Race and Remdesivir: Examination of Clinical Outcomes in a Racially and Ethnically Diverse Cohort in New York City.

Objective: To compare clinical characteristics and examine in-hospital length of stay (LOS) differences for COVID-19 patients who received remdesivir, by race or ethnicity. Design: Retrospective descriptive analysis comparing cumulative LOS as a proxy of recovery time. Setting: A large academic medical center serving a minoritized community in Northern Manhattan, New York City. Participants: Inpatients (N=1024) who received remdesivir from March 30, 2020-April 20, 2021. Methods: We conducted descriptive analyses among patients who received remdesivir. Patients were described by proxies of social determinants of health (SDOH): race and ethnicity, residence, insurance coverage, and clinical characteristics. We calculated median hospital LOS as the cumulative incidence of hospitalized patients who were discharged alive, and tested differences between groups by using the Gray test. Patients who died or were discharged to hospice were censored at 29 days. Main Outcome Measures: The primary outcome was hospital LOS. The secondary outcome was in-hospital mortality. Results: Median LOS was 11.9 days (95% CI, 10.8-13.2) overall, with Black patients having the shortest (10.0 days, 95% CI, 8.0-13.2) and Asian patients having the longest (16.2 days, 95% CI, 8.3-27.2) LOS. A total of 214 patients (21%) died or were discharged to hospice, ranging from 16.5% to 23.7% of patients who identified as Black and Other (multiracial, biracial, declined), respectively. Conclusions: COVID-19 has disproportionately burdened communities of color. We observed no difference in median LOS between racial or ethnic groups, which supports the notion that the heterogeneous effect of remdesivir in the literature may be explained in part by underrecruitment or participation of Black, Hispanic, and Asian patients in clinical trials.

Characterization of Bacterial and Fungal Infections in Hospitalized Patients With Coronavirus Disease 2019 and Factors Associated With Health Care-Associated Infections.

BACKGROUND: Patients hospitalized with coronavirus disease 2019 (COVID-19) are at increased risk of health care-associated infections (HAIs), especially with prolonged hospital stays. We sought to identify incidence, antimicrobial susceptibilities, and outcomes associated with bacterial/fungal secondary infections in a large cohort of patients with COVID-19. METHODS: We evaluated adult patients diagnosed with COVID-19 between 2 March and 31 May 2020 and hospitalized >24 hours. Data extracted from medical records included diagnoses, vital signs, laboratory results, microbiological data, and antibiotic use. Microbiologically confirmed bacterial and fungal pathogens from clinical cultures were evaluated to characterize community- and health care-associated infections, including describing temporal changes in predominant organisms on presentation and throughout hospitalization. Univariable and multivariable logistic regression analyses were performed to investigate risk factors for HAIs. RESULTS: A total of 3028 patients were included and accounted for 899 positive clinical cultures. Overall, 516 (17%) patients with positive cultures met criteria for infection. Community-associated coinfections were identified in 183 (6%) patients, whereas HAIs occurred in 350 (12%) patients. Fifty-seven percent of HAIs were caused by gram-negative bacteria and 19% by fungi. Antibiotic resistance increased with longer hospital stays, with incremental increases in the proportion of vancomycin resistance among enterococci and ceftriaxone and carbapenem resistance among Enterobacterales. Intensive care unit stay, invasive mechanical ventilation, and steroids were associated with HAIs. CONCLUSIONS: HAIs occur in a small proportion of patients hospitalized with COVID-19 and are most often caused by gram-negative and fungal pathogens. Antibiotic resistance is more prevalent with prolonged hospital stays. Antimicrobial stewardship is imperative in this population to minimize unnecessary broad-spectrum antibiotic use.

What about tocilizumab? A retrospective study from a NYC Hospital during the COVID-19 outbreak.

BACKGROUND: Tocilizumab, an interleukin-6 receptor blocker, has been used in the inflammatory phase of COVID-19, but its impact independent of corticosteroids remains unclear in patients with severe disease. METHODS: In this retrospective analysis of patients with COVID-19 admitted between March 2 and April 14, 2020 to a large academic medical center in New York City, we describe outcomes associated with tocilizumab 400 mg (without methylprednisolone) compared to a propensity-matched control. The primary endpoints were change in a 7-point ordinal scale of oxygenation and ventilator free survival, both at days 14 and 28. Secondary endpoints include incidence of bacterial superinfections and gastrointestinal perforation. Primary outcomes were evaluated using t-test. RESULTS: We identified 33 patients who received tocilizumab and matched 74 controls based on demographics and health measures upon admission. After adjusting for illness severity and baseline ordinal scale, we failed to find evidence of an improvement in hypoxemia based on an ordinal scale at hospital day 14 in the tocilizumab group (OR 2.2; 95% CI, 0.7-6.5; p = 0.157) or day 28 (OR 1.1; 95% CI, 0.4-3.6; p = 0.82). There also was no evidence of an improvement in ventilator-free survival at day 14 (OR 0.8; 95% CI, 0.18-3.5; p = 0.75) or day 28 (OR 1.1; 95% CI, 0.1-1.8; p = 0.23). There was no increase in secondary bacterial infection rates in the tocilizumab group compared to controls (OR 0.37; 95% CI, 0.09-1.53; p = 0.168). CONCLUSIONS: There was no evidence to support an improvement in hypoxemia or ventilator-free survival with use of tocilizumab 400 mg in the absence of corticosteroids. No increase in secondary bacterial infections was observed in the group receiving tocilizumab.

