Category: Research

Researchers from the University of Kent, the Goethe-University in Frankfurt am Main (Germany), and the Hannover Medical School (Germany) have identified a drug with the potential to provide a treatment for COVID-19.
The international team led by Professor Martin Michaelis, Dr Mark Wass (both School of Biosciences, University of Kent), and Professor Jindrich Cinatl (Institute of Medical Virology, Goethe-University) found that the approved protease inhibitor aprotinin displayed activity against SARS-CoV-2, the coronavirus that causes COVID-19, in concentrations that are achieved in patients. Aprotinin inhibits the entry of SARS-CoV-2 into host cells and may compensate for the loss of host cell protease inhibitors that are downregulated upon SARS-CoV-2 infection.

Aprotinin aerosols are approved in Russia for the treatment of influenza and could be readily tested for the treatment of COVID-19.

Professor Martin Michaelis said: “The aprotinin aerosol has been reported to be tolerated extremely well in influenza patients. Hence, it may have a particular potential to prevent severe COVID-19 disease when applied early after diagnosis.”

Bojkova D, Bechtel M, McLaughlin K-M, McGreig JE, Klann K, Bellinghausen C, Rohde G, Jonigk D, Braubach P, Ciesek S, Münch C, Wass MN, Michaelis M, Cinatl J Jr.
Aprotinin Inhibits SARS-CoV-2 Replication.
Cells 2020, 9, 2377. 10.3390/cells9112377

The AstraZeneca Oxford COVID-19 vaccine (ChAdOx1 nCoV-19 and also known as AZD1222) now undergoing Phase III clinical trials, has already undergone rigorous testing to ensure the highest standards of quality and safety. Now a team at Bristol University has used recently developed techniques to further validate that the vaccine accurately follows the genetic instructions programmed into it by the Oxford team. This novel analysis provides even greater clarity and detail about how the vaccine successfully provokes a strong immune response.
The findings, led by scientists at the University of Bristol and published on the pre-print server ResearchSquare, represent the most in-depth analysis of any of the COVID-19 vaccine candidates, going significantly above and beyond any regulatory requirements anywhere in the world.

Work on the vaccine, developed by researchers at the University of Oxford’s Jenner Institute and Oxford Vaccine Group, began in January 2020. Now undergoing Phase III clinical trials by the University of Oxford and AstraZeneca, the Bristol researchers’ focus was to assess how often and how accurately the vaccine is copying and using the genetic instructions provided by the Oxford team. These instructions detail how to make the spike protein from the coronavirus, SARS-CoV-2 that causes COVID-19.

The Oxford vaccine is made by taking a common cold virus (adenovirus) from chimpanzees and deleting about 20 per cent of the virus’s instructions. This means it is impossible for the vaccine to replicate or cause disease in humans, but it can still be produced in the laboratory under special conditions. By removing these genetic instructions there is space to add the instructions for the spike protein from SARS-CoV-2. Once inside a human cell the genetic instructions for the spike protein need to be ’photocopied’ many times – a process known as transcription. In any vaccine system, it is these ’photocopies’ that are directly used to make large amounts of the spike protein.

Once the spike protein is made, the immune system will react to it and this pre-trains the immune system to identify a real COVID-19 infection. So, when the person vaccinated is confronted with the SARS-CoV-2 virus their immune system is pre-trained and ready to attack it.

Adenoviruses have been used for many years to make vaccines, and these are always tested to very high standards to make sure every batch of vaccine has the correct copy of genetic instructions embedded in the vaccine. However, thanks to very recent advances in genetic sequencing and protein analysis technology, researchers at Bristol were for the first time also able to directly check thousands and thousands of the ‘photocopied’ instructions produced by the Oxford vaccine within a cell. In this way they were able to directly validate that the instructions are copied correctly and accurately, providing greater assurance that the vaccine is performing exactly as programmed. At the same time, the researchers checked the spike protein being made by the vaccine inside human cells also accurately reflects the instructions as programmed. This brand-new approach may be more routinely used in the future to help researchers fine tune the performance of these kinds of vaccines.

Dr David Matthews, Reader in Virology from Bristol’s School of Cellular and Molecular Medicine (CMM), who led the research, said: “This is an important study as we are able to confirm that the genetic instructions underpinning this vaccine, which is being developed as fast as safely possible, are correctly followed when they get into a human cell.

“Until now, the technology hasn’t been able to provide answers with such clarity, but we now know the vaccine is doing everything we expected and that is only good news in our fight against the illness.”

