COVID-19 and the impact of arterial hypertension-An analysis of the international HOPE COVID-19 Registry (Italy-Spain-Germany).

BACKGROUND: A systematic analysis of concomitant arterial hypertension in COVID-19 patients and the impact of angiotensin-converting-enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) have not been studied in a large multicentre cohort yet. We conducted a subanalysis from the international HOPE Registry (https://hopeprojectmd.com, NCT04334291) comparing COVID-19 in presence and absence of arterial hypertension. MATERIALS AND METHODS: Out of 5837 COVID-19 patients, 2850 (48.8%) patients had the diagnosis arterial hypertension. 1978/2813 (70.3%) patients were already treated with ACEI or ARBs. The clinical outcome of the present subanalysis included all-cause mortality over 40 days of follow-up. RESULTS: Patients with arterial hypertension suffered significantly more from different complications including respiratory insufficiency (60.8% vs 39.5%), heart failure (9.9% vs 3.1%), acute kidney injury (25.3% vs 7.3%), pneumonia (90.6% vs 86%), sepsis (14.7% vs 7.5%), and bleeding events (3.6% vs 1.6%). The mortality rate was 29.6% in patients with concomitant arterial hypertension and 11.3% without arterial hypertension (P < .001). Invasive and non-invasive respiratory supports were significantly more required in presence of arterial hypertension as compared without it. In the multivariate cox regression analysis, while age≥65, benzodiazepine, antidepressant at admission, elevated LDH or creatinine, respiratory insufficiency and sepsis might be a positive independent predictors of mortality, antiviral drugs, interferon treatment, ACEI or ARBs at discharge or oral anticoagulation at discharge might be an independent negative predictor of the mortality. CONCLUSIONS: The mortality rate and in-hospital complications might be increased in COVID-19 patients with a concomitant history of arterial hypertension. The history of ACEI or ARBs treatments does not seem to impact the outcome of these patients.

Characteristics of patients with kidney injury associated with COVID-19.

To explore the characteristics of COVID-19 infection related kidney injury, we retrospectively collected cases of COVID-19 patients with definite clinical outcomes (discharge or death) and relevant laboratory results from Jan 3 to Mar 30, 2020 in Tongji hospital, Wuhan, China. 1509 patients were included, 1393 cases with normal baseline serum creatinine, and 116 cases with elevated baseline serum creatinine (EBSC). On admission, the prevalence of elevated serum creatinine, elevated blood urea nitrogen (BUN) and estimated glomerular filtration (eGFR) under 60 ml/min/1.73 m2 were 7.7%, 6.6% and 7.2%, respectively. The incidence of in-hospital death in the patients with EBSC was 7.8%, which was significantly higher than those with normal serum creatinine (1.2%). Inflammatory, immunological, and organ damage indices were relatively higher in the EBSC group, in which lymphocytes, albumin, and hemoglobin were significantly lower. Kaplan-Meier analysis revealed age above 65 years, males, comorbidities (especially for cardiovascular disease and tumor patients), lymphocyte count < 1.5 × 109/L, leukocyte count > 10 × 109/L, EBSC, eGFR < 60 ml/min/1.73 m2 were associated with in-hospital death. Multivariate Cox proportional hazard regression confirmed that EBSC (HR: 2.643, 95% CI: 1.111-6.285, P = 0.028), eGFR < 60 ml/min/1.73 m2 (HR: 3.889, 95% CI: 1.634-9.257, P = 0.002), were independent risk factors after adjusting for age, sex, any comorbidity, leukocyte and lymphocyte count. Therefore, the prevalence of kidney injury in patients with COVID-19 was high and associated with in-hospital mortality. Early detection and effective intervention of kidney injury may reduce COVID-19 deaths.

Clinical characteristics of Egyptian male patients with COVID-19 acute respiratory distress syndrome.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in severe cases associated with acute respiratory distress syndrome (ARDS). OBJECTIVE: To describe the clinical characteristics of patients with ARDS-COVID-19. MATERIALS AND METHODS: This study involved 197 male Egyptian participants, among them111 COVID-19 patients presented with ARDS, 60 COVID-19 patients presented with non-ARDS, and 26 Non-COVID-19 patients. We reported the analysis results of clinical and laboratory information, including blood routine tests, blood biochemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine and C-reactive protein (CRP)], thrombotic activity (D-dimer) and serum ferritin and lactate dehydrogenase (LDH). RESULTS: The levels of hemoglobin, AST, creatinine, monocyte count, monocyte %, RBC count, TLC, and platelet count were not significantly different among the groups. The lymphopenia and increased CRP, ALT, D-dimer, ferritin, and LDH were observed in patients with ARDS-COVID-19. CONCLUSION: COVID-19 patients with ARDS presented with lymphopenia, increased thrombotic activity, increased CRP, LDH, and ferritin levels. The results revealed that CRP, D-dimer, LDH levels, and lymphopenia have a significant association with the COVID-19 severity and can be used as biomarkers to predict the disease severity.

