Alveolar Neutrophilic Recruitment in COVID-19 May Not be Mediated by Th17 Response

Abstract

Introduction: The COVID-19 current pandemic disease differs from the H1N1pdm09 caused by Influenza A virus H1N1 subtype, by how it induces a pro-inflammatory response in infected lungs. Objective: Investigate the role of Th17 response in the pathogenesis of COVID-19 injury by analyzing the tissue expression of interleukins 8 and 17A and the neutrophils in lung samples of patients who die of COVID-19, comparing to H1N1pdm09. Study design and post-mortem results: Six lung samples from patients SARS-CoV-2 infected (COVID-19 group), and ten lung samples from adults who died from H1N1pdm09 (H1N1 group), were tested. A control group was also added to the study. H&E slides were used for neutrophils scoring. The tissue expression of IL-8 and IL-17A was identified by immunohistochemistry. Tissue expression increasing of IL-17A and IL-8 and a higher number of neutrophils were identified in samples from the H1N1 group when compared to the COVID-19 group. Discussion: It is suggested that the SARS-CoV-2 virus evokes an exacerbated response of the host's immune system but differs from that observed in the H1N1pdm09 disease because it may not be trigger by Th17 response. With the low expression of IL-8, IL-17A, neutrophil recruitment to the site of infection becomes impaired, resulting in viral persistence. On the other hand, in the COVID-19 disease, the immune response by Th2 cells seems to be exacerbated, observed by the extent of the lung injury. This uncontrolled response and, mainly, the lack of a therapeutic target, culminates in disease progression and, consequently, in shorter survival time.

Deregulated miRNA expression is associated with endothelial dysfunction in post-mortem lung biopsies of COVID-19 patients

“…The miRNAs expression levels were significantly correlated with the expression of four of the seven inflammatory biomarkers previously analyzed (3,21,22) in the COVID-19 patients. MiR-26a-5p expression was observed inversely correlated with IL-6 tissue expression, one of the cytokines directly regulated by this miRNA (28).…”

“…This clinical scenario is directly associated with the cytokine storm (8,9). Several studies, including from our collaborators, have shown an increase in the cytokines levels, and CASP-1 in patients with COVID-19 (3,8,9,21,22). The capillary-alveolar endothelial cells under the COVID-19 cytokines storm are activated and produce NF-κB and adhesion molecules such as ICAM-1 (9).…”

“…The inflammatory protein expression was previously performed by immunohistochemistry (IHC) in the lung biopsies for the Control (n = 10) and COVID-19 (n = 6) groups by our collaborators (3,21,22), for the following seven biomarkers: IL-4, IL-6, IL-8, IL-13, TNF-a, intercellular adhesion molecule 1 (ICAM-1), and Caspase-1 (CASP-1). All of these biomarkers presented significant increase in tissue expression in the COVID-19 group compared to the Control group (Table 1).…”

“…The coefficient of determination r square (r 2 ) by Pearson's test was used to determine the degree of correlation between the miRNAs expression levels and the inflammatory biomarkers expression previously evaluated in the same lung biopsies (1,21,25), considering r 2 ! 0.5 and r !…”