Faculty Bibliography

BACKGROUND:Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. METHODS:In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168. FINDINGS/RESULTS:Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012). INTERPRETATION/CONCLUSIONS:In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered. FUNDING/BACKGROUND:National Institute of Allergy and Infectious Diseases.

The Covid-19 pandemic has exposed the difficulty of the US public health system to respond effectively to vulnerable subpopulations, causing disproportionate rates of morbidity and mortality. New York Haredi-Orthodox Jewish communities represent a group that have been heavily impacted by Covid-19. Little research has examined their experience or perceptions toward Covid-19 and vaccines. We conducted a cross-sectional, observational study to explore the experience of Covid-19 among Haredim. Paper surveys were self-administered between December 2020 and January 2021 in Haredi neighborhood pediatricians' offices in Brooklyn, New York. Of 102 respondents, 43% reported either a positive SARS-CoV-2 viral or antibody test. Participants trusted their physicians, Orthodox medical organizations, and rabbinic leaders for medical information. Knowledge of Covid-19 transmission and risk was good (69% answered ≥ 4/6 questions correctly). Only 12% of respondents would accept a Covid-19 vaccine, 41% were undecided and 47% were strongly hesitant. Independent predictors of strong vaccine hesitancy included believing natural infection to be better than vaccination for developing immunity (adjusted odds ratio [aOR] 4.28; 95% confidence interval [CI] 1.23-14.86), agreement that prior infection provides a path toward resuming communal life (aOR 4.10; 95% CI 1.22-13.77), and pandemic-related loss of trust in physicians (aOR 5.01; 95% CI 1.05-23.96). The primary disseminators of health information for self-protective religious communities should be stakeholders who understand these groups' unique health needs. In communities with significant Covid-19 experience, vaccination messaging may need to be tailored toward protecting infection-naïve individuals and boosting natural immunity against emerging variants.

This study assesses distress and anxiety symptoms associated with quarantine due to COVID-19 exposure among the first quarantined community in the United States and identifies potential areas of intervention. All participants were directly or peripherally related to "patient 1,"-the first confirmed community-acquired case of COVID-19 in the New York Area. As such, this is a historically significant sample whose experiences highlight a transitional moment from a pre-pandemic to a pandemic period in the United States. In March 2020, an anonymous survey was distributed to 1,250 members of a NYC area community that was under community-wide quarantine orders due to the COVID-19 outbreak. Distress was measured using the Subjective Units of Distress Scale (SUDS) and symptoms of anxiety were measured using the Beck Anxiety Inventory (BAI). A variety of psychosocial predictors relevant to the current crisis were explored. Three hundred and three individuals responded within forty-eight hours of survey distribution. Mean levels of distress in the sample were heightened and sustained, with 69% reporting moderate to severe distress on the SUDS and 53% of the sample reported mild, moderate, or severe anxiety symptoms on the BAI. The greatest percentage of variance of distress and anxiety symptoms was accounted for by modifiable factors amenable to behavioral and psychological interventions.

Background/UNASSIGNED:Effective therapies to combat coronavirus 2019 (COVID-19) are urgently needed. Hydroxychloroquine (HCQ) has in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the clinical benefit of HCQ in treating COVID-19 is unclear. Randomized controlled trials are needed to determine the safety and efficacy of HCQ for the treatment of hospitalized patients with COVID-19. Methods/UNASSIGNED:We conducted a multicenter, double-blind randomized clinical trial of HCQ among patients hospitalized with laboratory-confirmed COVID-19. Subjects were randomized in a 1:1 ratio to HCQ or placebo for 5 days and followed for 30 days. The primary efficacy outcome was a severe disease progression composite end point (death, intensive care unit admission, mechanical ventilation, extracorporeal membrane oxygenation, and/or vasopressor use) at day 14. Results/UNASSIGNED: = .350). There were no significant differences in COVID-19 clinical scores, number of oxygen-free days, SARS-CoV-2 clearance, or adverse events between HCQ and placebo. HCQ was associated with a slight increase in mean corrected QT interval, an increased D-dimer, and a trend toward an increased length of stay. Conclusions/UNASSIGNED:In hospitalized patients with COVID-19, our data suggest that HCQ does not prevent severe outcomes or improve clinical scores. However, our conclusions are limited by a relatively small sample size, and larger randomized controlled trials or pooled analyses are needed.

