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.

SARS-CoV-2 virus dynamics in recently infected people - data from a household transmission study (preprint)

We used daily real-time reverse-transcription polymerase chain reaction (rRT-PCR) results from 67 cases of SARS-CoV-2 infection in a household transmission study to examine the trajectory of cycle threshold (Ct) values, an inverse correlate of viral RNA concentration, from nasal specimens collected between April 2020 and May 2021. Ct values varied over the course of infection, across RT-PCR platforms, and by participant age. Specimens collected from children and adolescents showed higher Ct values and adults aged [≥]50 years showed lower Ct values than adults aged 18-49 years. Ct values were lower on days when participants reported experiencing symptoms.

Comparison of influenza and COVID-19-associated hospitalizations among children < 18 years old in the United States - FluSurv-NET (October-April 2017-2021) and COVID-NET (October 2020-September 2021) (preprint)

Background: Influenza virus and SARS-CoV-2 are significant causes of respiratory illness in children. Methods: Influenza and COVID-19-associated hospitalizations among children <18 years old were analyzed from FluSurv-NET and COVID-NET, two population-based surveillance systems with similar catchment areas and methodology. The annual COVID-19-associated hospitalization rate per 100 000 during the ongoing COVID-19 pandemic (October 1, 2020-September 30, 2021) was compared to influenza-associated hospitalization rates during the 2017-18 through 2019-20 influenza seasons. In-hospital outcomes, including intensive care unit (ICU) admission and death, were compared. Results: Among children <18 years old, the COVID-19-associated hospitalization rate (48.2) was higher than influenza-associated hospitalization rates: 2017-18 (33.5), 2018-19 (33.8), and 2019-20 (41.7). The COVID-19-associated hospitalization rate was higher among adolescents 12-17 years old (COVID-19: 59.9; influenza range: 12.2-14.1), but similar or lower among children 5-11 (COVID-19: 25.0; influenza range: 24.3-31.7) and 0-4 (COVID-19: 66.8; influenza range: 70.9-91.5) years old. Among children <18 years old, a higher proportion with COVID-19 required ICU admission compared with influenza (26.4% vs 21.6%; p<0.01). Pediatric deaths were uncommon during both COVID-19- and influenza-associated hospitalizations (0.7% vs 0.5%; p=0.28). Conclusions: In the setting of extensive mitigation measures during the COVID-19 pandemic, the annual COVID-19-associated hospitalization rate during 2020-2021 was higher among adolescents and similar or lower among children <12 years old compared with influenza during the three seasons before the COVID-19 pandemic. COVID-19 adds substantially to the existing burden of pediatric hospitalizations and severe outcomes caused by influenza and other respiratory viruses.

Estimating COVID-19 Hospitalizations in the United States with surveillance data using a Bayesian Hierarchical model (preprint)

IntroductionIn the United States, COVID-19 is a nationally notifiable disease, cases and hospitalizations are reported to the CDC by states. Identifying and reporting every case from every facility in the United States may not be feasible in the long term. Creating sustainable methods for estimating burden of COVID-19 from established sentinel surveillance systems is becoming more important. We aimed to provide a method leveraging surveillance data to create a long-term solution to estimate monthly rates of hospitalizations for COVID-19. MethodsWe estimated monthly hospitalization rates for COVID-19 from May 2020 through April 2021 for the 50 states using surveillance data from COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) and a Bayesian hierarchical model for extrapolation. We created a model for six age groups (0-17, 18-49, 50-64, 65-74, 75-84, and [≥]85 years), separately. We identified covariates from multiple data sources that varied by age, state, and/or month, and performed covariate selection for each age group based on two methods, Least Absolute Shrinkage and Selection Operator (LASSO) and Spike and Slab selection methods. We validated our method by checking sensitivity of model estimates to covariate selection and model extrapolation as well as comparing our results to external data. ResultsWe estimated 3,569,500 (90% Credible Interval:3,238,000 - 3,934,700) hospitalizations for a cumulative incidence of 1,089.8 (988.6 - 1,201.3) hospitalizations per 100,000 population with COVID-19 in the United States from May 2020 through April 2021. Cumulative incidence varied from 352 - 1,821per 100,000 between states. The age group with the highest cumulative incidence was aged [≥]85 years (5,583.1; 5,061.0 - 6,157.5). The monthly hospitalization rate was highest in December (183.8; 154.5 - 218.0). Our monthly estimates by state showed variations in magnitudes of peak rates, number of peaks and timing of peaks between states. ConclusionsOur novel approach to estimate COVID-19 hospitalizations has potential to provide sustainable estimates for monitoring COVID-19 burden, as well as a flexible framework leveraging surveillance data.

