Category: COVID

Closure Threat for SA’s COVID Vaccine Plant as Orders Dry up

Female scientist in laboratory
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South Africa’s COVID vaccine production plant, the first of its kind in Africa is at risk of closure after failing to secure a single according to a report from Reuters. President Cyril Ramaphosa is reported to be in talks with three other African nations in effort to save the venture.

The World Health Organization had called the licensing deal between Johnson & Johnson and Aspen Pharmacare to manufacture the Aspenovax COVID vaccine, a “transformative moment” in the pursuit of equitable access to vaccines. The vaccine is the J&J adenovirus vector vaccine sold under the Aspen brand.

However, after initial vaccine delivery shortfalls, the African continent is now well stocked with vaccines, while the poor infrastructure hampers vaccine distribution.

“There’ve been no orders received for Aspenovax,” Reuters reported, citing a phone conversation with Aspen senior director Stavros Nicolaou.

“If we don’t get orders, we would have to repurpose these lines back into other things that we were previously doing,” he told CapeTalk.

There are several other such vaccine plants in various stages, as the African Union aims at 60% of locally produced vaccines for continent locally by 2040, up from the current 1%.

“If Aspen doesn’t get production, what chance is there for any of the other initiatives?” Nicolaou remarked.

Regarding possible options, he said: “We are exploring various options. It is our medium-to-long-term objective to look at providing a sterile [processing] platform and solutions for the continent but the short-term needs to be sorted out.”

Moderna announced an agreement with Kenya to set up its first mRNA manufacturing facility in Africa with the aim of producing up to 500 million doses a year.

Source: Seeking Alpha

Two Doses of Pfizer or J&J Vaccine are Effective vs Severe Omicron

Image of a syring for vaccination
Photo by Mika Baumeister on Unsplash

A South African-led study published in the New England Journal of Medicine has shown that two doses of the Pfizer or the Johnson and Johnson (J&J) vaccine are equally effective against severe COVID caused by the omicron variant.

The omicron variant has been shown to escape antibody neutralisation by both the Pfizer/BioNTech mRNA and the Johnson & Johnson adenovirus viral vector vaccine, the only two COVID vaccines available in South Africa. As of May 1, 44.8% of adults in South Africa had been fully vaccinated. Assessing vaccine effectiveness is critical for national vaccine programs.

Starting in October 2021, health care workers who were participating in phase 3b of the Sisonke study of the early vaccine access program were eligible to receive a second dose of the J&J vaccine. Discovery Health data was accessed for Pfizer vaccine effectiveness. Severe COVID was defined as hospitalisation or admission to an intensive care unit (ICU) or to high care.

Vaccine effectiveness was compared between the two vaccine groups according to the number of days since the second vaccine dose had been administered. However longer follow-ups were not available for the J&J group as booster had been initiated later for them.

PCR results were analysed from participants who had received two doses of the Pfizer vaccine given at least 42 days apart or two doses of the J&J vaccine given 4 to 6 months apart. Among these participants, the test positivity rate was 34%; of those with a positive PCR test, 1.6% had been admitted to a hospital and 0.5% to an ICU or to high care.

Effectiveness against hospitalisation in the J&J group, was found to be 55% within 13 days after the second dose, 74% at 14 to 27 days, and 72% at 1 to 2 months. For the Pfizer group, the vaccine’s effectiveness was 81% within 13 days after the second dose, 88% at 14 to 27 days, 70% at 1 to 2 months, 71% at 3 to 4 months, and 67% at > 5 months. Among J&J vaccine recipients, the vaccine effectiveness against ICU admission or high care was 69% at 14 to 27 days and 82% at 1 to 2 months after the second dose; among the Pfizer recipients, effectiveness against ICU admission or high care was 70% at 1 to 2 months, 73% at 3 to 4 months, and 71% at > 5 months.

Gray et al concluded, “After two doses, both vaccines were equally effective against severe disease caused by the omicron variant. These estimates of vaccine effectiveness were calculated in a South African population with a high background prevalence of SARS-CoV-2 exposure during the Covid-19 pandemic. These data provide reassurance about the continued value of the national Covid-19 vaccine program during a surge in the omicron variant.”

Natural Facial Asymmetry Affects Mask Fit

Image by Quicknews

In research published in Physics of Fluids, researchers used computer modelling investigate mask fit and found that face shape, especially natural facial asymmetry, influences the most ideal fit. The findings suggested that double masking with improperly fitted masks may not greatly improve mask efficiency and produces a false sense of security.

