Understanding Early Pandemic Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in a Medical Center by Incorporating Public Sequencing Databases to Mitigate Bias.

BACKGROUND: Throughout the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, healthcare workers (HCWs) have faced risk of infection from within the workplace via patients and staff as well as from the outside community, complicating our ability to resolve transmission chains in order to inform hospital infection control policy. Here we show how the incorporation of sequences from public genomic databases aided genomic surveillance early in the pandemic when circulating viral diversity was limited. METHODS: We sequenced a subset of discarded, diagnostic SARS-CoV-2 isolates between March and May 2020 from Boston Medical Center HCWs and combined this data set with publicly available sequences from the surrounding community deposited in GISAID with the goal of inferring specific transmission routes. RESULTS: Contextualizing our data with publicly available sequences reveals that 73% (95% confidence interval, 63%-84%) of coronavirus disease 2019 cases in HCWs are likely novel introductions rather than nosocomial spread. CONCLUSIONS: We argue that introductions of SARS-CoV-2 into the hospital environment are frequent and that expanding public genomic surveillance can better aid infection control when determining routes of transmission.

Serological responses to human virome define clinical outcomes of Italian patients infected with SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic respiratory infectious disease COVID-19. However, clinical manifestations and outcomes differ significantly among COVID-19 patients, ranging from asymptomatic to extremely severe, and it remains unclear what drives these disparities. Here, we studied 159 sequentially enrolled hospitalized patients with COVID-19-associated pneumonia from Brescia, Italy using the VirScan phage-display method to characterize circulating antibodies binding to 96,179 viral peptides encoded by 1,276 strains of human viruses. SARS-CoV-2 infection was associated with a marked increase in immune antibody repertoires against many known pathogenic and non-pathogenic human viruses. This antiviral antibody response was linked to longitudinal trajectories of disease severity and was further confirmed in additional 125 COVID-19 patients from the same geographical region in Northern Italy. By applying a machine-learning-based strategy, a viral exposure signature predictive of COVID-19-related disease severity linked to patient survival was developed and validated. These results provide a basis for understanding the role of memory B-cell repertoire to viral epitopes in COVID-19-related symptoms and suggest that a unique anti-viral antibody repertoire signature may be useful to define COVID-19 clinical severity.

Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19.

Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease, including multisystem inflammatory syndrome in children (MIS-C) and chilblain-like lesions (CLLs), otherwise known as "COVID toes," remains unclear. Studying multinational cohorts, we found that, in CLLs, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs after disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased NET levels when compared with other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients.

Coronavirus Disease 2019 Vaccine Impact on Rates of Severe Acute Respiratory Syndrome Coronavirus 2 Cases and Postvaccination Strain Sequences Among Health Care Workers at an Urban Academic Medical Center: A Prospective Cohort Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccine trials and post-implementation data suggest that vaccination decreases infections. We examine vaccination's impact on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case rates and viral diversity among health care workers (HCWs) during a high community prevalence period. METHODS: In this prospective cohort study, HCW received 2 doses of BNT162b2 or mRNA-1273. We included confirmed cases among HCWs from 9 December 2020 to 23 February 2021. Weekly SARS-CoV-2 rates per 100,000 person-days and by time from first injection (1-14 and ≥15 days) were compared with surrounding community rates. Viral genomes were sequenced. RESULTS: SARS-CoV-2 cases occurred in 1.4% (96/7109) of HCWs given at least a first dose and 0.3% (17/5913) of HCWs given both vaccine doses. Adjusted rate ratios (95% confidence intervals) were 0.73 (.53-1.00) 1-14 days and 0.18 (.10-.32) ≥15 days from first dose. HCW ≥15 days from initial dose compared to 1-14 days were more often older (46 vs 38 years, P = .007), Latinx (10% vs 8%, P = .03), and asymptomatic (48% vs 11%, P = .0002). SARS-CoV-2 rates among HCWs fell below the surrounding community, an 18% vs 11% weekly decrease, respectively (P = .14). Comparison of 50 genomes from post-first dose cases did not indicate selection pressure toward known spike antibody escape mutations. CONCLUSIONS: Our results indicate an early positive impact of vaccines on SARS-CoV-2 case rates. Post-vaccination isolates did not show unusual genetic diversity or selection for mutations of concern.

Seroprevalence of SARS-CoV-2 IgG antibodies and risk factors in health care workers at an academic medical center in Boston, Massachusetts.

Healthcare workers (HCWs) are at an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that causes Coronavirus Disease (COVID-19). We aim to assess the seroprevalence of SARS-CoV-2 IgG among healthcare workers and compare risk-factors between seropositive and seronegative HCWs. In this observational study, serum samples were collected from HCWs between July 13th to 26th, 2020 at Boston Medical Center (BMC). Samples were subsequently tested for SARS-CoV-2 IgG antibody using the Abbott SARS-CoV-2 IgG assay. Participants also answered a questionnaire capturing data on demographics, history of COVID-19 symptoms, occupation, infection prevention and control measures. Overall, 95 of 1743 (5.5%) participants tested positive for SARS-CoV-2 IgG. Of these, 1.8% of the participants had mild or no COVID-19 symptoms and did not require a diagnostic test. Seropositivity was not associated with gender, occupation, hand hygiene and personal protective equipment (PPE) practices amongst HCWs. However, lack of physical distancing among health care workers in work areas and break room was associated with seropositivity (p = 0.05, p = 0.003, respectively). The majority of the HCWs are negative for SARS-CoV-2 IgG. This data highlights the need to promote infection prevention measures, and the importance of distance amongst co-workers to help mitigate infection rates.