Aspirin with or without statin in the treatment of endotheliitis, thrombosis, and ischemia in coronavirus disease

Florêncio, Francisco Kleyton Zacarias; Tenório, Maiza de Oliveira; Macedo Júnior, Aluísio Roberto Andrade; Lima, Sandro Gonçalves de

doi:10.1590/0037-8682-0472-2020

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Major Article • Rev. Soc. Bras. Med. Trop. 53 • 2020 • https://doi.org/10.1590/0037-8682-0472-2020 linkcopy

Aspirin with or without statin in the treatment of endotheliitis, thrombosis, and ischemia in coronavirus disease

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INTRODUCTION: In the genesis of coronavirus disease (COVID-19), there is a process of endotheliitis associated with thrombotic changes, no studies have reported the use of acetylsalicylic acid (ASA) as a possible therapeutic approach. Statins could potentiate the ASA therapy.

METHODS: This is a series of 14 cases with a laboratory-confirmed diagnosis of COVID-19. All patients underwent the ASA therapy. Those who had risk factors for vascular disease also underwent the high-potency statin therapy. When symptoms were totally or practically resolved, patients were discharged and advised to continue medications for a complementary time, according to the clinical evolution of each patient.

RESULTS: The mean age of monitored patients was 48.6 years. A total of 78.6% patients presented with at least one comorbidity, which could have contributed as a risk factor for a poor prognosis in the evolution of COVID-19. Four patients had secondary bacterial infections; three patients needed hospitalization. None of the cases progress to stage III, and all patients had remission of symptoms, with 100% survival.

CONCLUSIONS: the process of endothelial dysfunction in COVID-19 involves disseminated thrombosis, initially microvascular and later expansion into larger vessels. ASA could act as a secondary prophylaxis and prevent thrombosis from developing and reaching stage III of the disease. As this was a case series, we cannot provide definitive conclusions; however, this study allows us to formulate hypotheses and support clinical trials to evaluate benefits of the ASA therapy in the treatment of COVID-19.

Keywords:
COVID-19; Aspirin; Thrombosis; Endothelium; Hydroxymethylglutaryl-CoA Reductase Inhibitors

AGE (in years)	COMORBIDITIES/HISTO RY	TREATMENT	OUTCOMES (from the	COMPLICATIONS
			beginning of follow-up to
			being discharged)
37	None	ASA^a	Oligosymptomatic^e on the 10^th day	None
48	Asthma and hypothyroidism	ASA^a + atorvastatin	Oligosymptomatic^e on the 9^th day	None
41	Asthma	ASA^a + atorvastatin	Asymptomatic on the 10^th day	None
39	Hypertension, obesity	ASA^a + atorvastatin + oral amoxicillin (875 mg) potassium clavulanate (125 mg) q8h for 7 days	Oligosymptomatic^e on the 4^th day	RTI^b
58	Hypertension, diabetes mellitus, obesity	ASA^a habitual^c + atorvastatin + oral ceftriaxone 2 g/day intravenous for 6 days + azithromycin 500 mg/day for 5 days	Oligosymptomatic^e on the 2^nd day	RTI^b + hospitalization
52	Diabetes mellitus, coronary artery disease, overweight	ASA^a habitual^c + clopidogrel habitual^c; sinvastatin replaced with atorvastatin	Asymptomatic on the 10^th day	None
55	History of non-Hodgkin lymphoma	ASA^a + atorvastatin	Oligosymptomatic^e on the 7^th day	None
55	Hypertension, obesity	ASA^a + atorvastatin	Asymptomatic on the 7^th day	None
81	Hypertension, diabetes mellitus, ex-smoker	ASA^a + atorvastatin + IV ceftriaxone 2 g/day for 10 days + oral azithromycin 500 mg/day for 5 days	Asymptomatic on the 21^st day	RTI^b+ hospitalization
36	Overweight, ex-smoker, circulation problem in the lower limbs	ASA^a	Asymptomatic on the 14^th day	None
13	None	ASA^a	Asymptomatic on the 11^th day	Hospitalization
63	Hypertension	ASA^a + atorvastatin	Oligosymptomatic^e on the 7^th day	None
60	Hypertension, diabetes mellitus, dyslipidemia, obesity, lower limb varicose veins, ex-smoker	ASA^a+ rosuvastatin habitual^b+ oral nitrofurantoin 100 mg q6h for 7 days	Asymptomatic on the 17^th day	UTI^d
43	Overweight	ASA^a + atorvastatin	Asymptomatic on the 14^th day	None

STAGES	DESCRIPTION
Viral endotheliits	● diffuse multisystemic endothelial lesion caused by the virus
	● diffuse endotheliitis
	● microvascular stasis due to endotheliitis
Progressive thrombosis	● platelet aggregation, microvascular thrombosis
	● inflammation and thrombosis of larger vessels, intravascular coagulation;
Diffuse ischemia	● multisystemic ischemia, SIRS^a and DIVC^b
	● refractory shock, MOF^c and death

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E-mail: rsbmt@sbmt.org.br

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[TFN1] Clinical, therapeutic, and evolutionary details of each patient Keys: (a) ASA: acetylsalicylic acid; (b) RTI: respiratory tract infection; (c) Habitual: medication that the patient already used routinely before the first visit and was maintained for the treatment of COVID-19; (d) UTI: urinary tract infection (e) Oligosymptomatic: patient presents with residual cough or some degree of olfactory change, but without dyspnea.