The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

Background While people who inject drugs (PWID) are vulnerable to the adverse outcomes of events like COVID-19, little is known regarding the impact of the current pandemic on PWID. We examine how COVID-19 has affected PWID in New York City across four domains: substance use, risk behaviors, mental health, and service utilization. Methods As part of a randomized trial to improve access to HCV treatment for PWID, we recruited 165 participants. Eligibility criteria included detectable HCV RNA and recent drug injection. The present cross-sectional analysis is based on a subsample of 106 participants. We compared responses between two separate samples: 60 participants interviewed prior to the pandemic (pre-COVID-19 sample) and 46 participants interviewed during the pandemic (COVID-19 sample). We also assessed differences by study group [accessible care (AC) and usual care (UC)]. Results Compared to the pre-COVID-19 sample, those interviewed during COVID-19 reported higher levels of mental health issues, syringe reuse, and alcohol consumption and greater reductions in syringe-service programs and buprenorphine utilization. In the analysis conducted by study group, the UC group reported significantly higher injection risk behaviors and lower access to buprenorphine treatment during COVID-19, while during the same period, the AC group reported lower levels of substance use and injection risk behaviors. Conclusion The current study provides insight on how COVID-19 has negatively affected PWID. Placing dispensing machines of harm-reduction supplies in communities where PWID live and increasing secondary exchange, mobile services, and mail delivery of supplies may help maintain access to lifesaving supplies during big events, such as COVID-19. Trial registration ClinicalTrials.gov NCT03214679. Registered July 11 2017. https://clinicaltrials.gov/ct2/show/NCT03214679.

With a rising incidence of COVID-19–associated morbidity and mortality worldwide, it is critical to elucidate the innate and adaptive immune responses that drive disease severity. We performed longitudinal immune profiling of peripheral blood mononuclear cells from 45 patients and healthy donors. We observed a dynamic immune landscape of innate and adaptive immune cells in disease progression and absolute changes of lymphocyte and myeloid cells in severe versus mild cases or healthy controls. Intubation and death were coupled with selected natural killer cell KIR receptor usage and IgM+ B cells and associated with profound CD4 and CD8 T-cell exhaustion. Pseudo-temporal reconstruction of the hierarchy of disease progression revealed dynamic time changes in the global population recapitulating individual patients and the development of an eight-marker classifier of disease severity. Estimating the effect of clinical progression on the immune response and early assessment of disease progression risks may allow implementation of tailored therapies.

IMPORTANCETo achieve hepatitis C elimination, treatment programs need to engage, treat, and cure people who inject drugs.OBJECTIVE To compare a low-threshold, nonstigmatizing hepatitis C treatment program that was colocated at a syringe service program (accessible care) with facilitated referral to local clinicians through a patient navigation program (usual care). DESIGN, SETTING, AND PARTICIPANTSThis single-site randomized clinical trial was conducted at the Lower East Side Harm Reduction Center, a syringe service program in New York, New York, and included 167 participants who were hepatitis C virus RNA-positive and had injected drugs during the prior 90 days. Participants enrolled between July 2017 and March 2020. Data were analyzed after all patients completed 1 year of follow-up (after March 2021).INTERVENTIONS Participants were randomized 1:1 to the accessible care or usual care arm. MAIN OUTCOMES AND MEASURESThe primary end point was achieving sustained virologic response within 12 months of enrollment. RESULTS Among the 572 participants screened, 167 (mean [SD] age, 42.0 [10.6] years; 128 (77.6%) male, 36 (21.8%) female, and 1 (0.6) transgender individuals; 8 (4.8%) Black, 97 (58.5%) Hispanic, and 53 (32.1%) White individuals) met eligibility criteria and were enrolled, with 2 excluded postrandomization (n = 165). Baseline characteristics were similar between the 2 arms. In the intention-to-treat analysis, 55 of 82 participants (67.1%) in the accessible care arm and 19 of 83 participants (22.9%) in the usual care arm achieved a sustained virologic response (P < .001). Loss to follow-up (12.2% [accessible care] and 16.9% [usual care]; P = .51) was similar in the 2 arms. Of the participants who received therapy, 55 of 64 (85.9%) and 19 of 22 (86.3%) achieved a sustained virologic response in the accessible care and usual care arms, respectively (P = .96). Significantly more participants in the accessible care arm achieved all steps in the care cascade, with the greatest attrition in the usual care arm seen in referral to hepatitis C virus clinician and attending clinical visit. CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, among people who inject drugs with hepatitis C infection, significantly higher rates of cure were achieved using the accessible care model that focused on low-threshold, colocated, destigmatized, and flexible hepatitis C care compared with facilitated referral. To achieve hepatitis C elimination, expansion of treatment programs that are specifically geared toward engaging people who inject drugs is paramount.

This article proposes a strategy for primary care providers to begin treating patients with hepatitis C virus (HCV). We are motivated by the need to expand HCV treatment and by developments that have simplified treatment for most patients. This article presents 5 steps to achieving quality HCV treatment in the primary care setting: (1) accurate diagnosis via reflex testing; (2) risk stratification and identifying comorbidities via pretreatment evaluation; (3) simple, once-daily, pan-genotypic HCV treatment regimens; (4) minimized on-treatment monitoring: and (5) posttreatment monitoring and high-quality care for comorbidities such as cirrhosis and injection drug use. We provide indications for referral to specialists: notably children, patients with genotype 3 and cirrhosis, advanced liver or kidney disease, previous treatment failures, drug interactions with recommended regimens, and hepatitis B co-infection. Finally, potential barriers for providers are discussed, as well as further research findings and policy interventions that can promote HCV treatment in the primary care setting. We believe that a substantial portion of patients with HCV can be treated safely and effectively by nonspecialists and that the engagement of primary care providers is critical to efforts to end the HCV epidemic.