Evidence For and Against Direct Kidney Infection by SARS-CoV-2 in Patients with COVID-19.

Despite evidence of multiorgan tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19), direct viral kidney invasion has been difficult to demonstrate. The question of whether SARS-CoV2 can directly infect the kidney is relevant to the understanding of pathogenesis of AKI and collapsing glomerulopathy in patients with COVID-19. Methodologies to document SARS-CoV-2 infection that have been used include immunohistochemistry, immunofluorescence, RT-PCR, in situ hybridization, and electron microscopy. In our review of studies to date, we found that SARS-CoV-2 in the kidneys of patients with COVID-19 was detected in 18 of 94 (19%) by immunohistochemistry, 71 of 144 (49%) by RT-PCR, and 11 of 84 (13%) by in situ hybridization. In a smaller number of patients with COVID-19 examined by immunofluorescence, SARS-CoV-2 was detected in 10 of 13 (77%). In total, in kidneys from 102 of 235 patients (43%), the presence of SARS-CoV-2 was suggested by at least one of the methods used. Despite these positive findings, caution is needed because many other studies have been negative for SARS-CoV-2 and it should be noted that when detected, it was only in kidneys obtained at autopsy. There is a clear need for studies from kidney biopsies, including those performed at early stages of the COVID-19-associated kidney disease. Development of tests to detect kidney viral infection in urine samples would be more practical as a noninvasive way to evaluate SARS-CoV-2 infection during the evolution of COVID-19-associated kidney disease.

COVID-19 Risk Factors and Mortality Outcomes Among Medicare Patients Receiving Long-term Dialysis.

Importance: There is a need for studies to evaluate the risk factors for COVID-19 and mortality among the entire Medicare long-term dialysis population using Medicare claims data. Objective: To identify risk factors associated with COVID-19 and mortality in Medicare patients undergoing long-term dialysis. Design, Setting, and Participants: This retrospective, claims-based cohort study compared mortality trends of patients receiving long-term dialysis in 2020 with previous years (2013-2019) and fit Cox regression models to identify risk factors for contracting COVID-19 and postdiagnosis mortality. The cohort included the national population of Medicare patients receiving long-term dialysis in 2020, derived from clinical and administrative databases. COVID-19 was identified through Medicare claims sources. Data were analyzed on May 17, 2021. Main Outcomes and Measures: The 2 main outcomes were COVID-19 and all-cause mortality. Associations of claims-based risk factors with COVID-19 and mortality were investigated prediagnosis and postdiagnosis. Results: Among a total of 498 169 Medicare patients undergoing dialysis (median [IQR] age, 66 [56-74] years; 215 935 [43.1%] women and 283 227 [56.9%] men), 60 090 (12.1%) had COVID-19, among whom 15 612 patients (26.0%) died. COVID-19 rates were significantly higher among Black (21 787 of 165 830 patients [13.1%]) and Hispanic (13 530 of 86 871 patients [15.6%]) patients compared with non-Black patients (38 303 of 332 339 [11.5%]), as well as patients with short (ie, 1-89 days; 7738 of 55 184 patients [14.0%]) and extended (ie, ≥90 days; 10 737 of 30 196 patients [35.6%]) nursing home stays in the prior year. Adjusting for all other risk factors, residing in a nursing home 1 to 89 days in the prior year was associated with a higher hazard for COVID-19 (hazard ratio [HR] vs 0 days, 1.60; 95% CI 1.56-1.65) and for postdiagnosis mortality (HR, 1.31; 95% CI, 1.25-1.37), as was residing in a nursing home for an extended stay (COVID-19: HR, 4.48; 95% CI, 4.37-4.59; mortality: HR, 1.12; 95% CI, 1.07-1.16). Black race (HR vs non-Black: HR, 1.25; 95% CI, 1.23-1.28) and Hispanic ethnicity (HR vs non-Hispanic: HR, 1.68; 95% CI, 1.64-1.72) were associated with significantly higher hazards of COVID-19. Although home dialysis was associated with lower COVID-19 rates (HR, 0.77; 95% CI, 0.75-0.80), it was associated with higher mortality (HR, 1.18; 95% CI, 1.11-1.25). Conclusions and Relevance: These results shed light on COVID-19 risk factors and outcomes among Medicare patients receiving long-term chronic dialysis and could inform policy decisions to mitigate the significant extra burden of COVID-19 and death in this population.

Clinical efficacy and safety of combination therapy of tocilizumab and steroid pulse therapy for critical COVID-19 in HD patients.