Assessment of Acute Kidney Injury and Longitudinal Kidney Function After Hospital Discharge Among Patients With and Without COVID-19.

Importance: Acute kidney injury (AKI) occurs in up to half of patients hospitalized with coronavirus disease 2019 (COVID-19). The longitudinal effects of COVID-19-associated AKI on kidney function remain unknown. Objective: To compare the rate of change in estimated glomerular filtration rate (eGFR) after hospital discharge between patients with and without COVID-19 who experienced in-hospital AKI. Design, Setting, and Participants: A retrospective cohort study was conducted at 5 hospitals in Connecticut and Rhode Island from March 10 to August 31, 2020. Patients who were tested for COVID-19 and developed AKI were screened, and those who survived past discharge, did not require dialysis within 3 days of discharge, and had at least 1 outpatient creatinine level measurement following discharge were included. Exposures: Diagnosis of COVID-19. Main Outcomes and Measures: Mixed-effects models were used to assess the association between COVID-19-associated AKI and eGFR slope after discharge. The secondary outcome was the time to AKI recovery for the subgroup of patients whose kidney function had not returned to the baseline level by discharge. Results: A total of 182 patients with COVID-19-associated AKI and 1430 patients with AKI not associated with COVID-19 were included. The population included 813 women (50.4%); median age was 69.7 years (interquartile range, 58.9-78.9 years). Patients with COVID-19-associated AKI were more likely to be Black (73 [40.1%] vs 225 [15.7%]) or Hispanic (40 [22%] vs 126 [8.8%]) and had fewer comorbidities than those without COVID-19 but similar rates of preexisting chronic kidney disease and hypertension. Patients with COVID-19-associated AKI had a greater decrease in eGFR in the unadjusted model (-11.3; 95% CI, -22.1 to -0.4 mL/min/1.73 m2/y; P = .04) and after adjusting for baseline comorbidities (-12.4; 95% CI, -23.7 to -1.2 mL/min/1.73 m2/y; P = .03). In the fully adjusted model controlling for comorbidities, peak creatinine level, and in-hospital dialysis requirement, the eGFR slope difference persisted (-14.0; 95% CI, -25.1 to -2.9 mL/min/1.73 m2/y; P = .01). In the subgroup of patients who had not achieved AKI recovery by discharge (n = 319), COVID-19-associated AKI was associated with decreased kidney recovery during outpatient follow-up (adjusted hazard ratio, 0.57; 95% CI, 0.35-0.92). Conclusions and Relevance: In this cohort study of US patients who experienced in-hospital AKI, COVID-19-associated AKI was associated with a greater rate of eGFR decrease after discharge compared with AKI in patients without COVID-19, independent of underlying comorbidities or AKI severity. This eGFR trajectory may reinforce the importance of monitoring kidney function after AKI and studying interventions to limit kidney disease after COVID-19-associated AKI.

A Valid Warning or Clinical Lore: an Evaluation of Safety Outcomes of Remdesivir in Patients with Impaired Renal Function from a Multicenter Matched Cohort.

Per prescribing guidance, remdesivir is not recommended for SARS-CoV-2 in patients with renal disease given the absence of safety data in this patient population. This study was a multicenter, retrospective chart review of hospitalized patients with SARS-CoV-2 who received remdesivir. Safety outcomes were compared between patients with an estimated creatinine clearance (eCrCl) of <30 ml/min and an eCrCl of ≥30 ml/min. The primary endpoint was acute kidney injury (AKI) at the end of treatment (EOT). Of 359 patients who received remdesivir, 347 met inclusion criteria. Patients with an eCrCl of <30 ml/min were older {median, 80 years (interquartile range [IQR], 63.8 to 89) versus 62 (IQR, 54 to 74); P < 0.001}, were more likely to be on vasopressors on the day of remdesivir administration (30% versus 12.7%; P = 0.003), and were more likely to be mechanically ventilated during remdesivir therapy (27.5% versus 12.4%; P = 0.01) than those with an eCrCl of ≥30 ml/min. Despite these confounders, there was no significant difference in the frequency of EOT AKI (5% versus 2.3%; P = 0.283) or early discontinuation due to abnormal liver function tests (LFTs) (0% versus 3.9%; P = 0.374). Of the 5% of patients who developed EOT AKI on remdesivir with an eCrCl <30 ml/min, no cases were attributable to remdesivir administration per the treating physician. Comparable safety outcomes were observed when 1:1 nearest neighbor matching was applied to account for baseline confounders. In conclusion, remdesivir administration was not significantly associated with increased EOT AKI in patients with an eCrCl of <30 ml/min compared to patients with an eCrCl of ≥30 ml/min.

