Among 1376 patients with Covid-19 admitted to a New York City hospital, 59% were treated with hydroxychloroquine. Patients selected for treatment were more severely ill. After adjustment for ...patients’ baseline characteristics, there was no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04; 95% CI, 0.82 to 1.32).
In a randomized, double-blind, placebo-controlled phase 3 trial of the ChAdOx1 nCoV-19 vaccine in over 32,000 participants from the United States, Chile, and Peru, the incidence of serious adverse ...effects was low (including no cases of vaccine-induced immune thrombotic thrombocytopenia) and the vaccine efficacy was 74%. Efficacy was documented in a range of demographic subgroups.
Abstract
We describe the characteristics of 31 people living with human immunodeficiency virus hospitalized for severe acute respiratory syndrome coronavirus 2 infection. All patients were on ...antiretroviral therapy and virologically suppressed at the time of admission. Clinical course and outcomes were similar to those reported in other hospitalized cohorts.
VRC01 is an HIV-1 CD4 binding site broadly neutralizing antibody (bnAb) that is active against a broad range of HIV-1 primary isolates in vitro and protects against simian-human immunodeficiency ...virus (SHIV) when delivered parenterally to nonhuman primates. It has been shown to be safe and well tolerated after short-term administration in humans; however, its clinical and functional activity after longer-term administration has not been previously assessed.
HIV Vaccine Trials Network (HVTN) 104 was designed to evaluate the safety and tolerability of multiple doses of VRC01 administered either subcutaneously or by intravenous (IV) infusion and to assess the pharmacokinetics and in vitro immunologic activity of the different dosing regimens. Additionally, this study aimed to assess the effect that the human body has on the functional activities of VRC01 as measured by several in vitro assays. Eighty-eight healthy, HIV-uninfected, low-risk participants were enrolled in 6 United States clinical research sites affiliated with the HVTN between September 9, 2014, and July 15, 2015. The median age of enrollees was 27 years (range, 18-50); 52% were White (non-Hispanic), 25% identified as Black (non-Hispanic), 11% were Hispanic, and 11% were non-Hispanic people of diverse origins. Participants were randomized to receive the following: a 40 mg/kg IV VRC01 loading dose followed by five 20 mg/kg IV VRC01 doses every 4 weeks (treatment group 1 T1, n = 20); eleven 5 mg/kg subcutaneous (SC) VRC01 (treatment group 3 T3, n = 20); placebo (placebo group 3 P3, n = 4) doses every 2 weeks; or three 40 mg/kg IV VRC01 doses every 8 weeks (treatment group 2 T2, n = 20). Treatment groups T4 and T5 (n = 12 each) received three 10 or 30 mg/kg IV VRC01 doses every 8 weeks, respectively. Participants were followed for 32 weeks after their first VRC01 administration and received a total of 249 IV infusions and 208 SC injections, with no serious adverse events, dose-limiting toxicities, nor evidence for anti-VRC01 antibodies observed. Serum VRC01 levels were detected through 12 weeks after final administration in all participants who received all scheduled doses. Mean peak serum VRC01 levels of 1,177 μg/ml (95% CI: 1,033, 1,340) and 420 μg/ml (95% CI: 356, 494) were achieved 1 hour after the IV infusion series of 30 mg/kg and 10 mg/kg doses, respectively. Mean trough levels at week 24 in the IV infusion series of 30 mg/kg and 10 mg/kg doses, respectively, were 16 μg/ml (95% CI: 10, 27) and 6 μg/ml (95% CI: 5, 9) levels, which neutralize a majority of circulating strains in vitro (50% inhibitory concentration IC50 > 5 μg/ml). Post-infusion/injection serum VRC01 retained expected functional activity (virus neutralization, antibody-dependent cellular cytotoxicity, phagocytosis, and virion capture). The limitations of this study include the relatively small sample size of each VRC01 administration regimen and missing data from participants who were unable to complete all study visits.
VRC01 administered as either an IV infusion (10-40 mg/kg) given monthly or bimonthly, or as an SC injection (5 mg/kg) every 2 weeks, was found to be safe and well tolerated. In addition to maintaining drug concentrations consistent with neutralization of the majority of tested HIV strains, VRC01 concentrations from participants' sera were found to avidly capture HIV virions and to mediate antibody-dependent cellular phagocytosis, suggesting a range of anti-HIV immunological activities, warranting further clinical trials.
Clinical Trials Registration: NCT02165267.
The B.1.1.529/Omicron variant of SARS-CoV-2 was only recently detected in southern Africa, but its subsequent spread has been extensive, both regionally and globally
. It is expected to become ...dominant in the coming weeks
, probably due to enhanced transmissibility. A striking feature of this variant is the large number of spike mutations
that pose a threat to the efficacy of current COVID-19 vaccines and antibody therapies
. This concern is amplified by the findings of our study. Here we found that B.1.1.529 is markedly resistant to neutralization by serum not only from patients who recovered from COVID-19, but also from individuals who were vaccinated with one of the four widely used COVID-19 vaccines. Even serum from individuals who were vaccinated and received a booster dose of mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies against all known epitope clusters on the spike protein, we noted that the activity of 17 out of the 19 antibodies tested were either abolished or impaired, including ones that are currently authorized or approved for use in patients. Moreover, we also identified four new spike mutations (S371L, N440K, G446S and Q493R) that confer greater antibody resistance on B.1.1.529. The Omicron variant presents a serious threat to many existing COVID-19 vaccines and therapies, compelling the development of new interventions that anticipate the evolutionary trajectory of SARS-CoV-2.