BACKGROUND:Hepatitis C virus (HCV) is a major public health problem in correctional settings. HCV treatment is often not possible in U.S. jails due to short lengths of stay. Linkage to care is crucial in these settings, but competing priorities complicate community healthcare engagement and retention after incarceration. METHODS:We conducted a single arm clinical trial of a combined transitional care coordination (TCC) and patient navigation intervention and assessed the linkage rate and factors associated with linkage to HCV care after incarceration. RESULTS:During the intervention, 84 participants returned to the community after their index incarceration. Most participants were male and Hispanic, with a history of mental illness and a mean age of 45 years. Of those who returned to the community, 26 (31%) linked to HCV care within a median of 20.5 days; 17 (20%) initiated HCV treatment, 15 (18%) completed treatment, 9 (11%) had a follow-up lab drawn to confirm sustained virologic response (SVR), and 7 (8%) had a documented SVR. Among those with follow-up labs the known SVR rate was (7/9) 78%. Expressing a preference to be linked to the participant's existing health system, being on methadone prior to incarceration, and feeling that family or a loved one were concerned about the participant's wellbeing were associated with linkage to HCV care. Reporting drinking alcohol to intoxication prior to incarceration was negatively associated with linkage to HCV care. CONCLUSION/CONCLUSIONS:We demonstrate that an integrated strategy with combined TCC and patient navigation may be effective in achieving timely linkage to HCV care. Additional multicomponent interventions aimed at treatment of substance use disorders and increasing social support could lead to further improvement. TRIAL REGISTRATION/BACKGROUND:Clinicaltrials.gov NCT04036760 July 30th, 2019 (retrospectively registered).

Background. Despite the high efficacy of PrEP, it continues to be underutilized. We examined the extent to which patients with a documented positive test for STIs were provided PrEP at an urban municipal medical center. Methods. We reviewed data of all patients seen between January 1, 2014 and July 30, 2017 who were > 18 years old and had an initial HIV negative test and >=1 positive test for Chlamydia, Gonorrhea, or Syphilis. We examined PrEP prescription data by gender, race/ethnicity, and clinic location. Differences between groups were compared using Chi-squared analysis and logistic regression. Results. Of 1,142 initially HIV- patients who were identified as having a positive STI result, 52% were female, 89% either Black or Hispanic, with a median age of 40 years (quartiles 30, 47). 58% had Medicare/Medicaid and 34% were self-pay or uninsured (Table 1). Only 25 (2.1%) of 1,142 patients who had >=1 STI test positive were prescribed PrEP. No women received PrEP. Whites (aOR: 21.7 [95% CI:4.4, 107, P < 0.001] and Hispanics (aOR:6.64 [95% CI:1.35, 32.8, P = 0.02] were both more likely to receive PrEP than Blacks, after adjusting for age, sex, marital status, and insurance. All PrEP prescriptions originated from the Medicine, Emergency, or HIV specialty clinics although most STI testing was obtained in Emergency and Obstetrical/Gynecological clinics (Table 2). Conclusion. There were significant missed opportunities for HIV prevention among patients with STIs within the medical center, particularly among Hispanic and Black patients. Enrichment programs to educate providers and increase PrEP prescriptions may have a major impact on expanding HIV prevention, especially for women. (Figure Presented)

Following cessation of continuous Ebola virus (EBOV) transmission within Western Africa, sporadic EBOV disease (EVD) cases continued to re-emerge beyond the viral incubation period. Epidemiological and genomic evidence strongly suggests that this represented transmission from EVD survivors. To investigate whether persistent infections are characterized by ongoing viral replication, we sequenced EBOV from the semen of nine EVD survivors and a subset of corresponding acute specimens. EBOV evolutionary rates during persistence were either similar to or reduced relative to acute infection rates. Active EBOV replication/transcription continued during convalescence, but decreased over time, consistent with viral persistence rather than viral latency. Patterns of genetic divergence suggest a moderate relaxation of selective constraints within the sGP carboxy-terminal tail during persistent infections, but do not support widespread diversifying selection. Altogether, our data illustrate that EBOV persistence in semen, urine, and aqueous humor is not a quiescent or latent infection.