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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.

NADPH oxidase plays a critical role in antimicrobial host defense, as evident in chronic granulomatous disease (CGD), an inherited disorder of the NADPH oxidase characterized by severe bacterial and fungal diseases. Invasive aspergillosis and other moulds are the major cause of mortality in CGD. We also learn from CGD patients that NADPH oxidase plays an important role in regulating infl ammation; CGD patients are prone to developing infl ammatory diseases such as infl ammatory bowel disease, obstructive granulomata of the genitourinary tract, and hypersensitivity pneumonitis. Indeed, the NADPH oxidase plays an essential role in calibrating innate and T-cell responses to control the growth of inhaled fungi while protecting against excessive and injurious infl ammation. Knowledge gained on the mechanisms by which NADPH oxidase kills fungi and regulates infl ammation may lead to new therapeutics for CGD and will have broad relevance to understanding host-pathogen interactions between mammals and ubiquitous moulds to which we are continually exposed.

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.