Early Introduction and Community Transmission of SARS-CoV-2 Omicron Variant, New York, New York, USA.

The Omicron variant of SARS-CoV-2 has become dominant in most countries and has raised significant global health concerns. As a global commerce center, New York, New York, USA, constantly faces the risk for multiple variant introductions of SARS-CoV-2. To elucidate the introduction and transmission of the Omicron variant in the city of New York, we created a comprehensive genomic and epidemiologic analysis of 392 Omicron virus specimens collected during November 25-December 11, 2021. We found evidence of 4 independent introductions of Omicron subclades, including the Omicron subclade BA.1.1 with defining substitution of R346K in the spike protein. The continuous genetic divergence within each Omicron subclade revealed their local community transmission and co-circulation in New York, including both household and workplace transmissions supported by epidemiologic evidence. Our study highlights the urgent need for enhanced genomic surveillance and effective response planning for better prevention and management of emerging SARS-CoV-2 variants.

Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection.

BACKGROUND: Patients with multidrug-resistant human immunodeficiency virus type 1 (HIV-1) infection have limited treatment options. Lenacapavir is a first-in-class capsid inhibitor that showed substantial antiviral activity in a phase 1b study. METHODS: In this phase 3 trial, we enrolled patients with multidrug-resistant HIV-1 infection in two cohorts, according to the change in the plasma HIV-1 RNA level between the screening and cohort-selection visits. In cohort 1, patients were first randomly assigned in a 2:1 ratio to receive oral lenacapavir or placebo in addition to their failing therapy for 14 days; during the maintenance period, starting on day 15, patients in the lenacapavir group received subcutaneous lenacapavir once every 6 months, and those in the placebo group received oral lenacapavir, followed by subcutaneous lenacapavir; both groups also received optimized background therapy. In cohort 2, all the patients received open-label oral lenacapavir with optimized background therapy on days 1 through 14; subcutaneous lenacapavir was then administered once every 6 months starting on day 15. The primary end point was the percentage of patients in cohort 1 who had a decrease of at least 0.5 log10 copies per milliliter in the viral load by day 15; a key secondary end point was a viral load of less than 50 copies per milliliter at week 26. RESULTS: A total of 72 patients were enrolled, with 36 in each cohort. In cohort 1, a decrease of at least 0.5 log10 copies per milliliter in the viral load by day 15 was observed in 21 of 24 patients (88%) in the lenacapavir group and in 2 of 12 patients (17%) in the placebo group (absolute difference, 71 percentage points; 95% confidence interval, 35 to 90). At week 26, a viral load of less than 50 copies per milliliter was reported in 81% of the patients in cohort 1 and in 83% in cohort 2, with a least-squares mean increase in the CD4+ count of 75 and 104 cells per cubic millimeter, respectively. No serious adverse events related to lenacapavir were identified. In both cohorts, lenacapavir-related capsid substitutions that were associated with decreased susceptibility developed in 8 patients during the maintenance period (6 with M66I substitutions). CONCLUSIONS: In patients with multidrug-resistant HIV-1 infection, those who received lenacapavir had a greater reduction from baseline in viral load than those who received placebo. (Funded by Gilead Sciences; CAPELLA ClinicalTrials.gov number, NCT04150068.).

SARS-CoV-2 Continuous Genetic Divergence and Changes in Multiplex RT-PCR Detection Pattern on Positive Retesting Median 150 Days after Initial Infection.

Being in the epicenter of the COVID-19 pandemic, our lab tested 193,054 specimens for SARS-CoV-2 RNA by diagnostic multiplex reverse transcription polymerase chain reaction (mRT-PCR) starting in March 2020, of which 17,196 specimens resulted positive. To investigate the dynamics of virus molecular evolution and epidemiology, whole genome amplification (WGA) and Next Generation Sequencing (NGS) were performed on 9516 isolates. 7586 isolates with a high quality were further analyzed for the mutation frequency and spectrum. Lastly, we evaluated the utility of the mRT-PCR detection pattern among 26 reinfected patients with repeat positive testing three months after testing negative from the initial infection. Our results show a continuation of the genetic divergence in viral genomes. Furthermore, our results indicate that independent mutations in the primer and probe regions of the nucleocapsid gene amplicon and envelope gene amplicon accumulate over time. Some of these mutations correlate with the changes of detection pattern of viral targets of mRT-PCR. Our data highlight the significance of a continuous genetic divergence on a gene amplification-based assay, the value of the mRT-PCR detection pattern for complementing the clinical diagnosis of reinfection, and the potential for WGA and NGS to identify mutation hotspots throughout the entire viral genome to optimize the design of the PCR-based gene amplification assay.

Fatal case of disseminated cryptococcal infection and meningoencephalitis in the setting of prolonged glucocorticoid use in a Covid-19 positive patient.

Based on the RECOVERY trial, glucocorticoids have become the mainstay of treatment for COVID-19, thus increasing the risk of opportunistic infections. We report a case of disseminated Cryptococcus neoformans with documented meningoencephalitis in a patient with severe COVID-19 in the setting of prolonged glucocorticoid administration with poor outcome likely due to adrenal involvement.