Background and Aims
Coronavirus disease 2019 (COVID‐19) has been associated with acute liver injury (ALI) manifested by increased liver enzymes in reports worldwide. Prevalence of liver injury and ...associated clinical characteristics are not well defined. We aim to identify the prevalence of and risk factors for development of COVID‐19‐associated ALI in a large cohort in the United States.
Approach and Results
In this retrospective cohort study, all patients who underwent SARS‐CoV‐2 testing at three hospitals in the NewYork‐Presbyterian network were assessed. Of 3,381 patients, 2,273 tested positive and had higher initial and peak alanine aminotransferase (ALT) than those who tested negative. ALI was categorized as mild if ALT was greater than the upper limit of normal (ULN) but <2 times ULN, moderate if ALT was between 2 and 5 times the ULN, and severe if ALT was >5 times the ULN. Among patients who tested positive, 45% had mild, 21% moderate, and 6.4% severe liver injury (SLI). In multivariable analysis, severe ALI was significantly associated with elevated inflammatory markers, including ferritin (odds ratio OR, 2.40; P < 0.001) and interleukin‐6 (OR, 1.45; P = 0.009). Patients with SLI had a more severe clinical course, including higher rates of intensive care unit admission (69%), intubation (65%), renal replacement therapy (RRT; 33%), and mortality (42%). In multivariable analysis, peak ALT was significantly associated with death or discharge to hospice (OR, 1.14; P = 0.044), controlling for age, body mass index, diabetes, hypertension, intubation, and RRT.
Conclusions
ALI is common in patients who test positive for SARS‐CoV‐2, but is most often mild. However, among the 6.4% of patients with SLI, a severe disease course should be anticipated.
The identification of the Omicron (B.1.1.529.1 or BA.1) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Botswana in November 2021
immediately caused concern owing to the ...number of alterations in the spike glycoprotein that could lead to antibody evasion. We
and others
recently reported results confirming such a concern. Continuing surveillance of the evolution of Omicron has since revealed the rise in prevalence of two sublineages, BA.1 with an R346K alteration (BA.1+R346K, also known as BA.1.1) and B.1.1.529.2 (BA.2), with the latter containing 8 unique spike alterations and lacking 13 spike alterations found in BA.1. Here we extended our studies to include antigenic characterization of these new sublineages. Polyclonal sera from patients infected by wild-type SARS-CoV-2 or recipients of current mRNA vaccines showed a substantial loss in neutralizing activity against both BA.1+R346K and BA.2, with drops comparable to that already reported for BA.1 (refs.
). These findings indicate that these three sublineages of Omicron are antigenically equidistant from the wild-type SARS-CoV-2 and thus similarly threaten the efficacies of current vaccines. BA.2 also exhibited marked resistance to 17 of 19 neutralizing monoclonal antibodies tested, including S309 (sotrovimab)
, which had retained appreciable activity against BA.1 and BA.1+R346K (refs.
). This finding shows that no authorized monoclonal antibody therapy could adequately cover all sublineages of the Omicron variant, except for the recently authorized LY-CoV1404 (bebtelovimab).
Objective To identify demographic and clinical factors predictive of having a missed opportunity (MO) for HIV screening. Design Retrospective cohort study. Methods Electronic medical records were ...queried for individuals newly diagnosed with HIV in different sites within a large urban academic medical center in New York City between 2018 and 2022. The primary outcome was having one or more MO for HIV screening within the institution, defined as any encounter at which screening was not performed in the 365 days preceding the HIV diagnosis. Results Over one third of new diagnoses had at least one MO in the preceding year. Older individuals, cisgender women and those assigned female sex at birth, and heterosexual individuals were more likely to have at least one MO. An initial CD4 < 200 cells/ul was more likely among men who have sex with women specifically. Most MOs occurred in the emergency department and outpatient settings, with minimal HIV prevention discussions documented during each MO. Conclusions These findings suggest that populations perceived to be at lower risk for HIV are more likely to have MOs and possibly late diagnoses, and that universal HIV screening must be implemented into the workflows of emergency department and outpatient settings to facilitate early diagnosis and reduce the incidence of HIV.
In an efficacy trial, 2504 persons at high risk for HIV-1 acquisition received either a DNA prime–recombinant adenovirus type 5 boost (DNA/rAd5) vaccine or placebo. The vaccine regimen did not reduce ...either HIV-1 acquisition or viral load.
The epidemic infection caused by the human immunodeficiency virus type 1 (HIV-1) is now in its fourth decade, with an estimated 2.5 million new infections occurring annually worldwide.
1
The number of newly infected persons, although diminishing, outpaces the number of patients who initiate antiretroviral therapy. Despite a number of successful prevention interventions that have been reported, including preexposure prophylaxis and treatment as prevention,
2
–
9
ultimate control of the HIV epidemic will most likely come only with the development of a safe and effective preventive vaccine.
This goal has proved to be elusive. Of the efficacy trials of HIV vaccines that . . .
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