COVID-19 May Be Associated with Novel Pulmonary-Specific Vasculopathy

A study published in the British Journal of Haematology found that severe coronavirus disease 2019 (COVID-19) infection is correlated with a significant coagulopathy that correlates with disease severity.¹

The researchers suggested that the collective data indicated that the diffuse bilateral pulmonary inflammation observed in COVID-19 is associated with a novel pulmonary-specific vasculopathy, which the authors have termed, “pulmonary intravascular coagulopathy,” which is distinct from disseminated intravascular coagulation (DIC). 

Given that thrombotic risk is significantly affected by race, the researchers suggested that these findings may suggest that pulmonary vasculopathy may contribute to the unexplained differences that have emerged in regard to racial susceptibility to COVID-19 mortality.

“In addition to pneumonia affecting the small air sacs within the lungs, we are also finding hundreds of small blood clots throughout the lungs. This scenario is not seen with other types of lung infection, and explains why blood oxygen levels fall dramatically in severe COVID-19 infection,” James O’Donnell, director of the Irish Centre for Vascular Biology at RCSI and consultant hematologist in the National Coagulation Centre in St James's Hospital, Dublin, said in a press release.² “Understanding how these micro-clots are being formed within the lung is critical so that we can develop more effective treatments for our patients, particularly those in high risk groups.”

Adult patients with COVID-19 were recruited from St. James’s Hospital between March 13, 2020 and April 10, 2020 for the study. Criteria for hospital admission were defined as those requiring inpatient care as a result of the severity of illness.

Following admission, all patients received supportive care in line with best international practice, including the use of supplemental oxygen when necessary. Epidemiological, demographic, treatment, and outcome data were derived from the hospital electronic patient record, and samples from each patient were collected at admission and additional timepoints throughout their admission. 

A total of 83 patients were enrolled in the study, including 67 patients who were Caucasian (81%), 10 who were Asian (12%), 5 who were African (6%), and 1 who was of Latino/Hispanic ethnicity (1%). The researchers indicated that at the time of writing, 50 patients (60.2%) had fully recovered and were discharged from hospital, while 20 (24.1%) remained in the hospital and 13 (15.7%) had died. Moreover, 50 patients (60.3%) were discharged without requiring ICU admission, 23 patients (27.7%) were admitted to ICU during their disease course, and 10 patients (12%) required ICU support but were ultimately deemed clinically unsuitable for ICU admission. 

In order to assess whether COVID-19 coagulopathy at the time of admission was indicative of future clinical outcomes, the patients were divided into 2 groups, including those who required ICU admission for ventilatory support or who died due to COVID-19 infections and those who were discharged without requiring ICU support. Notably, the median age of non-survivors was 75.2 years (range 63.5 to 92) compared to 60.2 years (range 26.9 to 89) in survivors. Individuals whose admission resulted in an ICU stay or death were found to be more likely to have underlying co-morbidities compared with those who survived and did not require ICU admission.

Similar to previously reported Chinese data, the researchers observed that abnormal coagulation parameters on admission were also associated with a poor prognosis in Caucasian patients with COVID-19. Specifically, median D-dimer levels were significantly higher in the subgroup who eventually needed ICU admission (1003 versus 804 ng/mL; P = 0.018). Further, fibrinogen and CRP levels were also both significantly elevated in the poor prognosis group. 

While no significant difference was observed in prothrombin time (PT) between the 2 groups at admission, the median PT was found to be higher in the adverse prognostic group by day +4 (13.1 versus 12.5 sec; P = 0.007). Additionally, D-dimer levels remained significantly higher in the poor prognosis group at Day +4. 

“Our novel findings demonstrate that COVID-19 is associated with a unique type of blood clotting disorder that is primarily focused within the lungs and which undoubtedly contributes to the high levels of mortality being seen in patients with COVID-19,” said O’Donnell. 

In contrast to previously reported Chinese data, the researchers did not observe a progressive increase in PT in the adverse prognostic group. However, this may be reflective of the fact that the cohort in this study was predominantly Caucasian, as well as that the patients were started on low-molecular-weight heparin (LMWH) at the time of admission. Importantly though, despite the evidence of a progressive COVID-19 coagulopathy over time, none of the patients in the study cohort maintained on prophylactic LMWH developed systemic DIC. This is apparent given that platelet count, activated partial thromboplastin time, and fibrinogen levels did not differ over the study period. 

“Further studies will be required to investigate whether different blood thinning treatments may have a role in selected high-risk patients in order to reduce the risk of clot formation,” O’Donnell said.

References:

1. Fogarty H, Townsend L, Cheallaigh CN, et al. COVID-19 Coagulopathy in Caucasian patients. British Journal of Haematology. doi: 10.1111/bjh.16749.

2. Blood clotting a significant cause of death in patients with COVID-19 [news release]. Dublin. Published April 30, 2020. Accessed April 30, 2020.