ABSTRACT
SARS-CoV-2 infection is associated with a spectrum of acute neurological syndromes. A subset of these syndromes promotes higher in-hospital mortality than is predicted by traditional parameters defining critical care illness. This suggests that deregulation of components of the central and peripheral nervous systems compromises the interplay with systemic cellular, tissue and organ interfaces to mediate numerous atypical manifestations of COVID-19 through impairments in organismal homeostasis. This unique dyshomeostasis syndrome involves components of the ACE-2/1 lifecycles, renin-angiotensin system regulatory axes, integrated nervous system functional interactions and brain regions differentially sculpted by accelerated evolutionary processes and more primordial homeostatic functions. These biological contingencies suggest a mechanistic blueprint to define long-term neurological sequelae and systemic manifestations such as premature aging phenotypes, including organ fibrosis, tissue degeneration and cancer. Therapeutic initiatives must therefore encompass innovative combinatorial agents, including repurposing FDA-approved drugs targeting components of the autonomic nervous system and recently identified products of SARS-CoV-2-host interactions.
ABSTRACT
BACKGROUND: There is limited clinical patient data comparing the first and second waves of the coronavirus disease 2019 (COVID-19) in the United States and the effects of a COVID-19 resurgence on different age, racial and ethnic groups. We compared the first and second COVID-19 waves in the Bronx, New York, among a racially and ethnically diverse population. METHODS: Patients in this retrospective cohort study were included if they had a laboratory-confirmed SARS-CoV-2 infection by a real-time PCR test of a nasopharyngeal swab specimen detected between March 11, 2020, and January 21, 2021. Main outcome measures were critical care, in-hospital acquired disease and death. Patient demographics, comorbidities, vitals, and laboratory values were also collected. FINDINGS: A total of 122,983 individuals were tested for SARS-CoV-2 infection, of which 12,659 tested positive. The second wave was characterized by a younger demographic, fewer comorbidities, less extreme laboratory values at presentation, and lower risk of adverse outcomes, including in-hospital mortality (adj. OR = 0·23, 99·5% CI = 0·17 to 0·30), hospitalization (adj. OR = 0·65, 99·5% CI = 0·58 to 0·74), invasive mechanical ventilation (adj. OR = 0·70, 99·5% CI = 0·56 to 0·89), acute kidney injury (adj. OR = 0·62, 99·5% CI = 0·54 to 0·71), and length of stay (adj. OR = 0·71, 99·5% CI = 0·60 to 0·85), with Black and Hispanic patients demonstrating most improvement in clinical outcomes. INTERPRETATION: The second COVID-19 wave in the Bronx exhibits improved clinical outcomes compared to the first wave across all age, racial, and ethnic groups, with minority groups showing more improvement, which is encouraging news in the battle against health disparities.
ABSTRACT
BACKGROUND: Hospital-acquired liver injury is associated with worse outcomes in COVID-19. This study investigated the temporal progression of clinical variables of in-hospital liver injury in COVID-19 patients. METHODS: COVID-19 patients (n = 1361) were divided into no, mild and severe liver injury (nLI, mLI and sLI) groups. Time courses of laboratory variables were time-locked to liver-injury onset defined by alanine aminotransferase level. Predictors of liver injury were identified using logistic regression. RESULTS: The prevalence of mLI was 39.4% and sLI was 9.2%. Patients with escalated care had higher prevalence of sLI (23.2% vs. 5.0%, p < 0.05). sLI developed 9.4 days after hospitalization. sLI group used more invasive ventilation, anticoagulants, steroids, and dialysis (p < 0.05). sLI, but not mLI, had higher adjusted mortality odds ratio (= 1.37 [95% CI 1.10, 1.70], p = 0.005). Time courses of the clinical variables of the sLI group differed from those of the nLI and mLI group. In the sLI group, alanine aminotransferase, procalcitonin, ferritin, and lactate dehydrogenase showed similar temporal profiles, whereas white-blood-cell count, D-dimer, C-reactive protein, respiration and heart rate were elevated early on, and lymphocyte and SpO2 were lower early on. The top predictors of sLI were alanine aminotransferase, lactate dehydrogenase, respiration rate, ferritin, and lymphocyte, yielding an AUC of 0.98, 0.92, 0.88 and 0.84 at 0, - 1, - 2 and - 3 days prior to onset, respectively. CONCLUSIONS: This study identified key clinical variables predictive of liver injury in COVID-19, which may prove useful for management of liver injury. Late onset of sLI and more aggressive care are suggestive of treatment-related hepatotoxicity.