Using more layers results in a less porous face covering, leading to more flow forced out the sides, top, and bottom of masks with a less secure fit. Double layers increase filtering efficiency only with good mask fit, however they could also lead to difficulties in breathing.

The researchers modelled a moderate cough jet from a mouth of an adult male wearing a cloth mask over the nose and mouth with elastic bands wrapped around the ears. They calculated the maximum volume flow rates through the front of mask and peripheral gaps at different material porosity levels.

To create a more realistic 3D face shape and size, the researchers used head scan data for 100 adult male and 100 adult female heads.

Their model showed how the slight asymmetry typical in all facial structures can affect proper mask fitting. For example, a mask can have a tighter fit on the left side of the face than on the right side.

“Facial asymmetry is almost imperceivable to the eye but is made obvious by the cough flow through the mask,” explained co-author Tomas Solano, from Florida State University. “For this particular case, the only unfiltered leakage observed is through the top. However, for different face shapes, leakage through the bottom and sides of the mask is also possible.”

Producing individually customised ‘designer masks’ is not practical at large scales. Still, better masks can be designed for different populations by revealing general differences between male and female or child versus elderly facial structures and the associated air flow through masks.

Source: American Institute of Physics

Omicron Sub-lineages are Evolving Increased Immune Escape Potential

SARS-CoV-2 lineages. Credit: Professor Ryan Gregory, University of Guelph

A paper published May 1 on the medRxiv preprint server on two new sub-lineages of Omicron, BA.4 and BA.5, reported evidence that they may escape immunity conferred by previous BA.1 infection. The study’s authors suggest that this immune escape potential may drive another wave of infections.

In recent weeks, the BA.4 and BA.5 variants have been detected circulating in South Africa, and are close descendants of the Omicron BA.2 lineage.

Researchers isolated live BA.4 and BA.5 viruses and tested their ability to evade infection to 24 participants who had been infected with BA.1 but unvaccinated and 15 vaccinated participants with breakthrough BA.1 infection.

In unvaccinated individuals, FRNT50, the inverse of the dilution for 50% neutralisation, declined from 275 for BA.1 to 36 for BA.4 and 37 for BA.5, a 7.6 and 7.5-fold drop, respectively. In vaccinated BA.1 breakthroughs, FRNT50 declined from 507 for BA.1 to 158 for BA.4 (3.2-fold) and 198 for BA.5 (2.6-fold). Absolute BA.4 and BA.5 neutralisation levels were about 5-fold higher in this group versus unvaccinated BA.1 infected participants.

The observed escape of BA.4 and BA.5 from immunity elicited by BA.1 was more moderate than of BA.1 against previous immunity, the researchers found. The researchers warned that the low absolute neutralisation levels for BA.4 and BA.5, particularly in the unvaccinated group, are unlikely to protect well against symptomatic infection. They suggest that, based on neutralisation escape, BA.4 and BA.5 have potential to result in a new infection wave.

Experts warn however that even these sub-lineages are unlikely to be the last, with plenty of potential remaining for new mutations.

Professor of evolutionary biology T. Ryan Gregory at the University of Guelph, Canada, laid out in a series of tweets that these new sub-lineages are not the final “Pokemon” evolution of SARS-CoV-2. He warned that with all of the replication that is still going on, the virus is still mutating rapidly, especially around the Spike protein, and thus is capable of producing new variants.

Alpha and Delta, which drove two major waves around the world with high levels of mortality, did not give rise to Omicron, but now the variants of concern are increasingly emerging from within the Omicron clade. Prof Gregory noted that a growing number of variants are being seen with transmission or immune escape advantages.

“Sorry to say it, but this pandemic isn’t over,” he concluded.

Montelukast Can Block Harmful SARS-CoV-2 Protein and Protect Immune Cells

Targeting Nsp1 with montelukast helps prevent shutdown of host protein synthesis Credit: Mohammad Afsar

Montelukast can bind to and block a crucial protein produced by SARS-CoV-2, reducing viral replication in human immune cells, according to a new study by researchers at the Indian Institute of Science (IISc).

Montelukast has been around for more than 20 years and is usually prescribed to reduce inflammation caused by conditions like asthma, hay fever and hives.

In the study, published in eLife, the researchers showed that the drug binds strongly to the C-terminal, which is one end of a SARS-CoV-2 protein called Nsp1, which is one of the first viral proteins unleashed inside human cells. NSp1 can bind to ribosomes inside immune cells, shutting down production of vital proteins that the immune system needs, thereby weakening it. Nsp1 could therefore be a target to reduce the virus’s damage.

