Acute transverse myelitis associated with SARS-CoV-2: A Case-Report

Hisham Valiuddin, DO,^∗ Brandon Skwirsk, MD, and Patricia Paz-Arabo, MD

doi: 10.1016/j.bbih.2020.100091

Highlights

• • The third case of acute transverse myelitis due to SARS-CoV-2 reported in the world.
• • Possible inflammatory complications affecting the myelin in spinal cord.
• • We must be vigilant of the critical neurological illnesses associated with COVID-19.

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1. Introduction

We describe the third reported case of transverse myelitis in a patient with the onset of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although it is a well-known fact now that strains of SARS-CoV-2 can cause neurological manifestations such as anosmia and dysgeusia, recent literature has found complex neurological disease associations such as Guillain–Barré syndrome and early-onset large-vessel strokes (^{Xydakis et al., 2020; Oxley et al., 2020; Toscano et al., 2020}). It has become apparent that Covid-19 causes an inflammatory cascade that results in multiple organ system being affected. In this case, inflammatory complications affecting the myelin in spinal cord occurred without the classic Covid-19 symptoms.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275168/

Ivermectin: A Closer Look at a Potential Remedy

Karim O. Elkholy, Omar Hegazy, Burak Erdinc, Hesham Abowali

DOI: 10.7759/cureus.10378

PDF: https://www.cureus.com/articles/37039-ivermectin-a-closer-look-at-a-potential-remedy#

Abstract

Amid the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the search for effective treatment and vaccines has been exponentially on the rise. Finding effective treatment has been the core of attention of many scientific reports and antivirals are in the center of those treatments. Numerous antivirals are being studied for the management of the coronavirus disease 2019 (COVID-19) pneumonia caused by the SARS-CoV-2. Remdesivir was the first drug to gain emergency FDA approval to be used in COVID-19. Similarly, favipiravir, an anti-influenza drug, is being studied as a potential agent against COVID-19. Contrastingly, hydroxychloroquine has been a controversial drug in the management of COVID-19. Nevertheless, the National Institute of Health (NIH), along with the World Health Organization (WHO), have discontinued clinical trials for hydroxychloroquine as the drug showed little or no survival benefit. Ivermectin, an antihelminthic drug, has shown antiviral properties previously. Additionally, it was described to be effective in vivo against the SARS-CoV-2. However, its survival benefit in patients with COVID-19 has not been documented. We herein propose the theory of inhaled ivermectin which can attain the desired lung concentration that will render it effective against SARS-CoV-2.

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

https://www.cureus.com/articles/37039-ivermectin-a-closer-look-at-a-potential-remedy#article-disclosures-acknowledgements

AstraZeneca COVID-19 vaccine study saga reflects risks in race

The recent (possible) safety signal-prompted hiccup in AstraZeneca’s (NYSE:AZN) large-scale pivotal study of COVID-19 vaccine candidate AZD1222 exemplifies the risky nature of these types of trials, especially the ones involving vaccines against SARS-CoV-2 infection considering the profound global need and intense investor scrutiny. Every unexpected event, no matter how insignificant, will be guaranteed a full vetting in this environment.

On September 8, shares dropped over 8% after hours (a shining example of off-hours volatility) in the U.S. in reaction to the news that the company voluntarily stopped the trial after a UK patient fell ill after inoculation, an appropriate and expected action to a commonly encountered event, especially in a study involving 30K people. Investors apparently agreed. Shares in the U.S. ended the day up 2% from the close of $53.58 on Friday, September 4. Shares in London were up 0.8% from the day before.

The next day, reports came out that the participant experienced serious neurological symptoms, later reported as transverse myelitis, an inflammatory condition of the spinal cord, quickly disabused by the company, explaining that no final diagnosis had been made since some test results were pending.

Yesterday, AZN chief Pascal Soriot reiterated that he was unsure on the specific length of the study pause but the company still plans to have a dataset to support a regulatory filing and the vaccine ready by year-end.

Even if the independent safety committee determines that the patient’s condition was caused by the vaccine, the study will resume. In these cases, the study sponsor typically updates the disclosure documents and investigator (trial site) guidelines to account for the event.

https://seekingalpha.com/news/3613391-astrazeneca-covidminus-19-vaccine-study-saga-reflects-risks-in-race-to-finish-line

COVID-19 vaccine trials ramp up as world awaits efficacy data

Public health authorities and government officials across the world are anxiously waiting for preliminary results from large-scale studies of COVID-19 vaccine candidates as they firm up distribution plans for the ones that pass muster with regulators. Data readouts could start as early as month-end or early October.