The Clinical Characteristics and Risk Factors of Severe COVID-19.

OBJECTIVE: We aim to investigate the clinical characteristics and risk factors for the severe cases of coronavirus disease 2019 (COVID-19) in comparison with the non-severe patients. METHODS: We searched PubMed, EMBASE, Web of Science, and CNKI to collect all relevant studies published before July 26, 2020, and a total of 30 papers were included in this meta-analysis. RESULTS: In the severe COVID-19 patients, 60% (95% CI = 56-64%) were male, 25% (95% CI = 21-29%) were over 65 years old, 34% (95% CI = 24-44%) were obese, and 55% (95% CI = 41-70%) had comorbidities. The most prevalent comorbidities were hypertension (34%, 95% CI = 25-44%), diabetes (20%, 95% CI = 15-25%), and cardiovascular disease (CVD; 12%, 95% CI = 9-16%). The most common blood test abnormalities were elevated C-reactive protein (CRP; 87%, 82-92%), decreased lymphocyte count (68%, 58-77%), and increased lactate dehydrogenase (69%, 95% CI = 57-81%). In addition, abnormal laboratory findings revealing organ dysfunctions were frequently observed in the severe cases, including decrease in albumin (43%, 95% CI = 24-63%) and increase in aspartate aminotransferase (47%, 95% CI = 38-56%), alanine aminotransferase (28%, 95% CI = 16-39%), troponin I/troponin T (TnI/TnT; 29%, 95% CI = 13-45%), and serum Cr (SCr; 10%, 95% CI = 5-15%). CONCLUSION: The male, elderly and obese patients and those with any comorbidities, especially with hypertension, diabetes, and CVD, were more likely to develop into severe cases. But the association between hypertension, diabetes, CVD, and severity of COVID-19 was declined by the increase of age. A significant elevation in cardiac TnI/TnT, the hepatic enzymes, and SCr and the reduction in lymphocytes with elevated CRPs are important markers for the severity. Specific attention should be given to the elderly male and obese patients and those with indications of severe immune injury in combination with bacterial infection and indication of multi-organ dysfunction or damages.

Treatment Options for Coronavirus Disease 2019 in Patients With Reduced or Absent Kidney Function.

Coronavirus disease 2019, the disease caused by the severe acute respiratory syndrome coronavirus 2 virus, was first identified in the Hubei Province of China in late 2019. Currently, the only role for therapy is treatment of the disease, as opposed to postexposure prophylaxis, however multiple clinical trials are currently ongoing for both treatment and prophylaxis. Treating coronavirus disease 2019 relies on two components; the first is inhibition of the viral entrance and replication within the body and the second is inhibition of an exacerbated immune response which can be seen in patients with severe disease. Many drugs have shown in vitro antiviral activity; however, clinical trials have not been as promising. This review summarizes the current data for the most commonly used drugs for coronavirus disease 2019 and will cover the unique factors that may affect the dosing of these medications in patients with CKD. While clinical trials are ongoing, most are in patients with normal kidney function. During a pandemic, when patients with CKD are at higher risk of both infection and death, it is imperative to include patients these patients in the clinical trials.

