Hydroxychloroquine and antivirals for treatment of COVID-19

The use of antimalarials for COVID-19 treatment has been an ongoing discussion since the onset of the pandemic. In this article, authors discuss the use of hydroxychloroquine and chloroquine for COVID-19 treatment and prevention as an off-label use. The article discusses trials which used these medications and data-designed observational studies. Based on the current randomized control trials and high-quality evidence from large observational studies, the use of hydroxychloroquine for the treatment of mild, moderate, or severe COVID-19 is not efficacious. In addition, authors state that the use of HCQ as post-exposure prophylaxis for COVID-19 is also not efficacious. There is no current evidence that chronic therapy is supported among those with rheumatic disease, and the risk of developing new cardiac arrhythmias while on antimalarials may be heightened in those with COVID-19. Further research studies are needed to investigate the cardiovascular risks of long term HCQ use.

In another publication, authors discuss the study of multiple antivirals targeting RdRp, proteases, and Spike protein from SARS-CoV-2. The researchers used drug repurposing, HTS, and virtual inhibitor screening to find antivirals. Despite rigorous studies and collaborations, these authors agree that no drugs have been shown to have a “remarkable” inhibitory effect against SARS-CoV-2. This article discusses several medications that have been repurposed and studies which have used these medications, as well as their results. Of interest, the authors discuss Traditional Oriental medicine and its inhibition of the virus, blocking of infection, and regulation of the immune response, decreases inflammation, and promotes repair of the body.

Risk factors for hospitalization in patients with inflammatory rheumatic and musculoskeletal diseases

In this article, authors discuss whether patients with inflammatory rheumatic and musculoskeletal disease (RMD) are at higher risk to develop severe courses of COVID-19. Using data from 468 patients with RMD’s and SARS-CoV-2 infection, the researchers used multivariable logistic regression to estimate hospitalization due to COVID-19. The most frequent diagnosis in this group was rheumatoid arthritis (48%). Of this group, 29% were hospitalized, 5.5% required mechanical ventilation, nineteen of these patients passed during the study. Multivariable analysis showed that >75 years, cardiovascular disease, interstitial lung disease and/or COPD, chronic kidney disease, moderate to high RMD disease activity and treatment with >5mg/day glucocorticoids were associated with higher risk for hospitalization. The researchers conclude that age was a major risk factor as well as comorbidities as a risk factor for hospitalization. RMD disease activity is also an independent risk factor for hospitalization, underlining the importance of continuing treatment for patients with RMD during the pandemic.

Origin of SARS-CoV-2: Lab created or natural selection?

In this publication, authors discuss the speculation that SARS-CoV-2 was created in a laboratory but give specific data to dispute the claim. Researchers compared the genome of SARS-CoV-2 with those of the other six coronaviruses that are known to infect humans which include: SARS-CoV and MERS-CoV which are known to cause severe disease, and HKU1, NL63, OC43, and 229E which generally cause mild disease in humans. The SARS-CoV-2 virus binds to the human ACE2 receptor and it’s spike protein has a unique polybasic cleavage site which facilitates entry into a cell and led to the predicted acquisition of three O-linked glycans that provide immune evasion. Genetic data shows that SARS-CoV-2 is not derived from any previously used virus backbone. The researchers acknowledge that bat SARS-CoV-like coronaviruses have been grown in cell culture and animal models for research, genetic analysis does not support that this specific virus resulted from inadvertent lab release. Instead, the researchers liken the receptor-binding spike protein of this virus to a receptor-binding domain in known pangolin coronaviruses which they believe is a likely origin. The authors of this article all agree that available evidence indicates that SARS-CoV-2 arose by natural selection, either in an animal host prior to zoonotic transfer or in humans following initial cryptic zoonotic transfer. Authors strongly state that COVID-19 is not a laboratory created or purposefully manipulated virus.

COVID-19 Reinfection & Testing

In the months since the pandemic emerged, there have been cases of COVID-19 reinfection after the initial recoveries were reported. At the time of this writing, the extent and protective immunity after SARS-CoV-2 infection is still not known. It seems that reinfection after an initial case of COVID-19 is due to a different variant or mutant strain of SARS-CoV-2. These mutations have raised diagnostic challenges with RT-PCR testing and decreased sensitivity. This article seeks to offer a detailed biology of SARS-CoV-2 re-infections and explore implications on immune response, lab testing, and control measures against COVID-19. The discussion concludes that patients with COVID-19 reinfections are unlikely to have been caused by a natural viral evolution which indicates that SARS-CoV-2 may adapt easily with an innate immune response in a manner to re-establish detectable levels of infection. The authors urge further investigations to provide robust genomics and immunology data to correlate with transmissibility and viral shedding. They also highlight the need for globally standardized laboratory criteria and case definitions that will highlight a re-infection versus a primary infection to avoid mis-diagnosis.