Gabrielle Ientile, Assistant Editor

Approximately 50% of patients hospitalized for severe COVID-19 and with elevated troponin levels presented lasting heart damage, including myocarditis, infarction, ischemia, as well as combinations of all 3, according to a recent study.

Investigators from London, United Kingdom, utilized multi-parametric cardiovascular magnetic resonance (CMR) to diagnose causes of elevated troponin in patients who recovered from SARS-CoV-2.1 The study, published in the 

Acute respiratory infections and sepsis are often indicative of elevated serum troponin levels in hospitalized patients, which may lead to death even after a patient’s recovery, investigators explained.

The study recruited 148 patients with severe infection of the virus, defined as requiring hospitalization, and 48% of which additionally required ventilation support, who experienced troponin elevation up to June 2020 among 6 hospitals across 3 NHS Foundation trusts: Royal Free London, Imperial College Healthcare, and University College London Hospital.

COVID-19 infection was diagnosed through either:

a positive combined oro/nasopharyngeal throat swab or tracheal aspirate for SARS-CoV-2 by reverse-transcriptase-polymerase chain reaction (PCR), or

a negative SARS-CoV-2 swab with a demonstration of illness, including cough, fever, myalgia, as well as typical blood biomarkers and high likelihood of viral infection.

Following hospital discharge, the 148 patients with an abnormal high-sensitivity troponin (hsTnT14 ng/L for Royal Free and UCLH; hsTnI14 ng/L for females and 30 mL/min/m2 for males for Imperial) underwent CMR scans. All volunteer participants did not have symptoms or a history of cardiovascular disease or hypertension, and the control group was matched for age, gender, diabetes, and hypertension but with no clinical suspicion of myocardial injury, including myocardial infarction (MI) or myocarditis.

Of the 148 patients, 133 underwent a full tissue characterization protocol (LGE, T1 and T2 mapping). Investigators reported that the mean age of patients was 64 12 years, with 70% of patients being male (104). Eighty-six percent (128) of patients were PCR-positive, and 93% (138) presented typical symptoms of COVID-19. Additionally, the median length of stay in the hospital was 9 days; 32% (48) of patients required admission to the intensive care unit in order to receive ventilation support.

As for cardiac function, left ventricular dysfunction was present in 11% (17) of patients, with 9 cases a result of myocardial infarction, 6 of whom had a history of ischemic heart disease. The average right ventricular ejection fraction (RVEF) was 61% 9% and was the same in the healthy volunteers (RVEF 61% 5%, 

 = 0.85); however, RVEF was lower in the matched control group (RVEF 64% 7%, 

After follow up of at least 1 month, scarring or injury to the heart muscle was found in 54% (80) of patients, stemming from inflammation (26%), infarction or ischemia (22%), or both (6%), with 8% of patients showing ongoing heart inflammation, according to investigators.

"These findings give us 2 opportunities: firstly, to find ways of preventing the injury in the first place, and from some of the patterns we have seen, blood clotting may be playing a role, for which we have potential treatments,” said co-lead researcher Marianna Fontana, professor of cardiology at University College London, United Kingdom.

“Secondly, detecting the consequences of injury during convalescence may identify subjects who would benefit from specific supporting drug treatments to protect heart function over time.”

Study authors stipulated that it remains uncertain whether the findings demonstrate preexisting disease or that brought on by COVID-19, and more research is necessary.

“We found evidence of high rates of heart muscle injury that could be seen on the scans a month or 2 after discharge. Whilst some of this may have been preexisting, MRI scanning shows that some were new, and likely caused by COVID-19,” Fontana said.

“Importantly, the pattern of damage to the heart was variable, suggesting that the heart is at risk of different types of injury. While we detected only a small amount of ongoing injury, we saw injury to the heart that was present even when the heart's pumping function was not impaired and might not have been picked up by other techniques. In the most severe cases, there are concerns that this injury may increase the risks of heart failure in the future, but more work is needed to investigate this further."

