Abstract
Severe pneumonia and multiorgan dysfunction in COVID-19 and dengue haemorrhagic fever (DHF) are two diseases that can associate with an altered immune response to the infecting virus. To determine the similarities and differences in the cytokine and chemokine responses in these two infections, we compared responses in patients with varying severity of COVID-19 and acute dengue at different time points of illness. During early disease, patients who proceeded to develop COVID-19 severe pneumonia (SP) and DHF had significantly higher levels of IL-6, IL-10 and MIP3α than those who developed mild illness. The lowest levels of IFNγ in early illness were seen in those who succumbed to their illness due to COVID-19. Levels of serum IL-10 (p = 0.0001), IL-6 (p = 0.002), MIP-3α (p = 0.02) and CD40-L levels (p = 0.002) significantly increased from 5 to 9 day of illness to 10–21 day of illness in patients with moderate-to-severe COVID-19, but not in those with mild illness. In contrast, these cytokine/chemokine levels remained unchanged in those with DHF or dengue fever (DF) during febrile and critical phases. Although IL-10 levels were significantly higher in COVID-19 patients with SP, patients with DHF had 25-fold higher levels, whereas IL-6 levels were 11-fold higher in those with COVID-19 SP. IL-10 and other cytokines were evaluated in a larger cohort of patients during early illness (≤ 4 days) who proceeded to develop DF (n = 71) or DHF (n = 64). Of the cytokines evaluated, IL-10 was significantly higher (p < 0.0001) in those who went on to develop DHF compared to DF. Low IFNγ response to the SARS-CoV2 and high levels of immunosuppressive IL-10 in both COVID-19 and dengue during early illness are indicators of an altered antiviral response potentially contributing to disease severity.
Highlights
COVID-19, caused by the SARS-CoV2 virus, has currently infected over 25 million individuals, resulting in over 850,000 deaths worldwide, within a period of 8 m onths[1]
Acute dengue infection is caused by one of the four dengue viruses (DENVs), is asymptomatic in a majority of infected individuals. It may manifest as an undifferentiated viral fever, dengue fever (DF), or may progress into severe illness resulting in dengue haemorrhagic fever (DHF) with or without shock[7]
As IL-10 was significantly higher in patients who proceeded to develop DHF, we evaluated the usefulness of IL-10 in early illness by assessing the area under the curve (AUC) values by comparing levels of those with DHF and DF
Summary
COVID-19, caused by the SARS-CoV2 virus, has currently infected over 25 million individuals, resulting in over 850,000 deaths worldwide, within a period of 8 m onths[1]. Many inflammatory cytokines and chemokines such as IL-6, IL-1β, IL-8, CCL8, CXCL9, CXCL16, MCP-1 and IP-10 and immunosuppressive cytokines such as IL-10 are elevated in both infections and associate with clinical disease severity[4,11,24,25,26,27] Both dengue and COVID-19 are associated with a cytokine storm and multiorgan involvement, the pathogenesis, disease course and recovery are very much different. In order to develop a better insight into both infections and to understand the role of these cytokines in disease pathogenesis and the changes along the course of illness, we compared the cytokine and chemokine responses in patients with varying severity of acute dengue and acute COVID-19 illness during the acute/febrile phase and the critical phase of illness. As we were able to identify unique cytokine/chemokine signatures associated with dengue and COVID-19, we further proceeded to evaluate the predictive values of relevant cytokines in early acute dengue, in order to determine subsequent disease severity
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