Day: July 12, 2021

Woman, 90, Succumbs to Double COVID Variant Infection

Double COVID Variant Infection

Researchers in Belgium report on the case of a 90-year-old woman who was simultaneously infected with two different COVID variants.

On March 3 2021, the woman, with an unremarkable medical history, was admitted to a Belgian hospital after a spate of falls. She tested positive for COVID on the same day. She received nursing care at home, where she lived alone, and had not received a COVID vaccination.

At first, no signs of respiratory distress were seen, and oxygen saturation was good. However, she went on to develop rapidly worsening respiratory symptoms, and died five days later.

PCR testing revealed that she had been infected by two different strains of the virus — one which originated in the UK, known as B.1.1.7 (Alpha), and another that was first detected in South Africa (B.1.351; Beta).

“This is one of the first documented cases of co-infection with two SARS-CoV-2 variants of concern”, says lead author and molecular biologist Dr. Anne Vankeerberghen from the OLV Hospital in Aalst, Belgium. “Both these variants were circulating in Belgium at the time, so it is likely that the lady was co-infected with different viruses from two different people. Unfortunately, we don’t know how she became infected.”

The Alpha variant had been detected in the south east of England in December and within weeks, this variant displaced the viral strains circulating there. Since then, it has spread to more than 50 countries, including Belgium. The Beta variant was reported on December 18, 2020, and has since spread to 40 countries, which also includes Belgium.
Scientists in Brazil reported in January 2021 that two people had been simultaneously infected with two different strains of the coronavirus—the Brazilian variant known as B.1.1.28 (E484K) and a novel variant VUI-NP13L, which had previously been discovered in Rio Grande do Sul. However, this study has yet to be published in a scientific journal.

“Whether the co-infection of the two variants of concern played a role in the fast deterioration of the patient is difficult to say”, said Vankeerberghen. “Up to now, there have been no other published cases. However, the global occurrence of this phenomenon is probably underestimated due to limited testing for variants of concern and the lack of a simple way to identify co-infections with whole genome sequencing.”

She continued, “Since co-infections with variants of concern can only be detected by VOC-analysis of positive samples, we would encourage scientists to perform fast, easy and cheap VOC-analysis by PCR on a large proportion of their positive samples, rather than just whole genome sequencing on a small proportion. Independent of the technique used, being alert to co-infections remains crucial.”

Source: EurekAlert!

Emerging Variants Threaten a Worsening of the Pandemic

Photo by Viktor Forgacs on Unsplash

Progress against the COVID pandemic has been impeded by the emergence of new variants of concern (VOC), and new ones may further worsen and prolong it.

VOCs increase the transmissibility of the SARS-CoV-2 virus and hence raise the reproduction number. Furthermore, they enhance the immune escape capabilities of the virus and blunt the effectiveness of available vaccines. Finally, they increase the pathogenicity of the infection.

Alpha, Beta, and Gamma VOCs with the N501Y mutation replaced the initial wild-type SARS-CoV-2 strains in Ontario, Canada, and then the Delta variant dominated during the period between February to June 2021. While enhanced virulence of VOCs having the N501Y mutation has been reported, there is a lack of comprehensive analyses that demonstrate increased virulence of the Delta variant.

Researchers from Toronto University, Canada, recently showed that these emerging VOCs were linked to increased virulence, as determined by hospitalisation risk, ICU admission, and mortality. This study is currently available on the medRxiv preprint server.

The researchers created a retrospective cohort of patients testing positive for SARS-CoV-2 in Ontario and screening for VOCs between February 3 and July 1, 2021. Case data was gathered from the Ontario provincial Case and Contact Management (CCM) database. All PCR positive COVID-19 specimens with a cycle threshold (Ct) ≤ 35 were screened for the N501Y mutation using the real-time PCR assay from the Public Health Ontario Laboratory. Whole genome sequencing (WGS) was performed on 5% of specimens regardless of the presence of mutations.

Results show that infection by VOCs with the N501Y mutation significantly elevated risk of hospitalization, ICU admission, and death in patients in Ontario.

Compared to non-VOC strains of SARS-CoV-2, the increase in risk associated with N501Y-positive variants was 138% (105-176%) for ICU admission; 74% (62-86%) for hospitalisation; and 83% (57-114%) for death, after adjusting for age, sex, and comorbidity. Increase in risks associated with the delta variant was even higher- 241% (163-344%) for ICU admission; 105% (80-133%) for hospitalisation; and 121% (57-211%) for death.

VOCs with the N501Y mutation were found to be associated with a significantly higher risk of hospitalisation, ICU admission, and death in infected individuals in Ontario, Canada. They also reveal that the Delta variant, becoming dominant in Ontario, has increased these risks even further.

“Individuals infected with VOCs were, on average, younger and less likely to have comorbid conditions than those infected with non-VOC, but nonetheless had higher crude risks of hospitalisation and ICU admission,” the authors found.

