Macrolides for the treatment of COVID-19: a living, systematic review

Abstract

Objective This living, systematic review aims to provide a timely, rigorous, and continuously updated summary of the evidence available on the role of macrolides for treating patients with COVID-19. Design A living, systematic review. Database We conducted searches in the centralized repository L·OVE (Living OVerview of Evidence). L·OVE is a platform that maps PICO questions to evidence from the Epistemonikos database. In response to the COVID-19 emergency, L·OVE was adapted to expand the range of evidence it covers and customized to group all COVID-19 evidence in one place. Today it is maintained through regular searches in 39 databases. Methods We included randomized trials evaluating the effect of macrolides — as monotherapy or in combination with other drugs — versus placebo or no treatment in patients with COVID-19. Randomized trials evaluating macrolides in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomized studies in COVID-19 were searched in case we found no direct evidence from randomized trials. Two reviewers independently screened each study for eligibility, extracted data, and assessed the risk of bias. Measures included all-cause mortality; the need for invasive mechanical ventilation; extracorporeal membrane oxygenation, length of hospital stay, respiratory failure, serious adverse events, time to SARS-CoV-2 RT-PCR negativity. We applied the GRADE approach to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it every time the conclusions change or whenever there are substantial updates. Results The search in the L·OVE platform retrieved 424 references. We considered 260 as potentially eligible and were reviewed in full texts. We included one randomized clinical trial that evaluated the use of azithromycin in combination with hydroxychloroquine compared to hydroxychloroquine alone in hospitalized patients with COVID 19. The estimates for all outcomes evaluated resulted in insufficient power to draw conclusions. The quality of the evidence for the main outcomes was low to very low. Conclusions Macrolides in the management of patients with COVID 19 showed no beneficial effects compared to standard of care. The evidence for all outcomes is inconclusive. Larger trials are needed to determine the effects of macrolides on pulmonary and other outcomes in COVID-19 patients. Systematic review registration PROSPERO Registration number: CRD42020181032 Protocol preprint DOI: 10.31219/osf.io/rvp59

Antibiotic Prescription and In-Hospital Mortality in COVID-19: A Prospective Multicentre Cohort Study

“…Azithromycin, ceftriaxone, and broad-spectrum antibiotics used to treat community-acquired pneumonia were the most commonly prescribed antibiotic regimens during the pandemic, probably due to the concern of bacterial co-infection [ 15 , 16 ]. Initially, azithromycin was also prescribed due to its supposed immunomodulatory and antiviral action, but later studies have shown no additional effect on survival or clinical outcomes compared to the standard of care [ 17 , 18 , 19 ]. In addition, regarding its antimicrobial effects, in Romania, as rates of macrolide resistance of S. pneumoniae are high, azithromycin is of little value in treating potential community bacterial co- or superinfections.…”

COVID-19 and the Importance of Being Prepared: A Multidisciplinary Strategy for the Discovery of Antivirals to Combat Pandemics

“…For example, Ginsenoside has shown both antiviral [ 51 , 52 , 53 ] and anti-COVID-19 [ 54 ] activities. Josamycin is considered to have anti-COVID-19 activity [ 55 , 56 ] while Pepstatin A has been reported as antiviral [ 57 , 58 , 59 ] as well as a SARS-CoV-2 protease inhibitor [ 60 , 61 , 62 ]. As far as we know, no antiviral activity has been reported for Docetaxel, Molport-046-067-769, and Molport-046-568-802.…”

Characteristics of Living Systematic Review for COVID-19

“…In the production phase of LSR, most of the LSRs registered 16–22 , 25 , 26 , 28–33 , 35 , 37 , 39–42 , 45–62 , 65–67 , 69–73 , 76–79 (81.2%) and wrote the protocol 16–35 , 37 , 39–43 , 45–67 , 69–73 , 76–79 (92.2%) before the study started. Less than one third of the LSRs searched the Chinese database 16–18 , 23 , 25 , 34 , 35 , 43 , 46 , 48 , 57 , 62–64 , 70 , 79 (25%), and less than half of the LSRs searched the preprint database 16 , 20 , 21 , 23–26 , 28 , 37 , 39 , 40 , 43 , 45 , 46 , 48 , 51 , 53 , 57 , 62–64 , 67 , 68 , 73 , 76 , 77 , 79 (42.2%), and two-thirds of the LSRs searched 12 COVID-19 databases 16 , 17 , 20–23 , 27 , 30 , 32 , 33 , 37–42 , 44–46 , 48 , 49 ...…”