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Background: Identifying subtypes of acute respiratory failure survivors may facilitate patient selection for post-intensive care unit (ICU) follow-up clinics and trials.Methods: We conducted a single-centre prospective cohort study of 185 acute respiratory failure survivors, aged ≥ 65 years. We applied latent class modelling to identify frailty subtypes using frailty phenotype and cognitive impairment measurements made during the week before hospital discharge. We used Fine-Gray competing risks survival regression to test associations between frailty subtypes and recovery, defined as returning to a basic Activities of Daily Living disability count less than or equal to the pre-hospitalisation count within 6 months. We characterised subtypes by pre-ICU frailty (Clinical Frailty Scale score ≥ 5), the post-ICU frailty phenotype, and serum inflammatory cytokines, hormones and exosome proteomics during the week before hospital discharge.Results: We identified five frailty subtypes. The recovery rate decreased 49% across each subtype independent of age, sex, pre-existing disability, comorbidity and Acute Physiology and Chronic Health Evaluation II score (recovery rate ratio: 0.51, 95% CI 0.41 to 0.63). Post-ICU frailty phenotype prevalence increased across subtypes, but pre-ICU frailty prevalence did not. In the subtype with the slowest recovery, all had cognitive impairment. The three subtypes with the slowest recovery had higher interleukin-6 levels (p=0.03) and a higher prevalence of ≥ 2 deficiencies in insulin growth factor-1, dehydroepiandrostersone-sulfate, or free-testosterone (p=0.02). Exosome proteomics revealed impaired innate immunity in subtypes with slower recovery.Conclusions: Frailty subtypes varied by prehospitalisation frailty and cognitive impairment at hospital discharge. Subtypes with the slowest recovery were similarly characterised by greater systemic inflammation and more anabolic hormone deficiencies at hospital discharge. [ABSTRACT FROM AUTHOR]

BACKGROUND: We developed a systematic method of cleaning and calibration-checking for the pneumotachometer tube of the SpiroPro portable spirometer; this method maximized spirometry accuracy in a population-based study in a remote area of Nepal. METHODS: We tested 10 factorycalibrated pneumotachometer tubes. Each use consisted of a full set of spirometry maneuvers, per the American Thoracic Society (ATS) spirometry criteria. RESULTS: The pneumotachometers remained accurate, per the ATS criteria, for 5-9 disinfections, but began to drift toward inaccuracy after the first disinfection. All the pneumotachometers had become inaccurate, per the ATS criteria, after 10 disinfections. CONCLUSIONS: In a remote field setting the SpiroPro pneumotachometer tube can be cleaned and reused 5-9 times before it becomes inaccurate per the ATS criteria. Rigorous rinsing in distilled water and repeated calibration checks, at various flows up to 12 L/s, are essential for precise and accurate spirometry with the SpiroPro. Reusing the SpiroPro pneumotachometer in a remote setting may impose measurement bias. Single use of SpiroPro pneumotachometers, albeit more costly, will provide better data. [ABSTRACT FROM AUTHOR]

Fibrotic-like abnormalities are present in 60% of a single-center, longitudinal, multi-ethnic cohort 3-years after severe COVID-19. They are independently associated with male sex, low BMI, shorter telomere length, increased severity of illness, and mechanical ventilation; Black race and asthma are protective. Participants with fibrotic-like abnormalities are more likely to have reduced diffusion capacity and 6-minute walk distance. Fibrotic-like abnormalities persist but modestly improve over time. Transbronchial biopsies show small airways histopathology, consistent with high prevalence of air trapping in expiration, and infrequent interstitial thickening. This study highlights the need for continued monitoring of patients with persistent fibrosis after severe COVID-19.

Cardiac injury is associated with critical COVID-19, yet its etiology remains debated. To elucidate the pathogenic mechanisms of COVID-19-associated cardiac injury, we conducted a single-center prospective cohort study of 69 COVID-19 decedents. Of six cardiac histopathologic features, microthrombi was the most commonly detected (n=48, 70%). We tested associations of cardiac microthrombi with biomarkers of inflammation, cardiac injury, and fibrinolysis and with in-hospital antiplatelet therapy, therapeutic anticoagulation, and corticosteroid treatment, while adjusting for multiple clinical factors, including COVID-19 therapies. Higher peak ESR and CRP during hospitalization were independently associated with higher odds of microthrombi. Using single nuclei RNA-sequence analysis, we discovered an enrichment of pro-thrombotic/anti-fibrinolytic, extracellular matrix remodeling, and immune-potentiating signaling amongst cardiac fibroblasts in microthrombi-positive COVID-19 hearts relative to microthrombi-negative COVID-19. Non-COVID-19 non-failing hearts were used as reference controls. Our cumulative findings identify the specific transcriptomic changes in cardiac fibroblasts as salient features of COVID-19-associated cardiac microthrombi.

