Temporal profiling of plasma cytokines, chemokines and growth factors from mild, severe and fatal COVID-19 patients

Abstract

, a novel coronavirus that is related to severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) in phylogenetic distance was identified. 1 This virus, which was later designated as SARS-CoV-2, also causes acute respiratory disease syndrome (ARDS) termed coronavirus disease 2019 (COVID-19), which was declared as a pandemic by the World Health Organization in March 2020. Although the majority of patients of COVID-19 show moderate symptoms such as dry cough and fatigue, up to 20% cases develop severe symptoms characterized as ARDS, a clinical pulmonary phenomenon marked by the development of bilateral infiltrates and hypoxemia. 2 The median incubation period of SARS-CoV-2 infection is~4-5 days before symptom onset, and the majority of symptomatic patients develop symptoms within 11.5 days. Within 5-6 days of symptom onset, SARS-CoV-2 viral load reaches its peak, which is much earlier than SARS-CoV. 3 Severe COVID-19 cases progress to ARDS with hypoxemia around 8-12 days after symptom onset. 2 Although various independent factors such as older age and existing diseases contribute to mortality, the majority of fatal patients die of complications such as ARDS, myocardial injury, acute kidney injury, and sepsis. 2,3 The pathogenesis of COVID-19 has been heavily investigated in the past months. Pathophysiology in COVID-19 is characterized by diffuse alveolar damage, focal reactive hyperplasia of pneumocytes, inflammatory cellular infiltration, vasculitis, hypercoagulability, neutrophilia, and lymphopenia. 4 Studies have suggested that hyper-inflammation is linked to more severe disease of COVID-19, which is characterized by a cytokine releasing syndrome (CRS). 3,5 It has been reported that some inflammatory cytokines (such as IL-6, IL-10, and TNF-α) and chemokines (such as CXCL10/ IP-10, CCL2/MCP-1, and CCL3/MIP-1α) are upregulated in COVID-19 patients. 2 However, these studies are limited by the small sample size, narrowed cytokine and chemokine spectrum, and absence of temporal kinetic analysis of these factors with disease progression. Currently, limited information is available on host factors and biomarkers affecting individual outcomes in COVID-19. Identification of host plasma factors that are correlated to COVID-19 progression may provide potential biomarkers and targets for developing therapeutics. To systematically investigate the kinetic changes of plasma levels of cytokines, chemokines and growth factors (CCGFs) over the disease courses in COVID-19 patients as well as the correlations between the CCGF profiles and disease severity, we measured levels of 48 CCGFs in plasma of mild, severe and fatal COVID-19 patients collected at different stages of disease courses. We collected sera from 6 fatal, 7 severe, and 10 mild patients at day 1, 5, 10, and 14 after diagnosis. One sample was collected from each of the 4 healthy donors. We measured the levels of

A Review on the Neurological Manifestations of COVID-19 Infection: a Mechanistic View

“…The MAPK, which plays a critical role in the release of various cytokines, including IL-1, IL-10, IL-12, and TNFα, is also modulated by Ang II [66]. Several clinical studies have indicated a marked increase of proinflammatory cytokines, like IL-2, IL-6, and TNF-α, in severe and moderate cases of COVID-19 [67][68][69][70][71][72][73].…”

SARS-CoV-2 spike protein promotes IL-6 trans-signaling by activation of angiotensin II receptor signaling in epithelial cells

“…Recent clinical studies have found that COVID-19 patients with severe illness had elevated levels of certain cytokines including IL-6, TNF-α, IL-10, MCP-1 and IP-10 [6][7][8]. The pathophysiology of COVID-19 is far from being understood, and the absence of an effective medical regimen has led to the development of new therapeutic strategies based on pathophysiological assumptions.…”

COVID-19 Infection in a Patient With Fragile-X Syndrome

“…Therefore, a person with FXS may have impaired immunity and may be more susceptible to infectious diseases. CXCL-10 has also been implicated in the cytokine storm linked to a more severe disease among patients with COVID-19 [ 6 , 8 , 9 ]. Consequently, one hypothesis could be that patients with FXS infected with COVID-19 should display a lesser degree of inflammation and milder disease.…”