ABSTRACT
Background. Although not validated, cycle threshold (Ct) values from real-time (r)RT-PCR are sometimes used as a proxy for infectiousness to inform public health decision-making. A better understanding of variant-specific viral dynamics, including RNA and infectious virus relationships, is needed to clarify implications for diagnostics and transmission. Methods. Non-hospitalized SARS-CoV-2-infected individuals were recruited <= 5 days post-onset and self-collected nasal swabs daily for two weeks. Sequencing was used to determine variant, an in-house quantitative rRT-PCR targeting N gene was used to produce Ct values and determine RNA load, and cytopathic effect was used to assess the presence or absence of infectious virus (binary outcome). We used a Ct threshold of 30 to define high-Ct (Ct > 30) or low-Ct (Ct <= 30) specimens and assessed the percentage of RNA-positive specimens that had infectious virus;variantspecific percentages were compared by chi2 test. Results. We included 113 and 200 RNA-positive specimens from 18 and 28 Omicron- and Delta-infected participants, respectively;timing of RNA-positive specimen collection was similar in both groups (median = 8d post-onset). Maximum observed RNA levels occurred at median of 5 days post-onset for both variants but were lower for participants with Omicron vs Delta [mean RNA copies/mL = 105.2 vs 107.9]. Despite lower RNA levels, infectious virus was frequently detected for both variants [Omicron: median duration = 4.5d;Delta: median = 6d;p = 0.13]. Omicron specimens with infectious virus had higher Cts vs Delta specimens [mean Ct = 29.9 vs 23.2, p < 0.001]. In high-Ct specimens (Ct > 30;Table), the percentage of specimens with infectious virus was typically higher for Omicron vs Delta, and was significantly higher in adults [27.3% vs 9.5%]. In low-Ct specimens (Ct <= 30), the percentage with infectious virus was similar or higher for Omicron vs Delta, and was significantly higher in children [87.5% vs 53.8%] and in those unvaccinated [94.1% vs 47.4%]. Conclusion. CDC does not recommend the use of Ct values as a proxy for infectiousness. These data further highlight that Ct values may not provide a reliable or consistent proxy for infectiousness across variants.
ABSTRACT
Background. The biological determinants of post-acute sequelae of SARS-CoV-2 infection (PASC), defined as the persistence or recurrence of symptoms not explained by an alternative medical diagnosis, are poorly understood. We assessed viral and immunological determinants during acute SARS-CoV-2 infection for an association with PASC at 4 to 8 months. Methods. From September 2020 to February 2022, symptomatic nonhospitalized individuals with laboratory-confirmed SARS-CoV-2 infection were identified within 5 days of symptom onset. We used anterior nasal biospecimens to measure the magnitude and duration of RNA and infectious viral shedding as well as blood samples to measure soluble markers of inflammation during the acute phase (first 28 days post-enrollment). PASC was defined as self-report of 1 or more COVID-19 attributed symptoms between 4 and 8 months after initial illness. We compared virologic and inflammatory markers, GFAP (a marker of neuronal damage) and neutralizing antibody levels from the acute phase between those with and without PASC using Mann-Whitney U tests or repeated measures mixed effects linear models. Results. Among 71 SARS-CoV-2-positive participants with a completed follow-up visit between 4 to 8 months, we included 69 with virologic data and 61 with inflammatory marker data. Median age was 37 (IQR: 29 to 48) Overall, 16/72 (23%) reported at least one qualifying PASC symptom. Report of PASC was associated with >9 days of RNA shedding (p=0.04);all participants stopped RNA shedding by day 20. During acute illness, those with subsequent PASC had increased levels of INF-alpha, INF-gamma, IP-10, IL-10, and MCP-1;these differences were greatest in the early period and normalized over 2 to 3 weeks post-illness onset. Compared to those without PASC, during the acute illness those with PASC had increased levels of GFAP and decreased levels of neutralizing antibodies but these differences were not statistically significant. Conclusion. We found indications that viral and immunological factors during acute illness may be associated with PASC, suggesting acute immunologic response to SARS-CoV-2 may have longer term effects and play a role in PASC. Further understanding of the clinically significance of these observations is needed.
ABSTRACT
What is already known about this topic? Data are limited regarding the risks for SARS-CoV-2 infection and hospitalization after COVID-19 vaccination and previous infection. What is added by this report? During May-November 2021, case and hospitalization rates were highest among persons who were unvaccinated without a previous diagnosis. Before Delta became the predominant variant in June, case rates were higher among persons who survived a previous infection than persons who were vaccinated alone. By early October, persons who survived a previous infection had lower case rates than persons who were vaccinated alone. What are the implications for public health practice? Although the epidemiology of COVID-19 might change as new variants emerge, vaccination remains the safest strategy for averting future SARS-CoV-2 infections, hospitalizations, long-term sequelae, and death. Primary vaccination, additional doses, and booster doses are recommended for all eligible persons. Additional future recommendations for vaccine doses might be warranted as the virus and immunity levels change.
