Delta-Omicron recombinant escapes therapeutic antibody neutralization.

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.

Coinfections and antimicrobial use in patients hospitalized with coronavirus disease 2019 (COVID-19) across a single healthcare system in New York City: A retrospective cohort study.

Background and objective: 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. Setting: This study was conducted in 3 tertiary-care referral university teaching hospitals in New York City. Methods: 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. Results: 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. Conclusions: 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.

Failure of an Approximately Six Week Course of Tafenoquine to Completely Eradicate Babesia microti Infection in an Immunocompromised Patient.

Although tafenoquine was highly effective for eliminating microscopically detectable parasitemia in mouse models of Babesia microti infection, all of the mice which were assessed developed a relapse of infection, except for those which had been treated concomitantly with artesunate. We report an immunocompromised patient with a similar relapse of parasitemia despite a 46-day course of tafenoquine treatment. More data on whether a longer duration of tafenoquine treatment or using a higher maintenance dose, versus adding a second drug to the regimen, will prevent relapse when tafenoquine is used to treat a highly immunocompromised patient with babesiosis should be investigated.

Delta-Omicron recombinant escapes therapeutic antibody neutralization.

Background: The emergence of recombinant viruses is a threat to public health. Recombination of viral variants may combine variant-specific features that together catalyze viral escape from treatment or immunity. The selective advantages of recombinant SARS-CoV-2 isolates over their parental lineages remain unknown. Methods: Multi-method amplicon and metagenomic sequencing of a clinical swab and the in vitro grown virus allowed for high-confidence detection of a novel recombinant variant. Mutational, phylogeographic, and structural analyses determined features of the recombinant genome and spike protein. Neutralization assays using infectious as well as pseudotyped viruses and point mutants thereof defined the recombinant's sensitivity to a panel of monoclonal antibodies and sera from vaccinated and/or convalescent individuals. Results: A novel Delta-Omicron SARS-CoV-2 recombinant was identified in an unvaccinated, immunosuppressed kidney transplant recipient treated with monoclonal antibody Sotrovimab. The recombination breakpoint is located in the spike N-terminal domain, adjacent to the Sotrovimab quaternary binding site, and results in a 5'-Delta AY.45 and a 3'-Omicron BA.1 mosaic spike protein. Delta and BA.1 are sensitive to Sotrovimab neutralization, whereas the Delta-Omicron recombinant is highly resistant to Sotrovimab, both with and without the RBD resistance mutation E340D. Conclusions: Recombination between circulating SARS-CoV-2 variants can functionally contribute to immune escape. It is critical to validate phenotypes of mosaic viruses and monitor immunosuppressed COVID-19 patients treated with monoclonal antibodies for the selection of recombinant and immune escape variants. (Funded by NYU, the National Institutes of Health, and others).

Recognizing Cutibacterium acnes as a cause of infectious pericarditis: A case report and review of literature.

Cutibacterium acnes is an anaerobic bacterium commonly thought of as a culture contaminant rather than a pathogen. We present a case of Cutibacterium acnes pericarditis in a 22-year-old immunocompetent woman managed with surgical pericardial window and a 4-week course of penicillin G and review related literature on Cutibacterium acnes pericarditis.

Association of SARS-CoV-2 genomic load trends with clinical status in COVID-19: A retrospective analysis from an academic hospital center in New York City.

The Infectious Diseases Society of America has identified the use of SARS-CoV-2 genomic load for prognostication purposes as a key research question. We designed a retrospective cohort study that included adult patients with COVID-19 pneumonia who had at least 2 positive nasopharyngeal tests at least 24 hours apart to study the correlation between the change in the genomic load of SARS-CoV-2, as reflected by the Cycle threshold (Ct) value of the RT-PCR, with change in clinical status. The Sequential Organ Failure Assessment (SOFA) score was used as a surrogate for patients' clinical status. Among 457 patients with COVID-19 pneumonia between 3/31/2020-4/10/2020, we identified 42 patients who met the inclusion criteria. The median initial SOFA score was 2 (IQR 2-3). 20 out of 42 patients had a lower SOFA score on their subsequent tests. We identified a statistically significant inverse correlation between the change in SOFA score and change in the Ct value with a decrease in SOFA score by 0.05 (SE 0.02; p<0.05) for an increase in Ct values by 1. This correlation was independent of the duration of symptoms. Our findings suggest that an increasing Ct value in sequential tests may be of prognostic value for patients diagnosed with COVID-19 pneumonia.

Treating COVID-19 With Hydroxychloroquine (TEACH): A Multicenter, Double-Blind Randomized Controlled Trial in Hospitalized Patients.

BACKGROUND: 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: 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: A total of 128 patients were included in the intention-to-treat analysis. Baseline demographic, clinical, and laboratory characteristics were similar between the HCQ (n = 67) and placebo (n = 61) arms. At day 14, 11 (16.4%) subjects assigned to HCQ and 6 (9.8%) subjects assigned to placebo met the severe disease progression end point, but this did not achieve statistical significance (P = .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: 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.