Tag: covid

UK to Look at Mixing of Different Vaccines

The UK is launching a trial to explore the mixing of vaccines can be combined. Some, like Russia’s Sputnik vaccine, already combine two different types of vaccines, but these were specifically designed and tested to work together. 

Current guidance in the UK says that anyone who receives a Pfizer-BioNTech or Oxford-AstraZeneca vaccine dose should get the second dose of that same vaccine. Only in exceptional circumstances such as not knowing what vaccine was given will a different vaccine be administered.

The main aim was to enhance logistical flexibility. The Oxford/AstraZeneca, Johnson & Johnson and Novavax vaccines can all be stored at normal refrigerator temperatures, while the Moderna vaccine must be stored at -20C, within normal freezer range, and Pfizer/BioNTech’s vaccine needs an ultra-cold -70C. Not requiring a second dose of the same vaccine could ease up storage requirements. 

However, with previous vaccines, mixing different vaccine types worked and even strengthened their overall effectiveness. Some Ebola immunisation programmes, for example, combine two different vaccines to achieve greater protection.

The trial will comprise some 800 participants aged 50 or older, receiving a combination of Oxford/AstraZeneca and Pfizer/BioNTech in either order.

Some vaccines that work by using a virus to deliver the antigens, and there is some evidence to suggest that the immune system starts to focus on the viral delivery system instead of the antigen. Thus, combining vaccines will keep the immune system’s attention on the antigens.

Chief investigator, Prof Matthew Snape from the University of Oxford, said the “tremendously exciting study” would provide critical information for vaccine rollouts.

Animal studies have shown “a better antibody response with a mixed schedule rather than the straight schedule” of vaccine doses, he said.

“It will be really interesting to see if the different delivery methods actually could lead to an enhanced immune response [in humans],” he said, “or at least a response that’s as good as giving the straight schedule of the same doses”.

Source: BBC News

UK Teen Awakens from 10 Month Coma, Unaware of Pandemic

A British teenager who has been in a coma for 10 months, has awakened but is still largely unaware of the scale of the COVID pandemic. 

Joseph Flavill, 19, was hit by a car while walking on 1 March 2020, which was three weeks before the UK entered into its first national lockdown. Having suffered a traumatic brain injury, he has since been in a coma but is now making a slow recovery and is responsive. Ironically, he has caught COVID twice while in hospital but had recovered both times.

His aunt, Sally Flavill Smith, told the Guardian: “He won’t know anything about the pandemic as he’s been asleep for 10 months. His awareness is starting to improve now but we just don’t know what he knows.

“I just don’t know where to start with it. A year ago if someone had told me what was going to happen over the last year, I don’t think I would have believed it. I’ve got no idea how Joseph’s going to come to understand what we’ve all been through.”

He is now able to respond to commands, such as touching his left or right ear, respond with yes/no by blinking, and is able to smile.

His family had trained to explain in video calls why they can’t see him in person due to COVID restrictions, but had not tried to convey the scale of the pandemic. She says that they will try to explain it to him when they are able to visit him in person. His mother was able to see him in December, wearing full PPE, but he was not as aware as he is now. The family has put together a fundraiser to help his recovery.

Source: The Guardian

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

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

Stellenbosch Doctors Urge Patience on Ivermectin

The South African public should be patient and wait for data on Ivermectin’s effectiveness against COVID, according to Stellenbosch doctors, who urge patience. The doctors wrote an article published in the South African Medical Journal explaining that further studies need to be completed before ivermectin can be authorised for use.

A veterinarian parasiticide that may have relevant antiviral and anti-inflammatory properties, ivermectin has gathered considerable attention for possible use in COVID prophylaxis and treatment since a number of small trials appeared to show effectiveness. However, close examination shows that they are very weak. Doubts have been raised over whether the necessary concentrations used in vitro can be achieved in vivo.

In their article, the doctors noted that several large randomised controlled trials are underway, and the results of these will allow the possible effectiveness of ivermectin to be gauged. “Data for Ivermectin from larger RCTs are expected in early 2021,” the doctors wrote. “These data are very promising, showing large treatment effects and acceptable adverse effect profiles for ivermectin against Covid-19, especially when combined in meta-analyses.”

They pointed out that the hoped-for effectiveness of other medications had not been borne out. “As a recent example, the widely proclaimed benefits of hydroxychloroquine and chloroquine from observational studies proved to be unfounded in larger RCTs,” they wrote.

