between cities with different recommendations on the use of face masks in schools. COVID-19 case numbers were obtained from the National Infectious Disease Registry (NIDR) of the Finnish Institute for Health and Welfare, where clinical microbiology laboratories report all positive SARS-CoV-2 tests with unique identifiers in a timely manner, including information such as date of birth, gender, and place of residence. The NIDR is linked to the population data registry, enabling calculation of incidences. We compared the differences in trends of 14-day incidences between Helsinki and Turku among 10–12-year-olds, and for comparison, also among ages 7–9 and 30–49 by using joinpoint regression. According to our analysis, no additional effect seemed to be gained from this, based on comparisons between the cities and between the age groups of the unvaccinated children (10–12 years versus 7–9 years).
·medrxiv.org·
Use of face masks did not impact COVID-19 incidence among 10–12-year-olds in Finland
Hospitalisations in Children with Confirmed SARS-CoV-2 Infection During December 2020 to January 2022: Retrospective Single-Centre Cohort, London, England
Hospitalisations in Children with Confirmed SARS-CoV-2 Infection During December 2020 to January 2022: Retrospective Single-Centre Cohort, London, England
Hospitalisations are often used as proxies for severe disease and to measure the impact of variants and vaccination during the COVID-19 pandemic. Unlike adults,
·papers.ssrn.com·
Hospitalisations in Children with Confirmed SARS-CoV-2 Infection During December 2020 to January 2022: Retrospective Single-Centre Cohort, London, England
Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS-CoV-2 vaccination
Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS-CoV-2 vaccination
Initial vaccination with ChAdOx1 nCoV-19 resulted in lower anti-spike-RBD-IgG compared with BNT162b2 (70 ± 114 vs. 226 ± 279 BAU/ml, p .01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV-19 at T2 (anti-spike-RBD-IgG: ChAdOx1 nCoV-19/BNT162b2 2387 ± 1627 and homologous BNT162b2 3202 ± 2184 vs. homologous ChAdOx1 nCoV-19 413 ± 461 BAU/ml, both p .001; spike-induced T-cell interferon-γ release: ChAdOx1 nCoV-19/BNT162b2 5069 ± 6733 and homologous BNT162b2 4880 ± 7570 vs. homologous ChAdOx1 nCoV-19 1152 ± 2243 mIU/ml, both p .001). No significant differences were detected between BNT162b2-boostered groups at T2. For ChAdOx1 nCoV-19, no booster effect on T-cell activation could be observed. We found associations between anti-spike-RBD-IgG levels (ChAdOx1 nCoV-19/BNT162b2 and homologous BNT162b2) and T-cell responses (homologous ChAdOx1 nCoV-19 and ChAdOx1 nCoV-19/BNT162b2) from T1 to T2. Additionally, anti-spike-RBD-IgG and T-cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2.
·onlinelibrary.wiley.com·
Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS-CoV-2 vaccination
Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants
Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants
In comparing breakthrough infections from the SARS-CoV-2 Delta and Omicron variants, the latter, though milder than Delta infections, were associated with lower antibody titers and limited cross-neutralizing immunity, suggesting reduced protection against re-infection or infection from a future variant.
·cell.com·
Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants
Lower Risk of Multisystem Inflammatory Syndrome in Children (MIS-C) with the Delta and Omicron variants of SARS-CoV-2
Lower Risk of Multisystem Inflammatory Syndrome in Children (MIS-C) with the Delta and Omicron variants of SARS-CoV-2
Little is known about the MIS-C risk with different SARS-CoV-2 variants. In Southeast England, MIS-C rates per confirmed SARS-CoV-2 infections in 0-16 years-olds were 56% lower (rate ratio, 0.34; 95%CI, 0.23-0.50) during pre-vaccine Delta, 66% lower (0.44; 0.28-0.69) during post-vaccine Delta and 95% lower (0.05; 0.02-0.10) during the Omicron period.