Remdesivir has been granted emergency use authorization for treatment of severe COVID-19. Remdesivir's pricing is based on a presumed reduction of hospital length of stay (LOS) by four days. But the Adaptive COVID-19 Treatment Trial (ACTT-1) that suggested this treatment benefit excluded patients who were expected to be discharged within 72 hours. Perhaps as a result, median time to recovery was unusually long in both arms of the study (15 days vs 11 days). Remdesivir requires a 5-day inpatient stay, so patients who would otherwise be discharged in fewer than 5 days may remain hospitalized to complete treatment while patients who would be discharged between 5 and 8 days, would only have potential reductions in their hospital LOS of 0-3 days. In a retrospective analysis of 1643 adults with severe COVID-19 admitted to Columbia University Medical Center and the Allen community hospital between March 9, 2020 and April 23, 2020, median hospital LOS was 7 (3-14) days. Five-hundred and eighty-six patients (36%) had a LOS of 1-4 days, 384 (23%) had a LOS of 5-8 days, and 673 (41%) were hospitalized for greater than or equal to 9 days. Remdesivir treatment may not provide the LOS reductions that the company relied on when pricing the therapy: 36% of the cohort would need to have LOS prolonged to receive a 5-day course, and only 41% of patients in our cohort had LOS of 9 days or more, meaning they could have their LOS shortened by 4 days and still receive a full Remdesivir course. Further investigation of shorter treatment courses and programs to facilitate outpatient intravenous Remdesivir administration are needed.

Objective: To characterize patients with coronavirus disease 2019 (COVID-19) in a large New York City (NYC) medical center and describe their clinical course across the emergency department (ED), inpatient wards, and intensive care units (ICUs)., Design: Retrospective manual medical record review., Setting: NewYork-Presbyterian/Columbia University Irving Medical Center (NYP/CUIMC), a quaternary care academic medical center in NYC., Participants: The first 1000 consecutive patients with laboratory-confirmed COVID-19., Methods: We identified the first 1000 consecutive patients with a positive RT-SARS-CoV-2 PCR test who first presented to the ED or were hospitalized at NYP/CUIMC between March 1 and April 5, 2020. Patient data was manually abstracted from the electronic medical record., Main Outcome Measures: We describe patient characteristics including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition., Results: Among the first 1000 patients, 150 were ED patients, 614 were admitted without requiring ICU-level care, and 236 were admitted or transferred to the ICU. The most common presenting symptoms were cough (73.2%), fever (72.8%), and dyspnea (63.1%). Hospitalized patients, and ICU patients in particular, most commonly had baseline comorbidities including of hypertension, diabetes, and obesity. ICU patients were older, predominantly male (66.9%), and long lengths of stay (median 23 days; IQR 12 to 32 days); 78.0% developed AKI and 35.2% required dialysis. Notably, for patients who required mechanical ventilation, only 4.4% were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at 3-4 and 9 days. As of April 30, 90 patients remained hospitalized and 211 had died in the hospital., Conclusions: Hospitalized patients with COVID-19 illness at this medical center faced significant morbidity and mortality, with high rates of AKI, dialysis, and a bimodal distribution in time to intubation from symptom onset., Competing Interests: Conflict of Interest Disclosures: All authors have completed the ICMJE uniform disclosure form and declare: no support from any organization for the submitted work; no competing interests with regards to the submitted work. MMS reports grants from Amgen, outside the submitted work. JJC reports personal fees from Allergan, outside the submitted work. RGB reports grants from Alpha1 Foundation and COPD Foundation, outside the submitted work. GH reports grants from Janssen Research, outside the submitted work. The remaining authors MGA, SLB, CLS, JRT, KN, RC, MRB, BPC, NG, PG, AMM, AAP, MSR, NWS, SS, MDS, KN, PAA, FMB, RB, MFC, MIC, LAC, JHD, LBD, SAD, KAE, ZPG, DTG, AAH, NH, SH, LEK, EL, AL, AYS, ACS, ZES, CPS, YX, HWZ, and RL have nothing to disclose.

Background: Nearly 30,000 patients with coronavirus disease-2019 (COVID-19) have been hospitalized in New York City as of April 14th, 2020. Data on the epidemiology, clinical course, and outcomes of critically ill patients with COVID-19 in this setting are needed., Methods: We prospectively collected clinical, biomarker, and treatment data on critically ill adults with laboratory-confirmed-COVID-19 admitted to two hospitals in northern Manhattan between March 2nd and April 1st, 2020. The primary outcome was in-hospital mortality. Secondary outcomes included frequency and duration of invasive mechanical ventilation, frequency of vasopressor use and renal-replacement-therapy, and time to clinical deterioration following hospital admission. The relationship between clinical risk factors, biomarkers, and in-hospital mortality was modeled using Cox-proportional-hazards regression. Each patient had at least 14 days of observation., Results: Of 1,150 adults hospitalized with COVID-19 during the study period, 257 (22%) were critically ill. The median age was 62 years (interquartile range [IQR] 51-72); 170 (66%) were male. Two-hundred twelve (82%) had at least one chronic illness, the most common of which were hypertension (63%; 162/257) and diabetes mellitus (36%; 92/257). One-hundred-thirty-eight patients (54%) were obese, and 13 (5%) were healthcare workers. As of April 14th, 2020, in-hospital mortality was 33% (86/257); 47% (122/257) of patients remained hospitalized. Two-hundred-one (79%) patients received invasive mechanical ventilation (median 13 days [IQR 9-17]), and 54% (138/257) and 29% (75/257) required vasopressors and renal-replacement-therapy, respectively. The median time to clinical deterioration following hospital admission was 3 days (IQR 1-6). Older age, hypertension, chronic lung disease, and higher concentrations of interleukin-6 and d-dimer at admission were independently associated with in-hospital mortality., Conclusions: Critical illness among patients hospitalized with COVID-19 in New York City is common and associated with a high frequency of invasive mechanical ventilation, extra-pulmonary organ dysfunction, and substantial in-hospital mortality.