Patients with SARS-CoV-2-Induced Viral Sepsis Simultaneously Show Immune Activation, Impaired Immune Function and a Procoagulatory Disease State

Abstract

Background: It is widely accepted that SARS-CoV-2 causes a dysregulation of immune and coagulation processes. In severely affected patients, viral sepsis may result in life endangering multiple organ dysfunction. Furthermore, most therapies for COVID-19 patients target either the immune system or coagulation processes. As the exact mechanism causing SARS-CoV-2-induced morbidity and mortality was unknown, we started an in-depth analysis of immunologic and coagulation processes. Methods: 127 COVID-19 patients were treated at the University Hospital Essen, Germany, between May 2020 and February 2022. Patients were divided according to their maximum COVID-19 WHO ordinal severity score (WHO 0–10) into hospitalized patients with a non-severe course of disease (WHO 4–5, n = 52) and those with a severe course of disease (WHO 6–10, n = 75). Non-infected individuals served as healthy controls (WHO 0, n = 42). Blood was analyzed with respect to cell numbers, clotting factors, as well as pro- and anti-inflammatory mediators in plasma. As functional parameters, phagocytosis and inflammatory responses to LPS and antigen-specific stimulation were determined in monocytes, granulocytes, and T cells using flow cytometry. Findings: In the present study, immune and coagulation systems were analyzed simultaneously. Interestingly, many severe COVID-19 patients showed an upregulation of pro-inflammatory mediators and at the same time clear signs of immunosuppression. Furthermore, severe COVID-19 patients not only exhibited a disturbed immune system, but in addition showed a pronounced pro-coagulation phenotype with impaired fibrinolysis. Therefore, our study adds another puzzle piece to the already complex picture of COVID-19 pathology implying that therapies in COVID-19 must be individualized. Conclusion: Despite years of research, COVID-19 has not been understood completely and still no therapies exist, fitting all requirements and phases of COVID-19 disease. This observation is highly reminiscent to sepsis. Research in sepsis has been going on for decades, while the disease is still not completely understood and therapies fitting all patients are lacking as well. In both septic and COVID-19 patients, immune activation can be accompanied by immune paralysis, complicating therapeutic intervention. Accordingly, therapies that lower immune activation may cause detrimental effects in patients, who are immune paralyzed by viral infections or sepsis. We therefore suggest individualizing therapies and to broaden the spectrum of immunological parameters analyzed before therapy. Only if the immune status of a patient is understood, can a therapeutic intervention be successful.

ICU-Acquired Colonization and Infection Related to Multidrug-Resistant Bacteria in COVID-19 Patients: A Narrative Review

“…Notably, there is a high incidence of lymphopenia affecting both B and T cell populations, with subsequent impacts on cellular and humoral responses. Furthermore, studies have also indicated the presence of monocyte dysfunction, whose intensity seemingly correlates with disease severity [ 42 , 43 , 44 , 45 ]. These immune alterations collectively contribute to the development of an immunodeficient state intrinsically linked to COVID-19, thereby rendering severe COVID-19 patients more susceptible to MDR infections.…”

Hemorrhagic cystitis induced by JC polyomavirus infection following COVID-19: a case report

“…Coronavirus disease 2019 (COVID-19) is an illness caused by the novel coronavirus SARS-CoV-2 and has resulted in a global pandemic with over 700 million confirmed cases and approximately 7 million deaths [ 1 ]. Studies have found that patients with COVID-19 infection exhibit both elevated pro-inflammatory mediators and significant immune suppression, which may be attributed to immune dysregulation in response to the infection [ 2 ]. In the state of immunological derangement, polyomavirus can transition from a latent phase to a pathogenic phase.…”