Methods for Estimation of SARS-CoV-2 Seroprevalence and Reported COVID-19 Cases in U.S. Children, August 2020 - May 2021 (preprint)

Background and ObjectivesCase-based surveillance of pediatric COVID-19 cases underestimates the prevalence of SARS-CoV-2 infections among children and adolescents. Our objectives were to: 1) estimate monthly SARS-CoV-2 antibody seroprevalence among children aged 0-17 years and 2) calculate ratios of SARS-CoV-2 infections to reported COVID-19 cases among children and adolescents in 14 U.S. states. MethodsUsing data from commercial laboratory seroprevalence surveys, we estimated monthly SARS-CoV-2 antibody seroprevalence among children aged 0-17 years from August 2020 through May 2021. Seroprevalence estimates were based on SARS-CoV-2 anti-nucleocapsid immunoassays from February to May 2021. We compared estimated numbers of children infected with SARS-CoV-2 by May 2021 to cumulative incidence of confirmed and probable COVID-19 cases from case-based surveillance, and calculated infection: case ratios by state and type of anti-SARS-CoV-2 nucleocapsid immunoassay used for seroprevalence testing. ResultsAnalyses included 67,321 serum specimens tested for SARS-CoV-2 antibodies among children in 14 U.S. states. Estimated ratios of SARS-CoV-2 infections to reported confirmed and probable COVID-19 cases among children and adolescents varied by state and type of immunoassay, ranging from 0.8-13.3 in May 2021. ConclusionsThrough May 2021, the majority of children in selected states did not have detectable SARS-CoV-2 nucleocapsid antibodies. Case-based surveillance underestimated the number of children infected with SARS-CoV-2, however the predicted extent of the underestimate varied by state, immunoassay, and over time. Continued monitoring of pediatric SARS-CoV-2 antibody seroprevalence should inform prevention and vaccination strategies.

Severity of the COVID-19 pandemic assessed with all-cause mortality in the United States during 2020. (preprint)

Background: In the United States, infection with SARS-CoV-2 caused 380,000 reported deaths from March to December 2020. Methods. We adapted the Moving Epidemic Method to all-cause mortality data from the United States to assess the severity of the COVID-19 pandemic across age groups and all 50 states. By comparing all-cause mortality during the pandemic with intensity thresholds derived from recent, historical all-cause mortality, we categorized each week from March to December 2020 as either low severity, moderate severity, high severity, or very high severity. Results. Nationally for all ages combined, all-cause mortality was in the very high severity category for 9 weeks. Among people 18 to 49 years of age, there were 29 weeks of consecutive very high severity mortality. Forty-seven states, the District of Columbia, and New York City each experienced at least one week of very high severity mortality for all ages combined. Conclusions. These periods of very high severity of mortality during March through December 2020 are likely directly or indirectly attributable to the COVID-19 pandemic. This method for standardized comparison of severity over time across different geographies and demographic groups provides valuable information to understand the impact of the COVID-19 pandemic and to identify specific locations or subgroups for deeper investigations into differences in severity.

