Restrained memory CD8+ T cell responses favors viral persistence and elevated IgG responses in patients with severe Long COVID. (preprint)

During the COVID-19 pandemic it was widely described that certain individuals infected by SARS-CoV-2 experience persistent disease signs and symptoms, Long COVID, which in some cases is very severe with life changing consequences. To maximize our chances of identifying the underpinnings of this illness, we have focused on 121 of the most severe cases from >1000 patients screened in specialized clinics in Sweden and Belgium. We restricted this study to subjects with objective measures of organ damage or dysfunction, >3 months following a verified, but mild-to-moderate SARS-CoV-2 infection. By performing systems-level immunological testing and comparisons to controls fully convalescent following a similar mild/moderate COVID-19 episode, we identify elevated serological responses to SARS-CoV-2 in severe Long COVID suggestive of chronic antigen stimulation. Persistent viral reservoirs have been proposed in Long COVID and using multiple orthogonal methods for detection of SARS-CoV-2 RNA and protein in plasma we identify a subset of patients with detectable antigens, but with minimal overlap across assays, and no correlation to symptoms or immune measurements. Elevated serologic responses to SARS-CoV-2 on the other hand were inversely correlated with clonally expanded memory CD8+ T cells, indicating that restrained clonal expansion enables viral persistence, chronic antigen exposure and elevated IgG responses, even if antigen-detection in blood is not universally possible.

Risk of SARS-CoV-2 exposure among hospital healthcare workers in relation to patient contact and type of care (preprint)

AimWe aimed to assess the risk for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in a large cohort of healthcare workers (HCWs). MethodsFrom May 11 until June 11, 2020, 3,981 HCWs at a large Swedish Emergency Care hospital provided serum samples and questionnaire data. Exposure was measured by assaying IgG antibodies to SARS-CoV-2. ResultsThe total seroprevalence was 17.7% and increased during the study period. Among the seropositive HCWs, 10.5% had been entirely asymptomatic. Participants who worked with COVID-19 patients had higher odds for seropositivity: ORadj 1.96 (95% CI 1.59 - 2.42). HCWs from three of the departments managing COVID-19 patients had significantly higher seroprevalences, whereas the prevalence among HCWs from the Intensive Care Unit (also managing COVID-19 patients) was significantly lower. ConclusionHCWs in contact with SARS-CoV-2 infected patients had a variable, but on average higher, likelihood for SARS-CoV-2 infections.