A search in ClinicalTrials.gov identified the following Phase 3 trials:

AstraZeneca’s (with University of Oxford) (NYSE:AZN) AZD1222: 100-subject open-label study in Russia. Two doses 28 days apart. Estimated start date: August 26. Estimated primary completion date: March 5, 2021. Estimated study completion date: March 5, 2021.

AZD1222: Global 30K-subject randomized parallel assignment study. Two doses 28 days apart. Estimated start date: August 17. Estimated primary completion date: December 2. Estimated study completion date: October 5, 2022.

University of Oxford’s ChAdOx1. Single dose and two doses 4-6 weeks apart. 12,330-subject study in the UK. Estimated start date: May 28. Estimated primary completion date: August 2021. Estimated study completion date: August 2021.

University of Oxford’s ChAdOx1. Single dose and two doses 4-12 weeks apart. 5K-subject study in Brazil. Estimated start date: June 2. Estimated primary completion date: September 2021. Estimated study completion date: September 2021.

Sinovac Life Sciences’ (NASDAQ:SVA) Absorbed COVID-19 (inactivated) Vaccine. 8,870 subject study in Brazil. Two doses 14 days apart. Start date: July 21. Estimated primary completion date: September 2021. Estimated study completion date: October 2021.

Gamaleya Research Institute’s Gam-COVID-Vac. 40K-subject study in Russia. Two doses 21 days apart (+/- 2 days). Estimated start date: August 31. Estimated primary completion date: May 1, 2021. Estimated study completion date: May 1, 2021.

China National Biotec Group’s Vero Cell inactivated vaccine. 45K-subject study in Bahrain and UAE. Two doses 21 days apart. Estimated start date: July 16. Estimated primary completion date: March 16, 2021. Estimated study completion date: September 16, 2021.

Fundació Institut Germans Trias i Pujol’s RUTI Vaccine. Two doses 14 days apart (+/- 3 days). 315-subject study in Spain. Estimated start date: July 30. Estimated primary completion date: December. Estimated study completion date: December.

CanSino Biologics’ Ad5-nCoV (AAV5 vector). Single dose. 40K-subject study in China. Estimated start date: August 30. Estimated primary completion date: December 30, 2021. Estimated study completion date: January 30, 2022.

NPO Petrovax’s Ad5-nCov (AAV5 vector). Single dose. 500-subject study in Russia. Estimated start date: September 7. Estimated primary completion date: November 30. Estimated study completion date: July 31, 2021.

Moderna’s (NASDAQ:MRNA) mRNA-1273. Two doses 28 days apart. 30K-subject study in U.S. Estimated start date: July 27. Estimated primary completion date: October 27, 2022. Estimated study completion date: October 27, 2022.

PT Bio Farma’s SARS-CoV-2 Vaccine (inactivated). Two doses 14 days apart. 1,620-subject study in Indonesia. Estimated start date: August 10. Estimated primary completion date: January 2021. Estimated study completion date: September 2021.

Pfizer (NYSE:PFE)/BioNTech’s (NASDAQ:BNTX): BNT162b2. Two doses 21 days apart. Global 29,481-subject study. Estimated start date: April 29. Estimated primary completion date: April 19, 2021. Estimated study completion date: November 14, 2022.

Johnson & Johnson’s (NYSE:JNJ) Ad26.COV2.S. Single dose. Global 60K-subject study. Estimated start date: September 5. Estimated primary completion date: March 10, 2023. Estimated study completion date: March 10, 2023.

Sanofi (NASDAQ:SNY) and adjuvant supplier GlaxoSmithKline (NYSE:GSK) launched a Phase 1/2 study of their vaccine candidate last week. A Phase 3 should start by year-end.

https://seekingalpha.com/news/3612966-covidminus-19-vaccine-trials-ramp-up-world-awaits-efficacy-data

Cardio MRI Findings in Competitive Athletes Recovering From COVID-19

Saurabh Rajpal, MBBS, MD¹; Matthew S. Tong, DO¹; James Borchers, MD, MPH¹; et al

doi:10.1001/jamacardio.2020.4916

Myocarditis is a significant cause of sudden cardiac death in competitive athletes and can occur with normal ventricular function.¹ Recent studies have raised concerns of myocardial inflammation after recovery from coronavirus disease 2019 (COVID-19), even in asymptomatic or mildly symptomatic patients.² Our objective was to investigate the use of cardiac magnetic resonance (CMR) imaging in competitive athletes recovered from COVID-19 to detect myocardial inflammation that would identify high-risk athletes for return to competitive play.

