Although the novel SARS-CoV-2 virus (COVD-19) is classified as an acute respiratory infection, emerging data show that morbidity and mortality are driven by disseminated intravascular coagulopathy. Untreated CAC leads to microangiopathic thromboses, causing multiple systems organ failure and consuming enormous healthcare resources. Identifying strategies to prevent CAC are therefore crucial to reducing COVID-19 hospitalization rates. The pathogenesis of CAC is unknown, but there are major overlaps between severe COVID-19 and vitamin D insufficiency (VDI). We hypothesize that VDI is a major underlying contributor to CAC. Preliminary data from severe COVID-19 patients in New Orleans support this hypothesis. The purpose of the proposed multi-center, prospective, randomized controlled trial is to test the hypothesis that low-risk, early treatment with aspirin and vitamin D in COVID-19 can mitigate the prothrombotic state and reduce hospitalization rates.
Although the novel SARS-CoV-2 virus (COVD-19) is classified as an acute respiratory
infection, emerging data show that morbidity and mortality are driven by disseminated
intravascular coagulopathy. Data from Wuhan showed that COVID-19-associated coagulopathy
(CAC) was present in 71% of deaths vs. 0.4% of survivors. Untreated CAC leads to
microangiopathic thromboses, causing multiple systems organ failure and consuming enormous
healthcare resources. Identifying strategies to prevent CAC are therefore crucial to reducing
COVID-19 hospitalization rates.
The high prevalence of CAC in severely ill COVID-19 patients led the American Society of
Hematology to recommend that all hospitalized COVID-19 patients be prophylactically
anticoagulated. However, there are no data and no recommendations regarding outpatient
prevention of CAC.
The pathogenesis of CAC is unknown. Given the demographic, geographic, pathologic, and
treatment overlap between severe COVID-19 and vitamin D insufficiency (VDI), we hypothesize
that VDI is a major underlying contributor to CAC. Preliminary data from critically ill
COVID-19 patients in New Orleans support this hypothesis. Furthermore, mouse models of VDI
developed aggravated multiorgan thrombus formation after lipopolysaccharide injection; this
phenotype parallels CAC.
Given these lines of evidence, the purpose of the proposed multi-center, prospective,
randomized controlled trial is to test the hypothesis that low-risk, early treatment with
aspirin and vitamin D in COVID-19 (The LEAD COVID-19 Trial) can mitigate the prothrombotic
state and reduce hospitalization rates.
Drug: Aspirin 81 mg
Aspirin 81 mg to be taken orally once daily for 14 days.
Dietary Supplement: Vitamin D
Vitamin D 50,000 IU to be taken orally once weekly for 2 weeks
Inclusion Criteria:
- Patients > 18 years
- Written informed consent
- New (within 24 hours) COVID-19 diagnosis
Exclusion Criteria:
- Pregnant patients or Prisoners
- History of GI bleeding or peptic ulcer disease, or spontaneous bleeding from other
sites; History of thrombocytopenia; History of chronic kidney disease; Concurrent use
of nonsteroidal anti-inflammatory drugs, or steroids.
- Hypervitaminosis D and associated risk factors: Renal failure, Liver failure,
Hyperparathyroidism, Sarcoidosis, Histoplasmosis
Frank H Lau, MD, Principal Investigator
LSUHSC-NO