Efficiency of nicotinamide-based supportive therapy in lymphopenia for patients with ordinary or severe COVID-19: A randomized controlled trial.

BACKGROUND: This study aimed to investigate the efficiency of nicotinamide-based supportive therapy for lymphopenia in patients with coronavirus disease-2019 (COVID-19). METHODS: Twenty four patients diagnosed with COVID-19 were randomly divided into 2 groups (n = 12) during hospitalization in a ratio of 1:1. Based on conventional treatment, the treatment group was administered 100 mg nicotinamide 5 times a day for 2 days. The control group received routine treatment only. The primary endpoint was the change in the absolute lymphocyte count. The secondary endpoints included both in-hospital death and the composite endpoint of aggravation, according to upgraded oxygen therapy, improved nursing level, and ward rounds of superior physicians for changes in conditions. RESULTS: Full blood counts before and after nicotinamide administration were comparable in each group (all P > .05). Before and after receiving nicotinamide, mean absolute lymphocyte counts were similar between the two groups ([0.94 ± 0.26] × 109/L vs [0.89 ± 0.19] × 109/L, P = .565; [1.15 ± 0.48] × 109/L vs [1.02 ± 0.28] × 109/L, P = .445, respectively). Therefore, there was no statistically significant difference in the lymphocyte improvement rate between the two groups (23.08 ± 46.10 vs 16.52 ± 24.10, P = .67). There was also no statistically significant difference in the secondary endpoints between the two groups. CONCLUSION: Among patients with COVID-19, there was no statistically significant difference in the change of whole blood counts and absolute lymphocyte counts before and after intervention in both groups. Therefore, no new evidence has been found regarding the effect of niacinamide on lymphopenia in COVID-19 patients.

Neutrophil infiltration and myocarditis in patients with severe COVID-19: A post-mortem study

Aims To investigate cardiac pathology in critically ill patients with coronavirus disease 2019 (COVID-19) and identify associations between pathological changes and clinical characteristics. Methods The present autopsy cohort study included hearts from 26 deceased patients hospitalized in intensive care units due to COVID-19, and was conducted at four sites in Wuhan, China. Cases were divided into a neutrophil infiltration group and a no-neutrophil group based on the presence or absence of histopathologically identified neutrophilic infiltrates. Results Among the 26 patients, histopathological examination identified active myocarditis in four patients. All patients with myocarditis exhibited extensive accompanying neutrophil infiltration, and all patients without myocarditis did not. The neutrophil infiltration group exhibited significantly higher rates of detection of interleukin-6 (100 vs. 4.6%) and tumor necrosis factor-alpha (100 vs. 31.8%) than the no-neutrophil group (both p < 0.05). On admission, four patients with neutrophil infiltration in myocardium had significantly higher baseline levels of aspartate aminotransferase, D dimer, and high-sensitivity C reactive protein than the other 22 patients (all p < 0.05). During hospitalization, patients with neutrophil infiltration had significantly higher maximum creatine kinase-MB (median 280.0 IU/L vs. 38.7 IU/L, p = 0.04) and higher troponin I (median 1.112 ng/ml vs. 0.220 ng/ml, p = 0.56) than patients without neutrophil infiltration. Conclusion Active myocarditis was frequently associated with neutrophil infiltration in the hearts of deceased patients with severe COVID-19. Patients with neutrophil-infiltrated myocarditis had a series of severely abnormal laboratory test results on admission, and high maximum creatine kinase-MB during hospitalization. The role of neutrophils in severe heart injury and systemic conditions in patients with COVID-19 should be emphasized.

Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death among patients with chronic heart failure and a left ventricular ejection fraction of 40% or less. Whether SGLT2 inhibitors are effective in patients with a higher left ventricular ejection fraction remains less certain. METHODS: We randomly assigned 6263 patients with heart failure and a left ventricular ejection fraction of more than 40% to receive dapagliflozin (at a dose of 10 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of worsening heart failure (which was defined as either an unplanned hospitalization for heart failure or an urgent visit for heart failure) or cardiovascular death, as assessed in a time-to-event analysis. RESULTS: Over a median of 2.3 years, the primary outcome occurred in 512 of 3131 patients (16.4%) in the dapagliflozin group and in 610 of 3132 patients (19.5%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.92; P<0.001). Worsening heart failure occurred in 368 patients (11.8%) in the dapagliflozin group and in 455 patients (14.5%) in the placebo group (hazard ratio, 0.79; 95% CI, 0.69 to 0.91); cardiovascular death occurred in 231 patients (7.4%) and 261 patients (8.3%), respectively (hazard ratio, 0.88; 95% CI, 0.74 to 1.05). Total events and symptom burden were lower in the dapagliflozin group than in the placebo group. Results were similar among patients with a left ventricular ejection fraction of 60% or more and those with a left ventricular ejection fraction of less than 60%, and results were similar in prespecified subgroups, including patients with or without diabetes. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction. (Funded by AstraZeneca; DELIVER ClinicalTrials.gov number, NCT03619213.).

COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives.

Coronavirus disease 2019 (COVID-19), caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic that has affected the lives of billions of individuals. Extensive studies have revealed that SARS-CoV-2 shares many biological features with SARS-CoV, the zoonotic virus that caused the 2002 outbreak of severe acute respiratory syndrome, including the system of cell entry, which is triggered by binding of the viral spike protein to angiotensin-converting enzyme 2. Clinical studies have also reported an association between COVID-19 and cardiovascular disease. Pre-existing cardiovascular disease seems to be linked with worse outcomes and increased risk of death in patients with COVID-19, whereas COVID-19 itself can also induce myocardial injury, arrhythmia, acute coronary syndrome and venous thromboembolism. Potential drug-disease interactions affecting patients with COVID-19 and comorbid cardiovascular diseases are also becoming a serious concern. In this Review, we summarize the current understanding of COVID-19 from basic mechanisms to clinical perspectives, focusing on the interaction between COVID-19 and the cardiovascular system. By combining our knowledge of the biological features of the virus with clinical findings, we can improve our understanding of the potential mechanisms underlying COVID-19, paving the way towards the development of preventative and therapeutic solutions.

CSC Expert Consensus on Principles of Clinical Management of Patients With Severe Emergent Cardiovascular Diseases During the COVID-19 Epidemic.

In response to the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, the Chinese Society of Cardiology (CSC) issued this consensus statement after consulting with 125 medical experts in the fields of cardiovascular disease and infectious disease. The over-arching principles laid out here are the following: 1) Consider the prevention and control of COVID-19 transmission as the highest priority, including self-protection of medical staff; 2) Patient risk assessment of both infection and cardiovascular issues. Where appropriate, preferential use of conservative medical therapeutic approaches to minimize disease spread; 3) At all times, medical practices and interventional procedures should be conducted in accordance with the directives of the infection control department of local hospitals and local health commissions.