According to the authors, the clear and significant elevation of risks of even delayed outcomes such as death visible in their analysis is remarkable given the relatively small number of delta variant infections in the time period of this study. The fact that Canada is one of the leading countries in the world in terms of COVID vaccination rates has certainly mitigated the impact of these VOCs.

In summary, the researchers showed that despite excellent vaccination rates in Ontario, Canada, and VOCs infecting predominantly younger and healthier individuals, these VOCs are associated with an increase in virulence and risk of death. In particular, the Delta variant is more virulent compared to previously dominant VOCs possessing the N501Y mutation. It is the authors’ view that the progressive increase in transmissibility, immune escape and virulence of emerging VOCs could result in the pandemic being more drawn out and deadly.

Source: News-Medical.Net

Young Boy’s Triumph Over Rare Heart Condition

Photo by Danijel Durkovic on Unsplash
Photo by Danijel Durkovic on Unsplash

Hannah Lewis was expecting to learn the sex of her first child at 20 weeks of her pregnancy. Anxious about becoming a mother at just 19, Lewis was thrilled when she learned she was having a boy.

However, with a worried look on her face, her doctor told her that the baby’s organs looked healthy – except for his heart.

The baby was diagnosed with hypoplastic left heart syndrome, or HLHS, a rare condition where the heart’s left side is underdeveloped, doubling the workload for the right side. Days later, doctors at a children’s hospital in Nashville, Tennessee, confirmed the diagnosis.

But Lewis said her faith gave her the strength to believe she was meant to raise this child as a single mother, as well as her own experiences being raised by a single mother herself.

The rest of the pregnancy was filled with checkups and tests but remained uneventful. Then, at 37 weeks, doctors realised he was developing foetal hydrops, a life-threatening condition in which an abnormal amount of fluid accumulates in the tissue around the lungs, heart or abdomen, or under the skin.

Even in shock from induced labour followed by a caesarean, she remembers hearing her son’s first cries:

“They let me see him for just a second,” she said. “I loved him at first sight obviously, but I was super scared because they took him directly to the heart cath lab and for like 12 hours, we didn’t know what was going on. I was very sick so they wouldn’t let me go see him.”

She named him Bennett after learning the moniker means “God’s gift of hope” or “little blessed one”.

“It was so fitting for what he was about to face,” Lewis said.

HLHS is usually treated with either three different surgeries at certain stages of development or a heart transplant.

Because of the complications introduced by foetal hydrops, Bennett Sayles was 6 days old when he underwent his first open-heart surgery. Although the procedure went well, Bennett remained in critical condition on a ventilator. Then, when he was 2 months old, he had a stroke.

After three open-heart surgeries, 9 month old Bennett had stabilised enough to go home. But shortly before he was discharged, he went into cardiac arrest, and was without a heartbeat for six minutes.

“Then, out of nowhere, his heartbeat came back and it was strong,” Lewis said.

Two weeks later, days before his first Christmas, Bennett went home for the first time. After he turned 2, Bennett underwent the second HLHS surgery, which didn’t work and days later, he needed a fifth open-heart surgery.

Some weeks later he went home, but in hours, Bennett was back in the emergency room with staph infection in his chest. However, Bennett made it home again in time for Christmas. And ever since that series of setbacks, things have improved for him.

“His mental capacity is anywhere from 3 to 5 years old, but he’s got this amazing personality,” Lewis said. “He’s just got such a caring heart. When he’s in the room, he really does light it up and he changes the way you see things. I’m inspired every day because of how amazing he is and he doesn’t let anything hold him back or stop him.”

Two years ago, Bennett’s doctors determined that he would never be a candidate for the other surgeries needed to treat HLHS. He could, however, become eligible for a heart transplant.

“It’s debatable whether he’ll get there, but having known Bennett for the last nine years is not surprising at all that he has progressed to this point,” said Dr. Gerald Johnson, the boy’s paediatric cardiologist. “One of the beauties of working with kids is that they fight and they work to get better, and they work through things in ways that we as adults don’t necessarily do. Bennett’s been a particular fighter on that score and his mother is very proactive and in tune with his needs.”

Raising Bennett has taught Lewis and her family to focus on the present. “We don’t know what’s in store for Bennett,” Lewis said. “He could live his whole life like this or we can have him just a few more years. We love every minute we get to have with him.”

Source: American Heart Association

Probe over Controversial Alzheimer’s Drug’s Approval

Amyloid plaques and neurons. Source: NIAH

The interim commissioner of the US Food and Drug Administration, Janet Woodcock, MD, last week requested the country’s Office of Inspector General to perform an independent investigation into the regulator’s decision to approve Biogen’s controversial Alzheimer’s drug Aduhelm.

Dr Woodcock noted in her letter that there “continues to be concerns raised” regarding the contact between FDA officials and Biogen ahead of the agency’s decision, “including some that may have occurred outside of the formal correspondence process.”

