Rates of Positive M-CHAT-R Screenings by Pandemic Birth and Prenatal SARS-CoV-2 Exposure (preprint)

Maternal stress and viral illness during pregnancy are associated with neurodevelopmental conditions in offspring. Children born during the COVID-19 pandemic, including those exposed prenatally to maternal SARS-CoV-2 infections, are reaching the developmental age for the assessment of risk for neurodevelopmental conditions. We examined associations between birth during the COVID-19 pandemic, prenatal exposure to maternal SARS-CoV-2 infection, and rates of positive screenings on the Modified Checklist for Autism in Toddlers-Revised (M-CHAT-R). Data were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. Participants completed the M-CHAT-R as part of routine clinical care (COMBO-EHR cohort) or for research purposes (COMBO-RSCH cohort). Maternal SARS-CoV-2 status during pregnancy was determined through electronic health records. The COMBO-EHR cohort includes n=1664 children (n=442 historical cohort, n=1222 pandemic cohort; n=997 SARS-CoV-2 unexposed prenatally, n=130 SARS-CoV-2 exposed prenatally) who were born at affiliated hospitals between 2018-2023 and who had a valid M-CHAT-R score in their health record. The COMBO-RSCH cohort consists of n=359 children (n=268 SARS-CoV-2 unexposed prenatally, n=91 SARS-CoV-2 exposed prenatally) born at the same hospitals who enrolled into a prospective cohort study that included administration of the M-CHAT-R at 18-months. Birth during the pandemic was not associated with greater likelihood of a positive M-CHAT-R screen in the COMBO-EHR cohort. Maternal SARS-CoV-2 was associated with lower likelihood of a positive M-CHAT-R screening in adjusted models in the COMBO-EHR cohort (OR=0.40, 95% CI=0.22 - 0.68, p=0.001), while analyses in the COMBO-RSCH cohort yielded similar but non-significant results (OR=0.67, 95% CI=0.31-1.37, p=0.29).These results suggest that children born during the first 18 months of the COVID-19 pandemic and those exposed prenatally to a maternal SARS-CoV-2 infection are not at greater risk for screening positive on the M-CHAT-R.

Reduced risk of SARS-CoV-2 infection among household contacts with recent vaccination and past COVID-19 infection: results from two multi-site case-ascertained household transmission studies (preprint)

Background COVID-19 vaccines reduce the risk of severe disease, but it is less clear what effect vaccines have on reducing the risk of infection in high contact settings like households, alone or in combination with prior infection. Methods Households with an individual who tested positive for SARS-CoV-2 during Sep 2021-May 2023 were screened nationwide and at 7 sentinel sites and enrolled if the index cases illness onset was [≤]6 days prior. Household members had daily self-collected nasal swabs tested by RT-PCR for SARS-CoV-2. COVID-19 vaccination status was assessed by plausible self-report (with date) or vaccination records. Prior infection was assessed by self-reported prior testing and by anti-nucleocapsid antibodies presence at enrollment. The effects of prior immunity, including vaccination, prior infection, or hybrid immunity (both vaccination and prior infection) on SARS-CoV-2 infection risk among household contacts were assessed by robust, clustered multivariable Poisson regression. Findings There were 1,532 contacts from 905 households included in this analysis. Of these, 67% were enrolled May-November 2022, when Omicron BA.4/5 predominated. Most contacts (89%) had some immunity to SARS-CoV-2 at the time of household exposure: 8% had immunity from prior infection alone, 51% from vaccination alone, and 29% had hybrid immunity. Sixty percent of contacts tested SARS-CoV-2-positive during follow-up. The risk of SARS-CoV-2 infection was not significantly reduced by vaccination but was reduced among those with prior infection considering such immunity separately (adjusted relative risk 0.83; 95% confidence interval: 0.77, 0.90); however, when accounting for both sources of immunity, only contacts with vaccination and prior infection had significantly reduced risk of infection (aRR: 0.81, 95% CI: 0.70, 0.93). The risk of infection was lower when the last immunizing event (vaccination or infection) occurred [≤]6 months before COVID-19 affected the household (aRR: 0.69, 95% CI: 0.57, 0.83). Interpretation Immunity from COVID-19 vaccination and prior infection was synergistic in protecting household contacts from SARS-CoV-2 infection. These data support COVID-19 vaccination, even for those who have been previously infected.

