Evolution of a globally unique SARS-CoV-2 Spike E484T monoclonal antibody escape mutation in a persistently infected, immunocompromised individual.

Prolonged infections in immunocompromised individuals may be a source for novel SARS-CoV-2 variants, particularly when both the immune system and antiviral therapy fail to clear the infection, thereby promoting adaptation. Here we describe an approximately 16-month case of SARS-CoV-2 infection in an immunocompromised individual. Following monotherapy with the monoclonal antibody Bamlanivimab, the individuals virus was resistant to this antibody via a globally unique Spike amino acid variant (E484T) that evolved from E484A earlier in infection. With the emergence and spread of the Omicron Variant of Concern, which also contains Spike E484A, E484T may arise again as an antibody-resistant derivative of E484A.

Vaccinated and unvaccinated individuals have similar viral loads in communities with a high prevalence of the SARS-CoV-2 delta variant

The SARS-CoV-2 Delta Variant of Concern is highly transmissible and contains mutations that confer partial immune escape. The emergence of Delta in North America caused the first surge in COVID-19 cases after SARS-CoV-2 vaccines became widely available. To determine whether individuals infected despite vaccination might be capable of transmitting SARS-CoV-2, we compared RT-PCR cycle threshold (Ct) data from 20,431 test-positive anterior nasal swab specimens from fully vaccinated (n = 9,347) or unvaccinated (n=11,084) individuals tested at a single commercial laboratory during the interval 28 June - 1 December 2021 when Delta variants were predominant. We observed no significant effect of vaccine status alone on Ct value, nor when controlling for vaccine product or sex. Testing a subset of low-Ct (<25) samples, we detected infectious virus at similar rates, and at similar titers, in specimens from vaccinated and unvaccinated individuals. These data indicate that vaccinated individuals infected with Delta variants are capable of shedding infectious SARS-CoV-2 and could play a role in spreading COVID-19.

Prevention and Attenuation of COVID-19 by BNT162b2 and mRNA-1273 Vaccines

BACKGROUNDInformation is limited on messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection or attenuating disease when administered in real-world conditions. METHODSProspective cohorts of 3,975 healthcare personnel, first responders, and other essential and frontline workers completed weekly SARS-CoV-2 testing during December 14 2020--April 10 2021. Self-collected mid-turbinate nasal swabs were tested by qualitative and quantitative reverse-transcription-polymerase-chain-reaction (RT-PCR). VE was calculated as 100%x(1-hazard ratio); adjusted VE was calculated using vaccination propensity weights and adjustments for site, occupation, and local virus circulation. RESULTSSARS-CoV-2 was detected in 204 (5.1%) participants; 16 were partially ([≥]14 days post-dose-1 to 13 days after dose-2) or fully ([≥]14 days post-dose-2) vaccinated, and 156 were unvaccinated; 32 with indeterminate status (<14 days after dose-1) were excluded. Adjusted mRNA VE of full vaccination was 91% (95% confidence interval [CI]=76%-97%) against symptomatic or asymptomatic SARS-CoV-2 infection; VE of partial vaccination was 81% (95% CI=64%-90%). Among partially or fully vaccinated participants with SARS-CoV-2 infection, mean viral RNA load (Log10 copies/mL) was 40% lower (95% CI=16%-57%), the risk of self-reported febrile COVID-19 was 58% lower (Risk Ratio=0.42, 95% CI=0.18-0.98), and 2.3 fewer days (95% CI=0.8-3.7) were spent sick in bed compared to unvaccinated infected participants. CONCLUSIONSAuthorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infections when administered in real-world conditions and attenuated viral RNA load, febrile symptoms, and illness duration among those with breakthrough infection despite vaccination.

Performance of Repeat BinaxNOW SARS-CoV-2 Antigen Testing in a Community Setting, Wisconsin, November-December 2020

Repeating the BinaxNOW antigen test for SARS-CoV-2 by two groups of readers within 30 minutes resulted in high concordance (98.9%) in 2,110 encounters. BinaxNOW test sensitivity was 77.2% (258/334) compared to real-time reverse transcription-polymerase chain reaction. Repeating antigen testing on the same day did not significantly improve test sensitivity while specificity remained high.

Population Changes in Seroprevalence among a Statewide Sample in the United States

Antibody surveillance provides essential information for public health officials to work with communities to discuss the spread and impact of COVID-19. At the start of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in the United States, diagnostic testing was limited with many asymptomatic and thus undetected cases. Irrespective of symptom severity, antibodies develop within two to three weeks after exposure and may persist 6 months or more.; Thus, antibody surveillance is an important tool for tracking trends in past infections across diverse populations. This study includes adults and children ([≥]12 years old) recruited from a statewide sample of past 2014-2020 Survey of the Health of Wisconsin (SHOW) participants. SHOW, an ongoing population-based health examination study including a randomly selected sample of households, partnered with the Wisconsin Department of Health Services and the Wisconsin State Laboratory of Hygiene to conduct longitudinal antibody surveillance using the Abbott Architect SARS-CoV-2 IgG antibody test, which detects antibodies against the nucleocapsid protein. Three WAVES of sample collection were completed in 2020-2021, tracking mid-summer, late fall, and early spring COVID-19 trends prior to vaccine availability. Crude estimates of seroprevalence in the total study population increased ten-fold from 1.4% during WAVE I to 11.5% in WAVE III. Within the statewide probability sample, weighted estimates increased from 1.6% (95% CI:0.6-2.5%), to 6.8% (95% CI:4.3-9.4%) in WAVE II and to 11.4% (95% CI:8.2, 14.6%) in WAVE III. Longitudinal trends in seroprevalence match statewide case counts. Local seroprevalence showed variation by state health region with increasing prevalence among higher income (>200% poverty income ratio), and rural health regions of the state seeing the highest increase in COVID-19 prevalence over time. Significant disparities in prevalence by racial and ethnic groups also exist, with greater than two times seroprevalence among Latino and black participants compared to non-Hispanic whites. This public health and academic partnership provides critical data for the ongoing pandemic response and lays the foundation for future research into longer-term immunity, health impacts and population-level disparities.