ABSTRACT
The inflammaging concept was introduced in 2000 by Prof. Franceschi. This was an evolutionary or rather a revolutionary conceptualization of the immune changes in response to a lifelong stress. This conceptualization permitted to consider the lifelong proinflammatory process as an adaptation which could eventually lead to either beneficial or detrimental consequences. This dichotomy is influenced by both the genetics and the environment. Depending on which way prevails in an individual, the outcome may be healthy longevity or pathological aging burdened with aging-related diseases. The concept of inflammaging has also revealed the complex, systemic nature of aging. Thus, this conceptualization opens the way to consider age-related processes in their complexity, meaning that not only the process but also all counter-processes should be considered. It has also opened the way to add new concepts to the original one, leading to better understanding of the nature of inflammaging and of aging itself. Finally, it showed the way towards potential multimodal interventions involving a holistic approach to optimize the aging process towards a healthy longevity.
ABSTRACT
Introduction: We present a case of severe rhabdomyolysis associated with COVID-19 infection without acute kidney injury (AKI). Case Description: A 43 year-old African American male with a history of medicationinduced rhabdomyolysis 6 years ago, renal cell carcinoma status post partial right nephrectomy, hypertension, type 2 diabetes, and morbid obesity presented to emergency department with upper respiratory symptoms, myalgia and discoloration of urine for one week. He reported taking atorvastatin and diltiazem for a long time but has neverdeveloped myalgia. There was no family history of myopathies, or binge alcohol intake beforehand. On physical examination, patient was hypertensive, euvolemic, and afebrile, with normal oxygenation. Chest x-ray showed subtle increased interstitial reticulation in the perihilar regions and COVID-19 rapid test returned positive. Laboratory data showed very high creatine kinase (CK) (208,456 U/L). Urinalysis showed trace proteinuria, large blood but only few red blood cells and confirmed myoglobinuria. However, his creatinine was normal (0.8 mg/dL), as well as serum calcium (8.4 mg/dL), phosphate (3.9 mg/dL), and uric acid (5.2mg/dL) levels. Patient was admitted for treatment of assumed severe rhabdomyolysis. COVID-19 was treated conservatively with oxygen supplementation. Atorvastatin and diltiazem were held, and normal saline and isotonic sodium bicarbonate fluids were administered. CK continued to rise with a peak of 499,020 U/L on day 3, but decreased steadily to 58,745 U/L on day 7. Renal function remained stable all the time during the treatment (serum Cr 0.68 - 0.82 mg/dL), with maintained urine output and well-preserved electrolytes and uric acid levels throughout. Discussion: There are increasing number of reports of COVID-19-associated rhabdomyolysis, but risk factors and characteristics are fairly known. The clinical and laboratory manifestations are suggestive of COVID-19 associated rhabodmyolysis rather than statin-induced. We are not aware of any other reports documenting such extreme CK values - with a proper rise and fall of CK - without impacting renal function. As far as we know, this is the first case of COVID-19 associated rhabdomyolysis with peak CK of 499,020 U/L, without AKI and concurrent electrolyte abnormalities. The relationship to COVID-19 vs. individual genetic susceptibility remains to be explored.
ABSTRACT
Background: The effect of angiotensin-receptor blockers (ARBs) and angiotensinconverting enzyme inhibitors (ACEi) on outcome and severity in COVID-19 patients has been postulated. Methods: We performed a systematic review in different databases to identify studies and research work that assessed the association of ACEi/ARBs on the severity of illness and mortality in COVID-19 subjects. Inclusion criteria for our meta-analysis were all studies that included human subjects with COVID-19 infection, reported mortality and severity of the disease, and described ACEi/ARB treatment. The data collected were the name of the first author, journal title, the country of the study, sample size, relative risk and confidence intervals for association of ACEi/ARB treatment and mortality and severity. We used the random-effects model for the meta-analysis and the funnel plot analysis to assess potential publication bias. Results: Out of 4,702 records reviewed in different databases, 11 papers were included in our meta-analysis. Altogether, 8,643 patients were included in the final analysis. Random effects model (REM) for the relationship between ACEi/ARB and survival showed that ACEi/ARB does not affect survival (relative risk [RR]=0.81, confidence interval ranges [CIR] from 0.53 to 1.23). There was no evidence of heterogeneity with I-squared =25.5% and p<0.235. By applying Egger's test, there was no evidence of small studies effect with P=0.64. REM for the relationship between ACEi/ARB and disease severity showed that ACEi/ARB are not related to disease severity (RR=0.90, CIR from 0.70 to 1.15). There was evidence of heterogeneity with I-squared =56.2% and p=0.01. By applying Egger's test, there was no evidence of small studies effect with P=0.93. Conclusions: Based on the results of this meta-analysis, ACEi/ARB are not associated with increased mortality or severity in COVID-19 subjects.