1. Kotecha T, Knight DS, Razvi Y, et al. Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance. 

https://doi.org/10.1093/eurheartj/ehab075

2. Damage to the heart found in more than half of COVID-19 patients discharged from hospital. News release. European Society of Cardiology; February 18, 2021. Accessed February 24, 2021. https://www.escardio.org/The-ESC/Press-Office/Press-releases/Damage-to-the-heart-found-in-more-than-half-of-COVID-19-patients-discharged-from-hospital 

Articles

Investigators used MRI scans of the heart to identify whether heart injury was caused by COVID-19 infection.   

Study Results Show Half of Severe COVID-19 Patients Have Damage to the Heart 

A panel of advisors to the FDA voted 22 to 0 to recommend the Janssen vaccine, named Ad26.COV2.S, for emergency approval, according to the FDA Advisory Committee Meeting held on Friday. The decision moves Ad26.COV2.S one step closer to receiving emergency use authorization (EUA) by the FDA. If approved, it will be the first single-dose vaccine for COVID-19 and the third vaccine to be authorized in the US for the virus.

Although both Pfizer and Moderna utilized messenger RNA (mRNA) technology, the Johnson & Johnson vaccine is an adenovirus-based vaccine that employs a portion of genetic material from a weakened pathogen in order to induce an immune response. The company leveraged its AdVac vaccine platform that has also been previously deployed to investigate Zika, RSV, and HIV investigational vaccine candidates.

Janssen’s request for EUA for its vaccine is based on its phase 3, randomized, double-blind, placebo-controlled ENSEMBLE clinical trials, which met all primary and key secondary end points; overall, the investigational vaccine demonstrated 66% efficacy in preventing moderate-to-severe COVID-19. Johnson & Johnson submitted its EUA request on February 4.

On Wednesday, the FDA released results of its analysis of the data, confirming the safety and efficacy of the vaccine. According to the data, vaccine efficacy against moderate to severe/critical COVID-19 was 66.9% (95% CI 59.0, 73.4) when considering cases occurring at least 14 days after the single-dose vaccination and 66.1% (55.0, 74.8) when considering cases occurring at least 28 days after vaccination. The vaccine was also demonstrated to be 76.6% and 85.4% effective against severe/critical cases after 14 days and 28 days, respectively.

A post hoc analysis showed no COVID-19 hospitalizations in the vaccine group after 28 days compared with 16 cases in the placebo group.

The briefing document provided a breakdown of efficacy rates in regions where the new SARS-CoV-2 variants emerged, looking at efficacy across 3 countries: United States, South Africa, Brazil. In a subgroup analysis, there was lower efficacy against moderate to severe/critical COVID-19 observed in South Africa compared with the United States. However, efficacy against severe/critical COVID-19 was comparably high across all 3 countries.

The company has also applied for authorization of the Janssen vaccine with several health agencies outside the US on a rolling basis and plans to submit a Conditional Marketing Authorization Application with the European Medicines Agency in the coming weeks.

Johnson & Johnson recently stated that upon authorization, vaccines will be shipped out to health care facilities and pharmacies immediately.

Kaitlyn Rivard, PharmD, BCPS, BCIDP, AAHIVP infectious diseases residency director at the Cleveland Clinic, recently discussed the significance of the Johnson & Johnson COVID-19 vaccine for at-risk populations in an interview with 

Pharmacist Leads COVID-19 Vaccination Clinic

“Certainly, a single dose vaccine will be incredibly helpful from a logistic standpoint, especially for patients who have trouble coming in for 2 doses,” Rivard said.

“I think it'll also depend on the federal government and where they allocate that product. I could see them focusing that product in areas where cold storage is a bigger concern, such as rural areas and underserved areas. I think there's still a lot more to learn about where Johnson & Johnson is going to fit in from a logistics standpoint,” she said.

For pharmacists, the Johnson & Johnson vaccine also means pivoting in terms of strategy in order to make room for additional products.

“I would encourage anyone who is currently working through the mRNA vaccines to begin planning for the next round of vaccines that are coming as well,” Rivard said. “We’re going to need as many products on hand as possible to get the population vaccinated to have the impact we’re aiming for.”

