Category: COVID

NSAIDs Suppress Antibodies in COVID Infections

A new study has found that non-steroidal anti-inflammatory drugs (NSAIDs) suppress antibody counts as well as inflammatory levels in mice infected with the SARS-CoV-2 virus.

NSAIDs inhibit the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), which are needed for prostaglandin generation – lipid molecules involved in homeostasis and inflammation. The study used ibuprofen and meloxicam in mice infected with SARS-CoV-2. The researchers aimed to observe: viral infection through modified expression of angiotensin-converting enzyme 2 (ACE2), the cell entry receptor for SARS-CoV-2, effects on viral replication and modulated response of the immune system. However, they did not observe altered viral infection or replication.

“NSAIDs are arguably the most commonly used anti-inflammatory medications,” said principal investigator Craig B Wilen, Assistant Professor of Laboratory Medicine and Immunology, Yale University School of Medicine.

As well as taking NSAIDs for chronic conditions, eg arthritis, people take them “for shorter periods of time during infections, and [during] acute inflammation as experienced with COVID-19, and for side effects from vaccination, such as soreness, fever, and malaise,” Dr Wilen explained.

“Our work suggests that the NSAID meloxicam dampens the immune response to SARS-CoV-2 infection. Taking NSAIDs during COVID-19 could be harmful or beneficial, depending on the timing of administration,” said Dr Wilen. Dexamethasone, a potent anti-inflammatory but not an NSAID, is detrimental when administered at early stages of COVID but beneficial at later stages. NSAIDs may similarly be detrimental at the early stage because they counteract beneficial inflammation.

An antibody reduction by NSAIDs might not be harmful, but it could also reduce the immune system’s ability to mount a defence early on, or even reduce the length or magnitude of immunity or vaccination protection, Dr Wilen said. Antipyretics such as paracetamol have also been observed to blunt immune system response to vaccination.  

According to Dr Wilen, the original motivation from the study “was a twitter thread, suggesting NSAIDs should not be used during COVID-19. This seemed suspicious to us, so we wanted to investigate.”

Dr Wilen and his team believed there would be no effect of NSAIDs on viral infection, which turned out to be correct. However, they also thought there would be no effect on antibody response.

“In fact, we initially didn’t even carefully look at the antibody response, because we didn’t expect it to be altered by NSAIDs. This turned out to be wrong,” commented Dr Wilen.

Source: Medical Xpress

Journal information: Jennifer S. Chen et al. Non-steroidal anti-inflammatory drugs dampen the cytokine and antibody response to SARS-CoV-2 infection, Journal of Virology (2021). DOI: 10.1128/JVI.00014-21

New “Double Antibodies” can Treat COVID Variants

A new generation of “double antibodies” has been developed which can protect against all SARS-CoV-2 variants, as well as inhibiting mutations against the antibodies.

These “bispecific”  antibodies were created by the Institute for Research in Biomedicine (IRB; Bellinzona, Switzerland), which is affiliated to the Università della Svizzera italiana (USI).

While traditional antibody-based immunisation is able to offer protection against SARS-CoV-2, there is still a need to protect against variants which may achieve “vaccine escape”, as well as inhibiting mutations which give rise to resistance, as with antibiotic resistance in bacteria.

The researchers overcame these difficulties by splicing together a pair of antibodies to make a “bispecific” antibody that simultaneously targets two viral sites. The bispecific antibody treatment has proved effective in mouse models, which maintained body weight when infected with SARS-CoV-2, compared to infected controls, which lost 20-30% body weight before humane euthanisation. The paper is available on the bioRxiv preprint server.

Study author Luca Varani of USI explained: “We exploited our knowledge of the molecular structure and biochemical traits of the virus to fuse together two human antibodies, obtaining a single bispecific molecule simultaneously attacking the virus in two independent sites critical for infectivity. Supercomputing simulations allowed us to refine and validate the bispecific antibody design, which was later produced and tested in the laboratory. Although the virus can mutate and escape from the attack of a single first-generation antibody, we have shown that it cannot do so against the double action of the bispecific.

“A single injection of the bispecific antibody provides instantaneous protection against the disease in pre-clinical trials. The antibody effectively reduces viral burden in the lungs and mitigates inflammation typical of COVID-19”, said Daniel Ruzek from the Czech Academy of Sciences who led the antibody pre-clinical testing.