Post-acute COVID-19 syndrome.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.

Limited Utility of Procalcitonin in Identifying Community-Associated Bacterial Infections in Patients Presenting with Coronavirus Disease 2019.

The role of procalcitonin in identifying community-associated bacterial infections among patients with coronavirus disease 2019 is not yet established. In 2,443 patients of whom 148 had bacterial coinfections, mean procalcitonin levels were significantly higher with any bacterial infection (13.16 ± 51.19 ng/ml; P = 0.0091) and with bacteremia (34.25 ± 85.01 ng/ml; P = 0.0125) than without infection (2.00 ± 15.26 ng/ml). Procalcitonin (cutoff, 0.25 or 0.50 ng/ml) did not reliably identify bacterial coinfections but may be useful in excluding bacterial infection.

Clinical Outcomes Associated With Methylprednisolone in Mechanically Ventilated Patients With COVID-19.

BACKGROUND: The efficacy and safety of methylprednisolone in mechanically ventilated patients with acute respiratory distress syndrome resulting from coronavirus disease 2019 (COVID-19) are unclear. In this study, we evaluated the association between use of methylprednisolone and key clinical outcomes. METHODS: Clinical outcomes associated with the use of methylprednisolone were assessed in an unmatched, case-control study; a subset of patients also underwent propensity-score matching. Patients were admitted between 1 March and 12 April, 2020. The primary outcome was ventilator-free days by 28 days after admission. Secondary outcomes included extubation, mortality, discharge, positive cultures, and hyperglycemia. RESULTS: A total of 117 patients met inclusion criteria. Propensity matching yielded a cohort of 42 well-matched pairs. Groups were similar except for hydroxychloroquine and azithromycin use, which were more common in patients who did not receive methylprednisolone. Mean ventilator-free days were significantly higher in patients treated with methylprednisolone (6.21 ±â€…7.45 vs 3.14 ±â€…6.22; P = .044). The probability of extubation was also increased in patients receiving methylprednisolone (45% vs 21%; P = .021), and there were no significant differences in mortality (19% vs 36%; P = .087). In a multivariable linear regression analysis, only methylprednisolone use was associated with a higher number of ventilator-free days (P = .045). The incidence of positive cultures and hyperglycemia were similar between groups. CONCLUSIONS: Methylprednisolone was associated with increased ventilator-free days and higher probability of extubation in a propensity-score matched cohort. Randomized, controlled studies are needed to further define methylprednisolone use in patients with COVID-19.

Carbapenemase-producing Enterobacterales causing secondary infections during the COVID-19 crisis at a New York City hospital.

BACKGROUND: Patients with COVID-19 may be at increased risk for secondary bacterial infections with MDR pathogens, including carbapenemase-producing Enterobacterales (CPE). OBJECTIVES: We sought to rapidly investigate the clinical characteristics, population structure and mechanisms of resistance of CPE causing secondary infections in patients with COVID-19. METHODS: We retrospectively identified CPE clinical isolates collected from patients testing positive for SARS-CoV-2 between March and April 2020 at our medical centre in New York City. Available isolates underwent nanopore sequencing for rapid genotyping, antibiotic resistance gene detection and phylogenetic analysis. RESULTS: We identified 31 CPE isolates from 13 patients, including 27 Klebsiella pneumoniae and 4 Enterobacter cloacae complex isolates. Most patients (11/13) had a positive respiratory culture and 7/13 developed bacteraemia; treatment failure was common. Twenty isolates were available for WGS. Most K. pneumoniae (16/17) belonged to ST258 and encoded KPC (15 KPC-2; 1 KPC-3); one ST70 isolate encoded KPC-2. E. cloacae isolates belonged to ST270 and encoded NDM-1. Nanopore sequencing enabled identification of at least four distinct ST258 lineages in COVID-19 patients, which were validated by Illumina sequencing data. CONCLUSIONS: While CPE prevalence has declined substantially in New York City in recent years, increased detection in patients with COVID-19 may signal a re-emergence of these highly resistant pathogens in the wake of the global pandemic. Increased surveillance and antimicrobial stewardship efforts, as well as identification of optimal treatment approaches for CPE, will be needed to mitigate their future impact.

Bacteremia and Blood Culture Utilization during COVID-19 Surge in New York City.

