Outpatient and inpatient anticoagulation therapy and the risk for hospital admission and death among COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. Limited data exist informing the relationship between anticoagulation therapy and risk for COVID-19 related hospitalization and mortality. METHODS: We evaluated all patients over the age of 18 diagnosed with COVID-19 in a prospective cohort study from March 4th to August 27th, 2020 among 12 hospitals and 60 clinics of M Health Fairview system (USA). We investigated the relationship between (1) 90-day anticoagulation therapy among outpatients before COVID-19 diagnosis and the risk for hospitalization and mortality and (2) Inpatient anticoagulation therapy and mortality risk. FINDINGS: Of 6195 patients, 598 were immediately hospitalized and 5597 were treated as outpatients. The overall case-fatality rate was 2•8% (n = 175 deaths). Among the patients who were hospitalized, the inpatient mortality was 13%. Among the 5597 COVID-19 patients initially treated as outpatients, 160 (2.9%) were on anticoagulation and 331 were eventually hospitalized (5.9%). In a multivariable analysis, outpatient anticoagulation use was associated with a 43% reduction in risk for hospital admission, HR (95% CI = 0.57, 0.38-0.86), p = 0.007, but was not associated with mortality, HR (95% CI=0.88, 0.50 - 1.52), p = 0.64. Inpatients who were not on anticoagulation (before or after hospitalization) had an increased risk for mortality, HR (95% CI = 2.26, 1.17-4.37), p = 0.015. INTERPRETATION: Outpatients with COVID-19 who were on outpatient anticoagulation at the time of diagnosis experienced a 43% reduced risk of hospitalization. Failure to initiate anticoagulation upon hospitalization or maintaining outpatient anticoagulation in hospitalized COVID-19 patients was associated with increased mortality risk. FUNDING: No funding was obtained for this study.

"SARS-CoV-2 Infection in Liver Transplant Recipients - Immunosuppression is the Silver Lining?"

BACKGROUND: COVID-19 is associated with higher mortality among patients who have comorbidities. However, evidences related to COVID-19 among post liver transplant recipients are scarce and evolving. METHODS: Adult Indian patients who had undergone liver transplantation at our centre since 2006 and were under regular follow-up, were contacted either telephonically or on email. Data were recorded related to symptoms and diagnosis of COVID-19, need for hospitalization, and need for ICU stay and mortality. RESULTS: Eighty one (3.71%) of the 2182 adult Liver transplant (LT) recipients on regular follow-up reported SARS-CoV-2 infection between 1st April 2020 and 31st May 2021. Mean age was 51.3(±9.8) years, and 74(91.4%) were males. Thirty five (43.2%) patients had one or more comorbidities. Twenty one (25.9%) patients were transplanted less than 1 year ago. Forty four (54.3% ) patients had mild disease only while 23(28.4%) patients had severe COVID-19 disease. Of the 81 patients 14 patients died and overall mortality was 17.3. CONCLUSION: Uncomplicated liver transplant recipients without comorbidities who acquire SARS-CoV-2 do not have poor outcome.

Remdesivir Inhibits Tubulointerstitial Fibrosis in Obstructed Kidneys.

Aim: Kidney impairment is observed in patients with COVID-19. The effect of anti-COVID-19 agent remdesivir on kidneys is currently unknown. We aimed to determine the effect of remdesivir on renal fibrosis and its downstream mechanisms. Methods: Remdesivir and its active nucleoside metabolite GS-441524 were used to treat TGF-ß stimulated renal fibroblasts (NRK-49F) and human renal epithelial (HK2) cells. Vehicle or remdesivir were given by intraperitoneal injection or renal injection through the left ureter in unilateral ureteral obstruction (UUO) mice. Serum and kidneys were harvested. The concentrations of remdesivir and GS-441524 were measured using LC-MS/MS. Renal and liver function were assessed. Renal fibrosis was evaluated by Masson's trichrome staining and Western blotting. Results: Remdesivir and GS-441524 inhibited the expression of fibrotic markers (fibronectin and aSMA) in NRK-49F and HK2 cells. Intraperitoneal injection or renal injection of remdesivir attenuated renal fibrosis in UUO kidneys. Renal and liver function were unchanged in remdesivir treated UUO mice. Two remdesivir metabolites were detected after injection. Phosphorylation of Smad3 that was enhanced in cell and animal models for renal fibrosis was attenuated by remdesivir. In addition, the expression of Smad7, an anti-fibrotic factor, was increased after remdesivir treatment in vitro and in vivo. Moreover, knockdown of Smad7 blocked the antifibrotic effect of GS and RDV on renal cells. Conclusion: Remdesivir inhibits renal fibrosis in obstructed kidneys.

Effect of COVID-19 on Pre-existing Liver disease: What Hepatologist Should Know?

