Risk of hospitalization for Covid-19 outpatients treated with various drug regimens in Brazil: Comparative analysis

Abstract

Background For the past few months, HMOs have faced crowded emergency rooms and insufficient hospital and intensive-care-unit beds, all from the worst pandemic of this century, COVID-19. Methods In a large HMO in Brazil, our approach was to allow treating physicians to prescribe antiviral medications immediately at presentation, and prednisone starting on day-6 of symptoms to treat pulmonary inflammation. We implemented this COVID-19 protocol for outpatients and studied 717 consecutive SARS-CoV-2-positive patients age 40 years or older presenting at our emergency rooms. Results Use of hydroxychloroquine (HCQ), prednisone or both significantly reduced hospitalization risk by 50–60%. Ivermectin, azithromycin and oseltamivir did not substantially reduce risk further. Hospitalization risk was doubled for people with type-2 diabetes or obesity, increased by two-thirds for people with heart disease, and by 75% for each decade of age over age 40. Similar magnitudes of reduced risk with HCQ and prednisone use were seen for mortality risk, though were not significant because of only 11 deaths among the 717 patients. No cardiac arrhythmias requiring medication termination were observed for any of the medications. Conclusions This work adds to the growing literature of studies that have found substantial benefit for use of HCQ combined with other agents in the early outpatient treatment of COVID-19, and adds the possibility of steroid use to enhance treatment efficacy.

Rationale for azithromycin in COVID-19: an overview of existing evidence

“…Studies that assess azithromycin monotherapy versus standard of care in hospitalised patients report a wide effect range, from a decreased adjusted OR for mortality of 0.60 (95% CI 0.42 to 0.85) in the retrospective cohort of Albani et al 70 to a non-significantly increased adjusted OR of 1.30 (95% CI 0.65 to 2.64) in Kuderer et al 71 Even more heterogeneity is seen in studies that assess the addition of azithromycin to hydroxychloroquine, with a survival benefit (adjusted HR of 0.294; 95% CI 0.218 to 0.396) seen by Arshad et al, 72 opposed to a significantly increased 30-day mortality (adjusted OR 2.93; 95% CI 1.79 to 4.79) reported again by Kuderer et al 71 In an outpatient setting, Guérin et al 73 reported a significant reduction in the mean time to clinical recovery with azithromycin (12.9 days with azithromycin vs 25.8 days without; p<0.0001). A significant difference in hospitalisation risk was, however, not withheld by Szente et al 74 (adjusted OR for azithromycincontaining vs no-azithromycin-containing regimens 0.93; 95% CI 0.72 to 1.90). The increased mortality reported for hydroxychloroquine-azithromycin combination by Kuderer et al 71 together with increased incidence of adverse events of this regimen in Rosenberg et al 75 and the randomised controlled trial of Cavalcanti et al 76 strengthen the concerns about QT-prolonging drug-drug interactions.…”

“…82 (preprint article, not included in table 1 ) are contradicted by Szente Fonseca et al . 74 At least, with only a short follow-up time needed to assess the risk of hospital admission, prospective data In this context (eg, ATOMIC2, ACTION) 83 84 should soon be able to provide more clarity.…”

“…A significant difference in hospitalisation risk was, however, not withheld by Szente et al . 74 (adjusted OR for azithromycin-containing vs no-azithromycin-containing regimens 0.93; 95% CI 0.72 to 1.90). The increased mortality reported for hydroxychloroquine-azithromycin combination by Kuderer et al 71 together with increased incidence of adverse events of this regimen in Rosenberg et al 75 and the randomised controlled trial of Cavalcanti et al 76 strengthen the concerns about QT-prolonging drug–drug interactions.…”

“…Guérin et al 73 one retrospective study: Guérin et al 73 Studies neutral to AZ six retrospective studies: Kuderer et al 71 Geleris et al 92 Rosenberg et al 75 Ip et al 93 Rodriguez-Molinero et al 94 Lammers et al 95 five retrospective studies: Satlin et al 96 Ip et al 93 Magagnoli et al 97 Ayerbe et al 98 Young et al 99 two retrospective studies: Kuderer et al 71 Szente et al 74 1 RCT: Cavalcanti et al 76 1 RCT: Furtado et al 100 Studies not favouring AZ 2 Retrospective studies: Kuderer et al 71 Rosenberg et al 75 one retrospective study: Kuderer et al 71 1 RCT: Cavalcanti et al 76 PubMed was searched with the search term ('COVID-19' or 'SARS-CoV-2') and 'azithromycin'. A total of 537 titles and/or abstracts were screened.…”

Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: a multi-center observational study

“…As the majority of COVID-19 patients are mildly symptomatic and treated in outpatient settings, our findings justify further exploration of hydroxychloroquine during this pandemic in this population. It should be noted a recent observational cohort study from Brazil found a similar reduction in hospitalization if outpatient hydroxychloroquine was given [25]. If the findings are confirmed, early hydroxychloroquine therapy to a broad outpatient population could have important implications for reducing limited healthcare resources.…”