The emergence of recombinant viruses is a threat to public health, as recombination may integrate variant-specific features that together result in escape from treatment or immunity. The selective advantages of recombinant SARS-CoV-2 isolates over their parental lineages remain unknown. We identified a Delta-Omicron (AY.45-BA.1) recombinant in an immunosuppressed transplant recipient treated with monoclonal antibody Sotrovimab. The single recombination breakpoint is located in the spike N-terminal domain adjacent to the Sotrovimab binding site. While Delta and BA.1 are sensitive to Sotrovimab neutralization, the Delta-Omicron recombinant is highly resistant. To our knowledge, this is the first described instance of recombination between circulating SARS-CoV-2 variants as a functional mechanism of resistance to treatment and immune escape.
Abstract Background In-hospital antimicrobial use among COVID-19 patients is widespread due to perceived bacterial and fungal co-infections. We aim to describe the incidence of these co-infections and antimicrobial use in patients hospitalized with COVID-19 to elucidate data for guiding effective antimicrobial use in this population. Methods This retrospective study included all patients admitted with COVID-19 from January 1, 2020, to February 1, 2021 at any of the three teaching hospitals of the NYU Langone Health system. Variables of interest were extracted from the health system’s de-identified clinical database. The nadir of hospital admissions between the first and second peaks of hospital admissions in the dataset was used to delineate the First Wave and Late Pandemic periods of observation. A cut-off of 48 hours after admission was used to differentiate Co-infections and Secondary infections respectively among isolates of clinically relevant bacterial or fungal pathogens in blood or sputum samples. Population statistics are presented as median with interquartile range (IQR) or total numbers with percentages. Results 663 of 7,213 (9.2%) inpatients were found to have a positive bacterial or fungal culture of the respiratory tract or blood during the entire course of their initial admission at our hospitals for COVID-19. Positive respiratory cultures were found in 437 (6.1%) patients, with 94 (1.3%) being collected within 48 hours of admission. Blood culture positivity occurred in 333 patients (4.6%), with 115 (1.6%) identified within 48 hours of admission. Infection-free survival decreased with duration of hospitalization, with rate of secondary infections steadily rising after the second week of hospitalization as seen in Figure 1. 70.2% of inpatients received antimicrobials for a median duration of 6 antimicrobial days (IQR 3.0 – 12.0) per patient. A higher proportion of patients received antimicrobials in the first wave than in the late pandemic period (82.6% vs. 51.8%). Table 1. Table 2 Figure 1 Infection free survival represented as duration of admission in days on the X-axis, and proportion of admitted patients remaining infection-free in the Y-axis. The blue line represents blood cultures and the orange line represents sputum cultures. Conclusion There was a very low incidence of co-infection with SARS-CoV-2 infection at admission. A longer duration of hospitalization was associated with an increased risk of secondary infections. Antimicrobial use far exceeded the true incidence and detection of co-infections in these patients. Disclosures All Authors: No reported disclosures
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.
Abstract Rationale The Infectious Diseases Society of America has identified the use of SARS-CoV-2 genomic load for prognostication purposes as a key research question. Objectives We explored the SARS-CoV-2 genomic load as a risk factor for adverse patient outcomes. Methods A retrospective cohort study among adult patients admitted to the hospital between March 31 st to April 10 th , 2020 with COVID-19 pneumonia was conducted. We segregated patients into 3 genomic load groups: low (Cycle threshold (Ct) ≥35), intermediate (25<Ct<35), and high (Ct≤ 25) using real-time polymerase chain reaction. Measurements A composite outcome of death, intubation, and/or extracorporeal membrane oxygenation was used. Secondary outcomes included the severity of pneumonia on admission, as measured by the Pneumonia Severity Index (PSI). Main Results Of 457 patients with COVID-19 pneumonia from March 31 st to April 10 th , 2020, 316 met inclusion criteria. Included patients were followed for a median of 25days (IQR 21-28). High genomic load at presentation was associated with higher Charlson Comorbidity Index (p=0.005), transplant recipient status (p<0.001), and duration of illness less than 7 days (p=0.005). Importantly, patients with high genomic load were more likely to reach the primary endpoint (p=0.001), and had higher PSI scores on admission (p=0.03). In multivariate analysis, a high genomic load remained an independent predictor of the primary outcome. Results remained significant in sensitivity analyses. Conclusions Our findings suggest that a high genomic load of SARS-CoV-2 at the time of admission is an independent predictor of adverse outcomes, that above and beyond age, comorbidity, and severity of illness on presentation, may be used to risk-stratify patients, and call for a quantitative diagnostic assay to become available.