Methods

We performed a comprehensive CMR examination including cine, T1 and T2 mapping, extracellular volume fraction, and late gadolinium enhancement (LGE), on a 1.5-T scanner (Magnetom Sola; Siemens Healthineers) using standardized protocols,³ in all competitive athletes referred to the sports medicine clinic after testing positive for COVID-19 (reverse transcriptase–polymerase chain reaction) between June and August 2020. The Ohio State University institutional review board approved the study, and informed consent in writing was obtained from participating athletes. Cardiac magnetic resonance imaging was performed after recommended quarantine (11-53 days). Electrocardiogram, serum troponin I, and transthoracic echocardiogram were performed on day of CMR imaging.

Results

We performed CMR imaging in 26 competitive college athletes (mean [SD] age, 19.5 [1.5] years; 15 male [57.7%]) from the following sports: football, soccer, lacrosse, basketball, and track. No athletes required hospitalization or received COVID-19–specific antiviral therapy. Twelve athletes (26.9%; including 7 female individuals) reported mild symptoms during the short-term infection (sore throat, shortness of breath, myalgias, fever), while others were asymptomatic. There were no diagnostic ST/T wave changes on electrocardiogram, and ventricular volumes and function were within the normal range in all athletes by transthoracic echocardiogram and CMR imaging. No athlete had elevated serum levels of troponin I. Four athletes (15%; all male individuals) had CMR findings consistent with myocarditis based on the presence of 2 main features of the updated Lake Louise Criteria: myocardial edema by elevated T2 signal and myocardial injury by presence of nonischemic LGE (Figure).⁴ Pericardial effusion was present in 2 athletes with CMR evidence of myocarditis. Two of these 4 athletes with evidence of myocardial inflammation had mild symptoms (shortness of breath), while the other 2 were asymptomatic. Twelve athletes (46%) had LGE (mean of 2 American Heart Association segments), of whom 8 (30.8%) had LGE without concomitant T2 elevation (Table). Mean (SD) T2 in those with suspected myocarditis was 59 (3) milliseconds compared with 51 (2) milliseconds in those without CMR evidence of myocarditis.

Discussion

Of 26 competitive athletes, 4 (15%) had CMR findings suggestive of myocarditis and 8 additional athletes (30.8%) exhibited LGE without T2 elevation suggestive of prior myocardial injury. COVID-19–related myocardial injury in competitive athletes and sports participation remains unclear. Cardiac magnetic resonance imaging has the potential to identify a high-risk cohort for adverse outcomes and may, importantly, risk stratify athletes for safe participation because CMR mapping techniques have a high negative predictive value to rule out myocarditis.⁴ A recent study by Puntmann et al² demonstrated cardiac involvement in a significant number of patients who had recovered from COVID-19. A recent expert consensus article recommended 2-week convalescence followed by no diagnostic cardiac testing if asymptomatic and an electrocardiogram and transthoracic echocardiogram in mildly symptomatic athletes with COVID-19 to return to play for competitive sports.⁵ However, emerging knowledge and CMR observations question this recommendation. Cardiac magnetic resonance imaging evidence of myocardial inflammation has been associated with poor outcomes, including myocardial dysfunction and mortality.⁶ Study limitations include lack of baseline CMR imaging and variable timing of CMR imaging from a positive COVID-19 test result. Athletic cardiac adaptation could be responsible for these abnormalities; however, in this cohort, mean (SD) T2 in those with suspected myocarditis was 59 (3) milliseconds vs 51 (2) milliseconds in those without, favoring pathology. Additionally, the rate of LGE (42%) is higher than in previously described normative populations. To conclude, while long-term follow-up and large studies including control populations are required to understand CMR changes in competitive athletes, CMR may provide an excellent risk-stratification assessment for myocarditis in athletes who have recovered from COVID-19 to guide safe competitive sports participation.

Conflict of Interest Disclosures: Dr Simonetti reports grants from Siemens, Myocardial Solutions, and Cook Medical outside the submitted work. No other disclosures were reported.

https://jamanetwork.com/journals/jamacardiology/fullarticle/2770645?alert=article

Merck COVID-19 vaccine begins human testing in Belgium study

Merck (NYSE:MRK) +1.5% after-hours following a WSJ report that it has started testing one of its experimental COVID-19 vaccine candidates in healthy volunteers.

The study, located in Belgium and seeking to enroll 260 subjects, was reported by Merck on a government database; it is projected to complete in April 2022, although it could finish much faster.

Merck’s experimental shot contains a weakened version of the virus that causes measles, which hopefully would deliver the coronavirus’ spike protein to the immune system to help trigger an immune response.

The company has said it wants to develop a vaccine that would provide protection with a single dose so a second shot is not needed and uses a proven technology that can be scaled up readily for manufacture.

Vaccines from Pfizer (NYSE:PFE) and partner BioNTech (NASDAQ:BNTX), and Moderna (NASDAQ:MRNA) both use the unproven mRNA gene-based technology and also require two shots; those vaccines, as well as a vaccine from AstraZeneca (NYSE:AZN), are in late-stage clinical trials.

https://seekingalpha.com/news/3613474-merck-covidminus-19-vaccine-begins-human-testing-in-belgium-study-wsj

Can the Brain ‘Bounce Back’ From Decline With Lifestyle Change?

