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Background Outpatient monoclonal antibodies are no longer effective and antiviral treatments for coronavirus disease 2019 (COVID-19) disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma (CCP) is promising, clinical trials among outpatients have shown mixed results. Methods We conducted an individual participant data meta-analysis from outpatient trials to assess the overall risk reduction for all-cause hospitalizations by day 28 in transfused participants. Relevant trials were identified by searching Medline, Embase, medRxiv, World Health Organization COVID-19 Research Database, Cochrane Library, and Web of Science from January 2020 to September 2022. Results Five included studies from 4 countries enrolled and transfused 2620 adult patients. Comorbidities were present in 1795 (69%). The virus neutralizing antibody dilutional titer levels ranged from 8 to 14 580 in diverse assays. One hundred sixty of 1315 (12.2%) control patients were hospitalized, versus 111 of 1305 (8.5%) CCP-treated patients, yielding a 3.7% (95% confidence interval [CI], 1.3%–6.0%; P =.001) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titer with a 7.6% absolute risk reduction (95% CI, 4.0%–11.1%; P =.0001) accompanied by at 51.4% relative risk reduction. 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. Conclusions Among outpatients with COVID-19, treatment with CCP reduced the rate of all-cause hospitalization and may be most effective when given within 5 days of symptom onset and when antibody titer is higher. [ABSTRACT FROM AUTHOR]

Background No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19. Methods Multicenter open-label, randomized, controlled trial conducted in Catalonia, Spain, between 17 March and 26 May 2020. Patients recently diagnosed with <5-day of symptom onset were assigned to receive HCQ (800 mg on day 1 followed by 400 mg once daily for 6 days) or usual care. Outcomes were reduction of viral load in nasopharyngeal swabs up to 7 days after treatment start, disease progression up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days. Results A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD, 12.6), mean viral load at baseline was 7.90 log10 copies/mL (SD, 1.82), and median time from symptom onset to randomization was 3 days. No differences were found in the mean reduction of viral load at day 3 (−1.41 vs −1.41 log10 copies/mL in the control and intervention arm, respectively) or at day 7 (−3.37 vs −3.44). Treatment did not reduce risk of hospitalization (7.1% control vs 5.9% intervention) nor shorten the time to complete resolution of symptoms (12 days, control vs 10 days, intervention). No relevant adverse events were reported. Conclusions In patients with mild COVID-19, no benefit was observed with HCQ beyond the usual care. [ABSTRACT FROM AUTHOR]

Background Treponema pallidum subsp pertenue and Haemophilus ducreyi are causative agents of cutaneous ulcer (CU) in yaws-endemic regions in the tropics. However, a significant proportion of CU patients remain polymerase chain reaction (PCR) negative for both bacterial agents. We aimed to identify potential additional etiological agents of CU in a yaws-endemic region. Methods This population-based cohort study included children in Lihir Island (Papua New Guinea) examined during a yaws eradication campaign in October 2013–October 2014. All consenting patients with atraumatic exudative ulcers of >1 cm diameter were enrolled. Lesional swabs were collected for real-time PCR testing for T. pallidum subsp pertenue and H. ducreyi. We then performed shotgun whole DNA metagenomics sequencing on extracted DNA and taxonomically assigned shotgun sequences using a human microbiome reference. Results Sequence data were available for 122 samples. Shotgun sequencing showed high classification agreement relative to PCR testing (area under the curve for T. pallidum/H. ducreyi was 0.92/0.85, respectively). Clustering analysis of shotgun data revealed compositional clusters where the dominant species (median relative abundance ranged from 32% to 66%) was H. ducreyi (23% of specimens), T. pallidum subsp pertenue (16%), Streptococcus dysgalactiae (12%), Arcanobacterium haemolyticum (8%), and Corynebacterium diphtheriae (8%). Sample clustering derived from ulcer microbial composition did not show geographical patterns. Conclusions These data suggest a diverse etiology of skin ulcers in yaws-endemic areas, which may help design more accurate diagnostic tools and more effective antimicrobial treatment approaches to the cutaneous ulcer syndrome. [ABSTRACT FROM AUTHOR]