Pathophysiology of acute respiratory syndrome coronavirus 2 infection: a systematic literature review to inform EULAR points to consider

Abstract

BackgroundThe SARS-CoV-2 pandemic is a global health problem. Beside the specific pathogenic effect of SARS-CoV-2, incompletely understood deleterious and aberrant host immune responses play critical roles in severe disease. Our objective was to summarise the available information on the pathophysiology of COVID-19.MethodsTwo reviewers independently identified eligible studies according to the following PICO framework: P (population): patients with SARS-CoV-2 infection; I (intervention): any intervention/no intervention; C (comparator): any comparator; O (outcome) any clinical or serological outcome including but not limited to immune cell phenotype and function and serum cytokine concentration.ResultsOf the 55 496 records yielded, 84 articles were eligible for inclusion according to question-specific research criteria. Proinflammatory cytokine expression, including interleukin-6 (IL-6), was increased, especially in severe COVID-19, although not as high as other states with severe systemic inflammation. The myeloid and lymphoid compartments were differentially affected by SARS-CoV-2 infection depending on disease phenotype. Failure to maintain high interferon (IFN) levels was characteristic of severe forms of COVID-19 and could be related to loss-of-function mutations in the IFN pathway and/or the presence of anti-IFN antibodies. Antibody response to SARS-CoV-2 infection showed a high variability across individuals and disease spectrum. Multiparametric algorithms showed variable diagnostic performances in predicting survival, hospitalisation, disease progression or severity, and mortality.ConclusionsSARS-CoV-2 infection affects both humoral and cellular immunity depending on both disease severity and individual parameters. This systematic literature review informed the EULAR ‘points to consider’ on COVID-19 pathophysiology and immunomodulatory therapies.

COVID-19 and immune-mediated inflammatory diseases: effect of disease and treatment on COVID-19 outcomes and vaccine responses

“…Severe COVID-19 is characterised by an excessive host immune response with overproduction of proinflammatory cytokines such as tumour necrosis factor (TNF), interleukin (IL)-6, growth factors such as granulocyte-macrophage colony-stimulating factor, and chemokines such as IL-8, a response known as cytokine storm ( figure 1 ). 2 , 3 Some proinflammatory cytokines induced in COVID-19 are therapeutic targets in the treatment of patients affected by immune-mediated inflammatory diseases. 4 Such cytokine inhibitors are widely used in the treatment of inflammatory arthritis, psoriasis, inflammatory bowel disease, and connective tissue disorders.…”

SARS-CoV-2 Serology Testing in an Asymptomatic, At-Risk Population: Methods, Results, Pitfalls

“…It is of note that only one of the IgM+ participants received a positive RT-PCR for SARS-CoV-2 (on D1), and RP-PCR testing was negative for other coronaviruses. No IgM+ individuals who initially tested positive only for IgM ever developed documented IgG antibodies (per the Wytcote test) during the course of the study, potentially suggesting that the IgM results that were obtained were false positives [ 24 , 25 ]. It is possible that IgG antibodies developed but remained at undetectable levels or that they developed outside of the study period.…”

Perforin, COVID‐19 and a possible pathogenic auto‐inflammatory feedback loop

“…1.5.2 | Overproduction of pro-inflammatory cytokines, increased neutrophil-lymphocyte ratio and monocytosis Five studies assessing the cytokine release in COVID-19 reported increase of IL-1α, IL-1β, IL-1Ra, IL-6, IL-8, IL-10, IL-17, IL-18, tumour necrosis factor-α (TNF-α), IFN-α 2, IFN-γ, granulocyte colony-stimulating factor (G-CSF). 44 Some are produced by neutrophils and IL-8, IL-17 and TNF-α promote or are chemotactic for neutrophils. [45][46][47] High-serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient mortality.…”