Clinical and pathological investigation of patients with severe COVID-19

Abstract

BACKGROUND. Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), has become a pandemic. This study addresses the clinical and immunopathological characteristics of severe COVID-19. METHODS. Sixty-nine patients with COVID-19 were classified into severe and nonsevere groups to analyze their clinical and laboratory characteristics. A panel of blood cytokines was quantified over time. Biopsy specimens from 2 deceased cases were obtained for immunopathological, ultrastructural, and in situ hybridization examinations. RESULTS. Circulating cytokines, including IL-8, IL-6, TNF-α, IP10, MCP1, and RANTES, were significantly elevated in patients with severe COVID-19. Dynamic IL-6 and IL-8 were associated with disease progression. SARS-CoV-2 was demonstrated to infect type II and type I pneumocytes and endothelial cells, leading to severe lung damage through cell pyroptosis and apoptosis. In severe cases, lymphopenia, neutrophilia, depletion of CD4 + and CD8 + T lymphocytes, and massive macrophage and neutrophil infiltrates were observed in both blood and lung tissues. CONCLUSIONS. A panel of circulating cytokines could be used to predict disease deterioration and inform clinical interventions. Severe pulmonary damage was predominantly attributed to both cytopathy caused by SARS-CoV-2 and immunopathologic damage. Strategies that prohibit pulmonary recruitment and overactivation of inflammatory cells by suppressing cytokine storm might improve the outcomes of patients with severe COVID-19.

Lymphocyte Subset Counts in COVID‐19 Patients: A Meta‐Analysis

“…CD4+ and/or CD8+ T‐cell counts from COVID‐19 patients with different disease severity status were reported in all 20 publications, and 10 of them also included CD19+ B cell and CD16 + CD56+ NK cell counts. These 20 peer‐reviewed publications were selected for meta‐analysis in this brief report (6‐25).…”

Oxidative Stress and Inflammation in COVID-19-Associated Sepsis: The Potential Role of Anti-Oxidant Therapy in Avoiding Disease Progression

“…Systemic cytokine profiles observed in severe COVID-19 patients present similarities to those observed in cytokine release syndromes, such as sepsis, with increased production of cytokines such as IL-6, IL-8, TNFα and other pro-inflammatory chemokines, including CC chemokine ligand 2 (CCL2), CCL3 and chemokine ligand 10 CXC (CXCL10). Another key inflammation mechanism, pyroptosis, also seems to be activated in both COVID-19 and sepsis [ 48 , 49 , 50 ]. This led to hypothesize that the dysregulated activation of a wide range of hyperinflammatory factors associated with COVID-19 could cause sepsis and septic shock in these patients [ 4 , 5 ].…”

“…It has been previously found in SARS-CoV infected patients that inflammation appears to be preceded by the activation of pyroptosis. In these patients, the virus mediated the release of IL-1β during early infection [ 48 , 49 , 50 ]. Importantly, the rapid progression to severe phenotypes in COVID-19 patients coincides with an abrupt shift from the NLRP3 cytokine storm to a compensatory immunosuppressive state [ 44 ].…”

Association of immunological features with COVID-19 severity: a systematic review and meta-analysis

“…SARS-CoV-2 infection is a potent inducer of proin ammatory chemokines that may be involved in the defense against viral infections [24]. Some studies reported higher concentrations of GM-CSF [5], IP-10 [5,23,24] , MCP-1 [23,24] , eotaxin [7] and RANTES [23] between severe cases and mild cases. However, other studies have not showed signi cant differences in the concentrations of GM-CSF [7,24], IP-10 [7], RANTES [24] , MCP-1 [7] , and eotaxin [24] .…”