·medrxiv.org·
Lower Risk of Multisystem Inflammatory Syndrome in Children (MIS-C) with the Delta and Omicron variants of SARS-CoV-2
Comprehensive profiling of antibody responses to the human anellome using programmable phage display
Comprehensive profiling of antibody responses to the human anellome using programmable phage display
Viruses belonging to the diverse Anelloviridae family represent a major constituent of the commensal human virome. Aside from their widespread prevalence and persistence in humans and their absence of detectable pathologic associations, little is known about the immunobiology of the human anellome. In this study, we employed the Phage ImmunoPrecipitation Sequencing (PhlP-Seq) assay for comprehensive analyses of antibody binding to 56 amino acid long anellovirus peptides. We designed and constructed a large and diverse “AnelloScan” T7 phage library comprising more than 32,000 non-redundant peptides representing the ORF1, ORF2, ORF3 and TTV-derived apoptosis-inducing protein (TAIP) sequences of more than 800 human anelloviruses (spanning three genera). We used this library to profile the antibody reactivities of serum samples from 156 subjects. The vast majority of anellovirus peptides were not reactive in any of the subjects tested (n=~28,000; ~85% of the library). Antibody reactive peptides were largely restricted to the C-terminal region of the putative capsid protein, ORF1. To characterize antibody responses to newly acquired anellovirus infections, we screened a longitudinal cohort of matched blood-transfusion donors and recipients. Most transmitted anelloviruses did not elicit detectable antibody reactivity in the recipient (29 out of a total of 40 transmitted anelloviruses) and the remainder demonstrated delayed reactivity (~100-150 days after transfusion). This study represents the first large-scale epitope-level serological survey of the antibody response to the human anellome. ![Figure][1] ### Competing Interest Statement TV declares no competing interests. HS, CAA, SMJ, AB, TD, DMN, SD, and NLY are employees of and hold equity interests in Ring Therapeutics. VM is an employee of and holds equity interests in Flagship Pioneering, which also holds an equity interest in Ring Therapeutics. HBL is an inventor on an issued patent (US20160320406A) filed by Brigham and Women's Hospital that covers the use of the VirScan technology, is a founder of ImmuneID, Portal Bioscience and Alchemab, and is an advisor to TScan Therapeutics. [1]: pending:yes
·biorxiv.org·
Comprehensive profiling of antibody responses to the human anellome using programmable phage display
Impact of post-COVID conditions on mental health: a cross-sectional study in Japan and Sweden - BMC Psychiatry
Impact of post-COVID conditions on mental health: a cross-sectional study in Japan and Sweden - BMC Psychiatry
Background Due to the coronavirus disease 2019 (COVID-19) pandemic, people have undermined their mental health. It has been reported that post-COVID conditions at a certain rate. However, information on the mental health of people with post-COVID conditions is limited. Thus, this study investigated the relationship between post-COVID conditions and mental health. Methods Design of the present study was an International and collaborative cross-sectional study in Japan and Sweden from March 18 to June 15, 2021. The analyzed data included 763 adults who participated in online surveys in Japan and Sweden and submitted complete data. In addition to demographic data including terms related to COVID-19, psychiatric symptoms such as depression, anxiety, and post-traumatic stress were measured by using the fear of COVID-19 scale (FCV-19S), Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 item (GAD-7), and Impact of Event Scale-Revised (IES-R). Results Of the 135 COVID-19 survivors among the 763 total participants, 37.0% (n = 50/135) had COVID-19-related sequelae. First, the results of the Bonferroni-corrected Mann Whitney U test showed that the group infected SARS-CoV-2 with post-COVID conditions scored significantly higher than those without one and the non-infected group on all clinical symptom scales (P ≤ .05). Next, there was a significant difference that incidence rates of clinical-significant psychiatric symptoms among each group from the results of the Chi-squared test (P ≤ .001). Finally, the results of the multivariate logistic model revealed that the risk of having more severe clinical symptoms were 2.44–3.48 times higher among participants with post-COVID conditions. Conclusion The results showed that approximately half had some physical symptoms after COVID-19 and that post-COVID conditions may lead to the onset of mental disorders. Trial registration The ethics committee of Chiba University approved this cross-sectional study (approval number: 4129). However, as no medical intervention was conducted, a clinical trial registration was not necessary.
·bmcpsychiatry.biomedcentral.com·
Impact of post-COVID conditions on mental health: a cross-sectional study in Japan and Sweden - BMC Psychiatry
Vitamin D Supplements for Prevention of Covid-19 or other Acute Respiratory Infections: a Phase 3 Randomized Controlled Trial (CORONAVIT) - 2022.03.22.22271707v1.full.pdf
Vitamin D Supplements for Prevention of Covid-19 or other Acute Respiratory Infections: a Phase 3 Randomized Controlled Trial (CORONAVIT) - 2022.03.22.22271707v1.full.pdf
METHODS: We randomly assigned 6200 U.K. adults to receive an offer of a postal finger-prick 25-hydroxyvitamin D (25[OH]D) test with provision of a 6-month supply of higher-dose vitamin D (3200 IU/d, n=1550) or lower-dose vitamin D (800 IU/d, n=1550) to those with blood 25(OH)D concentration 75 nmol/L, vs. no offer of testing or supplementation (n=3100). The primary outcome was the proportion of participants experiencing at least one swab test- or doctor-confirmed acute respiratory infection (ARI) of any cause at six months. Secondary outcomes included incidence of swab test-confirmed Covid-19. RESULTS: Of 3100 participants offered testing, 2958 (95.4%) accepted, and 2690 (86.8%) had 25(OH)D 75 nmol/L and were sent vitamin D supplements (1356 higher-dose, 1334 lower-dose). 76 (5.0%) vs. 87 (5.7%) vs. 136 (4.6%) participants in higher-dose vs. lower-dose vs. no-offer groups experienced at least one ARI of any cause (odds ratio [OR] for higher-dose vs. no-offer 1.09, 95% CI 0.82-1.46; lower-dose vs. no-offer 1.26, 0.96-1.66). 45 (3.0%) vs. 55 (3.6%) vs. 78 (2.6%) participants in higher-dose vs. lower-dose vs. no-offer groups developed Covid-19 (OR for higher-dose vs. no-offer 1.13, 0.78-1.63; lower-dose vs. no-offer 1.39, 0.98- 1.97). CONCLUSIONS: Among adults with a high baseline prevalence of vitamin D insufficiency, implementation of a test-and-treat approach to vitamin D replacement did not reduce risk of all-cause ARI or Covid-19.