The effectiveness of the bispecific antibodies holds promise for human clinical trials, with the prospect of being both an effective prevention and treatment of COVID.

Source: News-Medical.Net

Journal information: Gasparo, R D., et al. (2020) Bispecific antibody prevents SARS-CoV-2 escape and protects mice from disease. bioRxiv.doi.org/10.1101/2021.01.22.427567.

Severe COVID May Lead to Stronger Immunity

Researchers from La Jolla Institute for Immunology (LJI), The University of Liverpool and the University of Southampton have discovered that the degree of COVID severity appears to be linked to how long-lasting and strong the subsequent immunity is. 

“The data from this study suggest people with severe COVID-19 cases may have stronger long-term immunity,” said study co-leader LJI Professor Pandurangan Vijayanand, MD, PhD.

The research examines T-cells from COVID infections in unprecedently high detail.

“This study highlights the enormous variability in how human beings react to a viral challenge,” added co-leader Christian Ottensmeier, MD, PhD, FRCP, a professor at the University of Liverpool and adjunct professor at LJI.

Vijayanand and Ottensmeier have been studying how antibodies and the different subsets of T-cells control COVID disease severity. In this study, they examined CD8+ T-cells, which are the T-cells responsible for destroying virus-infected cells, and “memory” CD8+ T-cells are also important for guarding the body against reinfections of the same virus. These memory T-cells are poised to rapidly proliferate and engage their cell-destroying functions on subsequent antigen encounters. They can reside in peripheral organs and their memory can also be shaped by infection history.

Utilising a new technique called single-cell transcriptomics analysis, they were able to study expressions of individual genes of 80 000 CD8+ T-cells drawn from 39 COVID patients and from 10 non-exposed donors, whose blood samples had been taken before the pandemic. Of the COVID patients, 17 cases were mild and non-hospitalised, 13 were hospitalised and 9 had required ICU care.

Surprisingly, the researchers found that the strongest CD8+ T-cell responses were from those with the more severe form of the disease, and not the milder cases.”There is an inverse link between how poorly T cells work and how bad the infection is,” observed Ottensmeier. “I think that was quite unexpected.” A stronger response would be expected from CD8+ T-cells in mild cases due to having the resources of a better functioning immune system. However, the mild group of CD8+ T-cells showed signs of “exhaustion”, which happens when the immune system overloads the T-cells, causing them to lose effectiveness.

The researchers believe that it will be beneficial to study whether this phenomenon may hinder the ability to build long-term immunity.

“People who have severe disease are likely to end up with a good number of memory cells,” said Vijayanand. “People with milder disease have memory cells, but they seem exhausted and dysfunctional—so they might not be effective for long enough.

“What the researchers would like to look at next is to look at T-cells from lung tissue as opposed to blood samples, because that is where the infection hits hardest.

“This study is very much a first step in understanding the spectrum of immune responses against infectious agents,” said Ottensmeier. The researchers will also look at T-cells in cancer patients who are also infected with COVID.

Source: Medical Xpress

Journal information: Anthony Kusnadi et al, Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells, Science Immunology  21 Jan 2021: Vol. 6, Issue 55, eabe4782 DOI: 10.1126/sciimmunol.abe4782

Biden’s Promise to “Manage the Hell” out of COVID

Almost immediately upon assuming office, the newly sworn-in President Joe Biden started to deliver on his promise to tackle the COVID pandemic raging in the United States.

On Wednesday, shortly after being sworn in, he wrote to both the United Nations Secretary General and the WHO Director General to notify them of the United States’ return to the WHO – a move no doubt welcomed around the world. He also began to sign a raft of orders related to the COVID pandemic.

Following up on his promise to “manage the hell” out of the COVID pandemic, President Biden signed a directive which “seeks to support the international health and humanitarian response to the COVID-19 pandemic and its secondary impacts, global health security and diplomacy, and better biopreparedness and resilience for emerging and future biological threats.”