COVID-19 is characterized by predominant respiratory and gastrointestinal symptoms. Liver enzymes derangement is seen in 15-55% of the patients. Advanced age, hypertension, diabetes, obesity, malignancy, and cardiovascular disease predispose them to severe disease and the need for hospitalization. Data on pre-existing liver disease in patients with COVID-19 is limited, and most studies had only 3-8% of these patients. Patients with metabolic dysfunction-associated fatty liver (MAFLD) had shown a 4-6 fold increase in severity of COVID-19, and its severity and mortality increased in patients with higher fibrosis scores. Patients with chronic liver disease had shown that cirrhosis is an independent predictor of severity of COVID-19 with increased hospitalization and mortality. Increase in Child Turcotte Pugh (CTP) score and model for end-stage liver disease (MELD) score increases the mortality in these patients. Few case reports had shown SARS-CoV-2 as an acute event in the decompensation of underlying chronic liver disease. Immunosuppression should be reduced prophylactically in patients with autoimmune liver disease and post-transplantation with no COVID-19. Hydroxychloroquine and remdesivir is found to be safe in limited studies in a patient with cirrhosis and COVID-19. For hepatologists, cirrhosis with COVID-19 is a pertinent issue as the present pandemic will have severe disease in patients with chronic liver disease leading to more hospitalization and decompensation.

Clinical characteristics and outcomes of in-hospital cardiac arrest among patients with and without COVID-19.

AIMS: To define outcomes of patients with COVID-19 compared to patients without COVID-19 suffering in-hospital cardiac arrest (IHCA). MATERIALS AND METHODS: We performed a single-center retrospective study of IHCA cases. Patients with COVID-19 were compared to consecutive patients without COVID-19 from the prior year. Return of spontaneous circulation (ROSC), 30-day survival, and cerebral performance category (CPC) at 30-days were assessed. RESULTS: Fifty-five patients with COVID-19 suffering IHCA were identified and compared to 55 consecutive IHCA patients in 2019. The COVID-19 cohort was more likely to require vasoactive agents (67.3% v 32.7%, p = 0.001), invasive mechanical ventilation (76.4% v 23.6%, p < 0.001), renal replacement therapy (18.2% v 3.6%, p = 0.029) and intensive care unit care (83.6% v 50.9%, p = 0.001) prior to IHCA. Patients with COVID-19 had shorter CPR duration (10 min v 22 min, p = 0.002). ROSC (38.2% v 49.1%, p = 0.336) and 30-day survival (20% v 32.7%, p = 0.194) did not differ. A 30-day cerebral performance category of 1 or 2 was more common among non-COVID patients (27.3% v 9.1%, p = 0.048). CONCLUSIONS: Return of spontaneous circulation and 30-day survival were similar between IHCA patients with and without COVID-19. Compared to previously published data, we report greater ROSC and 30-day survival after IHCA in COVID-19.

The CSN COVID-19 Rapid Response Program.

The coronavirus disease (COVID-19) pandemic has created unprecedented challenges in caring for individuals living with kidney disease. In response to a growing call for up-to-date information and evidence-informed advice, the Canadian Society of Nephrology has established a COVID-19 Rapid Response Team that will leverage existing evidence and national expertise to inform kidney care practices in the COVID-19 era. Given limited published evidence and compressed timelines, formal clinical practice guidelines are not feasible, and we have adopted rapid review methods to instead provide interim guidance across identified priority areas. In this article, we describe the methodological approach that was applied in developing a first iteration of guidance documents addressing clinical and operational aspects of care for patients treated with in-center hemodialysis, home dialysis, those with advanced chronic kidney disease, those with glomerulonephritis, and those with acute kidney injury. We further describe strategies for maintaining ongoing engagement with the renal community to elicit emerging needs and perspectives as the situation unfolds.

Management of Advanced Chronic Kidney Disease During the COVID-19 Pandemic: Suggestions From the Canadian Society of Nephrology COVID-19 Rapid Response Team.