BACKGROUND: Critical coronavirus disease 2019 (COVID-19) has a high fatality rate, especially in hemodialysis (HD) patients, with this poor prognosis being caused by systemic hyperinflammation; cytokine storms. Steroid pulse therapy or tocilizumab (TCZ) have insufficient inhibitory effects against cytokine storms in critical cases. This study evaluated the clinical effects and safety of combining steroid pulse therapy and TCZ. METHODS: From September 2020 to May 2021, 201 patients with COVID-19 were admitted to our hospital. Before February 2021, patients with an oxygen demand exceeding 8 L/min were intubated and treated with standard therapy (dexamethasone and antiviral therapy). After February 2021, patients underwent high-flow nasal cannula oxygen therapy and were treated with TCZ (8 mg/kg) and methylprednisolone (mPSL) (500 mg/day [≤ 75 kg], 1000 mg/day [> 75 kg]) for 3 days. We compared background characteristics, laboratory findings, and prognosis between non-HD and HD patients and between patients who received and did not receive TCZ and mPSL pulse therapy. RESULTS: Among non-HD patients, the TCZ + mPSL pulse group had significantly higher survival rates and lower secondary infection rates (p < 0.05), than the standard therapy group. All HD patients in the standard therapy group with oxygen demand exceeding 8 L/min died. Contrastingly, all patients in the TCZ + mPSL pulse group survived, with their oxygen demand decreasing to 0-1 L/min within 3 weeks post-administration. CONCLUSION: TCZ combined with mPSL pulse therapy improved the survival rate without significant adverse events in critical HD and non-HD patients with COVID-19 by strongly suppressing systemic hyperinflammation.

Obesity is independently associated with septic shock, renal complications, and mortality in a multiracial patient cohort hospitalized with COVID-19.

BACKGROUND: Obesity has emerged as a risk factor for severe coronavirus disease 2019 (COVID-19) infection. To inform treatment considerations the relationship between obesity and COVID-19 complications and the influence of race, ethnicity, and socioeconomic factors deserves continued attention. OBJECTIVE: To determine if obesity is an independent risk factor for severe COVID-19 complications and mortality and examine the relationship between BMI, race, ethnicity, distressed community index and COVID-19 complications and mortality. METHODS: A retrospective cohort study of 1,019 SARS-CoV-2 positive adult admitted to an academic medical center (n = 928) and its affiliated community hospital (n-91) in New York City from March 1 to April 18, 2020. RESULTS: Median age was 64 years (IQR 52-75), 58.7% were men, 23.0% were Black, and 52.8% were Hispanic. The prevalence of overweight and obesity was 75.2%; median BMI was 28.5 kg/m2 (25.1-33.0). Over the study period 23.7% patients died, 27.3% required invasive mechanical ventilation, 22.7% developed septic shock, and 9.1% required renal replacement therapy (RRT). In the multivariable logistic regression model, BMI was associated with complications including intubation (Odds Ratio [OR]1.03, 95% Confidence Interval [CI]1.01-1.05), septic shock (OR 1.04, CI 1.01-1.06), and RRT (OR1.07, CI 1.04-1.10), and mortality (OR 1.04, CI 1.01-1.06). The odds of death were highest among those with BMI ≥ 40 kg/m2 (OR 2.05, CI 1.04-4.04). Mortality did not differ by race, ethnicity, or socioeconomic distress score, though Black and Asian patients were more likely to require RRT. CONCLUSIONS AND RELEVANCE: Severe complications of COVID-19 and death are more likely in patients with obesity, independent of age and comorbidities. While race, ethnicity, and socioeconomic status did not impact COVID-19 related mortality, Black and Asian patients were more likely to require RRT. The presence of obesity, and in some instances race, should inform resource allocation and risk stratification in patients hospitalized with COVID-19.

Plasma ACE2 predicts outcome of COVID-19 in hospitalized patients.

AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin converting enzyme 2 (ACE2) enabling entrance of the virus into cells and causing the infection termed coronavirus disease of 2019 (COVID-19). Here, we investigate associations between plasma ACE2 and outcome of COVID-19. METHODS AND RESULTS: This analysis used data from a large longitudinal study of 306 COVID-19 positive patients and 78 COVID-19 negative patients (MGH Emergency Department COVID-19 Cohort). Comprehensive clinical data were collected on this cohort, including 28-day outcomes. The samples were run on the Olink® Explore 1536 platform which includes measurement of the ACE2 protein. High admission plasma ACE2 in COVID-19 patients was associated with increased maximal illness severity within 28 days with OR = 1.8, 95%-CI: 1.4-2.3 (P < 0.0001). Plasma ACE2 was significantly higher in COVID-19 patients with hypertension compared with patients without hypertension (P = 0.0045). Circulating ACE2 was also significantly higher in COVID-19 patients with pre-existing heart conditions and kidney disease compared with patients without these pre-existing conditions (P = 0.0363 and P = 0.0303, respectively). CONCLUSION: This study suggests that measuring plasma ACE2 is potentially valuable in predicting COVID-19 outcomes. Further, ACE2 could be a link between COVID-19 illness severity and its established risk factors hypertension, pre-existing heart disease and pre-existing kidney disease.