His actions and executive orders include:– Increased equipment procurement. Using the Defense Production Act (DPA) to accelerate manufacturing and meet shortfalls in COVID-related equipment and supplies.
– Increased COVID testing. Another order establishes a testing board to help expand the supply of tests and testing equipment, as well as supporting the public healthcare force.
– Increasing studies on COVID-19 treatments. More studies requested on COVID, as well as on COVID in diverse populations. Also requests more healthcare workers.
– Speeding up vaccinations. Federal Emergency Management Agency (FEMA) is directed to begin deploying vaccination centres, aiming toward a goal of 100 in the next month.
– Reopening schools and businesses. The Departments of Education and Health and Human Services (HHS) are directed to provide guidance on safe reopening and operating for education institutions and child care providers.
– Improving protections for workers. Clear guidance for employers to keep employees safe from COVID exposure.
– Increasing travel safety. Masks are to be worn in federal buildings, and mask requirements are extended to interstate travel, including on planes, trains, and buses. People flying into the US from another country will need to test negative for COVID prior to departure and quarantine upon arrival.

President Biden’s plan and the full texts of the executive orders were detailed in a 200 page document which was made available on Thursday.

At a White House signing ceremony, he affirmed his commitment to “following the science” on COVID, saying: “We will make sure that scientists and public health experts will speak directly to you — not the president, but real, genuine experts and scientists.” He added that they will work free of political interference.

He also warned Americans of a “dark winter” ahead, and the nation was in a national emergency and that “we should treat it like one.”

Source: MedPage Today

UCT Expert Talks COVID and Warns of Third Wave

If South Africa does not pursue a rapid vaccination programme to achieve herd immunity, it may face a third wave as a consequence, warned a leading local expert.

Professor Marc Mendelson of UCT’s Division of Infectious Diseases and HIV Medicine at Groote Schuur Hospital made these statements while speaking during a virtual Summer School lecture on Saturday, titled “COVID-19 Insights and Lessons”.

“Without rapid vaccination of at least two thirds of the population, we [South Africa] are not going to get to population immunity, and without that, we will see another wave,” Mendelson warned.

However, he emphasised that much had been accomplished in the battle against COVID. “It is associated with a scientific endeavour that we have never seen before. We’re definitely better off a year down the line, but there are a huge number of things that we need to answer. As a country we still face deep problems with severe issues around vaccine strategy, and we haven’t even talked about vaccine denial,” he said.

Criticism has been directed at the South African government because of its failure to start a vaccination programme, despite its huge case load and status as Africa’s most wealthy nation. A leaked phone call from a Pfizer executive has only added to this, as it was revealed that for months SA health officials had not been responding to requests for vaccine discussions.

Regarding COVID transmission, he said that the virus resided in the upper respiratory tract as well as the lungs, and that it could be expelled in aerosol droplets. The clinical and epidemiological evidence suggested that larger, heavier droplets carried the virus.

“The household infection rates were high. A very large number of cases, the vast majority [in fact], were within families in close proximity [to one another]. This, epidemiologically, suggests that large droplets play a role in transmission.

“If you want to reduce transmission from large droplets, then you need to increase the distance you are from someone. Also, because droplets drop onto surfaces … you will need to clean surfaces and wash your hands well. This is the science behind the use of masks, handwashing, social distancing and ventilation.”

However, he added that a number of studies had found the virus in remote corners of hospitals at a distance from patients, suggesting that it had been carried there by smaller, aerosolised particles.

“If you want to reduce aerosols, one way of doing that is to improve ventilation. The more the air is changed, the [quicker] it will dilute small droplets,” he said.

Source: University of Cape Town

WHO Warns of ‘Catastrophic Failure’ over COVID Vaccination

The World Health Organization head, Dr Tedros Adhanom Ghebreyesus, has warned that the world faces a “catastrophic moral failure” because of unequal access to COVID vaccines. 

He said that 49 wealthier states had conducted 39 million vaccinations between them, but one poor country had only 25 doses.

To date, the US, China, India, Russia and the UK have all developed vaccines, and mostly prioritised their own populations to receive them – although the German company BioNTech developed theirs in collaboration with Pfizer, and even so, the EU failed to secure vaccines sufficiently in advance. 

Dr Tedros spoke to an executive board session of the WHO, saying: “I need to be blunt: the world is on the brink of a catastrophic moral failure – and the price of this failure will be paid with lives and livelihoods in the world’s poorest countries.”

He warned that a selfish approach to vaccination would lead to hoarding and rising prices.

