Studying the clinical, radiological, histological, microbiological, and immunological evolution during the different COVID-19 disease stages using minimal invasive autopsy

Valentino D’Onofrio,Reinoud Cartuyvels,Lotte Keulen,Martin Lammens,Judith Fraussen,Marie-Elena Vanden Abeele,Ruth Achten,Veerle Somers,Janneke Cox,Jan Vanrusselt,Jasperina Dubois,Ann Driessen,Niels Hellings,Annelore Vandendriessche,Lukasz Augsburg,Amélie Dendooven,Patrick Vandormael

doi:10.1038/s41598-022-05186-y

Abstract

The WHO defines different COVID-19 disease stages in which the pathophysiological mechanisms differ. We evaluated the characteristics of these COVID-19 disease stages. Forty-four PCR-confirmed COVID-19 patients were included in a prospective minimal invasive autopsy cohort. Patients were classified into mild-moderate (n = 4), severe-critical (n = 32) and post-acute disease (n = 8) and clinical, radiological, histological, microbiological and immunological data were compared. Classified according to Thoracic Society of America, patients with mild-moderate disease had no typical COVID-19 images on CT-Thorax versus 71.9% with typical images in severe-critical disease and 87.5% in post-acute disease (P < 0.001). Diffuse alveolar damage was absent in mild-moderate disease but present in 93.8% and 87.5% of patients with severe-critical and post-acute COVID-19 respectively (P = 0.002). Other organs with COVID-19 related histopathological changes were liver and heart. Interferon-γ levels were significantly higher in patients with severe-critical COVID-19 (P = 0.046). Anti-SARS CoV-2 IgG was positive in 66%, 40.6% and 87.5% of patients with mild-moderate, severe-critical and post-acute COVID-19 respectively (n.s.). Significant differences in histopathological and immunological characteristics between patients with mild-moderate disease compared to patients with severe-critical disease were found, whereas differences between patients with severe-critical disease and post-acute disease were limited. This emphasizes the need for tailored treatment of COVID-19 patients.

Highlights

The WHO defines different COVID-19 disease stages in which the pathophysiological mechanisms differ
In none of the four patients with radiologically confirmed COVID-19 we found evidence of SARS-CoV-2 infection
Post-mortem SARS-CoV-2 polymerase chain reaction (PCR) on lung tissue and serological testing for SARS-CoV-2 antibodies at death were negative for all four patients

Summary

Introduction

The WHO defines different COVID-19 disease stages in which the pathophysiological mechanisms differ. Significant differences in histopathological and immunological characteristics between patients with mild-moderate disease compared to patients with severecritical disease were found, whereas differences between patients with severe-critical disease and post-acute disease were limited. This emphasizes the need for tailored treatment of COVID-19 patients. Patients may either remain asymptomatic, or develop symptoms including fever, fatigue, cough, myalgia, loss of smell or gastro-intestinal complaints, so called mild disease. This can progress to moderate disease, in which the lower. A clear understanding of the pathophysiology during the different disease stages provides important information for the development of treatment s trategies[8]

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Conclusion