Characteristics, comorbidities and survival analysis of young adults hospitalized with COVID-19 in New York City.

This study reviewed 395 young adults, 18-35 year-old, admitted for COVID-19 to one of the eleven hospitals in New York City public health system. Demographics, comorbidities, clinical course, outcomes and characteristics linked to hospitalization were analyzed including temporal survival analysis. Fifty-seven percent of patients had a least one major comorbidity. Mortality without comorbidity was in 3.8% patients. Further investigation of admission features and medical history was conducted. Comorbidities associated with mortality were diabetes (n = 54 deceased/73 diagnosed,74% tested POS;98.2% with diabetic history deceased; Wilcoxon p (Wp) = .044), hypertension (14/44,32% POS, 25.5%; Wp = 0.030), renal (6/16, 37.5% POS,11%; Wp = 0.000), and cardiac (6/21, 28.6% POS,11%; Wp = 0.015). Kaplan survival plots were statistically significant for these four indicators. Data suggested glucose >215 or hemoglobin A1c >9.5 for young adults on admission was associated with increased mortality. Clinically documented respiratory distress on admission was statistically significant outcome related to mortality (X2 = 236.6842, df = 1, p < .0001). Overall, 28.9% required supportive oxygen beyond nasal cannula. Nasal cannula oxygen alone was required for 71.1%, who all lived. Non-invasive ventilation was required for 7.8%, and invasive mechanical ventilation 21.0% (in which 7.3% lived, 13.7% died). Temporal survival analysis demonstrated statistically significant response for Time to Death <10 days (X2 = 18.508, df = 1, p = .000); risk lessened considerably for 21 day cut off (X2 = 3.464, df = 1, p = .063), followed by 31 or more days of hospitalization (X2 = 2.212, df = 1, p = .137).

COVID-19 and Renal Diseases: An Update.

BACKGROUND: It becomes increasingly evident that the SARS-CoV-2 infection is not limited to the respiratory system. In addition to being a target of the virus, the kidney also seems to have a substantial influence on the outcomes of the disease. METHODS: Data was obtained by a comprehensive and non-systematic search in the PubMed, Cochrane, Scopus and SciELO databases, using mainly the terms "SARS-CoV-2", "COVID-19", "chronic kidney disease", "renal transplantation", acute kidney injury" and "renal dysfunction" Discussion: The membrane-bound angiotensin-converting enzyme 2 is the receptor for SARS-CoV- -2, and this interaction may lead to an imbalance of the Renin-Angiotensin System (RAS), associated with worse clinical presentations of COVID-19, including acute pulmonary injury, hyperinflammatory state and hematological alterations. In the framework of renal diseases, the development of acute kidney injury is associated mostly with immune alterations and direct cytopathic lesions by the virus, leading to higher mortality. As for chronic kidney disease, the patients at a non-terminal stage have a worse prognosis, while the hemodialysis patients appear to have mild courses of COVID-19, probably due to lower chances of being affected by the cytokine storm. Furthermore, the current scenario is unfavorable to kidney donation and transplantation. The relationship between COVID-19 and immunosuppression in kidney transplantation recipients has been greatly discussed to determine whether it increases mortality and how it interacts with immunosuppressive medications. CONCLUSION: The kidney and the RAS exert fundamental roles in the SARS-CoV-2 infection, and more research is required to have a complete understanding of the repercussions caused by COVID-19 in renal diseases.

Chronic heart diseases as the most prevalent comorbidities among deaths by COVID-19 in Brazil.

Age, sex and presence of comorbidities are risk factors associated with COVID-19. Hypertension, diabetes and heart disease are the most common comorbidities in patients with COVID-19. The objective of this study was to estimate the prevalence of patients with comorbidities who died of COVID-19 in Brazil. Searches of data were carried out on the official pages of the 26 State health departments and the federal district. The random-effect method was used to calculate the prevalence of patients with comorbidities who died. From the beginning of the pandemic in Brazil until May 20, 2020, 276,703 cases of COVID-19 were notified in Brazil, 6.4% died, 58.6% of whom were male. The prevalence of comorbidities among deaths was 83% (95% CI: 79 - 87), with heart disease and diabetes being the most prevalent. To our knowledge, this study represents the first large analysis of cases of patients with confirmed COVID-19 in Brazil. There is a high prevalence of comorbidities (83%) among patients who died from COVID-19 in Brazil, with heart disease being the most prevalent. This is important considering the possible secondary effects produced by drugs such as hydroxychloroquine.