Changes in Transmission and Symptoms of SARS-CoV-2 in United States Households, April 2020-September 2022 (preprint)

BackgroundThe natural history of SARS-CoV-2 infection and transmission dynamics may have changed as SARS-CoV-2 has evolved and population immunity has shifted. MethodsHousehold contacts, enrolled from two multi-site case-ascertained household transmission studies (April 2020-April 2021 and September 2021-September 2022), were followed for 10-14 days after enrollment with daily collection of nasal swabs and/or saliva for SARS-CoV-2 testing and symptom diaries. SARS-CoV-2 virus lineage was determined by whole genome sequencing, with multiple imputation where sequences could not be recovered. Adjusted infection risks were estimated using modified Poisson regression. Findings858 primary cases with 1473 household contacts were examined. Among unvaccinated household contacts, the infection risk adjusted for presence of prior infection and age was 58% (95% confidence interval [CI]: 49-68%) in households currently exposed to pre-Delta lineages and 90% (95% CI: 74-100%) among those exposed to Omicron BA.5 (detected May - September 2022). The fraction of infected household contacts reporting any symptom was similarly high between pre-Delta (86%, 95% CI: 81-91%) and Omicron lineages (77%, 70-85%). Among Omicron BA.5-infected contacts, 48% (41-56%) reported fever, 63% (56-71%) cough, 22% (17-28%) shortness of breath, and 20% (15-27%) loss of/change in taste/smell. InterpretationThe risk of infection among household contacts exposed to SARS-CoV-2 is high and increasing with more recent SARS-CoV-2 lineages. This high infection risk highlights the importance of vaccination to prevent severe disease. FundingFunded by the Centers for Disease Control and Prevention and the Food and Drug Administration. Key points- Monitoring the transmissibility and symptomatology of SARS-CoV-2 lineages is important for informing public health practice and understanding the epidemiology of COVID-19; household transmission studies contribute to our understanding of the natural history of SARS-CoV-2 infections and the transmissibility of SARS-CoV-2 variants. - The Omicron BA.5 sub-lineage is highly transmissible, similar to previous Omicron sub-lineages. - Over 80% of infected household contacts reported at least 1 symptom during their infection and the proportion of household contacts with asymptomatic infection did not differ by SARS-CoV-2 variant. The most common symptom was cough. Change in taste or smell was more common in Omicron BA.5 infections, compared to previous Omicron sub-lineages, but less common compared to pre-Delta lineages. - The high infection risk among household contacts supports the recommendations that individuals maintain up-to-date and lineage-specific vaccinations to mitigate further risks of severe disease.

Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design (preprint)

Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIHs REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of five cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n=10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. Conclusions and Relevance: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions.

COVID-19 Vaccine Effectiveness against SARS-CoV-2 Infections with the Delta Variant among Ages >=12 Years in Utah (preprint)

We conducted weekly surveillance for SARS-CoV-2 infection among a sample of households with [≥]1 child aged 0-17 years from selected Utah counties. A Cox proportional hazards model approach was used to calculate infection hazard rate and vaccine effectiveness. Findings show that the recommended primary series of COVID-19 vaccine was effective against circulating variants during a Delta-predominant wave in Utah.

SARS-CoV-2 genomic diversity in households highlights the challenges of sequence-based transmission inference (preprint)

Background: The reliability of sequence-based inference of SARS-CoV-2 transmission is not clear. Sequence data from infections among household members can define the expected genomic diversity of a virus along a defined transmission chain. Methods: SARS-CoV-2 cases were identified prospectively among 2,369 participants in 706 households. Specimens with an RT-PCR cycle threshold less than or equal to 30 underwent whole genome sequencing. Intrahost single nucleotide variants (iSNV) were identified at greater than 5% frequency. Phylogenetic trees were used to evaluate the relationship of household and community sequences. Results: There were 178 SARS-CoV-2 cases in 706 households. Among 147 specimens sequenced, 106 yielded a whole genome consensus with coverage suitable for identifying iSNV. Twenty-six households had sequences from multiple cases within 14 days. Consensus sequences were indistinguishable among cases in 15 households, while 11 had greater than 1 consensus that differed by 1-2 mutations. Sequences from households and the community were often interspersed on phylogenetic trees. Identification of iSNV improved inference in 2 of 15 households with indistinguishable consensus sequences and 6 of 11 with distinct ones. Conclusions: In multiple infection households, whole genome consensus sequences differed by 0-1 mutations. Identification of shared iSNV occasionally resolved linkage, but the low genomic diversity of SARS-CoV-2 limits the utility of sequence-only transmission inference.