Long-Term Follow up of Renal and Other Acute Organ Failure in Survivors of Critical Illness Due to Covid-19.

BACKGROUND: Little is known about the long-term health sequelae and outcomes of various organ failures in ICU survivors of Covid-19. The aim of our research was to study the characteristics of 120-day ICU survivors of the initial pandemic surge and report their long term (>6 months) outcomes. METHODS: We conducted a telephone questionnaire-based follow up study of 120- day survivors of Covid-19 admitted to ICUs at Montefiore Medical Center, Bronx, NY from 3/10/2020 to 4/11/2020. The study period was 2 months (11/1/2020-12/31/2020). RESULTS: 126 out of 300 (42%) survived to 120-days post-hospital discharge. The median age of survivors was 54 (47-61) years. Seventy-eight (62%) patients developed acute kidney injury (AKI); thirty-five (44.9%) of them required renal replacement therapy (RRT). One hundred-five (83.3%) required invasive mechanical ventilation; ten of them required tracheotomy. 103 (81.7%) completed the telephone questionnaire-based study, at a median (IQR) of 216.5 (200-234.5) days after hospital discharge. 29 (28.2%) patients reported persistent shortness of breath, 24, (23.3%) complained of persistent cough, and persistent anosmia in 9 (8.8%). AKI resolved completely in 58 (74.4%) patients. Of 35 AKI patients who required initiation of RRT during hospitalization, 27 (77%) were liberated from RRT and 20 (57%) had resolution of AKI. Of 20 patients without AKI resolution, 12 developed chronic kidney disease, whereas 8 still require RRT. Thirty-three (32.4%) patients developed post-traumatic stress disorder (PTSD) and 10 (11.8%) reported major depression. Many of the patients (68%) regained baseline functional status. Readmissions occurred in 22.3% patients within first 6 months after discharge. CONCLUSION: Persistent symptoms of long Covid have been reported in ICU survivors of Covid-19 for extended durations. Outcomes of Covid-19 associated acute kidney injury are excellent. There is a high incidence of PTSD and depression in COVID-19 ICU survivors. Functional outcomes are good, but these patients remain at increased risk of hospital readmission.

Thromboembolic Events and Role of Point of Care Ultrasound in Hospitalized Covid-19 Patients Needing Intensive Care Unit Admission.

BACKGROUND: Covid-19 associated coagulopathy (CAC) is associated with prothrombotic state and thromboembolism. However, true incidence of thromboembolic events is difficult to determine in the ICU setting. The aim of our study was to investigate the cumulative incidence of thromboembolic events in Covid-19 patients needing intensive care unit (ICU) admission and assessing the utility of point of care ultrasound (POCUS) to screen for and diagnose lower extremity deep venous thrombosis (DVT). METHODS: We conducted a prospective observational study between April 22nd and May 26th, 2020 where all adult patients with the diagnosis of Covid-19 pneumonia admitted to 8 ICUs of Montefiore Medical Center were included. POCUS exam was performed on all patients at day 1 of ICU admission and at day 7 and 14 after the first exam. RESULTS: The primary outcome was to study the cumulative incidence of thromboembolic events in Covid-19 patients needing ICU admission. A total of 107 patients were included. All patients got POCUS exam on day 1 in the ICU, 62% got day 7 and 41% got day 14 exam. POCUS diagnosed 17 lower extremity DVTs on day 1, 3 new on day 7 and 1 new on day 14. Forty patients developed 52 thromboembolic events, with the rate of 37.3%. We found a high 45-day cumulative incidence of thromboembolic events of 37% and a high 45-day cumulative incidence of lower and upper extremity DVT of 21% and 10% respectively. Twelve (30%) patients had failure of therapeutic anticoagulation. Occurrence of a thromboembolic event was not associated with a higher risk of mortality (HR 1.08, p value = .81). CONCLUSIONS: Covid-19 patients in ICU have a high cumulative incidence of thromboembolic events, but not associated with higher mortality. POCUS is an excellent tool to help screen and diagnose DVT during a pandemic.

Role of NADPH oxidase versus neutrophil proteases in antimicrobial host defense.

NADPH oxidase is a crucial enzyme in mediating antimicrobial host defense and in regulating inflammation. Patients with chronic granulomatous disease, an inherited disorder of NADPH oxidase in which phagocytes are defective in generation of reactive oxidant intermediates (ROIs), suffer from life-threatening bacterial and fungal infections. The mechanisms by which NADPH oxidase mediate host defense are unclear. In addition to ROI generation, neutrophil NADPH oxidase activation is linked to the release of sequestered proteases that are posited to be critical effectors of host defense. To definitively determine the contribution of NADPH oxidase versus neutrophil serine proteases, we evaluated susceptibility to fungal and bacterial infection in mice with engineered disruptions of these pathways. NADPH oxidase-deficient mice (p47(phox-/-)) were highly susceptible to pulmonary infection with Aspergillus fumigatus. In contrast, double knockout neutrophil elastase (NE)(-/-)×cathepsin G (CG)(-/-) mice and lysosomal cysteine protease cathepsin C/dipeptidyl peptidase I (DPPI)-deficient mice that are defective in neutrophil serine protease activation demonstrated no impairment in antifungal host defense. In separate studies of systemic Burkholderia cepacia infection, uniform fatality occurred in p47(phox-/-) mice, whereas NE(-/-)×CG(-/-) mice cleared infection. Together, these results show a critical role for NADPH oxidase in antimicrobial host defense against A. fumigatus and B. cepacia, whereas the proteases we evaluated were dispensable. Our results indicate that NADPH oxidase dependent pathways separate from neutrophil serine protease activation are required for host defense against specific pathogens.