Background: Angiotensin receptor blockers (ARBs), such as telmisartan, have been postulated to treat Covid-19-induced lung inflammation. Methods: This is a parallel-group, randomized, two-arm, open-label, adaptive, multicenter superiority trial with 1:1 allocation ratio. Participants included patients from 18 years of age hospitalized with Covid-19 with 4 or fewer days since symptom onset enrolled at a university and a community hospital in Buenos Aires, Argentina. Exclusion criteria included prior intensive care unit (ICU) admission and use of ARBs/angiotensin converting enzyme inhibitors at randomization. Control arm received standard care alone and treatment arm telmisartan 80 mg twice daily for 14 days. Primary outcomes were C-reactive protein (CRP) plasma levels at day 5 and 8 after randomization. Secondary outcomes included time to discharge within 15 days, admission to ICU and death at 15-and 30-days. NCT04355936 (Completed). Findings: A pragmatic decision to end the study before the third interim analysis was made on Oct. 30th due to sharp reduction in recruitment. A total of 162 patients were randomized. 158 patients enrolled between May 14 and October 30 2020, were included in the analysis, 80 in the standard care and 78 in the telmisartan added to standard care group. Baseline absolute CRP serum levels were 5.53 § 6.19 mg/dL (95% CI 6.91 to 4.15, n = 80) and 9.04 § 7.69 (95% CI 9.04 to 10.82, n = 74) in the standard care and telmisartan added to standard care groups, respectively. Day 5 control-group CRP levels were 6.06 § 6.95 mg/dL (95% CI 7.79À4.35, n = 66) while telmisartan group were 3.83 § 5.08 mg/dL (95% CI 5.08À2.59, n = 66, p = 0.038). Day 8 CRP levels were 6.30 § 8.19 mg/dL (95% CI 8.79À3.81, n = 44) and 2.37 § 3.47 mg/dL (95% CI 3.44À1.30, n = 43, p = 0.0098) in the control and telmisartan groups, respectively (all values expressed as mean § SD). Kaplan-Meier analysis showed that telmisartan-treated patients had a lower median time-to-discharge (control=15 days; telmisartan=9 days). Death by day 30 was reduced in the telmisartan-treated group (control 22.54%,

Background. Covid-19, the disease caused by SARS-CoV-2, is associated with significant respiratory-related morbidity and mortality. Angiotensin receptor blockers (ARBs) have been postulated as tentative pharmacological agents to treat Covid-19-induced lung inflammation. Trial design. This trial is a parallel group, randomized, two arm, open label, multicenter superiority trial with 1:1 allocation ratio. Methods. Participants included patients who were 18 years of age or older and who had been hospitalized with confirmed Covid-19 with 4 or fewer days since symptom onset. Exclusion criteria included intensive care unit admission prior to randomization and use of angiotensin receptor blocker or angiotensin converting enzyme inhibitors at admission. Participants in the treatment arm received telmisartan 80 mg bid during 14 days plus standard care. Participants in the control arm received standard care alone. Primary outcome was to achieve significant reductions in plasma levels of C-reactive protein in telmisartan treated Covid-19 patients at day 5 and 8 after randomization. Key secondary outcomes included time to discharge evaluated at 15 days after randomization and admission to ICU and death at 15- and 30-days post randomization. We present here a preliminary report. Results. A total of 78 patients were included in the interim analysis, 40 in the telmisartan and 38 in the control groups. CRP levels at day 5 in the control group were 51.1 +/- 44.8 mg/L (mean +/- SD; n=28) and in the telmisartan group were 24.2 +/- 31.4 mg/L (mean +/- SD; n=32, p<0.05). At day 8, CRP levels were 41.6 +/- 47.6 mg/L (mean +/- SD; n=16) and 9.0 +/- 10.0 mg/L (mean +/- SD; n=13, p < 0.05) in the control and telmisartan groups, respectively. Also, analysis of time to discharge by Kaplan-Meier method showed that telmisartan treated patients had statistically significant lower time to discharge (median time to discharge control group=15 days; telmisartan group=9 days). No differences were observed for ICU admission or death. No significant adverse events related to telmisartan were reported. Conclusions. In the present preliminary report, despite the small number of patients studied, ARB telmisartan, a well-known inexpensive safe antihypertensive drug, administered in high doses, demonstrates anti-inflammatory effects and improved morbidity in hospitalized patients infected with SARS -CoV-2, providing support for its use in this serious pandemia (NCT04355936).

COVID-19 patients are susceptible to hypercoagulability. For the safe return to sports after COVID-19, athletes or individuals wanting to resume physical activity should complete screening for myocardial injury and myocarditis. In addition, patients with COVID-19 are reported at prevalence of 27% to 31% for venous thromboembolic events. The probability of deep vein thrombosis and pulmonary embolism prior to intensive exercise after COVID-19 infection should be considered. The prevalence of cardiac injury is reported at 19%, and the prevalence of deep vein thrombosis and pulmonary embolism is higher than that for myocarditis. Thus, the heart is not the only system needing screened. Examination for myocardial injury and myocarditis are mandatory. Also, deep vein thrombosis, and pulmonary thromboembolism must be considered, and when possible, blood troponin values, D-dimer prothrombin time, and activated partial thromboplastin time levels are determined for COVID-19 infection athletes or any individual before returning to sporting practice or intense physical activity or exercise.