·medrxiv.org·
Vitamin D Supplements for Prevention of Covid-19 or other Acute Respiratory Infections: a Phase 3 Randomized Controlled Trial (CORONAVIT) - 2022.03.22.22271707v1.full.pdf
COVID infection severity in children under 5 years old before and after Omicron emergence in the US
COVID infection severity in children under 5 years old before and after Omicron emergence in the US
Importance Pediatric SARS-CoV-2 infections and hospitalizations are rising in the US and other countries after the emergence of Omicron variant. However data on disease severity from Omicron compared with Delta in children under 5 in the US is lacking. Objectives To compare severity of clinic outcomes in children under 5 who contracted COVID infection for the first time before and after the emergence of Omicron in the US. Design, Setting, and Participants This is a retrospective cohort study of electronic health record (EHR) data of 79,592 children under 5 who contracted SARS-CoV-2 infection for the first time, including 7,201 infected between 12/26/2021-1/6/2022 when the Omicron predominated (Omicron cohort), 63,203 infected between 9/1/2021-11/15/2021 when the Delta predominated (Delta cohort), and another 9,188 infected between 11/16/2021-11/30/2021 when the Delta predominated but immediately before the Omicron variant was detected in the US (Delta-2 cohort). Exposures First time infection of SARS-CoV-2. Main Outcomes and Measures After propensity-score matching, severity of COVID infections including emergency department (ED) visits, hospitalizations, intensive care unit (ICU) admissions, and mechanical ventilation use in the 3-day time-window following SARS-CoV-2 infection were compared between Omicron and Delta cohorts, and between Delta-2 and Delta cohorts. Risk ratios, and 95% confidence intervals (CI) were calculated. Results Among 7,201 infected children in the Omicron cohort (average age, 1.49 ± 1.42 years), 47.4% were female, 2.4% Asian, 26.1% Black, 13.7% Hispanic, and 44.0% White. Before propensity score matching, the Omicron cohort were younger than the Delta cohort (average age 1.49 vs 1.73 years), comprised of more Black children, and had fewer comorbidities. After propensity-score matching for demographics, socio-economic determinants of health, comorbidities and medications, risks for severe clinical outcomes in the Omicron cohort were significantly lower than those in the Delta cohort: ED visits: 18.83% vs. 26.67% (risk ratio or RR: 0.71 [0.66-0.75]); hospitalizations: 1.04% vs. 3.14% (RR: 0.33 [0.26-0.43]); ICU admissions: 0.14% vs. 0.43% (RR: 0.32 [0.16-0.66]); mechanical ventilation: 0.33% vs. 1.15% (RR: 0.29 [0.18-0.46]). Control studies comparing Delta-2 to Delta cohorts show no difference. Conclusions and Relevance For children under age 5, first time SARS-CoV-2 infections occurring when the Omicron predominated (prevalence 92%) was associated with significantly less severe outcomes than first-time infections in similar children when the Delta variant predominated. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement National Institute on Aging (grants nos. AG057557, AG061388, AG062272), National Institute on Alcohol Abuse and Alcoholism (grant no. R01AA029831), National Institute on Drug Abuse (grant no. UG1DA049435), the Clinical and Translational Science Collaborative (CTSC) of Cleveland (grant no. 1UL1TR002548-01), National Cancer Institute Case Comprehensive Cancer Center (R25CA221718, P30 CA043703, P20 CA2332216). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The details of the IRB/oversight body that provided approval or exemption for the research described are given below: TriNetX is compliant with the Health Insurance Portability and Accountability Act (HIPAA), the US federal law which protects the privacy and security of healthcare data. TriNetX is certified to the ISO 27001:2013 standard and maintains an Information Security Management System (ISMS) to ensure the protection of the healthcare data it has access to and to meet the requirements of the HIPAA Security Rule. Any data displayed on the TriNetX Platform in aggregate form, or any patient level data provided in a data set generated by the TriNetX Platform, only contains de-identified data as per the de-identification standard defined in Section 164.514(a) of the HIPAA Privacy Rule. The process by which the data is de-identified is attested to through a formal determination by a qualified expert as defined in Section 164.514(b)(1) of the HIPAA Privacy Rule (reference). This formal determination by a qualified expert, refreshed in December 2020, supersedes the need for TriNetX's previous waiver from the Western Institutional Review Board (IRB). Because we only used de-identified data, we did not seek nor did we obtain Institutional Board Approval for this research. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. We have another TriNetX study published through medRxiv. It can be found at: https://www.medrxiv.org/content/10.1101/2021.12.30.21268495v1 I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript
·medrxiv.org·
COVID infection severity in children under 5 years old before and after Omicron emergence in the US