ABSTRACT
Background. Sharp declines in influenza and respiratory syncytial virus (RSV) circulation across the U.S. have been described during the pandemic in temporal association with community mitigation for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to determine relative frequencies of rhinovirus/ enterovirus (RV/EV) and other respiratory viruses in children presenting to emergency departments or hospitalized with acute respiratory illness (ARI) prior to and during the COVID-19 pandemic. Methods. We conducted a multi-center active prospective ARI surveillance study in children as part of the New Vaccine Surveillance Network (NVSN) from December 2016 through January 2021. Molecular testing for RV/EV, RSV, influenza, and other respiratory viruses [i.e., human metapneumovirus, parainfluenza virus (Types 1-4), and adenovirus] were performed on specimens collected from children enrolled children. Cumulative percent positivity of each virus type during March 2020-January 2021 was compared from March-January in the prior seasons (2017-2018, 2018-2019, 2019-2020) using Pearson's chi-squared. Data are provisional. Results. Among 69,403 eligible children, 37,676 (54%) were enrolled and tested for respiratory viruses. The number of both eligible and enrolled children declined in early 2020 (Figure 1), but 4,691 children (52% of eligible) were enrolled and tested during March 2020-January 2021. From March 2020-January 2021, the overall percentage of enrolled children with respiratory testing who had detectable RV/EV was similar compared to the same time period in 2017-2018 and 2019-2020 (Figure 1, Table 1). In contrast, the percent positivity of RSV, influenza, and other respiratory viruses combined declined compared to prior years, (p< 0.001, Figure 1, Table 1). Figure 1. Percentage of Viral Detection Among Enrolled Children Who Received Respiratory Testing, New Vaccine Surveillance Network (NVSN), United States, December 2016 - January 2021 Table 1. Percent of Respiratory Viruses Circulating in March 2020- January 2021, compared to March-January in Prior Years, New Vaccine Surveillance Network (NVSN), United States, March 2017 - January 2021 Conclusion. During 2020, RV/EV continued to circulate among children receiving care for ARI despite abrupt declines in other respiratory viruses within this population. These findings warrant further studies to understand virologic, behavioral, biological, and/or environmental factors associated with this continued RV/EV circulation.
ABSTRACT
Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits antibodies (Abs) that bind several viral proteins such as the spike entry protein and the abundant nucleocapsid (N) protein. We examined convalescent sera collected through 6 months (~24wks) post-SARS-CoV-2 infection in children to evaluate changes in neutralization potency and N-binding. Methods. Outpatient, hospitalized, and community recruited volunteers < 18 years with COVID-19 were enrolled in a longitudinal study at Seattle Children's Hospital. Analysis includes symptomatic and asymptomatic children with laboratory-confirmed SARS-CoV-2 infection who provided blood samples at approximately 4wks (range: 2-18wks, IQR:4-8wks) and 24 wks (range: 23-35wks, IQR:25-27wks) after diagnosis. We measured neutralizing Ab using an in-house pseudoneutralization assay and anti-N binding Ab using the Abbott Architect assay. Results. Of 32 children enrolled between April 2020 and January 2021, 27 had no underlying immunocompromised state and 25 of these 27 children had symptomatic disease. Ten of 27 had a > 2-fold decrease neutralization titers between 4 and 24wks (most were < 10-fold);12 had < 2-fold change;and 5 had neutralization titers that increased > 2-fold over time (Fig. 1A). All but one of these 27 children had detectable neutralizing activity at 24wks. Anti-N Abs were assessed for 25 children at 4wks and 17 children at 24wks (data pending for 14 samples);all children with paired samples had a > 1.75-fold Abbott index reduction at 24wks, and 5 children had no detectable anti-N Abs by 24wks (Fig. 2A). An additional 5 children with symptomatic disease had complicating immunosuppression or multiple blood transfusions;2 had decreasing neutralizing titers, 2 increased, and 1 had no change (Fig. 1B). Anti-N Abs were undetectable for one child by 24wks (data pending for 4 samples) (Fig. 2B). No participants received COVID-19 vaccine. Conclusion. We show neutralizing Abs wane to a small degree over 24wks post-SARS-CoV-2 infection and remain detectable in most children. In contrast, anti-N Abs decreased, becoming undetectable in some children by 24wks. These findings add to understanding of the natural history of SARS-CoV-2 immunity in children.