Comparison of Circulating Immune Cells Profiles and Kinetics Between Coronavirus Disease 2019 and Bacterial Sepsis*

Abstract

OBJECTIVES: Although clinical presentation of coronavirus disease 2019 has been extensively described, immune response to severe acute respiratory syndrome coronavirus 2 remains yet not fully understood. Similarities with bacterial sepsis were observed; however, few studies specifically addressed differences of immune response between both conditions. Here, we report a longitudinal analysis of the immune response in coronavirus disease 2019 patients, its correlation with outcome, and comparison between severe coronavirus disease 2019 patients and septic patients. DESIGN: Longitudinal, retrospective observational study. SETTING: Tertiary-care hospital during the first 2020 coronavirus disease 2019 outbreak in France. PATIENTS: All successive patients with confirmed severe acute respiratory syndrome coronavirus 2 infection admitted to the emergency department, medical ward, and ICU with at least one available immunophenotyping performed during hospital stay. MEASUREMENTS AND MAIN RESULTS: Between March and April 2020, 247 patients with coronavirus disease 2019 were included and compared with a historical cohort of 108 severe septic patients. Nonsevere coronavirus disease 2019 patients (n = 153) presented normal or slightly altered immune profiles. Severe coronavirus disease 2019 (n = 94) immune profile differed from sepsis. Coronavirus disease 2019 exhibited profound and prolonged lymphopenia (mostly on CD3, CD4, CD8, and NK cells), neutrophilia, and human leukocyte antigen D receptor expression on CD14+ monocytes down-regulation. Surprisingly, coronavirus disease 2019 patients presented a unique profile of B cells expansion, basophilia, and eosinophilia. Lymphopenia, human leukocyte antigen D receptor expression on CD14+ monocytes down-regulation, and neutrophilia were associated with a worsened outcome, whereas basophilia and eosinophilia were associated with survival. Circulating immune cell kinetics differed between severe coronavirus disease 2019 and sepsis, lack of correction of immune alterations in coronavirus disease 2019 patients during the first 2 weeks of ICU admission was associated with death and nosocomial infections. CONCLUSIONS: Circulating immune cells profile differs between mild and severe coronavirus disease 2019 patients. Severe coronavirus disease 2019 is associated with a unique immune profile as compared with sepsis. Several immune features are associated with outcome. Thus, immune monitoring of coronavirus disease 2019 might be of help for patient management.

Virlaza™ Inhibits Sars-COV-2-induced Inflammatory Response of Bronchial Epithelial Cells and Pulmonary Fibroblast

“…The quick spread of Coronavirus disease (COVID-19) resulted in a pandemic in the whole world, reaching more than 100 million cases and 2 million deaths due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. The progression, severity, and mortality of COVID-19 differ from no, mild, or moderate symptoms in most of the patients, while up to 15% develop the severe and critical form of the disease with high mortality rates [2].…”

Regulatory T Cells: Angels or Demons in the Pathophysiology of Sepsis?

“…Intervention strategies, such as anti-programmed cell death (PD)-1/PD-L1 mAb, blocking cytotoxic T lymphocyte antigen (CTLA)-4, and blocking 2B4, have improved survival in experimental models of sepsis and recent clinical trials through improved T cell-induced immunosuppression (46,(55)(56)(57)(58). The degree of sepsis-induced inflammation, including the level of immunosuppression, is defined by specific host factors (such as age, gender, alcoholism, repeated nosocomial infection, frequency in hospital, chronic comorbidities, immunosuppressant use, malignant tumor, site of infection, splenectomy, trauma, and stress state) (59-66), pathogen status (such as multiple drugresistant organisms, malaria, SARS-CoV-2) (7,26,67,68), and the duration of sepsis (6,28,35,44,46,61,69,70).…”

“…In addition, multiple clinical studies show that amplification of CD4+CD25+ Tregs and increased Foxp3 levels may increase risks of nosocomial infections or secondary infections in sepsis (61,68,147). Using a "two-hit" CLP model with intratracheal injection of Pseudomonas aeruginosa, which mimics clinical conditions of secondary infection, Hu et al demonstrated that the absolute number of Foxp3+ Tregs in both spleen and lungs increased 24 hours after secondary P. aeruginosa infection.…”

Insight Into Regulatory T Cells in Sepsis-Associated Encephalopathy

“…The systemic immune-inflammation/cytokine storm, which constitutes an exaggerated host immune response associated with excessive production of pro-inflammatory cytokines, chemokines and acute phase proteins, is a hallmark feature in the acute phase of sepsis (18,(64)(65)(66)(67)(68)(69)(70)(71). This is one of the main causes of death and ICU acquired complications, including SIRS and compensatory anti-inflammatory response syndrome (CARS), and is defined by the host status (57,(72)(73)(74)(75)(76), pathogens (77,78) and the time span of sepsis (71,(79)(80)(81)(82)(83)(84). T regs have been shown to have a role on the inhibition of sepsis-induced amplifying systemic immuno-inflammation/cytokine storm and on the protection of organs in the early stage of sepsis (53,85,86).…”