Abstract
Both severe SARS-CoV-2 infections and bacterial sepsis exhibit an immunological dyscrasia and propensity for secondary infections. The nature of the immunological dyscrasias for these differing etiologies and their time course remain unclear. In this study, thirty hospitalized patients with SARS-CoV-2 infection were compared with ten critically ill patients with bacterial sepsis over 21 days, as well as ten healthy control subjects. Blood was sampled between days 1 and 21 after admission for targeted plasma biomarker analysis, cellular phenotyping, and leukocyte functional analysis via enzyme-linked immunospot assay. We found that circulating inflammatory markers were significantly higher early after bacterial sepsis compared with SARS-CoV-2. Both cohorts exhibited profound immune suppression through 21 days (suppressed HLA-DR expression, reduced mononuclear cell IFN-gamma production), and expanded numbers of myeloid-derived suppressor cells (MDSCs). In addition, MDSC expansion and ex vivo production of IFN-gamma and TNF-alpha were resolving over time in bacterial sepsis, whereas in SARS-CoV-2, immunosuppression and inflammation were accelerating. Despite less severe initial physiologic derangement, SARS-CoV-2 patients had similar incidence of secondary infections (23% vs 30%) as bacterial sepsis patients. Finally, COVID patients who developed secondary bacterial infections exhibited profound immunosuppression evident by elevated sPD-L1 and depressed HLA-DR. Although both bacterial sepsis and SARS-CoV-2 are associated with inflammation and immune suppression, their immune dyscrasia temporal patterns and clinical outcomes are different. SARS-CoV-2 patients had less severe early inflammation and organ dysfunction but had persistent inflammation and immunosuppression and suffered worse clinical outcomes, especially when SARS-CoV-2 infection was followed by secondary bacterial infection.
Highlights
Serious SARS-CoV-2 infections manifest many of the classic sequelae of sepsis, including organ injury and immunological dyscrasia [1,2,3]
The substantial burden of long-term physical, cognitive, social, and psychological effects of sepsis and SARS-CoV-2 infection underscore the importance of early diagnosis and effective treatment to prevent progression to multiple organ failure, chronic critical illness (CCI), and the persistent inflammation, immunosuppression, and catabolism syndrome (PICS) [6, 7]
peripheral blood mononuclear cells (PBMC) samples were labeled with CD33+ conjugated to APC, CD11b+ conjugated to APC-Cy7, HLA-DR conjugated to FITC, CD14+ conjugated to Pac-blue, and CD66b+ conjugated to brilliant violet (BV421)
Summary
Serious SARS-CoV-2 infections manifest many of the classic sequelae of sepsis, including organ injury and immunological dyscrasia [1,2,3]. Whereas the incidence of SARS-CoV-2 infection is projected to decline substantially over time, bacterial sepsis will likely remain the most common cause of post-pandemic in-hospital mortality, morbidity, and healthcare expenditures [4, 5]. The substantial burden of long-term physical, cognitive, social, and psychological effects of sepsis and SARS-CoV-2 infection underscore the importance of early diagnosis and effective treatment to prevent progression to multiple organ failure, chronic critical illness (CCI), and the persistent inflammation, immunosuppression, and catabolism syndrome (PICS) [6, 7]. SARS-CoV-2 infection has similar challenges, but unlike sepsis, has no effective immediate pathogen source control; antiviral therapies and glucocorticoids are only supportive in nature. A more detailed, time-dependent comparison could confer deeper understanding of dynamic host immunity and its associations with clinical outcomes
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