BackgroundThe emerging SARS-CoV-2 variant of concern (VOC) B.1.6.17.2 (Delta) quickly displaced the B.1.1.7 (Alpha) and is associated with increases in COVID-19 cases nationally. The Delta variant has been associated with greater transmissibility and higher viral RNA loads in both unvaccinated and fully vaccinated individuals. Data is lacking regarding the infectious virus load in Delta infected individuals and how that compares to individuals infected with other SARS-CoV-2 lineages.MethodsWhole genome sequencing of 2,785 clinical isolates was used to characterize the prevalence of SARS-CoV-2 lineages circulating in the National Capital Region between January and July 2021. Clinical chart reviews were performed for the Delta, Alpha, and B.1.2 (a control predominant lineage prior to both VOCs) variants to evaluate disease severity and outcome and Cycle threshold values (Cts) were compared. The presence of infectious virus was determined using Vero-TMPRSS2 cells and anti-SARS-CoV-2 IgG levels were determined from upper respiratory specimen. An analysis of infection in unvaccinated and fully vaccinated populations was performed.ResultsThe Delta variant displaced the Alpha variant to constitute 88.2% of the circulating lineages in the National Capital Region by July, 2021. The Delta variant associated with increased breakthrough infections in fully vaccinated individuals that were mostly symptomatic when compared to the Alpha breakthrough infections, though it is important to note there was a significantly longer period of time between vaccination and infection with Delta infections. The recovery of infectious virus on cell culture was significantly higher with the Delta variant compared to Alpha in both vaccinated and unvaccinated groups. The impact of vaccination on reducing the recovery of infectious virus from clinical samples was only observed with Alpha variant infections but was strongly associated with low localized SARS-CoV-2 IgG for both variants. A comparison of Ct values showed a significant decrease in the Delta compared to Alpha with no significant differences between unvaccinated and vaccinated groups.ConclusionsOur data indicate that the Delta variant is associated with increased infectious virus loads when compared to the Alpha variant and decreased upper respiratory antiviral IgG levels. Measures to reduce transmission in addition to increasing vaccinations rates have to be implemented to reduce Delta variant spread.FundingNIH/NIAID Center of Excellence in Influenza Research and Surveillance contract HHS N2772201400007C, Johns Hopkins University, Maryland department of health, Centers for Disease Control and Prevention contract 75D30121C11061.

Background The SARS-CoV-2 variant of concern (VOC) B.1.617.2 (Delta) displaced B.1.1.7 (Alpha) and is associated with increases in COVID-19 cases, greater transmissibility, and higher viral RNA loads but data is lacking regarding the infectious virus load and antiviral antibody levels in the nasal tract. Methods Whole genome sequencing, cycle threshold (Ct) values, infectious virus, anti-SARS-CoV-2 IgG levels, and clinical chart reviews were combined to characterize SARS-CoV-2 lineages circulating in the National Capital Region between January and September 2021 and differentiate infections in vaccinated and unvaccinated individuals by the Delta, Alpha, and B.1.2 variants. Results The Delta variant displaced the Alpha variant to constitute 99% of the circulating lineages in the National Capital Region by August, 2021. In Delta infections, 28.5% were breakthrough cases in fully vaccinated individuals compared to 4% in the Alpha infected cohort. Breakthrough infections in both cohorts were associated with comorbidities, but only Delta infections were associated with a significant increase in the median days after vaccination . More than 74% of Delta samples had infectious virus compared to less than 30% from the Alpha cohort. The recovery of infectious virus with both variants was associated with low levels of local SARS-CoV-2 IgG. Conclusions Infection with the Delta variant was associated with more frequent recovery of infectious virus in vaccinated and unvaccinated individuals compared to the Alpha variant but was not associated with an increase in disease severity in fully vaccinated individuals. Infectious virus was correlated with the presence of low amounts of antiviral IgG in the nasal specimens.

Background SARS-CoV-2 Variants concerning for enhanced transmission, evasion of immune responses, or associated with severe disease have motivated the global increase in genomic surveillance. In this study, large scale whole genome sequencing was performed between November 2020 and end of March 2021 to provide a phylodynamic analysis of circulating variants over-time. In addition, we compared the viral genomic features of March 2020 and March 2021. Methods A total of 1,600 complete SARS-CoV-2 genomes were analyzed. Genomic analysis was associated with laboratory diagnostic volumes and positivity rates in addition to an analysis of the association of selected variants of concern/ interest with disease severity and outcomes. Our real-time surveillance features a cohort of specimens from patients who tested positive after the completion of vaccination. Results Our data showed genomic diversity over-time that was not limited to the Spike sequence. A significant increase in the B.1.1.7 lineage (alpha variant) in March 2021 as well as a transient circulation of regional variants that carried both the concerning S: E484K and S: P681H substitutions were noted. Lineage B.1.243 was significantly associated with ICU admission and mortality. Genomes recovered from fully-vaccinated individuals represented the predominant lineages circulating at specimen collection time, and those infections recovered with no hospitalizations. Conclusions Our results emphasize the importance of genomic surveillance coupled with laboratory, clinical, and metadata analysis for a better understanding of the dynamics of viral spread and evolution.

Background Our understanding of the co-circulation of infrequently targeted respiratory pathogens and their contribution to symptoms during the COVID-19 pandemic is currently limited. This research aims at 1) understanding the epidemiology of respiratory pathogens since the start of the pandemic, 2) assessing the contribution of non-SARS-CoV-2/influenza/RSV respiratory pathogens to symptoms, and 3) evaluating coinfection rates in SARS-CoV-2 positive patients, both vaccinated and unvaccinated. Methods Retrospective analysis of respiratory pathogens identified by the Johns Hopkins Diagnostic Laboratory between December 2019 and October 2021 was performed. In addition, we assessed the contribution of respiratory pathogens other than SARS-CoV-2 to symptomatic disease by re-testing two cohorts of specimens that were 1) collected from symptomatic patients and 2) received limited respiratory pathogen testing. The first cohort was patients tested negative by the standard of care SARS-CoV-2/influenza/RSV testing. The second was a cohort of SARS-CoV-2 positive symptomatic fully COVID-19 immunized and unimmunized patients. Results Between December 2019 and October 2021, a total of 11,806, 62,829, and 579,666 specimens were tested for an extended respiratory panel, influenza/RSV/with or without SARS-CoV-2 panel, or SARS-CoV-2, respectively. Positivity rates of different targets differed between different months and were impacted by the COVID-19 pandemic. The SARS-CoV-2 negative cohort had 8.5% positivity for other respiratory pathogens that included primarily enterovirus/rhinovirus (5.8%). In the SARS-CoV-2 positive cohort, no other respiratory pathogens were detected. Conclusions The COVID-19 pandemic impacted the circulation of certain respiratory pathogens. Other respiratory viral pathogens were associated with symptomatic infections; however, coinfections with SARS-CoV-2 were highly uncommon.