A surge of patients with coronavirus disease 2019 (COVID-19) presenting to New York City hospitals in March 2020 led to a sharp increase in blood culture utilization, which overwhelmed the capacity of automated blood culture instruments. We sought to evaluate the utilization and diagnostic yield of blood cultures during the COVID-19 pandemic to determine prevalence and common etiologies of bacteremia and to inform a diagnostic approach to relieve blood culture overutilization. We performed a retrospective cohort analysis of 88,201 blood cultures from 28,011 patients at a multicenter network of hospitals within New York City to evaluate order volume, positivity rate, time to positivity, and etiologies of positive cultures in COVID-19. Ordering volume increased by 34.8% in the second half of March 2020 compared to the level in the first half of the month. The rate of bacteremia was significantly lower among COVID-19 patients (3.8%) than among COVID-19-negative patients (8.0%) and those not tested (7.1%) (P < 0.001). COVID-19 patients had a high proportion of organisms reflective of commensal skin microbiota, which, when excluded, reduced the bacteremia rate to 1.6%. More than 98% of all positive cultures were detected within 4 days of incubation. Bloodstream infections are very rare for COVID-19 patients, which supports the judicious use of blood cultures in the absence of compelling evidence for bacterial coinfection. Clear communication with ordering providers is necessary to prevent overutilization of blood cultures during patient surges, and laboratories should consider shortening the incubation period from 5 days to 4 days, if necessary, to free additional capacity.

Breast conservation surgery versus total mastectomy among women with localized breast cancer in Soweto, South Africa.

PURPOSE: Breast conserving surgery (BCS) has become the preferred surgical option for the management of patients with nonmetastatic breast cancer in high-income countries. However, little is known about the distribution and determinants of BCS in low-and middle-income countries, especially those with high HIV prevalence. METHODS: We compared demographic and clinical characteristics of female patients who received BCS and those who received total mastectomy (TM) for nonmetastatic invasive carcinoma of the breast in Soweto, South Africa, 2009-2011. We also developed a multivariable logistic regression model of predictors of type of surgery. RESULTS: Of 445 patients, 354 (80%) underwent TM and 91 (20%) BCS. Of 373 patients screened for HIV, 59 (15.8%) tested positive. Eighty-two of 294 patients with stage I/II disease (28%), but just 9 of 151 (6%) with stage III disease had BCS (p<0.001). All women who received BCS (except for seven who received completion mastectomy within 6 weeks of BCS) and 235 (66.4%) women who received TM were referred for radiation therapy (RT). In our multivariable analysis, age group 50-59 years (OR = 2.28, 95% CI = 1.1-4.8) and ≥70 years (OR = 9.55, 95% CI = 2.9-31.2) vs. age group <40 years, stage at diagnosis (stage II (OR = 3.79, 95% CI = 1.6-8.2) and stage III (OR = 27.8, 95% CI = 9.0-78.8) vs. stage 1, HIV (HIV positive (OR = 3.19, 95% CI = 1.3-7.9) vs. HIV negative) and HER2-enriched subtype (OR = 3.50, 95% CI = 1.2-10.1) vs. triple negative were independently associated with TM. CONCLUSION: TM was more common than BCS among patients with nonmetastatic breast cancer in Soweto, not only among patients with locally advanced disease at diagnosis, but also among women with stage I and II disease.

An analysis of the relationship between metastases and cachexia in lung cancer patients.

Weight loss and hematogenous metastases are poor prognosis factors in lung cancer patients that can but do not necessarily co-occur. We retrospectively investigated the clinical association between cachexia, tumor characteristics (such as metastatic burden and mutational status), and treatment in lung cancer patients. The medical records of 394 lung cancer patients from two institutions (Columbia University, USA and Tohoku University, Japan) were reviewed. Information collected included the presence of cachexia, histologic subtype, tumor stage, number of metastases, mutation status, treatment, and survival. Descriptive statistics were performed. Only stage IV patients exhibited >5% weight loss (0.8%, 2.2%, 3.6%, and 5.1%, for stages I to IV; P = 0.0001). Patients with metastases developed cachexia more often than patients without metastases independent of treatment (6.0% and 7.1% weight loss in patients with metastases vs. 2.5% and 2.0% in patients without metastases, before [P = 0.0001] and after [P < 0.0001] treatment, respectively). The change in number of metastatic sites over time correlated with increasing weight loss (5.2%, 10.6%, 13.4%, and 13.4%, for an increase of 0, 1, 2, and ≥3 metastatic sites, from initial diagnosis to the endpoint; P < 0.0001). Patients with cachexia had worse survival than patients without cachexia (hazard ratio, 2.94; 95% confidence interval, 2.08-4.16; P < 0.0001). Tumors with mutated KRAS were associated with an increased risk of weight loss (11.4% weight loss in patients with mutated KRAS vs. 6.0% in patients with wild-type KRAS; P = 0.0011). Our findings suggest that the capabilities of lung cancer to metastasize and cause cachexia might be linked intrinsically and are independent of treatments administered. KRAS-mutated tumors were more commonly associated with cachexia.