The improvement of inflammatory markers and disease progression among moderate, severe, and critical COVID-19 patients: a cross-sectional study from two second referral hospitals in Surabaya, Indonesia

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Abstract
Background : To date, coronavirus diseases 2019 (COVID-19) has no definitive treatment. Thrombosis and hypercoagulation may occur in the advanced stage. Further study on how to use anticoagulants is still required to promote the best prognosis. Method s : A cross-sectional study of 110 moderate, 140 severe, and 81 critical patients receiving unfractioned heparin (UFH), low-molecular-weight heparin (LMWH), and fondaparinux was conducted. Data were collected from March 15th to August 31st 2020 at Universitas Airlangga and Husada Utama Hospital. A comparative study of white blood cell (WBC), neutrophils, lymphocytes, neutrophil-lymphocyte ratio (NLR), c-reactive protein (CRP), procalcitonin (PCT), D-dimer, all-cause mortality rate, length of stay, and days of death among three severities of COVID-19 was done. Univariate and multivariate analysis were used to determine the correlation between inflammatory state after anti-coagulant with patients’ mortality. Results: Two deaths occurred in moderate cases, 36 deaths in severe cases, and 70 deaths in critical cases on ventilators. On day 13, moderate and severe groups showed decreased WBC, neutrophils, NLR, CRP, and D-dimer (p < 0.05). NLR, CRP, and D-dimer (p<0.05) in critically ill and ventilated patients decreased. Day-13 evaluation revealed 32.73% decrease of inflammatory markers in moderate group; 32.86% in severe patients; and 16.05% in critically ill, ventilated patients. A significant correlation between day 13 inflammatory status with mortality was seen in moderate and critical cases with a ventilator (r=0.337; p< 0.05 and r=0.25; p 0.05). Inflammatory profile on day 6 (adjusted odds ratio [aOR] = 2.36; p < 0.05) and day 13 ([aOR] = 4.15; p < 0.05) was associated with patients’ mortality. Conclusion s : Anticoagulants in COVID-19 patients lower inflammation markers. Evaluating inflammatory status is essential to predict the mortality. Inflammatory markers on day 13, based on the severity of COVID-19 and comorbidities, were associated with mortality in moderate and critical cases.

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