Factors affecting mortality in geriatric patients hospitalized with COVID-19

Background/aim: We aimed to investigate the factors affecting the mortality of patients aged 65 years or older who were hospitalized with the diagnosis of new coronavirus pneumonia (COVID-19). Materials and methods: This is a retrospective study of patients 65 years old or older with COVID-19 who were hospitalized in Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty Hospital, between March 11 and May 28, 2020. Demographic, clinical, treatment, and laboratory data were extracted from electronic medical records. We used univariate and multivariate logistic regression methods to explore the risk factors for in-hospital death. Results: A total of 218 patients (112 men, 106 women) were included, of whom 166 were discharged and 52 died in hospital. With univariate analysis, various clinical features and laboratory variables were found to be significantly different (i.e. P < 0.05). In multivariate logistic regression analysis the following were independently associated with mortality: present malignancy [odds ratio (OR) = 4.817, 95% confidence interval (CI) = 1.107­20.958, P: 0.036]; dyspnea (OR = 4.652, 95% CI = 1.473­14.688, P: 0.009); neutrophil/lymphocyte ratio (NLR; OR = 1.097, 95% CI = 1.012­1.188, P: 0.025); the highest values of C-reactive protein (CRP; OR = 1.006, 95% CI = 1.000­1.012, P: 0.049), lactate dehydrogenase (LDH; OR = 1.002, 95% CI = 1.001­1.004, P: 0.003), and creatinine levels (OR = 1.497, 95% CI = 1.126­1.990, P: 0.006); oxygen saturation (SpO2) values on admission (OR = 0.897, 95% CI = 0.811­0.993, P: 0.036); and azithromycin use (OR = 0.239, 95% CI = 0.065­0.874, P: 0.031). Conclusion: The presence of malignancy; symptoms of dyspnea; high NLR; highest CRP, LDH, and creatinine levels; and low SpO2 on admission predicted mortality. On the other hand, azithromycin use was found to be protective against mortality. Knowing the causes predicting mortality will be important to treat future cases more successfully.

Characteristics of laboratory findings of COVID-19 patients with comorbid diabetes mellitus.

AIMS: Coronavirus disease (COVID-19), also referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is instigated by a novel coronavirus. The disease was initially reported in Wuhan, China, in December 2019. Diabetes is a risk factor associated with adverse outcomes. Herein, our objective was to investigate the characteristics of laboratory findings of type 2 diabetes mellitus (T2DM) patients infected with SARS-CoV-2. METHODS: This was a retrospective study and included 80 T2DM patients of Jinling Hospital from 2010 to 2020, as well as 76 COVID-19 patients without T2DM and 55 COVID-19 patients with T2DM who were treated at Huoshen hill Hospital from February 11 to March 18, 2020. We then compared the differences in laboratory test results between the three groups. RESULTS: The levels of lymphocytes, uric acid (UA), and globulin in the T2DM group were significantly higher. In contrast, C-reactive protein (CRP), creatinine, and lactic dehydrogenase (LDH)levels were lower than those in the COVID-19 (p < 0.05) and COVID-19 + T2DM groups (p < 0.05). No considerable difference was observed regarding the levels of alanine aminotransferase (ALT), white blood cell (WBC), aspartate aminotransferase (AST), globulin, and blood urea nitrogen (BUN) in the three groups (p > 0.05). CONCLUSION: T2DM patients infected with SARS-CoV-2 showed decreased levels of body mass index (BMI), lymphocytes, UA, and albumin, and increased CRP levels. The decreased BMI, UA, and albumin levels may be associated with oxidative stress response and nutritional consumption. The decreased lymphocyte counts and increased CRP levels may be related to the infection.

COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status.

BACKGROUNDReprogramming of host metabolism supports viral pathogenesis by fueling viral proliferation, by providing, for example, free amino acids and fatty acids as building blocks.METHODSTo investigate metabolic effects of SARS-CoV-2 infection, we evaluated serum metabolites of patients with COVID-19 (n = 33; diagnosed by nucleic acid testing), as compared with COVID-19-negative controls (n = 16).RESULTSTargeted and untargeted metabolomics analyses identified altered tryptophan metabolism into the kynurenine pathway, which regulates inflammation and immunity. Indeed, these changes in tryptophan metabolism correlated with interleukin-6 (IL-6) levels. Widespread dysregulation of nitrogen metabolism was also seen in infected patients, with altered levels of most amino acids, along with increased markers of oxidant stress (e.g., methionine sulfoxide, cystine), proteolysis, and renal dysfunction (e.g., creatine, creatinine, polyamines). Increased circulating levels of glucose and free fatty acids were also observed, consistent with altered carbon homeostasis. Interestingly, metabolite levels in these pathways correlated with clinical laboratory markers of inflammation (i.e., IL-6 and C-reactive protein) and renal function (i.e., blood urea nitrogen).CONCLUSIONIn conclusion, this initial observational study identified amino acid and fatty acid metabolism as correlates of COVID-19, providing mechanistic insights, potential markers of clinical severity, and potential therapeutic targets.FUNDINGBoettcher Foundation Webb-Waring Biomedical Research Award; National Institute of General and Medical Sciences, NIH; and National Heart, Lung, and Blood Institute, NIH.