Longitudinal changes of inflammatory parameters and their correlation with disease severity and outcomes in patients with COVID-19 from Wuhan, China

Abstract

Background Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease and rapidly escalating epidemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The pathogenesis of COVID-19 remains to be elucidated. We aimed to clarify correlation of systemic inflammation with disease severity and outcomes in COVID-19 patients. Methods In this retrospective study, baseline characteristics, laboratory findings, and treatments were compared among 317 laboratory-confirmed COVID-19 patients with moderate, severe, or critically ill form of the disease. Moreover, the longitudinal changes of serum cytokines, lactate dehydrogenase (LDH), high-sensitivity C-reactive protein (hsCRP), and hsCRP to lymphocyte count ratio (hsCRP/L) as well as their associations with disease severity and outcomes were investigated in 68 COVID-19 patients. Results Within 24 h of admission, the critically ill patients showed higher concentrations of inflammatory markers including serum soluble interleukin (IL)-2 receptor, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), ferritin, procalcitonin, LDH, hsCRP, and hsCRP/L than patients with severe or moderate disease. The severe cases displayed the similar response patterns when compared with moderate cases. The longitudinal assays showed the levels of pro-inflammatory cytokines, LDH, hsCRP, and hsCRP/L gradually declined within 10 days post admission in moderate, severe cases or those who survived. However, there was no significant reduction in cytokines, LDH, hsCRP, and hsCRP/L levels in critically ill or deceased patients throughout the course of illness. Compared with female patients, male cases showed higher serum concentrations of soluble IL-2R, IL-6, ferritin, procalcitonin, LDH, and hsCRP. Multivariate logistic regression analysis revealed that IL-6 > 50 pg/mL and LDH > 400 U/L on admission were independently associated with disease severity in patients with COVID-19. Conclusion Exuberant inflammatory responses within 24 h of admission in patients with COVID-19 may correlate with disease severity. SARS-CoV-2 infection appears to elicit a sex-based differential immune response. IL-6 and LDH were independent predictive parameters for assessing the severity of COVID-19. An early decline of these inflammation markers may be associated with better outcomes.

Different characteristics of critical COVID-19 and thinking of treatment strategies in non-elderly and elderly severe adult patients

“…Regarding COVID-19, changes in inflammation stimulation were also revealed to be closely associated with the disease progression and prognosis of COVID-19, which was indicated by hsCRP fluctuations. In previous studies, higher hsCRP fluctuation was related to an increase in the inflammatory response and was associated with disease prognosis in young and middle-aged patients [3] , [9] , [16] , [21] , [26] , indicating a greater inflammatory response in critical patients than severe patients, which supported our finding. Furthermore, worsening of the inflammatory state was not only the main cause of poor COVID-19 prognosis, but this finding could also be extended to other coronaviruses, including severe acute respiratory syndrome (SARS) [27] .…”

“…Thus this study proposed the association between the worsening of the inflammatory state and ICU admission in young and middle-aged severe patients, which was different from the findings in elderly severe patients. Recently, the preliminary studies reported that hyperactive immune responses mainly manifesting as increased inflammatory markers could be associated with COVID-19 disease severity and outcomes [8] , [9] , [10] . There was a proposed inflammatory model to explain the mechanism by which worsening of the inflammatory state was the main reason for critical COVID-19 in young and middle-aged patients that distinguished COVID-19 development into three stages [11] .…”

RETRACTED ARTICLE: lncRNA HAND2-AS1 is downregulated in osteoarthritis and regulates IL-6 expression in chondrocytes

“…IL-6 is a proinflammatory cytokine and has been proved participate in many inflammatory diseases [ 33 – 35 ]. Many studies showed that inhibition of IL-6 is a promising way to the treatment of inflammatory diseases [ 36 – 38 ].…”

Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study)

“…Serum level of inflammatory marker decrease with the duration of SARS-CoV-2 infection. 13 An anticipated additional decline in level of inflammatory marker by 20% with intervention was used for sample size calculation. Sample size came to be 16 participants in each group with power of 80% (beta error 0.2) and at 95% level of significance (alpha error 0.05).…”