Fatal Rhabdomyolysis in a COVID-19 Patient on Rosuvastatin

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Abstract

It is well-established by now that COVID-19 can have a wide variety of neuromuscular manifestations, including rhabdomyolysis. Weakness and elevated creatinine kinase (CK) have been documented as the initial presentation of COVID-19. Myopathy from statin use has also been well-established since the introduction of this class of medication, and the common pathologic mechanism of both entities may have been mitochondrial dysfunction. We present here the case of a COVID-19 patient on rosuvastatin who developed rhabdomyolysis with CK above 1,000,000 units/L. The patient did not present with any respiratory difficulty and responded poorly to treatment, resulting in his untimely demise. COVID-19 may have accentuated an otherwise survivable condition by means of extra stress on mitochondrial homeostasis. Understanding the actual mechanism will be important in the development and utilization of medications in the fight against COVID-19.

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Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography.

James E Voss, Marie-Christine Vaney, Stéphane Duquerroy … (2010)

Chikungunya virus (CHIKV) is an emerging mosquito-borne alphavirus that has caused widespread outbreaks of debilitating human disease in the past five years. CHIKV invasion of susceptible cells is mediated by two viral glycoproteins, E1 and E2, which carry the main antigenic determinants and form an icosahedral shell at the virion surface. Glycoprotein E2, derived from furin cleavage of the p62 precursor into E3 and E2, is responsible for receptor binding, and E1 for membrane fusion. In the context of a concerted multidisciplinary effort to understand the biology of CHIKV, here we report the crystal structures of the precursor p62-E1 heterodimer and of the mature E3-E2-E1 glycoprotein complexes. The resulting atomic models allow the synthesis of a wealth of genetic, biochemical, immunological and electron microscopy data accumulated over the years on alphaviruses in general. This combination yields a detailed picture of the functional architecture of the 25 MDa alphavirus surface glycoprotein shell. Together with the accompanying report on the structure of the Sindbis virus E2-E1 heterodimer at acidic pH (ref. 3), this work also provides new insight into the acid-triggered conformational change on the virus particle and its inbuilt inhibition mechanism in the immature complex.

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Statin-induced myopathy: a review and update.

Mary Jacobson, Abeer T. Abd Elkarim (2011)

Statin-induced myopathy is an important cause of statin intolerance and the most common cause of statin discontinuation. Observational studies estimate that 10 - 15% of statin users develop statin-related muscle side effects ranging from mild myalgia to more severe muscle symptoms with significant CPK elevations. This article reviews the epidemiology, clinical features, risk factors and mechanisms of statin-induced myopathy and provides an evidence-based algorithm for managing patients with statin myopathy. There are multiple risk factors for statin-induced myopathy that are both patient-related (age, genetics, co-morbidities) and drug-related (statin metabolism via the CYP system, drug-drug interactions and statin drug transport). Management options for statin-intolerant patients include statin switching, especially to low-dose, non-daily doses of long-acting statins, such as rosuvastatin and atorvastatin, and other non-statin lipid-lowering agents, such as ezetimibe and colesevelam, and possibly red yeast rice. In conclusion, statin-induced myopathy is a significant clinical problem that contributes considerably to statin therapy discontinuation. However, there exist multiple and effective management options for statin intolerant patients.

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Inhibition of Chikungunya virus infection in cultured human muscle cells by furin inhibitors: impairment of the maturation of the E2 surface glycoprotein.

Antoine Gessain, Frederic Tangy, Yves Jacob … (2008)

Chikungunya virus (CHIKV) is a mosquito-transmitted Alphavirus that causes in humans an acute infection characterized by polyarthralgia, fever, myalgia, and headache. Since 2005 this virus has been responsible for an epidemic outbreak of unprecedented magnitude. By analogy with other alphaviruses, it is thought that cellular proteases are able to process the viral precursor protein E3E2 to produce the receptor-binding E2 protein that associates as a heterodimer with E1. Destabilization of the heterodimer by exposure to low pH allows viral fusion and infection. We show that among a large panel of proprotein convertases, membranous furin but also PC5B can process E3E2 from African CHIKV strains at the HRQRR(64) / ST site, whereas a CHIKV strain of Asian origin is cleaved at RRQRR(64) / SI by membranous and soluble furin, PC5A, PC5B, and PACE4 but not by PC7 or SKI-1. Using fluorogenic model peptides and recombinant convertases, we observed that the Asian strain E3E2 model peptide is cleaved most efficiently by furin and PC5A. This cleavage was also observed in CHIKV-infected cells and could be blocked by furin inhibitor decanoyl-RVKR-chloromethyl ketone. This inhibitor was compared with chloroquine for its ability to inhibit CHIKV spreading in myoblast cell cultures, a cell-type previously described as a natural target of this virus. Our results demonstrate the role of furin-like proteases in the processing of CHIKV particles and point out new approaches to inhibit this infection.

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Author and article information

Journal

Journal ID (nlm-ta): Cureus

Journal ID (iso-abbrev): Cureus

Journal ID (issn): 2168-8184

Title: Cureus

Publisher: Cureus (Palo Alto (CA) )

ISSN (Electronic): 2168-8184

Publication date (Electronic, pub): 26 October 2020

Publication date (Electronic, collection): October 2020

Volume: 12

Issue: 10

Electronic Location Identifier: e11186

Affiliations

[1 ] Pulmonary and Critical Care, California Hospital Medical Center, Los Angeles, USA

[2 ] Family Medicine, California Hospital Medical Center, Los Angeles, USA

[3 ] Cardiology, California Hospital Medical Center, Los Angeles, USA

[4 ] Emergency Medicine, California Hospital Medical Center, Los Angeles, USA

[5 ] Neurology, Adventist Health White Memorial, Los Angeles, USA

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Antonio K. Liu anthonyseanliu@ 123456yahoo.com

Article

DOI: 10.7759/cureus.11186

PMC ID: 7593204

SO-VID: 7ee158f3-ac5e-4fff-b005-ed0e6f05248e

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This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Fatal Rhabdomyolysis in a COVID-19 Patient on Rosuvastatin

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Abstract

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Novel Coronavirus Disease COVID-19

Most cited references 14

Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography.

Statin-induced myopathy: a review and update.

Inhibition of Chikungunya virus infection in cultured human muscle cells by furin inhibitors: impairment of the maturation of the E2 surface glycoprotein.

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