Making lifestyle changes may help older adults with subjective cognitive decline by improving thinking and memory skills, results from a proof-of-concept study suggest.

After 6 months’ follow-up, adults in an 8-week intervention group had higher cognitive scores compared to control persons, suggesting that lifestyle-based changes may modify the course of cognitive decline.

“This study supports the idea that if people experiencing cognitive decline can improve their lifestyle, their brain retains sufficient neuroplasticity to bounce back from decline and potentially reduce their risk of dementia in the future,” lead investigator Mitchell McMaster, PhD student at the Australian National University, Acton, Australia, told Medscape Medical News.

The study was published online September 9 in the Journal of the American Geriatrics Society.

Novel Finding

Participants included 119 adults older than 65 years (mean age, 73 years; 61% women) with subjective cognitive decline (SCD). There were 57 patients in the intervention group and 62 in the control group.

Over 8 weeks, the control group completed four online educational modules covering dementia and lifestyle risk factors, Mediterranean diet, physical activity, and cognitive engagement. Participants were told to integrate this information into their lifestyle.

Over the same time frame, the intervention group completed the same online educational modules but also received help in making healthy lifestyle changes. For example, they met with a dietitian three times, had a session with an exercise physiologist, and participated in online brain training.

Lifestyle risk factors for Alzheimer’s disease were assessed using the Australian National University–Alzheimer’s Disease Risk Index (ANU-ADRI), and cognition was assessed using the Alzheimer’s Disease Assessment Scale–Cognitive subscale and other standard tests.

At the final 6-month follow-up, the intervention group had a significantly lower (better) score on the ANU-ADRI (P = .013) and a significantly higher cognition score (P = .026) than the control group.

“That improvements in lifestyle risk can lead to improvements in global cognition in this high-risk group is a novel finding,” said McMaster.

Participants in the intervention group were able to improve their lifestyle risk scores by 2.5 points, “which is approximately equivalent to a lifestyle with low vs moderate levels of exercise (–2 points) or having diabetes (+3 points),” he added.

“A change of 2 points or more has been shown to lead to differences in the risk of developing dementia ― for that reason, it is clinically relevant,” he added.

The main limitation of the study was the limited follow-up time of 6 months. Meta-analyses of nondrug interventions for SCD recommend a minimum follow-up of at least 12 months, the authors note in their article.

Caveats and Considerations

Reached for comment, Joanna Hellmuth, MD, with the Memory and Aging Center, Department of Neurology, University of California, San Francisco, said, “It’s good to see a more rigorous evaluation of lifestyle interventions, which is much needed in the field. Currently, there are no studies to my knowledge that support the idea that these types of lifestyle interventions can reverse cognitive decline.”

Hellmuth noted that SCD has many causes, including the normal patterns of cognitive aging, medication effects, medical conditions such as sleep apnea, vitamin B12 deficiency, thyroid disorders, and others. It’s unclear in this study “how rigorously other medical causes were excluded in these participants,” she noted.

A placebo effect also can’t be ruled out.

“The control group is exposed to online modules, while the intervention group also gets one-on-one sessions to support the lifestyle modifications. These one-on-one interactions could increase the placebo effect and contribute to the positive outcomes of the study,” Hellmuth said.

In her view, “it would have been a stronger study if the control group was exposed to similarly intensive on-on-one interventions, but for purposes unrelated to the lifestyle interventions.”

Hellmuth said she agrees with the authors’ statement that this study is a proof-of-concept randomized control trial of lifestyle interventions targeting dementia risk factors.

“These kinds of rigorous evaluations of lifestyle interventions are needed in the field and should be applauded. More studies need to be done on lifestyle interventions, as these lifestyle changes are standard-of-care recommendations in dementia clinics,” said Hellmuth.

However, Hellmuth said the authors’ conclusion – that the findings “support the hypothesis that individuals in the early stages of cognitive decline retain sufficient neuroplasticity to achieve cognitive improvements in the short term” – is a “stretch.”

“We don’t know with certainty that any of the individuals in the study would have had further cognitive decline or gone on to develop dementia, and the improvements from the study intervention could in part be from placebo effect, which was not controlled for sufficiently,” she told Medscape Medical News.

Support for the study was provided by the Dementia Australia Research Foundation, the Australian National University, and Neuroscience Research Australia. McMaster and Hellmuth have no disclosed no relevant financial relationships.

J Am Geriatr Soc. Published online September 9, 2020. Abstract

https://www.medscape.com/viewarticle/937243#vp_1