Ivermectin use has been banned by the government, to considerable resistance. A number of organisations have already demanded that ivermectin be administered as a COVID treatment, including Black First Land First, the New Economic Rights Alliance and AfriForum. Afriforum is contemplating legal action to have ivermectin authorised. These calls have come despite the South African Health Products Regulatory Authority (SAHPRA) repeatedly counselled against the use of ivermectin.

The doctors cautioned that although the data trends indicated a possible efficacy for ivermectin, the optimal dosage if effective still needed to be determined: “Higher than standard Ivermectin doses appear to be safe in humans, but at the time of writing there is still much uncertainty regarding the human dose required to achieve antiviral activity and a favourable benefit-to-risk balance.”

Source: IOL

Telemedicine Promising for Visits After Low-Risk Surgery

A pair of reports suggests that modern communication methods may be appropriate for post-surgery recovery, albeit at the risk of exacerbating the downsides of any language barriers and digital literacy.

In the midst of the COVID pandemic, telemedicine uptake and use has been greatly expanded by health care providers. In one small trial, cut short by COVID, researchers investigated whether telemedicine was an adequate form of patient follow-up after low-risk surgery.

The video-based post-discharge visits were as effective in terms of getting patients to return to the hospital within 30 days for a hospital encounter. The video visits were half an hour shorter but provided patients with the same amount of time with their surgeons.

However, out of 1645 individuals screened, many participants were excluded due to language difficulties, and 50 were excluded due to a “technology barrier”.

Caroline Reinke, MD, MSHP, of Carolinas Medical Center in Charlotte, North Carolina, and her team wrote, “Patients and clinicians should be reassured that the critical visit portion, time together discussing medical needs, is preserved. This information will help surgeons and patients feel more confident in using video-based virtual visits.”

Reinke and her team noted that COVID cut the study short: “Although we did not reach target enrollment, noninferiority was demonstrated for postdischarge virtual visits in our study sample and was further supported via a simulation model.”

In another study, Marie-Laure Cittanova, MD, PhD, of Clinique Saint Jean de Dieu in Paris, and her team compared using SMS to contact patients as opposed to calling them. When contacted after being told to expect a contact throughout the following day, 46.2% of patients were reachable by phone, compared to 85.3% by SMS.

Patients expressed similar levels of satisfaction with the SMS service, which was significantly cheaper than using phone calls. However, the single-centre study lacked generalisability.

Source: MedPage Today

Journal information (primary source): Harkey K, et al “Postdischarge virtual visits for low-risk surgeries: a randomized noninferiority clinical trial” JAMA Surg 2021; DOI: 10.1001/jamasurg.2020.6265.

Journal information (secondary source): Cittanova M, et al “Association of automated text messaging with patient response rate after same-day surgery” JAMA Surg 2021; DOI: 10.1001/jamanetworkopen.2020.33312.

WHO Team Arrives in China for COVID Origin Investigations

Following months of negotiations, and then a list minute hiccough when two team members were denied entry last week, a team of 10 specialists from the WHO arrives in China to carry out their investigations into the origins of COVID.

China, through rapid action and total lockdowns, managed to clamp down on the coronavirus outbreak inside its borders, preventing it from spreading significantly outside of Wuhan, while in Wuhan itself, life has largely returned to normal. In recent weeks, however, new cases have been appearing in Hebei province around Beijing and in Heilongjiang province in the northeast.

Just before travelling, team leader Peter Ben Embarek told AFP news agency that it “could be a very long journey before we get a full understanding of what happened”.

He cautioned against expecting instant results, saying, “I don’t think we will have clear answers after this initial mission, but we will be on the way,” he said.

For a number of months, China has been saying that the virus may not have originated in Wuhan. There has been a lot of unsubstantiated speculation that the SARS-CoV-2 might have been accidentally released from a lab.

Prof Dale Fisher, chair of the global outbreak and response unit at the WHO, told the BBC that he hoped the rest of the world would regard this as a scientific visit. “It’s not about politics or blame but getting to the bottom of a scientific question,” he said.

When the WHO team arrives in China, they will still have to wait through a two week quarantine. Fabian Leendertz, a professor in the epidemiology of highly pathogenic microorganisms at Germany’s public health institute and working remotely with the team, says that their plan of action will be developed over the next two weeks while they are still in quarantine. The team is expected to look at the infamous wet market in Wuhan where it was originally believed the virus made the jump from animals to humans, as well as working with Chinese colleagues and local clinics to establish a picture of the virus’ origins.

Source: BBC News