Lisa Holle, PharmD, BCOP, FHOPA, FISOPP, associate clinical professor at the University of Connecticut School of Pharmacy, agreed that the Janssen vaccine will make COVID-19 vaccination much more accessible for many Americans. 

"The significance of the EUA for Johnson & Johnson COVID-19 vaccine is huge," Holle wrote in an email to Drug Topics. "With more vaccines available on the market, more of the US population can be vaccinated more quickly. This in turn should help us more quickly return to normal life."

"Furthermore, with only requiring 1 dose not 2 doses, this may help more folks be able to get the vaccine as well. Two-dose vaccines may be difficult for some, especially in areas where vaccine clinic availability is only during typical M-F 9-5 type hours and they may work during those times," Holle wrote. 

The FDA is not required to follow the committee’s advice, but it is expected to do so.

1. US Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee – 2/26/2021.

2. FDA. FDA Briefing Document: Janssen Ad26.COV2.S Vaccine for the Prevention of COVID-19. Vaccine and Related Biological Products Advisory Committee Meeting, February 26, 2021. Accessed February 24, 2021. 

https://www.fda.gov/media/146217/download

On Friday, a panel of advisors to the FDA voted to recommend Johnson & Johnson's COVID-19 vaccine, named Ad26.COV2.S, for emergency approval.

FDA Panel Endorses Johnson & Johnson's COVID-19 Vaccine for EUA

The FDA has approved cemiplimab-rwlc (Libtayo; Regeneron) for the first-line treatment of advanced non-small cell lung cancer (NSCLC) for tumors with high PD-L1 expression (tumor proportion score 50%) and without certain aberrations in patients with either metastatic or locally advanced tumors that are not candidates for surgical resection or definitive chemoradiation.

The approval of cemiplimab-rwlc followed priority review by the agency, as well as a separate approval as a first immunotherapy indicated for certain patients with advanced basal cell carminoma (BCC). Investigators highlighted that the clinical trial on which the NSCLC approval was based included a patient population often underrepresented in key NSCLC clinical trials.

Cemiplimab-rwlc is a fully-human monoclonal antibody that targets the immune checkpoint receptor PD-1 on T-cells. In effect, the drug is able to block cancer cells from occupying the PD-1 pathway.

Lung cancer is the leading cause of cancer death worldwide, with approximately 2.2 million new cases diagnosed in 2020 alone. Cancer researchers have estimated that 84% of lung cancers are NSCLC, 75% of which are diagnosed in its advanced stages.

Approval for the first-line NSCLC indication was based on the open-label, randomized, multi-center phase 3 EMPOWER-Lung 1 clinical trial, which focused on investigating first-line treatment with cemiplimab-rwlc in patients with advanced NSCLC and who tested positive for PD-L1 in 50% of tumor cells and without EGFR, ALK, or ROS1 aberrations. Investigators confirmed PD-L1 expression through the Agilent Dako PD-L1 IHC 22C3 pharmDx kit.

The clinical trial measured overall survival (OS) and progression free survival (PFS) in 710 patients with either previously untreated metastatic, stage IV NSCLC, or locally advanced, stage IIIB/C NSCLC who were not candidates for surgical resection or definitive chemoradiation, or who had progressed following treatment with definitive chemoradiation. Patients were randomized to either receive cemiplimab-rwlc (n=283) or chemotherapy (n=280).

Data showed that cemiplimab-rwlc reduced the risk of death by 32% compared with chemotherapy. Patients treated with cemiplimab-rwlc showed a median PFS of 8 months, with a range between 6 and 9 months, whereas patients receiving chemotherapy exhibited 6-month median PFS rate, with a range from 5 to 6 months.

Researchers assessed safety in 355 patients in the treatment group; rash (15%) and cough (11%) were the most frequent adverse reactions. As for serious reactions, investigators reported pneumonitis (2%) most often. Six percent of patients discontinued treatment with cemiplimab-rwlc due to adverse reactions.

"We developed Libtayo to deliver clinically meaningful benefits to patients suffering from a diverse range of cancers and to establish a foundation for potential future immunotherapy combinations. Today's approval continues to support this vision," said Israel Lowy, MD, PhD, senior vice president of translational and clinical sciences, oncology at Regeneron.

