Long COVID: A proposed hypothesis-driven model of viral persistence for the pathophysiology of the syndrome
Long COVID (coronavirus disease 2019) syndrome includes a group of patients who, after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibit lingering mild-to-moderate symptoms and develop medical complications that can have lasting health problems. In this report, we propose a model for the pathophysiology of the long COVID presentation based on increased proinflammatory cytokine production that results from the persistence of the SARS-CoV-2 virus or one of its molecular components. Associated with this hyperproduction of inflammatory cytokines is a heightened activity of nuclear factor κ B (NF-κB) and p38 mitogen-activated protein kinase signaling pathways that regulate cytokine production.
The purpose of the present report was to review the causes of long COVID syndrome and suggest ways that can provide a basis for a better understanding of the clinical symptomatology for the of improved diagnostic and therapeutic procedures for the condition.
Extensive research was conducted in medical literature data bases by applying terms such as “long COVID” associated with “persistence of the SARS-CoV-2 virus” “spike protein' “COVID-19” and “biologic therapies.”
Results and Conclusions:
In this model of the long COVID syndrome, the persistence of SARS-CoV-2 is hypothesized to trigger a dysregulated immune system with subsequent heightened release of proinflammatory cytokines that lead to chronic low-grade inflammation and multiorgan symptomatology. The condition seems to have a genetic basis, which predisposes individuals to have a diminished immunologic capacity to completely clear the virus, with residual parts of the virus persisting. This persistence of virus and resultant hyperproduction of proinflammatory cytokines are proposed to form the basis of the syndrome.
Document Type: Research Article
Affiliations: 1: From the Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli Istituti di Ricovero e Cura a Carattere Scientifico, Rome, Italy; 2: Pediatric Section, Department of Surgery, Dentistry, Paediatrics, and Gynaecology, University of Verona, Verona, Italy; 3: Department of Pediatrics, Georgetown University Medical Center, Washington D.C.;
Publication date: May 1, 2022
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