Azithromycin for mild-to-moderate COVID-19 – Authors' reply

We thank Jigar Patel and colleagues for their comments. The mean duration of symptoms at enrolment was 5·77 days (SD 3·49) in the azithromycin group 6·27 (3·55) standard care group. 19 (13%) 147 participants 21 (14%) 148 had more than 10 randomisation. Most COVID-19-related deaths occur due to sudden, late respiratory decompensation, peaking day 14 after symptom onset.1Ruan Q Yang K Wang W Jiang L Song J Clinical predictors mortality COVID-19 based on an analysis data 150 patients from Wuhan, China.Intensive Care Med. 2020; 46: 846-848Crossref PubMed Scopus (3063) Google Scholar Azithromycin postulated have both antiviral anti-inflammatory properties, it presumed that latter might potential efficacy against decompensation. Eligible were deemed appropriate initial ambulatory management. By this definition, which applied uniformly all centres, we excluded people with severe disease (ie, those requiring supplemental oxygen) enrolment. Thoracic imaging not a prerequisite enrolment, but done most (265 [89%] 297) baseline as part routine clinical assessment. electronic case report form ensured randomisation occurred sequentially within few minutes, pathways rapid assessment discharge hospital care. To avoid failure detect clinically significant effect underdosing, selected highest dose already licensed UK any indication; namely, 500 mg daily recommended Lyme disease. This is known be well tolerated sufficient cover period during effects could beneficial. protocol2Hinks TSC Barber VS Black et al.A multi-centre open-label two-arm randomised superiority trial versus usual COVID-19: study protocol ATOMIC2 trial.Trials. 21: 718Crossref (16) antibiotics considered potentially relevant or properties follow-up. Other including β-lactams been taken various indications, treatment suspected bacterial pneumonia, they would expected confounders outcome interest COVID-19. Our strict definition full compliance administration first 4 h ingestion least 80% doses. A completed required two tablets, therefore, 24 tablets (22/28 only 78·6% doses, does reach compliance). 76 (52%) who achieved underestimation, excludes 20 whom rates unknown. Even 51 (35%) suboptimal took median six (IQR 2–17), equivalent 3 days, entire dosing schedule used PRINCIPLE trial. has long half-life approximately 72 h, lower concentrations detectable 30 days3Serisier DJ Risks population antimicrobial resistance associated chronic macrolide use inflammatory airway diseases.Lancet Respir 2013; 1: 262-274Summary Full Text PDF (117) marked accumulation granulocytes.2Hinks three compliers do number each reported taking 13 did having remaining adherence issues. Therefore, exposed drug several days. cited because explains rationale design references alternative concurrent studies. These studies targeted different phases shorter our study; individually, unable address early activities. It widely accepted antivirals are effective if given course. In COVID-19, viral load high 5 infection decreases rapidly thereafter, viable virus generally undetectable by 8.4Wolfel R Corman VM Guggemos al.Virological hospitalized COVID-2019.Nature. 581: 465-469Crossref (4286) Mathematical modelling showing benefit remdesivir 9 symptoms5Mehta RM Bansal S Bysani Kalpakam H onset (SORT) interval moderate-to-severe real-world analysis.Int Infect Dis. 2021; 106: 71-77Summary (21) support priority initiation antivirals. findings pragmatic, directly applicable presenting secondary diagnosed such settings many health-care systems globally, results PCR tests frequently unavailable guide immediate management decisions. Nonetheless, there no differences outcomes between intention-to-treat (ITT) ITT positive randomly assigned test swabs). therefore confident validity exclude described, particularly when assessed light concordant other controlled trials, COALTION I, COALITION II, PRINCIPLE, RECOVERY. TSCH received grants Pfizer, University Oxford, Wellcome Trust, Guardians Beit Fellowship, National Institute Health Research (NIHR) Oxford Biomedical Centre (BRC) conduct personal fees Astra Zeneca, TEVA, Peer Voice, outside submitted work. mild-to-moderate (ATOMIC2): open-label, trialIn managed without admission, adding reduce risk subsequent admission death. Full-Text Open AccessAzithromycin COVID-19Azithromycin evaluated its Timothy C Hinks colleagues1 adds value current literature, like share