“Ultimately, these actions will only prolong the pandemic, the restrictions needed to contain it, and human and economic suffering,” he added.

Calling on nations to accelerate their progress, he said: “My challenge to all member states is to ensure that by the time World Health Day arrives on 7 April, Covid-19 vaccines are being administered in every country, as a symbol of hope for overcoming both the pandemic and the inequalities that lie at the root of so many global health challenges.” 

Thus far, 180 countries have signed on to the Covax initiative, which aims to negotiate as a bloc for lower vaccine prices. The initiative aims to distribute vaccines to low- and middle income countries, 92 of which will have their vaccines paid for by the initiative. Dr Tedros said that two billion doses had been secured, with an option of a billion more, with the first doses delivered by February.

UK Health Secretary Matt Hancock said in a reaction to Dr Tedros’ warnings that, “The UK is the world’s biggest supporter, financial supporter, of the global programme to ensure access to vaccines in all countries in the world.”

The UK has contributed £548m ($734m) to the Covax initiative. Canada drew criticism after it was revealed that, due to vaccine hoarding, the 70 poorest countries would only be able to vaccinate 10% of their population, while Canada had secured enough vaccines for five times its population of nearly 38 million. However, these vaccines are “hypothetical” according to Karina Gould, Canada’s minister of international development. Canada is also contributing $380 million to Covax. Furthermore, discussions are reportedly under way for South Africa to secure some of the vaccines allocated to Canada.

Source: BBC News

SA Experts Confirm That COVID Variant is More Contagious

A panel of South African experts confirmed on Monday that the SA strain of COVID is 50% more transmissible than previous strains.

Collecting data from the main infection clusters around the country, the experts came to the conclusion that while more contagious, the new variant is not more lethal. 

“There is no evidence the new COVID variant is more severe than the original variant,” said epidemiologist Professor Salim Abdool Karim, co-chair of the Ministry of Health’s scientific committee.

However, the SA healthy system has been strained by the sheer number of cases. Concerns over more transmissible variants have prompted the UK government to switch to administering the first dose of two-dose vaccines such as the one from Pfizer, and leaving an extended period before a second dose is administered, even though protection will wane over time.

Another panel member, Dr Waasila Jassat, said that although hospital admissions had increased, the overall death rate had not, supporting the case for the variant not being more lethal.

The spread of the variant in December prompted the government to reinstate its lockdown. It also resulted in many countries banning flights from South Africa in a bid to stem the variant. Prof Karim said that it was not yet known if current vaccines would protect against the SA variant, although studies were underway.

Another panel member, virologist Professor Alex Sigal stated: “The world has underestimated this virus.” He added that it was evolving and adapting to humans.

The experts also urged that it should not be referred to as the “South African variant”. The variant could have turned up anywhere in the world, and it was only thanks to the country’s excellent genomic surveillance that it was picked up at all, they said.

Source: Medical Xpress

Nearly a Third of COVID Patients Are Readmitted to Hospital

According to a study reported by The Telegraph, almost a third of COVID patients are readmitted to hospital later. The new study, still on the MedRxiv preprint server and not yet peer reviewed, was conducted by Leicester University and the Office for National Statistics (ONS).

Approximately 1 in 10 people who are infected with COVID go on to develop long COVID symptoms, which include breathlessness, excessive fatigue and muscle aches. This appears to be causing hospital readmissions – and deaths.

The study looked at 47 780 individuals with a primary diagnosis of COVID who had a hospital visit between 1 January 2020 and 31 August 2020, and a COVID-negative control group admitted over the same period. The mean follow-up time was 140 days for those with a COVID diagnosis, and during this team 29.4% were readmitted and 12.3% died. The study also found a higher risk in those under 70 and of ethnic minority groups in the UK, most notably in respiratory diseases.

Study author Kamlesh Khunti, professor of primary care diabetes and vascular medicine at Leicester University, said: “This is the largest study of people discharged from hospital after being admitted with Covid.

“People seem to be going home, getting long-term effects, coming back in and dying. We see nearly 30 per cent have been readmitted, and that’s a lot of people. The numbers are so large.”The message here is we really need to prepare for long Covid. It’s a mammoth task to follow up with these patients and the NHS is really pushed at the moment, but some sort of monitoring needs to be arranged.”

