Abstract
SummaryThe kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range of disease severities over 12 weeks from symptom onset. An early robust bystander CD8+ T cell immune response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized individuals had delayed bystander responses and systemic inflammation that was already evident near symptom onset, indicating that immunopathology may be inevitable in some individuals. Viral load did not correlate with this early pathological response but did correlate with subsequent disease severity. Immune recovery is complex, with profound persistent cellular abnormalities in severe disease correlating with altered inflammatory responses, with signatures associated with increased oxidative phosphorylation replacing those driven by cytokines tumor necrosis factor (TNF) and interleukin (IL)-6. These late immunometabolic and immune defects may have clinical implications.
Highlights
The immune pathology associated with COVID-19 is complex (Wang et al, 2020; Zhou et al, 2020)
We found that the immune response in patients with progressive COVID-19 was delayed compared to those with mild disease and was inflammatory in nature from the outset
If we focused on the 16 patients in groups C–E sampled between 2 days before and 4 days after symptom onset, 15 had a C-reactive protein (CRP) >10 mg/L and/or neutrophil activation eigengene >0
Summary
The immune pathology associated with COVID-19 is complex (Wang et al, 2020; Zhou et al, 2020). Severe COVID-19 is associated with profound abnormalities in circulating immune cell subsets. Data on T helper (Th) cell subsets are variable, but there is evidence of increased Th17 cells and markedly reduced T follicular helper (Tfh) cells (Chen and John Wherry, 2020; Mathew et al, 2020; Su et al, 2020). There have been conflicting reports regarding B cell immunity, but increased circulating plasmablasts (Arunachalam et al, 2020; Hadjadj et al, 2020; Laing et al, 2020; Mathew et al, 2020) and reduced germinal center responses (Su et al, 2020) are consistently observed in severe COVID-19. Innate T cell subsets, including gamma-delta (gd) T cells and mucosal-associated invariant T (MAIT) cells, are reduced, as are non-classical monocytes and both plasmacytoid and myeloid dendritic cells (pDCs and mDCs) (Kuri-Cervantes et al, 2020; Laing et al, 2020)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