Household Transmission and Clinical Features of SARS-CoV-2 Infections by Age in 2 US Communities (preprint)

OBJECTIVESExamine age differences in SARS-CoV-2 transmission risk from primary cases and infection risk among household contacts, and symptoms among those with SARS-CoV-2 infection. METHODSPeople with SARS-CoV-2 infection in Nashville, Tennessee and central and western Wisconsin and their household contacts were followed daily for 14 days to ascertain symptoms and secondary transmission events. Households were enrolled between April 2020 and April 2021. Secondary infection risks (SIR) by age of the primary case and contacts were estimated using generalized estimating equations. RESULTSThe 226 primary cases were followed by 198 (49%) secondary SARS-CoV-2 infections among 404 household contacts. Age group-specific SIR among contacts ranged from 36% to 53%, with no differences by age. SIR was lower from primary cases aged 12-17 years than from primary cases 18-49 years (risk ratio [RR] 0.42; 95% confidence interval [CI] 0.19-0.91). SIR was 55% and 45%, respectively, among primary case-contact pairs in the same versus different age group (RR 1.47; 95% CI 0.98-2.22). SIR was highest among primary case-contacts pairs aged [≥]65 years (76%) and 5-11 years (69%). Among secondary SARS-CoV-2 infections, 19% were asymptomatic; there was no difference in the frequency of asymptomatic infections by age group. CONCLUSIONSBoth children and adults can transmit and are susceptible to SARS-CoV-2 infection. SIR did not vary by age, but further research is needed to understand age-related differences in probability of transmission from primary cases by age.

Seroprevalence of Antibodies to SARS-CoV-2 in Six Sites in the United States, March 23-May 3, 2020 (preprint)

ImportanceReported cases of SARS-CoV-2 infection likely underestimate the prevalence of infection in affected communities. Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected. ObjectiveTo estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the United States. DesignSerologic testing of convenience samples using residual sera obtained for routine clinical testing by two commercial laboratory companies. SettingConnecticut (CT), south Florida (FL), Missouri (MO), New York City metro region (NYC), Utah (UT), and Washington States (WA) Puget Sound region. ParticipantsPersons of all ages with serum collected during intervals from March 23 through May 3, 2020. ExposureSARS-CoV-2 virus infection. Main outcomes and measuresWe estimated the presence of antibodies to SARS-CoV-2 spike protein using an ELISA assay. We standardized estimates to the site populations by age and sex. Estimates were adjusted for test performance characteristics (96.0% sensitivity and 99.3% specificity). We estimated the number of infections in each site by extrapolating seroprevalence to site populations. We compared estimated infections to number of reported COVID-19 cases as of last specimen collection date. ResultsWe tested sera from 11,933 persons. Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein ranged from 1.13% (95% confidence interval [CI] 0.70-1.94) in WA to 6.93% (95% CI 5.02-8.92) in NYC (collected March 23-April 1). For sites with later collection dates, estimates ranged from 1.85% (95% CI 1.00-3.23, collected April 6-10) for FL to 4.94% (95% CI 3.61-6.52) for CT (April 26-May 3). The estimated number of infections ranged from 6 to 24 times the number of reported cases in each site. Conclusions and relevanceOur seroprevalence estimates suggest that for five of six U.S. sites, from late March to early May 2020, >10 times more SARS-CoV-2 infections occurred than the number of reported cases. Seroprevalence and under-ascertainment varied by site and specimen collection period. Most specimens from each site had no evidence of antibody to SARS-CoV-2. Tracking population seroprevalence serially, in a variety of specific geographic sites, will inform models of transmission dynamics and guide future community-wide public health measures. Key findingsO_ST_ABSQuestionC_ST_ABSWhat proportion of persons in six U.S. sites had detectable antibodies to SARS-CoV-2, March 23-May 3, 2020? FindingsWe tested 11,933 residual clinical specimens. We estimate that from 1.1% of persons in the Puget Sound to 6.9% in New York City (collected March 23-April 1) had detectable antibodies. Estimates ranged from 1.9% in south Florida to 4.9% in Connecticut with specimens collected during intervals from April 6-May 3. Six to 24 times more infections were estimated per site with seroprevalence than with case report data. MeaningFor most sites, evidence suggests >10 times more SARS-CoV-2 infections occurred than reported cases. Most persons in each site likely had no detectable SARS-CoV-2 antibodies.