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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.
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The risk factors for development of fibrotic interstitial lung abnormalities (ILA) after severe COVID-19 are incompletely described and the extent to which CT findings correlate with symptoms and physical function after hospitalization remain unclear. At 4 months after hospitalization, fibrotic ILA was more common in those who underwent mechanical ventilation (72%) than in those who did not (20%). We demonstrate that severity of initial illness, duration of mechanical ventilation, lactate dehydrogenase on admission, and leukocyte telomere length are independent risk factors for fibrotic ILA. These fibrotic changes correlate with lung function, cough and measures of frailty, but not with dyspnea.
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Immune responses to respiratory viruses like SARS-CoV-2 originate and function in the lung, yet assessments of human immunity are often limited to blood. Here, we conducted longitudinal, high-dimensional profiling of paired airway and blood samples from patients with severe COVID-19, revealing immune processes in the respiratory tract linked to disease pathogenesis. Survival from severe disease was associated with increased CD4+T cells and decreased monocyte/macrophage frequencies in the airway, but not in blood. Airway T cells and macrophages exhibited tissue-resident phenotypes and activation signatures, including high level expression and secretion of monocyte chemoattractants CCL2 and CCL3 by airway macrophages. By contrast, monocytes in blood expressed the CCL2-receptor CCR2 and aberrant CD163+ and immature phenotypes. Extensive accumulation of CD163+monocyte/macrophages within alveolar spaces in COVID-19 lung autopsies suggested recruitment from circulation. Our findings provide evidence that COVID-19 pathogenesis is driven by respiratory immunity, and rationale for site-specific treatment and prevention strategies.
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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.
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ObjectiveTo 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). DesignRetrospective manual medical record review. SettingNewYork-Presbyterian/Columbia University Irving Medical Center (NYP/CUIMC), a quaternary care academic medical center in NYC. ParticipantsThe first 1000 consecutive patients with laboratory-confirmed COVID-19. MethodsWe 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 measuresWe describe patient characteristics including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition. ResultsAmong 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. ConclusionsHospitalized 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.
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BackgroundNearly 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. MethodsWe 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. ResultsOf 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. ConclusionsCritical 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.
