Brazilian Guidelines for the pharmacological treatment of patients hospitalized with COVID-19

Abstract

Objective Several therapies are being used or proposed for COVID-19, and many lack appropriate evaluations of their effectiveness and safety. The purpose of this document is to develop recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil. Methods A group of 27 experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method. Results Sixteen recommendations were generated. They include strong recommendations for the use of corticosteroids in patients using supplemental oxygen, the use of anticoagulants at prophylactic doses to prevent thromboembolism and the nonuse of antibiotics in patients without suspected bacterial infection. It was not possible to make a recommendation regarding the use of tocilizumab in patients hospitalized with COVID-19 using oxygen due to uncertainties regarding the availability of and access to the drug. Strong recommendations against the use of hydroxychloroquine, convalescent plasma, colchicine, lopinavir + ritonavir and antibiotics in patients without suspected bacterial infection and also conditional recommendations against the use of casirivimab + imdevimab, ivermectin and rendesivir were made. Conclusion To date, few therapies have proven effective in the treatment of hospitalized patients with COVID-19, and only corticosteroids and prophylaxis for thromboembolism are recommended. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and promote economical resource use.

COVID-19: From Pathophysiology to Treatment

“…In newly emerging diseases, such as COVID-19, especially in a pandemic situation, interventions are mainly performed based on in vitro experiments, personal experiments, and small limited observational studies. The management of the disease depends largely on symptomatic and supportive treatments [14].…”

“…Worldwide, several pharmacological interventions have been proposed for COVID-19, such as anticoagulants, antimicrobials, chloroquine, hydroxychloroquine, convalescent plasma, remdesivir, and tocilizumab [14]. For severely or critically ill patients with acute respiratory distress syndrome (ARDS) and sepsis, in addition to supplemental oxygen, mechanical ventilation and specific therapies for ARDS, antiviral and antibiotic treatments should also be considered [15,16].…”

“…The potential benefit of its use would be in patients with moderate to severe ARDS, in selected cases and without suspicion of uncontrolled bacterial infection, 10-14 days after the onset of COVID-19 symptoms. The doses used in the studies ranged from 10 mg to 20 mg of dexamethasone and 40 mg to 120 mg of methylprednisolone per day for 5-10 days [14].…”

“…For patients with signs of bacterial infection, with latent infections such as tuberculosis or parasitic, care should be given to the possibility of reactivation of these with the administration of tocilizumab. In immunosuppressed patients, its use should be with caution, and in neutropenic individuals (<500 cells/mm 3 ), thrombocytopenic (< 50,000 platelets/mm 3 ) or with transaminases at levels five times greater than physiological value, tocilizumab should not be used at all [14].…”

“…But there is no recommendation for the use of intermediate doses in patients without signs of thromboembolism. Anticoagulants should be used, following a careful assessment of bleeding risk and presence of thrombocytopenias [14].…”