Coagulopathy of Patients with COVID-19 is Associated with Infectious and Inflammatory Markers

Abstract

Background

SARS-CoV-2 infection activates coagulation and stimulates innate immune system. Little is known about coagulopathy and response of inflammation and infection in ICU patients with COVID-19. Derangement of coagulation and markers of infection and inflammation induced by SARS-CoV-2 infection, as well as their correlations were elucidated.

Methods

One hundred eight ICU patients with COVID-19 (28 survivors and 80 non-survivors) in Tongji hospital and Wuhan Jinyintan hospital, in Wuhan, China were included. Coagulation parameters, infectious and inflammatory markers were dynamically analysed. The correlation between coagulopathy of patients and infectious and inflammatory markers was verified.

Results

SARS-CoV-2-associated coagulopathy occurred in most cases of critical illness. Raised values of d-dimer and FDP were measured in all patients, especially in non-survivors, who had longer PT, APTT, INR, as well as TT, and lower PTA and AT compared to survivors. SIC and DIC mostly occurred in non-survivors. CRP, ESR, serum ferritin, IL-8, and IL-2R increased in all patients, and were much higher in non-survivors who had significantly higher levels of IL-6 and IL-10. D-dimer was positively associated with CRP, serum ferritin (p = 0.02), PCT (p < 0.001), and IL-2R (p = 0.007). SIC scores were positively correlated with CRP (p = 0.006), PCT (p = 0.0007), IL-1β (p = 0.048), and IL-6 (p = 0.009). DIC scores were positively associated with CRP (p < 0.0001), ESR (p = 0.02), PCT (p < 0.0001), serum ferritin (p < 0.0001), IL-10 (p = 0.02), and IL-2R (p = 0.0005).

Conclusion

Prothrombotic state, SIC, and DIC are the characteristics of coagulation in ICU patients with COVID-19. CRP, ESR, serum ferritin, IL-8, IL-2R, IL-6, and PCT were stimulated by SARS-CoV-2 infection. CRP, PCT, serum ferritin, and IL-2R indicate the coagulopathy severity of patients with COVID-19.

Keywords:

• SARS-CoV-2
• COVID-19
• coagulopathy
• markers of infection and inflammation
• correlation

Acknowledgment

We deeply express our gratitude to the medical staff, patients, and their family members involved in this study.

Abbreviations

APTT, activated partial thromboplastin time; AT, antithrombin; CHD, coronary heart disease; CKD, chronic kidney disease; CLD, chronic liver disease; COPD, chronic obstructive pulmonary disease; COVID-19, Coronavirus disease 2019; CRP, C-reactive protein; DIC, disseminated intravascular coagulation; DVT, deep vein thrombus; ESR, erythrocyte sedimentation rate; Fbg, fibrinogen; FDP, fibrin or fibrinogen degradation product; GIB, gastrointestinal bleeding; ICU, intensive care unit; IFN-γ, interferon-γ; IL-10, interleukin-10; IL-1β, interleukin-1β; IL-2R, interleukin-2 receptor; IL-6, interleukin-6; IL-8, interleukin-8; PAI-1, plasminogen activator inhibitor type 1; INR, International normalised ratio; IQR, inter quartile range; ISTH, International Society on Thrombosis and Haemostasis; LMWH, low-molecular-weight heparin; MERS, Middle East respiratory syndrome; NGS, next-generation sequencing; PCT, procalcitonin; PT, prothrombin time; PTA, prothrombin activity; RT-PCR, real-time reverse transcriptase polymerase chain reaction; SARS, severe acute respiratory syndrome; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SEM, standard error of mean; SIC, sepsis-induced coagulopathy; SOFA, sequential or sepsis-related organ failure assessment; TNF-α, tumour necrosis factor-α; TT, thrombin time; WHO, World Health Organization.

Ethical Approval

The study was approved by the Ethics Committees and Institutional Review Boards of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Wuhan Jinyintan Hospital, Wuhan, China (TJ-IRB20200225), who approved a waiver of written informed consent from patients with COVID-19 by reason of emerging infectious diseases. Collection and analysis of data were anonymous.

Disclosure

The authors report no conflicts of interest for this work.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.