Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Cognitive changes in asymptomatic drug-naïve human immunodeficiency virus type 1 clade C infection

Asymptomatic human immunodeficiency virus (HIV) infection is associated with impaired cognitive functioning in both clade B and C infections. The nature of cognitive change longitudinally has not been studied in asymptomatic clade C infection. The present study evaluated changes in neuropsychological functioning over a 21/2-year period in a cohort of HIV-1 clade C-infected asymptomatic individuals from South India. Participants with CD4 counts below 250 were started on highly active antiretroviral therapy (HAART) as per National AIDS Control Organisation (NACO) guidelines and hence excluded. The sample consisted of 68 patients (30 men and 38 women), with a mean age of 29.4 years (SD = 5.6 years) and a mean education of 10.0 years (SD =2.7 years). A comprehensive neuropsychological assessment with 12 tests yielding 21 variables was used to examine cognitive functioning at baseline and subsequently at 6-monthly intervals for five follow-ups. Shift in CD4 and viral load categories measured by the McNemar’s test indicated disease progression. Latent growth curve (LGC) modeling assessed the nature of change in cognition over the 21/2-year study period. Ten variables representing attention, executive functions, and long-term memory fit the LGC model. Excepting visual working memory, the slope was nonsignificant for nine variables, indicating absence of deterioration in cognition over a 21/2-year period. However, CD4 and viral load levels worsened, indicating disease progression. Asymptomatic individuals with HIV-1 clade C infection do not show any significant decline on individual neuropsychological functions over 21/2 years despite disease progression, as evidenced by immune suppression and viral loads