“The mutation rate in this protein, especially the C-terminal region, is very low compared to the rest of the viral proteins,” explained IISc’s Assistant Professor Tanweer Hussain, senior author of the study. Since Nsp1 is unlikely to change in future variants, targeting it with drugs is a viable strategy, he added.

The researchers screened more than 1600 FDA-approved drugs with computational modelling to find the ones that bound strongly to Nsp1, coming up with a shortlist of drugs including montelukast and saquinavir, an anti-HIV drug. “The molecular dynamic simulations generate a lot of data, in the range of terabytes, and help to figure out the stability of the drug-bound protein molecule. To analyse these and identify which drugs may work inside the cell was a challenge,” said Mohammad Afsar, first author of the study.

The researchers then cultured human cells which produced Nsp1, treated them with montelukast and saquinavir separately, and found that only montelukast was able to rescue the inhibition of protein synthesis by Nsp1.

“There are two aspects [to consider]: one is affinity and the other is stability,” explained Afsar. This means that the drug needs to not only bind to the viral protein strongly, but also stay bound for a sufficiently long time to prevent the protein from affecting the host cell, he adds. “The anti-HIV drug (saquinavir) showed good affinity, but not good stability.” Montelukast, on the other hand, was found to bind strongly and stably to Nsp1, allowing the host cells to resume normal protein synthesis.

The researchers then tested the effect of the drug on live viruses and found that the drug was able to reduce viral numbers in infected cells in the culture.

“Clinicians have tried using the drug … and there are reports that said that montelukast reduced hospitalisation in COVID patients,” said A/Prof Hussain, adding that the exact mechanisms behind it still need to be fully understood. His team plans to work with chemists to see if they can modify the structure of the drug to increase its potency, and also plan to continue the hunt for more drugs.

Source: Indian Institute of Science

South Africa on Cusp of Fifth Wave as Public Apathy Mounts

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South Africa is now on the cusp of a fifth wave, experts warn, as indicators rise and new variants begin to circulate. Social media monitoring indicates a level of public apathy.

After a period of reduced cases, cases rose for three consecutive days, prompting concern. Health Department deputy director-general, Nicholas Crisp, noted possible explanations.

“It may be associated with one of the sub-variants of Omicron, certainly that is what’s dominant at the moment but it also might be just because we are all a bit lax at the moment, we don’t wear our masks so diligently,” he said.

Crisp said that they would be watching the data closely, before pronouncing on whether this was indeed the start of the fifth wave.

“We are not sure if this is the variant that’s going to do whatever is going to happen in the fifth wave, what we are seeing at the moment is what we call a flare-up,” Crisp said.

Wastewater monitoring has seen an uptick in coronavirus levels, according to the NICD’s weekly brief [PDF]. The BA.4 and BA.5 Omicron variants have been observed but it is not clear what impact they will have on the fifth wave. The Delta variant has been sequenced in wastewater, but the significance of this is still unclear.

Gauteng has reported the highest weekly incidence at 27.4 per 100 000 people, followed by Western Cape (23.4 per 100 000), and KwaZulu-Natal (13.4 per 100 000). However, testing rates are down in a number of provinces. The highest incidence is among young teenagers.

As of 25 April, 1954 new cases with a 19.3% positivity rate were recorded by the NICD.

The Health Department’s Vaccine Social Listening progamme has seen a significant drop in engagement across social media, down by 50% on Twitter, 60% on Facebook. Engagements with digital news articles are down 70%. Fears over a fifth wave have been dismissed on social media as “fear mongering” and there is a belief that “covid-19 is over”.

Business Leadership South Africa chief executive Busi Mavuso said the fifth wave will test the government’s new COVID regulations.

Writing in her weekly open letter, Mavuso noted South Africa is currently in the 30 day transition period from the end of the state of disaster on 5 April and the new National Health Act regulations.

She noted some risk, with mistakes from earlier regulations being built upon. However, increased background immunity levels was credited with the reduced impact of the Omicron wave in hospitalisation and deaths. Based on the assumption that the new wave will be less impactful, economically damaging measures can be avoided.

Mavuso added that the previous waves have proven that the country can find the best balance in managing the pandemic and the economy if there is full consultation so that the consequences of regulations can be understood and planned for. “I look forward to engaging our public sector counterparts to find that balance.”

