SARS-CoV-2 pneumonia and bacterial pneumonia patients differ in a second hit immune response model

Abstract

Secondary infections have been shown to complicate the clinical course and worsen the outcome of critically ill patients. Severe Coronavirus Disease 2019 (COVID-19) may be accompanied by a pronounced cytokine release, and immune competence of these patients towards most pathogenic antigens remains uncompromised early in the disease. Patients with bacterial sepsis also exhibit excessive cytokine release with systemic hyper-inflammation, however, typically followed by an anti-inflammatory phase, causing immune paralysis. In a second hit immune response model, leukocyte activation capacity of severely ill patients with pneumonia caused by SARS-CoV-2 or by bacteria were compared upon ICU admission and at days 4 and 7 of the ICU stay. Blood cell count and release of the pro-inflammatory cytokines IL-2, IFNγ and TNF were assessed after whole-blood incubation with the potent immune stimulus pokeweed mitogen (PWM). For comparison, patients with bacterial sepsis not originating from pneumonia, and healthy volunteers were included. Lymphopenia and granulocytosis were less pronounced in COVID-19 patients compared to bacterial sepsis patients. After PWM stimulation, COVID-19 patients showed a reduced release of IFNγ, while IL-2 levels were found similar and TNF levels were increased compared to healthy controls. Interestingly, concentrations of all three cytokines were significantly higher in samples from COVID-19 patients compared to samples from patients with bacterial infection. This fundamental difference in immune competence during a second hit between COVID-19 and sepsis patients may have implications for the selection of immune suppressive or enhancing therapies in personalized medicine.

Hematological Parameters and Procalcitonin as Discriminants between Bacterial Pneumonia-Induced Sepsis and Viral Sepsis Secondary to COVID-19: A Retrospective Single-Center Analysis

“…Our results regarding the hematological alterations are in line with data reported by Moser et al, except for lymphocytes [ 4 ]. In their study population, patients with bacterial sepsis secondary to pneumonia had a significantly higher proportion of neutrophils ( p = 0.025), but lower lymphocytes ( p = 0.033) and platelet numbers ( p < 0.001).…”

“…Whether bacterial or viral, sepsis is associated with profound disturbances of the normal homeostasis secondary to increased production of pro-inflammatory cytokines–the so called cytokine storm in COVID-19 sepsis, while in bacterial sepsis is known as the systemic inflammatory response syndrome (SIRS) [ 1 , 4 ]. The use of SIRS in the diagnosis of sepsis remains a matter of debate, as SIRS is present in various conditions [ 1 , 5 ].…”

“…Bacterial and viral sepsis are associated with qualitative and quantitative disturbances of all hematological parameters [ 2 , 4 , 5 , 6 ]. Quantitative changes of leukocytes or immature forms are part of the SIRS criteria [ 7 ].…”

“…In these patients, A CD8 T cell number of less than 75/μL is strongly associated with mortality (odds ratio = 3.982, 1.132–14.006, p < 0.001) [ 11 ]. In bacterial sepsis, persistent lymphopenia is associated with immune paralysis and in patients with suspected infection can differentiate between septic and non-septic patients [ 4 , 12 ]. Monocytes count and function alterations are frequently observed in patients with bacterial sepsis [ 5 , 13 ], while in COVID-19, monopenia and abnormal monocytic activity prevails [ 14 ].…”

“…In COVID-19 patients, leukocytes were still able to produce these cytokines. This could explain the different evolution of these two groups suggesting that: (i) patients with bacterial sepsis present with a higher degree of immune paralysis, (ii) in COVID-19 sepsis, a continuous, hyperinflammatory state is more probable during the first 7 days [ 4 ].…”