Dr Woodcock’s request comes after a bombshell report from Stat, which found that Biogen executives met with FDA officials, specifically Billy Dunn, MD, director of the FDA’s neuroscience unit, as early as 2019 to discuss a regulatory pathway for Aduhelm. The meetings took place even when it seemed there was no progress for the drug.

Earlier this week, a US House Representative, charged Biogen with “undue influence” over the FDA’s review process. Less than two weeks earlier, the House Committee on Oversight and Reform said it would conduct its own probe into the approval along with Biogen’s pricing strategies.

In the letter from Friday, Dr Woodcock said the agency would fully cooperate with the potential investigation to determine whether any of its interactions with Biogen were inconsistent with FDA policies and procedures.

“Given the ongoing interest and questions, today I requested that @OIGatHHS conduct an independent review and assessment of interactions between representatives of Biogen and FDA during the process that led to the approval of Aduhelm,” tweeted Dr Woodcock.

However, she maintained that she has “tremendous confidence” in the leadership at the FDA’s Center for Drug Evaluation and Research, which was involved in the review of Aduhelm.

“We believe this review and assessment will help ensure continued confidence in the integrity of FDA’s regulatory processes and decision-making,” Woodcock said in a tweet.

A spokesperson from Biogen told Fierce Pharma that the company would “of course” cooperate with “any inquiry in connection with a possible review of the regulatory process.”

The commissioner’s request is only the latest event in a bizarre and twisted story since the FDA’s Aduhelm approval just one month prior.

Facing fierce criticism of its wide-labelled approval, the FDA made the surprising move to narrow Aduhelm’s label last week Thursday, restricting the recommendation to just those with milder Alzheimer’s.

This comes after Biogen’s drug was essentially allowed access to the nation’s some 6 million Alzheimer’s patients. That decision was met with almost immediate pushback, as it was pointed out that the drug could overwhelm the payer budgets of most Alzheimer’s patients.

Source: Fierce Pharma

Positives as Well as Criticism for Ivermectin Review

Source: Pixabay CC0

An eagerly awaited review and meta-analysis on ivermectin for COVID has arrived, however while it seems positive there are many shortcomings and unanswered questions. 

The findings of the study, led by Andrew Hill, PhD, of the University of Liverpool, were published in Open Forum Infectious Diseases. The review and meta-analysis was conducted as part of the International Ivermectin Project Team from December 2020 to May 2021. Ivermectin proponents alleged that Dr Hill was conducting the analysis for the WHO, but MedPage Today was not able to make a confirmation of this. A separate review published on June 28 in the journal Clinical Infectious Diseases found no benefits for ivermectin use in COVID.

Dr Hill and colleagues assessed 24 randomised trials enrolling a total of 3328 patients that involved some type of control, whether it was standard of care or some other therapy. Sample sizes ranged from 24 to 400 participants. Of these, eight were published studies.

In the 11 trials with 2127 patients that focused on moderate or severe infection, a 56% reduction in mortality was seen (P=0.004), with 3% of patients on ivermectin dying compared with 9% of controls.

However, the researchers noted that the total number of deaths was small (128) and in the subgroup with severe disease, there was no difference between ivermectin and controls. As for moderate disease, they reported a 70% improvement in survival with ivermectin (P=0.0004).
Compared with controls, ivermectin use was also associated with a reduction in time to recovery of 1.58 days (P=0.01) and with a shorter duration of hospitalisation of 4.27 days (P=0.05).

However, the drug was not associated with a lower risk of hospitalisation, though a sensitivity analysis that included any hospitalizations within 12 hours of taking the drug did show a reduction with ivermectin (RR 0.32, 95% CI 0.13-0.80, P=0.01).

A key limitation was the lack of peer review for many studies included in the analysis; there was also wide variation in terms of dosage, treatment duration, and inclusion criteria. There were also many different comparators, including hydroxychloroquine, lopinavir/ritonavir, standard of care, and placebo.

The authors concluded that their results “need to be validated in larger confirmatory trials”. David Boulware, MD, MPH, of the University of Minnesota, agreed with this. Dr Boulware has been interested in evaluating ivermectin for COVID outpatients, agreed with. On Twitter, he noted that no mention was made of whether patients used steroids, which could seriously confound results.

Only two of seven trials showed a reduction in symptom duration in outpatient trials. No analysis was done to see if early treatment cut hospitalisation risk.

He tweeted that there was a need for phase III randomised clinical trials “in order to delineate what is the clinical benefit of early treatment”, such as quicker resolution and fewer symptoms. He would have also liked to see more distinction between outpatient and in-hospital therapy.

“Of course, rolling out vaccination as quickly and widespread as possible would negate the need to use ivermectin as a treatment,” he added. “So big picture, vaccines are the better solution.”

There are multiple ongoing phase III randomised controlled trials “which will provide definitive results,” Boulware noted. These include the UK-based PRINCIPLE outpatient trial which has a target of 1500 patients for its ivermectin arm.

Source: MedPage Today