Wits University’s Professor Shabir Madhi said that with a clear increase in cases, the country was on the cusp of a resurgence. The country will however be much better positioned with higher immunity levels and a demonstrated decoupling of infections and disease severity.

Further lockdowns would likely be unnecessary, given how past lockdowns have repeatedly failed.

Long COVID May be Due to Suppressed Immune System

Man wearing mask with headache
Source: Usman Yousaf on Unsplash

Scientists studying the effect of the monoclonal antibody Leronlimab on long COVID may have found a surprising clue to the baffling syndrome, one that contradicts their initial hypothesis. The cause may be down to an abnormally suppressed immune system, and not a persistently hyperactive one as they initially suspected.

The study was published in Clinical Infectious Diseases.

“While this was a small pilot study, it does suggest that some people with long COVID may actually have under-active immune systems after recovering from COVID, which means that boosting immunity in those individuals could be a treatment,” said senior author Professor Otto Yang.

COVID is known to be caused by hyperactive immune responses against SARS-CoV-2 resulting in damage to lungs and other organs, and sometimes a cytokine storm that overwhelms the individual, which could lead to severe illness and death.

For some who recover from COVID, various symptoms can persist for months, such as fatigue, mental haziness, and shortness of breath. Classified as long COVID, a limited understanding of the causes makes it difficult to develop treatments.

One suggested possibility is that persistence of immune hyperactivity after COVID is a major contributor. The researchers therefore ran a small exploratory trial of Leronlimab, an antibody that attaches to an immune receptor called CCR5 that is involved in inflammation, on 55 people with the syndrome. Leronlimab was originally being developed as an HIV treatment.

Participants were randomised to receiving either weekly injections of the antibody or a saline placebo for eight weeks, and changes in 24 symptoms associated with long COVID were tracked, including loss of smell and taste, muscle and joint pain, and brain fog.

Originally, the researchers believed that blocking CCR5 would calm an overactive immune system after COVID infection. Indeed, preliminary results from an earlier trial appeared to show an improvement with Leronlimab.

“But we found just the opposite,” Prof Yang said. “Patients who improved were those who started with low CCR5 on their T cells, suggesting their immune system was less active than normal, and levels of CCR5 actually increased in people who improved. This leads to the new hypothesis that long COVID in some persons is related to the immune system being suppressed and not hyperactive, and that while blocking its activity, the antibody can stabilize CCR5 expression on the cell surface leading to upregulation of other immune receptors or functions.”

The findings, the researchers wrote, “suggests a complex role for CCR5 in balancing inflammatory and anti-inflammatory effects, eg through T regulatory cells,” although the results need to be confirmed in a larger, more definitive study.

Source: University of California – Los Angeles Health Sciences

WHO Panel Recommends Paxlovid for at-Risk Mild COVID

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Pfizer’s oral antiviral Paxlovid (nirmatrelvir/ritonavir) is strongly recommended for patients with non-severe COVID with greater hospitalisation risk, such as unvaccinated, older, or immunosuppressed patients, according to a WHO Guideline Development Group writing in The BMJ. 

The experts explained that Pfizer’s Paxlovid, a comnbination of nirmatrelvir and ritonavir tablets, is likely a better choice for these patients because it may prevent more hospitalisations than the alternatives, is safer than molnupiravir, and is easier to administer than intravenous options such as remdesivir and antibody treatments. 

Use in low-risk patients is not recommended due to trivial benefits. It is also not recommended for patients with severe or critical COVID, as there are currently no trial data on nirmatrelvir/ritonavir for this group.

Their recommendation is based on new data from two randomised controlled trials with 3100 patients.

In these trials, moderate certainty evidence showed that nirmatrelvir/ritonavir reduced hospital admission (84 fewer admissions per 1000 patients), low certainty evidence suggested no important difference in mortality, and high certainty evidence suggested little or no risk of adverse effects leading to drug discontinuation.

Additionally, WHO also makes a conditional (weak) recommendation to use the antiviral drug remdesivir for patients with non-severe COVID at highest risk of hospitalisation.

This is based on new data from five randomised controlled trials involving 2700 patients and replaces a previous recommendation against treatment with remdesivir in all patients with covid-19 regardless of disease severity.

Antiviral drugs should be administered as early as possible, but this may be challenging in low- and middle-income countries, the panel noted, and also that access to these drugs is tied to COVID tests.

The emergence of resistance is also an uncertain risk, they add.