"Libtayo has already changed the treatment paradigm for certain patients with advanced cutaneous squamous cell carcinoma and is poised to do the same for advanced basal cell carcinoma. Now, Libtayo has the opportunity to make a meaningful difference for the many US patients battling advanced non-small cell lung cancer. Libtayo is being investigated in a variety of settings, and we hope to share updates later this year on our pivotal trials in cervical cancer and in combination with chemotherapy in advanced non-small cell lung cancer," Lowy said.

FDA Approves Libtayo® (cemiplimab-rwlc) Monotherapy for Patients with First-line Advanced Non-small Cell Lung Cancer with PD-L1 Expression of ≥50%. News Release. PRNewswire; February 22, 2021. Accessed February 23, 2021. 

https://www.prnewswire.com/news-releases/fda-approves-libtayo-cemiplimab-rwlc-monotherapy-for-patients-with-first-line-advanced-non-small-cell-lung-cancer-with-pd-l1-expression-of-50-301232638.html

 The approval of the first-line treatment was granted to Regeneron Pharmaceuticals.

FDA Approves Cemiplimab-rwlc for Advanced NSCLC in Certain Patients With High PD-L1 Expression

 reported that treatment with once weekly semaglutide, along with lifestyle intervention, in individuals who are overweight or obese resulted in sustained and clinically beneficial weight loss.

Obesity is a chronic disease that can lead to insulin resistance, hypertension, and dyslipidemia and is associated with type 2 diabetes and cardiovascular disease (CVD), among other conditions. Despite the prevalence of obesity worldwide, there remain few drugs indicated for the disease.

Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue currently approved to treat type 2 diabetes and to reduce the risk of cardiovascular events in individuals with type 2 diabetes and CVD.

The double-bind trial included 1961 participants with a body-mass index (BMI) of 30 or greater or 27 in participants with at least 1 weight-related coexisting condition who did not have diabetes. Investigators randomly assigned participants in a 2:1 ratio to either 68 weeks of treatment with once-weekly subcutaneous semaglutide at a 2.4-mg dose or placebo, in combination with a lifestyle intervention.

Data showed that the mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group and -2.4% in the placebo group, demonstrating an estimated treatment difference of -12.4 percentage points (95% CI, -13.4 to -11.5; 

Eighty-six percent (1047) of individuals in the semaglutide group achieved weight loss of 5% or more, compared with 31.5% (182) of participants receiving placebo, according to the investigators. Those who received semaglutide also more readily saw weight reductions of 10% or more than the placebo group: 838 (69.1%) and 69 (12.0%), respectively. For weight reductions of 15% or more, the semaglutide group reported that 612 (50.5%) achieved the weight loss measure, whereas only 28 (4.9%) in the placebo group achieved the same.

Study authors explained that by losing 5% or more of baseline body weight, participants displayed clinically meaningful responses. Weight loss of 10% to 15% or more is recommended in individuals with many complications from being overweight or obese - including prediabetes, hypertension, and obstructive sleep apnea . Therefore, the study results depict a clear clinical benefit.

Analysis of the data determined that semaglutide led to greater reduction in fat mass than lean body mass in those with obesity and in those with type 2 diabetes, which is on par with previous studies. 

Safety data were consistent with past studies as well. The most frequently reported adverse events (AEs) were mild-to-moderate gastrointestinal disorders; more participants receiving semaglutide than placebo stopped treatment due to AEs.

“Our trial showed that among adults with overweight or obesity (without diabetes), once-weekly subcutaneous semaglutide plus lifestyle intervention was associated with substantial, sustained, clinically relevant mean weight loss of 14.9%, with 86% of participants attaining at least 5% weight loss,” the study authors concluded.

Wilding JP, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. 

 February 10, 2021. Accessed February 18, 2021. doi: 10.1056/NEJMoa2032183.

Once-weekly semaglutide 2.4 mg resulted in sustained reductions in weight for those who are overweight or obese, the investigators reported.