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.

Background Patients hospitalized with COVID-19 are at increased risk of healthcare-associated infections 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 March 2 to May 31, 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 healthcare-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 healthcare-associated infections. Results A total of 3,028 patients were included and accounted for 899 positive clinical cultures. Overall, 516 (17%) with positive cultures met criteria for infection. Community-associated co-infections were identified in 183 (6%) patients, whereas healthcare-associated infections occurred in 350 (12%) patients. 57% of healthcare-associated infections 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. ICU stay, invasive mechanical ventilation, and steroids were associated with healthcare-associated infections. Conclusions Healthcare-associated infections 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 antibiotics.

27A surge of patients with coronavirus disease 2019 presenting to New York City hospitals in 28March 2020 led to a sharp increase blood culture utilization, which overwhelmed the capacity of 29 automated blood culture instruments. We sought to evaluate the utilization and diagnostic yield of blood 30 cultures during the COVID-19 pandemic to determine prevalence and common etiologies of bacteremia, 31 and to inform a diagnostic approach to relieve blood culture overutilization. We performed a retrospective 32 cohort analysis of 88,201 blood cultures from 28,011 patients at a multicenter network of hospitals within 33 New York City to evaluate order volume, positivity rate, time to positivity, and etiologies of positive 34 cultures in COVID-19. Ordering volume increased by 34.8% in the second half of March 2020 compared 35 to the first half of the month. The rate of bacteremia was significantly lower among COVID-19 patients 36 (3.8%) than COVID-19 negative patients (8.0%) and those not tested (7.1%), p < 0.001. COVID-19 37 patients had a high proportion of organisms reflective of commensal skin microbiota, reducing the 38 bacteremia rate to 1.6% when excluded. More than 98% of all positive cultures were detected within 4 39 days of incubation. Bloodstream infections are very rare for COVID-19 patients, which supports the 40 judicious use of blood cultures in the absence of compelling evidence for bacterial co-infection. Clear 41 communication with ordering providers is necessary to prevent overutilization of blood cultures during 42 patient surges, and laboratories should consider shortening the incubation period from 5 days to 4 days, if 43 necessary, to free additional capacity. 44 45 46 47 48

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.

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Background The efficacy and safety of methylprednisolone in mechanically ventilated patients with acute respiratory distress syndrome due to 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 March 1 and April 12, 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±7.45 versus 3.14±6.22; P = 0.044). The probability of extubation was also increased in patients receiving methylprednisolone (45% versus 21%; P = 0.021), and there were no significant differences in mortality (19% versus 36%; P = 0.087). In a multivariable linear regression analysis, only methylprednisolone use was associated with higher number of ventilator-free days (P = 0.045). 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.

The role of procalcitonin in identifying community-associated bacterial infections among patients with coronavirus disease 2019 is not yet established. In 2443 patients with 148 bacterial co-infections, 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 co-infections, but may be useful in excluding bacterial infection.

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.