With the coronavirus disease 2019 (COVID-19) pandemic, rates of in-hospital antimicrobial use increased due to perceived bacterial and fungal coinfections along with COVID-19. We describe the incidence of these coinfections and antimicrobial use in patients hospitalized with COVID-19 to help guide effective antimicrobial use in this population.This study was conducted in 3 tertiary-care referral university teaching hospitals in New York City.This multicenter retrospective observational cohort study involved all patients admitted with COVID-19 from January 1, 2020, to February 1, 2021. Variables of interest were extracted from a de-identified data set of all COVID-19 infections across the health system. Population statistics are presented as median with interquartile range (IQR) or proportions with 95% confidence intervals (CIs) as indicated.Among 7,209 of patients admitted with COVID-19, 663 (9.2%) had a positive culture from the respiratory tract or blood sometime during their initial hospital admission. Positive respiratory cultures occurred found in 449 (6.2%) patients, and 20% were collected within 48 hours of admission. Blood culture positivity occurred in 334 patients (4.6%), with 33.5% identified within 48 hours of admission. A higher proportion of patients received antimicrobials in the first wave than in the later pandemic period (82.4% vs 52.0%). Antimicrobials were prescribed to 70.1% of inpatients, with a median of 6 antimicrobial days per patient. Infection-free survival decreased over the course of hospitalization.We detected a very low incidence of coinfection with COVID-19 at admission. A longer duration of hospitalization was associated with an increased risk of coinfection. Antimicrobial use far exceeded the true incidence and detection of coinfections in these patients.
Rhabdomyolysis is a syndrome caused by injury to skeletal muscle. There is limited data of rhabdomyolysis in the elderly. The objective of this study is to investigate demographic data, etiologies, laboratory values, prognostic factors, and mortality of rhabdomyolysis in the geriatric population. A 4-years retrospective chart review study was conducted. Our inclusion criteria were age above 65 years and creatinine kinase level excess five times of normal upper limit. Among 167 patients, 47.3% were male. The median age at diagnosis was 80.11 (66-101) years. The duration of follow up in the study ranged from 0 to 48 months. Fall (with or without immobilization) was the most frequent cause of rhabdomyolysis in 56.9%. The mean baseline glomerular filtration rate (GFR), GFR at diagnosis, and peak decline in GFR was 76.94, 48.96, and 54.41 cc/min respectively. The mean CK at diagnosis and peak CK was 5097.22 and 6320.07. There were 45 deaths (21%) over the span of 4 years. Multivariate analysis demonstrated that number of medications pre-admission (Meds No.), peak decline in GFR, and acute kidney injury (AKI) are independent predictors for overall survival for rhabdomyolysis in the elderly. To our knowledge, this is the first epidemiological study of rhabdomyolysis in the elderly. Falls (with and without immobilization) were the most common etiology. Meds No. (>8), peak decline in GFR (<30 cc/min), and evidence of AKI are associated with shorter overall survival and can serve as potential independent prognostic markers for rhabdomyolysis in elderly patients.
The highest risk of opportunistic infections is from 1 to 6 months post-transplant. We report a rare case of Pneumocystis jirovecii pneumonia in a renal transplant recipient only on maintenance immunosuppression eleven years after transplant without concomitant CMV infection or recent episodes of graft rejection.
