Biologic correlates of beneficial convalescent plasma therapy in a COVID-19 patient reveal disease resolution mechanisms

BackgroundWhile the biomarkers of COVID-19 severity have been thoroughly investigated, the key biological dynamics associated with COVID-19 resolution are still insufficiently understood. Main bodyWe report a case of full resolution of severe COVID-19 due to convalescent plasma transfusion in a patient with underlying multiple autoimmune syndrome. Following transfusion, the patient showed fever remission, improved respiratory status, and rapidly decreased viral burden in respiratory fluids and SARS-CoV-2 RNAemia. Longitudinal unbiased proteomic analysis of plasma and single-cell transcriptomics of peripheral blood cells conducted prior to and at multiple times after convalescent plasma transfusion identified the key biological processes associated with the transition from severe disease to disease-free state. These included (i) temporally ordered upward and downward changes in plasma proteins reestablishing homeostasis and (ii) post-transfusion disappearance of a particular subset of dysfunctional monocytes characterized by hyperactivated Interferon responses and decreased TNF- signaling. ConclusionsMonitoring specific subsets of innate immune cells in peripheral blood may provide prognostic keys in severe COVID-19. Moreover, understanding disease resolution at the molecular and cellular level should contribute to identify targets of therapeutic interventions against severe COVID-19.

Dichotomy between the humoral and cellular responses elicited by mRNA and adenoviral vector vaccines against SARS-CoV-2.

Protection from severe disease and hospitalization by SARS-CoV-2 vaccination has been amply demonstrated by real-world data. However, the rapidly evolving pandemic raises new concerns. One pertains efficacy of adenoviral vector-based vaccines, particularly the single-dose Ad26.COV2.S, relative to mRNA vaccines. We investigated the immunogenicity of Ad26.COV2.S and mRNA vaccines in 33 subjects vaccinated with either vaccine class five months earlier on average. After controlling for time since vaccination, Spike-binding antibody and neutralizing antibody levels were higher in the mRNA-vaccinated subjects, while no significant differences in antigen-specific B cell and T cell responses were observed between the two groups. Thus, a dichotomy exists between humoral and cellular responses elicited by the two vaccine classes. Our results have implications for the need of booster doses in vaccinated subjects and might explain the dichotomy reported between the waning protection from symptomatic infection by SARS-CoV-2 vaccination and its persisting efficacy in preventing hospitalization and death.

Highly versatile antibody binding assay for the detection of SARS-CoV-2 infection

Monitoring the burden and spread of infection with the new coronavirus SARS-CoV-2, whether within small communities or in large geographical settings, is of paramount importance for public health purposes. Serology, which detects the host antibody response to the infection, is the most appropriate tool for this task, since virus-derived markers are most reliably detected during the acute phase of infection. Here we show that our ELISA protocol, which is based on antibody binding to the Receptor Binding Domain (RBD) of the S1 subunit of the viral Spike protein expressed as a novel fusion protein, detects antibody responses to SARS-CoV-2 infection and COVID-19 vaccination. We also show that our ELISA is accurate and versatile. It compares favorably with commercial assays widely used in clinical practice to determine exposure to SARS-CoV-2. Moreover, our protocol accommodates use of various blood- and non-blood-derived biospecimens, such as breast milk, as well as dried blood obtained with microsampling cartridges that are appropriate for remote collection. As a result, our RBD-based ELISA protocols are well suited for seroepidemiology and other large-scale studies requiring parsimonious sample collection outside of healthcare settings.

Prevalence of SARS-CoV-2 infection in previously undiagnosed health care workers at the onset of the U.S. COVID-19 epidemic

ImportanceHealthcare workers are presumed to be at increased risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection due to occupational exposure to infected patients. However, no epidemiological study has examined the prevalence of SARS-CoV-2 infection in a cohort of healthcare workers during the early phase of community transmission. ObjectiveTo determine the baseline prevalence of SARS-CoV-2 infection in a cohort of previously undiagnosed healthcare workers and a comparison group of non-healthcare workers. DesignProspective cohort study SettingA large U.S. university and two affiliated university hospitals Participants546 health care workers and 283 non-health care workers with no known prior SARS-CoV-2 infection ExposureHealthcare worker status and role Main outcome(s) and measure(s)SARS-CoV-2 infection status as determined by presence of SARS-CoV-2 RNA in oropharyngeal swabs. ResultsAt baseline, 41 (5.0%) of participants tested positive for SARS-CoV-2 infection, of whom 14 (34.2%) reported symptoms. The prevalence of SARS-CoV-2 infection was higher among healthcare workers (7.3%) than in non-healthcare workers (0.4%), representing a 7.0% greater absolute risk (95% confidence interval for risk difference 4.7%, 9.3%). The majority of infected healthcare workers (62.5%) worked as nurses. Positive tests increased across the two weeks of cohort recruitment in line with rising confirmed cases in the hospitals and surrounding counties. Conclusions and relevanceIn a prospective cohort conducted in the early phases of community transmission, healthcare workers had a higher prevalence of SARS-CoV-2 infection than non-healthcare workers, attesting to the occupational hazards of caring for patients in this crisis. Baseline data reported here will enable us to monitor the spread of infection and examine risk factors for transmission among healthcare workers. These results will inform optimal strategies for protecting the healthcare workforce, their families, and their patients. Clinicaltrials.gov registration number:NCT04336215 Key pointsO_ST_ABSQuestionC_ST_ABSAmong previously undiagnosed individuals, is the prevalence of SARS-CoV-2 infection higher in U.S. healthcare workers compared to non-healthcare workers in the early phase of the U.S. COVID-19 epidemic? FindingsThe prevalence of SARS-CoV-2 infection was 7.3% in healthcare workers and 0.4% in non-healthcare workers, representing 7.0% greater absolute risk in the former (95% confidence interval for risk difference 4.7%, 9.3%). Infections were most common among nursing staff. MeaningHealth care workers, particularly those with high levels of close patient contact, may be particularly vulnerable to SARS-CoV-2 infection. Additional strategies are needed to protect these critical frontline workers.