One finding which surprised the team was that many patients went back in and had a new diagnosis, such as liver, heart or kidney conditions, as well as diabetes. This means, according to Prof Khunti, that it is important for patients to receive follow-up and protective therapies such as statins or aspirin, adding: “We don’t know if it’s because Covid destroyed the beta cells which make insulin and you get Type 1 diabetes, or whether it causes insulin resistance, and you develop Type 2, but we are seeing these surprising new diagnoses of diabetes.”

Source: Yahoo News

SA Government Aims for a Corruption-free Vaccine Programme

In the past week, President Cyril Ramaphosa and health minister Zweli Mkhize have undertaken a publicity drive to demonstrate how the government is working to ensure a tightly controlled vaccine drive that is not plagued by corruption. This is to avoid a repeat of the corruption in PPE acquisition last year, with some R10.5 billion being investigated for looting, with an Auditor-General report finding some items being purchased at five times the going price.

These efforts include centralised transactions which involve the auditor-general looking out for any discrepancies. Vaccine acquisition and roll-out planning will be handled by the government, with the private sector being tapped for storage and distribution. “What we have done is to get the Treasury and the Department of Health’s office of the chief procurement officer to oversee any form of transaction that is going to happen.

“Right now the procurement of the vaccines is within government. It makes it easier because it’s a tight-knit set of people, the prices are known, the manufacturers are known, the deviation is specific and it’s not the same as what we had in PPE where there were so many vendors, suppliers and so many different prices,” he said.

Furthermore, there will be consultation with the Attorney General. “We are going to say [to the AG]… these are the risks we have identified and ask them to analyse our plans and see if there are further risks we must be aware of and how we can work together to prevent any risk of looting,” Mkhize said.

Medical aid schemes have voiced concerns over the process, having sourced vaccines for their members as well as contributing to the vaccination costs of those not covered by any medical aid scheme.

President Ramaphosa said that South Africa would have pre-paid like other countries to secure vaccines, even given the risks of them failing, if it had the funds to do so.

However, he affirmed that there are funds available to buy the vaccination scheme, saying: “we are going to have the money, it will come from Treasury. There is just no way we can say, when it comes to saving the lives of South Africans, that we don’t have the money. The money will be there. It has to be there to save the lives of South Africans. That one will be my bottom line.”

The Covax programme will provide a vaccine for 10% of the population in the second quarter of 2021, for which a deposit of R283 million has been paid. A further 1.5-million vaccine doses have been secured from AstraZeneca and 9-million from Johnson & Johnson (J&J). The J&J vaccine only requires a single dose to confer immunity, so should be able to cover 9 million people.

“J&J will be producing through Aspen here at home, and we are hoping to get the bulk of our supply from there, once the production starts,” said Ramaphosa.

Source: Times Live

EU Angered by Pfizer Delay

Pfizer has said in a statement on Friday that the drop in production is the result of the company upgrading its manufacturing processes, and that there will be an overall increase in supply as a result.

“Although this will temporarily impact shipments in late January to early February, it will provide a significant increase in doses available for patients in late February and March,” Pfizer said.

The German health ministry has said the delays are surprising and regrettable, pointing out that it had secured binding mid-February delivery dates from the company. EU Commission President Ursula von der Leyen said that she had been given assurances by Pfizer’s chief executive that all orders for the first quarter would arrive. She had previously said that Pfizer had promised to double its delivery of doses to the EU to 600 million this year.

However, the EU also has agreements in place with Moderna to supply vaccines, and this is not wholly dependent on Pfizer. However, Johnson & Johnson is also falling behind in its vaccine delivery targets, amidst reports that the US has failed to meet vaccination goals for the end of 2020, and may struggle to meet this year’s goals. Meanwhile, the UK is expected to be slightly impacted by the drop in supply but remains on track to meets its February immunisation goals.

However, the EU has lagged behind the UK in its vaccination programme, for a number of reasons including the fact that the UK ordered and approved its vaccines sooner, while Brussels’ negotiations were slower. Much of the delay is due to the added bureaucracy of the 27 nation political confederation and its decision to acquire vaccines as a single entity instead of individual countries further exacerbated this.

According to Reuters, citing a participant at a meeting last week, a third of the EU’s 27 countries reported difficulties in securing enough vaccines for their vaccination programmes.

Source: BBC News