PURPOSE OF PROGRAM: To provide guidance on the management of patients with advanced chronic kidney disease (CKD) not requiring kidney replacement therapy during the COVID-19 pandemic. SOURCES OF INFORMATION: Program-specific documents, pre-existing, and related to COVID-19; documents from national and international kidney agencies; national and international webinars, including webinars that we hosted for input and feedback; with additional information from formal and informal review of published academic literature. METHODS: Challenges in the care of patients with advanced CKD during the COVID-19 pandemic were highlighted within the Canadian Senior Renal Leaders Forum discussion group. The Canadian Society of Nephrology (CSN) developed the COVID-19 rapid response team (RRT) to address these challenges. They identified a lead with expertise in advanced CKD who identified further nephrologists and administrators to form the workgroup. A nation-wide survey of advanced CKD clinics was conducted. The initial guidance document was drafted and members of the workgroup reviewed and discussed all suggestions in detail via email and a virtual meeting. Disagreements were resolved by consensus. The document was reviewed by the CSN COVID-19 RRT, an ethicist and an infection control expert. The suggestions were presented at a CSN-sponsored interactive webinar, attended by 150 kidney health care professionals, for further peer input. The document was also sent for further feedback to experts who had participated in the initial survey. Final revisions were made based on feedback received until April 28, 2020. Canadian Journal of Kidney Health and Disease (CJKHD) editors reviewed the parallel process peer review and edited the manuscript for clarity. KEY FINDINGS: We identified 11 broad areas of advanced CKD care management that may be affected by the COVID-19 pandemic: (1) clinic visit scheduling, (2) clinic visit type, (3) provision of multidisciplinary care, (4) bloodwork, (5) patient education/support, (6) home-based monitoring essentials, (7) new referrals to multidisciplinary care clinic, (8) kidney replacement therapy, (9) medications, (10) personal protective equipment, and (11) COVID-19 risk in CKD. We make specific suggestions for each of these areas. LIMITATIONS: The suggestions in this paper are expert opinion, and subject to the biases associated with this level of evidence. To expedite the publication of this work, a parallel review process was created that may not be as robust as standard arms' length peer-review processes. IMPLICATIONS: These suggestions are intended to provide guidance for advanced CKD directors, clinicians, and administrators on how to provide the best care possible during a time of altered priorities and reduced resources.

Incidence and Risk Factors for Acute Kidney Injury and Its Effect on Mortality in Patients Hospitalized From COVID-19.

OBJECTIVE: To determine the incidence of and risk factors for the development of acute kidney injury (AKI) and investigate the association between AKI and mortality in patients hospitalized with coronavirus disease 2019 (COVID-19) infection. PATIENTS AND METHODS: This retrospective case series includes the first 370 patients consecutively hospitalized with confirmed COVID-19 illness between March 10, 2020, and May 13, 2020, at a 242-bed teaching hospital. To determine independent associations between demographic factors, comorbid conditions, and AKI incidence, multivariable logistic regression models were used to estimate odds ratios adjusted for clinical covariates. RESULTS: Median age of patients was 71 (interquartile range, 59-82) years and 44.3% (145 of 327) were women. Patients with AKI were significantly older with a higher comorbid condition burden and mortality rate (58.1% [104 0f 179] vs 19.6% [29 of 148]; P<.001) when compared with those without AKI. Increasing age, chronic kidney disease, hyperlipidemia, and being of African American descent showed higher odds of AKI. Patients with AKI had significantly higher odds of mortality when compared with patients without AKI, and this effect was proportional to the stage of AKI. Increasing age and acute respiratory distress syndrome also revealed higher adjusted odds of mortality. CONCLUSIONS: Acute kidney injury is a common complication among hospitalized patients with COVID-19 infection. We found significantly higher odds of AKI with increasing age and among patients with hyperlipidemia, those with chronic kidney disease, and among African Americans. We demonstrate an independent association between AKI and mortality with increasingly higher odds of mortality from progressively worsening renal failure in hospitalized patients with COVID-19 infection.

Demographic, clinical, and outcomes of confirmed cases of Middle East Respiratory Syndrome coronavirus (MERS-CoV) in Najran, Kingdom of Saudi Arabia (KSA); A retrospective record based study.

INTRODUCTION: MERS is caused by a viral infection, which was first identified in KSA, 2012. MERS-CoV infection consequences with either hospitalization or death. METHODS: All positive MERS-CoV cases that diagnosed in and reported to a referral hospital in Najran, KSA from March/2014 to December/2018 were revised retrospectively. We identified patients from infection control department and medical records. Demographic, clinical, and outcome data were collected. RESULTS: Of the 54 positive MERS-CoV cases, 3 cases were excluded because no available data. Therefore, the final number of the included cases in the study was 51 cases (94.4). Most of the patients were Saudi 36 (70.6%), and majority of cases were reported in the winter 18 (35.3) season. Fever 47 (92.2%), cough 44 (86.3%), and shortness of breath 37 (72.5%) were reported as most common symptoms. Most patients had diabetes mellitus and hypertension. Overall mortality rate was 37.3%, and interestingly the mortality rate dropped sharply over 5 years. In logistic regression analysis, Season and Chronic Kidney disease patients were the only two variables statistically significantly associated with death. The odds of death the patients infected by MERS-CoV during Autumn and Winter season were 4.09 times higher than those patients who infected during Spring and Summer season (OR = 4.09, CI 1.18-14.15, P < 0.026). Compared with MERS-CoV patients who had Non-Chronic kidney diseases, the odds of death the MERS-CoV patients who had chronic kidney diseases were 18.08 times higher (OR = 18.08, CI -2.01-162.99, P < 0.01). CONCLUSION: The case fatality rate of MERS-CoV infection was high. Further studies with large sample sizes are needed to explore the reasons behind the decrease in the mortality rate over the time period.