ABSTRACT
BackgroundMonoclonal antibody and antiviral treatments for COVID-19 disease remain largely unavailable worldwide, and existing monoclonal antibodies may be less active against circulating omicron variants. Although treatment with COVID-19 convalescent plasma (CCP) is promising, randomized clinical trials (RCTs) among outpatients have shown mixed results. MethodsWe conducted an individual participant data meta-analysis from all outpatient CCP RCTs to assess the overall risk reduction for all-cause hospitalizations by day 28 in all participants who had transfusion initiated. Relevant trials were identified by searching MEDLINE, Embase, MedRxiv, WHO, Cochrane Library, and Web of Science from January 2020 to September 2022. ResultsFive included studies from four countries enrolled and transfused 2,620 adult patients. Comorbidities were present in 1,795 (69%). The anti-Spike or virus neutralizing antibody titer range across all trials was broad. 160 (12.2%) of 1315 control patients were hospitalized, versus 111 (8.5%) of 1305 CCP-treated patients, yielding a 3.7% (95%CI: 1.3%-6.0%; p=.001) ARR and 30.1% RRR for all-cause hospitalization. The effect size was greatest in those with both early transfusion and high titer with a 7.6% ARR (95%CI: 4.0%-11.1%; p=.0001) accompanied by at 51.4% RRR. No significant reduction in hospitalization was seen with treatment > 5 days after symptom onset or in those receiving CCP with antibody titers below the median titer. ConclusionsAmong outpatients with COVID-19, treatment with CCP reduced the rate of all-cause hospitalization. CCP may be most effective when given within 5 days of symptom onset and when antibody titer is higher. Key PointsWhile the outpatient COVID-19 randomized controlled trial meta-analysis indicated heterogeneity in participant risk factors and convalescent plasma, the combined CCP efficacy for reducing hospitalization was significant, improving with transfusion within 5 days of symptom onset and high antibody neutralization levels.
ABSTRACT
During pandemics, out-of-hospital treatments reduce the health system burden. Controversies persist regarding the best treatment options for COVID-19 outpatients at risk for hospitalization. We assembled data from 47 randomized controlled trials investigating 51 distinct interventions in more than 60,000 outpatients until October 2022 with the endpoint of hospitalization. These trials, largely performed in unvaccinated cohorts during pre-Omicron waves, mostly targeted populations with at least one risk factor for COVID-19 hospitalization. Grouping by class, the COVID-19 convalescent plasma (CCP) (OR=0.69 [95% CI=0.53 to 0.9]), anti-Spike monoclonal antibodies (OR=0.32 [95% CI=0.24-0.42]) and small molecule antivirals (OR=0.57 [95% CI=0.3-1.09]) each had comparable efficacy for hospital relative risk reduction dependent on intervention dose and timing. Repurposed drugs had lower efficacy. The recent Omicron sublineages (XBB and BQ.1.1) in vitro resistance to monoclonal antibodies suggests a pressing need to reevaluate CCP recommendations for COVID-19 outpatients at risk for hospitalization, especially in constrained medical resource settings.