The burden on healthcare systems during the SARS-CoV-2 pandemic and the unpredictability of complications from the infection prompted the world to engage in rapid research and collaboration across all fields. Meta-analyses aimed at identifying risk factors for severe illness and mortality after infection found that individuals over 60 years old, men, and those with elevated body weight had a higher likelihood of infection and developing severe forms of the disease. Pre-existing inflammatory respiratory diseases, such as COPD, increase the likelihood of severe disease progression in the form of acute respiratory distress. Many studies focused on investigating the correlation between biochemical markers and the course of acute COVID-19, but fewer studies have examined long-term changes in these markers.
In this study, we focused on assessing the relationship between three serum biochemical markers of inflammation – C-reactive protein (CRP), interleukin-6 (IL-6), and ferritin – and the severity of COVID-19, as defined by the U.S. National Institutes of Health (NIH) guidelines. To understand whether levels of chosen inflammatory markers in the serum could be associated with the severity of illness, we compared serum concentrations of CRP, IL-6, and ferritin six months post-infection in illness severity categories.
The study included 72 participants who had recovered from COVID-19 on average in 181 ± 27 days (mean ± SD) before blood sample collection. Upon joining the study, participants completed a survey and donated blood for the measurement of anti-SARS-CoV-2 S antibodies, confirming their recovery from COVID-19. The average age of the participants was 44 ± 11 years (mean ± SD), with women predominating (77.8%). We divided the participants into four categories based on their disease severity and recovery, listed here in increasing severity order: asymptomatic, mild illness, moderate illness, and critically ill. We measured concentrations of the selected inflammatory markers CRP, IL-6, and ferritin in serum samples and compared serum values across the illness categories using the SPSS statistical program.
Consistent with the literature, anti-SARS-CoV-2 S antibody concentrations were higher in more severe cases of the illness. Six months after infection, the values of the three selected inflammatory parameters returned to reference ranges across all recovery categories, except CRP in critically ill patients. Elevated levels remained in 25% of critically ill patients and 10% in the mild disease category. We also found that serum ferritin levels six months after recovery correlated with anti-SARS-CoV-2 S antibody concentrations, and although within the reference range, they were significantly higher in the critically ill illness category.
Based on our results, we can conclude that inflammation had subsided after six months post-infection. However, serum levels of ferritin remained significantly higher in those who had been critically ill and treated in intensive care units. In this group, a significantly higher percentage of CRP levels remained above the reference range six months after infection. We believe it would be worthwhile to investigate other inflammatory parameters, hematological markers, and iron homeostasis parameters to provide a broader picture of the physiological processes occurring in the body six months after recovering from COVID-19. To gain a better understanding, studies should also be conducted on a larger number of recovered patients, with a more balanced or selective distribution by gender and illness severity.
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