Longitudinal Cytokine Profile in Patients With Mild to Critical COVID-19.

Lowell Ling,Apple C M Yeung,David S C Hui,Chun Kwok Wong,Kitty S C Fung,Wai Tat Wong,Paul K S Chan,Zigui Chen,Rita W Y Ng,Grace Lui,Veronica Chan,Eugene Y K Tso

doi:10.3389/fimmu.2021.763292

Lowell Ling, Apple C M Yeung + Show 10 more

Open Access

https://doi.org/10.3389/fimmu.2021.763292

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Abstract

The cytokine release syndrome has been proposed as the driver of inflammation in coronavirus disease 2019 (COVID-19). However, studies on longitudinal cytokine profiles in patients across the whole severity spectrum of COVID-19 are lacking. In this prospective observational study on adult COVID-19 patients admitted to two Hong Kong public hospitals, cytokine profiling was performed on blood samples taken during early phase (within 7 days of symptom onset) and late phase (8 to 12 days of symptom onset). The primary objective was to evaluate the difference in early and late cytokine profiles among patient groups with different disease severity. The secondary objective was to assess the associations between cytokines and clinical endpoints in critically ill patients. A total of 40 adult patients (mild = 8, moderate = 15, severe/critical = 17) hospitalized with COVID-19 were included in this study. We found 22 cytokines which were correlated with disease severity, as proinflammatory Th1-related cytokines (interleukin (IL)-18, interferon-induced protein-10 (IP-10), monokine-induced by gamma interferon (MIG), and IL-10) and ARDS-associated cytokines (IL-6, monocyte chemoattractant protein-1 (MCP-1), interleukin-1 receptor antagonist (IL-1RA), and IL-8) were progressively elevated with increasing disease severity. Furthermore, 11 cytokines were consistently different in both early and late phases, including seven (growth-regulated oncogene-alpha (GRO-α), IL-1RA, IL-6, IL-8, IL-10, IP-10, and MIG) that increased and four (FGF-2, IL-5, macrophage-derived chemokine (MDC), and MIP-1α) that decreased from mild to severe/critical patients. IL-8, followed by IP-10 and MDC were the best performing early biomarkers to predict disease severity. Among critically ill patients, MCP-1 predicted the duration of mechanical ventilation, highest norepinephrine dose administered, and length of intensive care stay.

Highlights

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus [1]
In this study on 40 patients hospitalized with COVID-19, we found 22 cytokines were associated with the severity of disease
monocyte chemoattractant protein (MCP)-1 level at intensive care unit (ICU) admission predicted the days on mechanical ventilation, highest dose of vasopressor required, and length of ICU stay

Summary

Introduction

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus [1]. Most patients infected with SARS-CoV-2 remain asymptomatic or only develop mild respiratory symptoms, but 5% develop critical illnesses [2, 3]. Age and comorbidities are important risk factors for mortality. The underlying reasons for why patients manifest a spectrum of disease severity despite infection with the same virus are unclear. The natural history of COVID-19 follows a distinct pattern starting with early mild respiratory illnesses with or without systemic symptoms shortly after infection. After 1 week from symptom onset, a small proportion of patients develop respiratory failure from pneumonia which may be complicated by multiorgan dysfunction with acute respiratory distress syndrome (ARDS), shock and renal failure [1]

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