This guidance adds to previous conditional recommendations for the use of molnupiravir for high-risk patients with non-severe COVID and for the use of sotrovimab or casirivimab-imdevimab (monoclonal antibody treatments) in selected patients; and against the use of convalescent plasma, ivermectin and hydroxychloroquine in patients with COVID regardless of disease severity. For patients with severe COVID, WHO strongly recommends corticosteroids, with the addition of IL-6 receptor blockers or baricitinib.

Source: EurekAlert!

About 30% of COVID Patients Develop Long COVID

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Photo by Joice Kelly on Unsplash

A new study published in Journal of General Internal Medicine found that 30% of people treated for COVID developed ‘Long COVID’. Risk of Long COVID was greater in people with a history of hospitalisation, diabetes, and higher BMI; and less in organ transplant recipients and those not on private health insurance. Surprisingly, ethnicity, older age, and socioeconomic status were not linked to the syndrome despite the link to greater risk of severe illness and mortality.

Of the 309 people with long COVID studied, the most persistent symptoms were fatigue and shortness of breath (31% and 15%, respectively) in hospitalised persons, and loss of sense of smell (16%) in outpatients.

The incidence and risk factors of Long COVID, and even how to define the syndrome, have remained unclear throughout the pandemic. The researchers sought evaluate its association with demographics and clinical characteristics in order to devise the most effective treatments.

The study examined 1038 people enrolled in the UCLA COVID Ambulatory Program from April 2020 to February 2021. Of those, 309 developed Long COVID, determined by them reporting persistent symptoms on questionnaires 60 or 90 days after infection or hospitalisation.

Potential weaknesses in the study include the subjective nature of how patients rated their symptoms, the limited number of symptoms the researchers evaluated, and limited information about patients’ pre-existing conditions.

“This study illustrates the need to follow diverse patient populations longitudinally to understand the Long COVID disease trajectory and evaluate how individual factors such as pre-existing co-morbidities, sociodemographic factors, vaccination status and virus variant type affect type and persistence of Long COVID symptoms,” said Dr Sun Yoo, health sciences assistant clinical professor at UCLA. “Studying outcomes in a single health system can minimise variation in quality of medical care. Our study also raises questions such as: Why were patients with commercial insurance twice as likely to develop Long COVID than patients insured through Medicaid? Because persistent symptoms can be subjective in nature, we need better tools to accurately diagnose Long COVID and to differentiate it from exacerbations of other emerging or chronic conditions. Finally, we need to ensure equitable access to outpatient Long COVID care.”

Source: University of California – Los Angeles Health Sciences

Vigorous Exercise and Talking Produce Similar Levels of Aerosols

Old man jogging
Photo by Barbra Olsen on Pexels

Vigorous exercise produces a similar level of aerosol particles as speaking, but high-intensity exercise produces more, according to new research published in Communications Medicine. This is the first study to measure exhaled aerosols generated during exercise, to help inform the risk of airborne viral transmission of SARS-CoV-2 for gyms and indoor physical training.

Inhalation of infectious aerosol is considered to be the main route of SARS-CoV-2 transmission. In this study, researchers performed a series of experiments to measure the size and concentration of exhaled particles (up to 20µm diameter) which are generated in our respiratory tracts and breathed out, during vigorous and high-intensity exercise.

Using a cardiopulmonary exercise test, 25 healthy participants (13 male, 12 female) with a range of athletic abilities were recruited to undertake four different activities (breathing at rest, speaking at normal conversational volume, vigorous exercise and high-intensity exercise) on a cycle ergometer. Airflow and particles emitted were measured by particle counter. Experiments were carried out in an orthopaedic operating theatre — an environment with ‘zero aerosol background’, letting the researchers to unambiguously identify the aerosols generated by the participants.

The results showed that the size of airborne particles emitted during vigorous exercise was consistent with those emitted while breathing at rest. However, the rate of aerosol mass exhaled during vigorous exercise was found to be similar to speaking at a conversational volume.

Jonathan Reid, scientific lead on the paper, said: “COVID has profoundly impacted sports and exercise, and this study provides a comprehensive analysis of the mass emission rates of aerosol that can potentially carry infectious virus produced from an individual during exercise. Our research has shown that the likely amount of virus that someone can exhale in small aerosol particles when exercising is comparable to when someone speaks at a conversational volume.  The most effective way to reduce risk is to ensure spaces are appropriately ventilated to reduce the risk of airborne transmission.”

Source: University of Bristol