Diagnosis of SARS-CoV-2 infection in the setting of the cytokine release syndrome

Abstract

Introduction: Coronavirus disease (COVID-19) can trigger a cytokine response storm (CRS) that is associated with high mortality but for which the underlying pathophysiology and diagnostics are not yet well characterized. This review provides an overview of the underlying immune profile of COVID-19related CRS as well as laboratory markers for acute diagnosis and chronic follow-up of patients with SARS-CoV-2 and CRS. Areas covered: Innate and acquired immune profiles in COVID-19-CRS, RNA-detection methods for SARS-CoV-2 in the setting of CRS including factors that affect assay performance, serology for SARS-CoV-2 in the setting of CRS, and other biomarkers for COVID-19 will be discussed. Expert opinion: Studies support the implication of CRS in the pathogenesis, clinical severity and outcome of COVID-19 through the production of multiple inflammatory cytokines and chemokines from activated innate and adaptive immune cells. Although these inflammatory molecules, including IL-6, IL-2 R, IL-10, IP-10 and MCP-1, often correlate with disease severity as possible biomarkers, the pathogenic contributions of individual molecules and the therapeutic benefits of targeting them are yet to be demonstrated. Detection of SARS-CoV-2 RNA is the gold standard method for diagnosis of COVID-19 in the context of CRS but assay performance varies and is susceptible to false-negative results even as patients clinically deteriorate due to decreased viral shedding in the setting of CRS. Biomarkers including CRP, ferritin, D-dimer and procalcitonin may provide early clues about progression to CRS and help identify thrombotic and infectious complications of COVID-19.

Update Advances on C-Reactive Protein in COVID-19 and Other Viral Infections

“…As we well known, CRP can enhance the phagocytosis of phagocytes through specific CRP receptor, and remove various pathogenic microorganisms. During the process of COVID-19 pneumonia, a cytokine response storm (CRS) can be triggered, which is associated with high mortality in COVID-19 ( 11 ). The cytokines such as IL-6, TNF-α, stimulate hepatocyte to produce CRP ( Figure 1 ).…”

Sex-disaggregated data confirm serum ferritin as an independent predictor of disease severity both in male and female COVID-19 patients

“…COVID-19 can trigger a cytokine response storm (CRS) that is associated with high mortality but for which the underlying pathophysiology and diagnostics are not yet well characterized. 4 Loss of balance between adaptive and innate immune systems may result in a hyper-inflammatory state and CRS. 5 It has been reported that male patients have a greater inflammatory reaction, with higher levels of LDH, ferritin, and CRP but a lower lymphocyte count than females, adjusted by age and comorbidity 6 .…”

Effect of polymerized type I collagen in hyperinflammation of adult outpatients with symptomatic COVID-19: a double blind, randomised, placebo-controlled clinical trial

“…31 Avoiding that patients progress to CRS has important therapeutic implications, since anti-inflammatory agents are likely to be more useful than anti-virals in this setting. 26 In this study, it has been demonstrated that PTIC treatment was useful for decreasing the levels of IP-10, IL-8, and M-CSF, all of them biomarkers of severe disease, during de first week of treatment. This finding is relevant, since Zhao Y., et al, have described that in the group of patients with mild disease, IP-10 levels decline from week 2 and return to normal in week 4, while in the severe cases the IP-10 levels remain high level at week 2 and start to decline at week 3 and further by week 4.…”

“…IL-8 can contribute to the destabilization of endothelial cells in CRS, leading to the development of vascular barrier impairment and capillary damage with multiorgan failure. 26 IL-8 levels are higher in COVID-19 patients with mild symptoms than in healthy people and further elevated in severe COVID-19 patients, for this reason may serve as a biomarker to indicate the COVID-19 disease prognosis. 31 Avoiding that patients progress to CRS has important therapeutic implications, since anti-inflammatory agents are likely to be more useful than anti-virals in this setting.…”