The study at Bristol was facilitated with support from Dr Andrew Davidson, Reader in Systems Virology in CMM and Bristol UNCOVER and through key collaborations with Sarah Gilbert, Professor of Vaccinology at the University of Oxford, and AstraZeneca.

Sarah Gilbert, Professor of Vaccinology at the University of Oxford and lead on the Oxford vaccine trial, added: “This is a wonderful example of cross-disciplinary collaboration, using new technology to examine exactly what the vaccine does when it gets inside a human cell. The study confirms that large amounts of the coronavirus spike protein are produced with great accuracy, and this goes a long way to explaining the success of the vaccine in inducing a strong immune response.”

The study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), the United States Food and Drug Administration (US FDA) and the Engineering and Physical Sciences Research Council (EPSRC).

‘SARS-CoV-2 candidate vaccine ChAdOx1 nCoV-19 infection of human cell lines reveals a normal low range of viral backbone gene expression alongside very high levels of SARS-CoV-2 S glycoprotein expression’ by Abdulaziz Almuqrin, Andrew D. Davidson, Maia Kavanagh Williamson, Phil Lewis, Kate Heesom, Susan Morris, Sarah Gilbert, David A. Matthews in ResearchSquare

Please note this is a preprint, so it is a preliminary piece of research that has not yet been through peer review and has not been published in a scientific journal – so this is early data.

A new study of beliefs and attitudes toward COVID-19 in five different countries – UK, US, Ireland, Mexico and Spain – has identified how much traction some prominent conspiracy theories have within these populations.
The research reveals ‘key predictors’ for susceptibility to fake pandemic news, and finds that a small increase in the perceived reliability of conspiracies equates to a larger drop in the intention to get vaccinated.

Scientists from the University of Cambridge gathered data from national samples in each country, and asked participants to rate the reliability of several statements, including six popular myths about COVID-19.

While a large majority of people in all five nations judged the misinformation to be unreliable, researchers found that certain conspiracy theories have taken root in significant portions of the population.

The conspiracy deemed most valid across the board was the claim that COVID-19 was engineered in a Wuhan laboratory. Between 22-23% of respondents in the UK and United States rated this assertion as “reliable”. In Ireland this rose to 26%, while in Mexico and Spain it jumped to 33% and 37% respectively.

This was followed by the idea that the pandemic is “part of a plot to enforce global vaccination”, with 22% of the Mexican population rating this as reliable, along with 18% in Ireland, Spain and the US, and 13% in the UK.

The notorious 5G conspiracy – that some telecommunication towers are worsening COVID-19 symptoms – holds sway over smaller but still significant segments: 16% in Mexico, 16% in Spain, 12% in Ireland, and 8% in both the UK and US. The study is published today in the journal Royal Society Open Science.

“Certain misinformation claims are consistently seen as reliable by substantial sections of the public. We find a clear link between believing coronavirus conspiracies and hesitancy around any future vaccine,” said Dr Sander van der Linden, co-author and Director of the Cambridge Social Decision-Making Lab.

“As well as flagging false claims, governments and technology companies should explore ways to increase digital media literacy in the population. Otherwise, developing a working vaccine might not be enough.”

Earlier this week, the Social Decision-Making Lab launched a project with the UK Cabinet Office: Go Viral!, a short online game that helps ‘inoculate’ players against fake news by lifting the lid on common misinformation techniques.

For the new study, the team – including Cambridge’s Winton Centre for Risk and Evidence Communication – looked at correlations between certain beliefs and demographic categories and the perceived reliability of misinformation.

Scoring highly on a series of numeracy tasks given as part of the study, as well as declaring high levels of trust in scientists, are ‘significantly and consistently’ associated with low levels of susceptibility to false information across all nations.

“Numeracy skills are the most significant predictor of resistance to misinformation that we found,” said Dr Jon Roozenbeek, lead author and Postdoctoral Fellow in Cambridge’s Department of Psychology.

“We all now deal with a deluge of statistics and R number interpretations. The fostering of numerical skills for sifting through online information could well be vital for curbing the ‘infodemic’ and promoting good public health behaviour.”

Moreover, and despite ‘boomer’ memes, the team found that being older is actually linked to lower susceptibility to COVID-19 misinformation in all nations except Mexico (where the opposite is true).

Identifying as more right-wing or politically conservative is associated with higher likelihood of believing COVID-19 conspiracies and falsehoods in Ireland, Mexico and Spain – but less so in the UK or US.

Trusting that politicians can effectively tackle the crisis predicts higher likelihood of buying into conspiracies in Mexico, Spain and the US, but not in the UK and Ireland. Exposure to information about the virus on social media is linked to misinformation susceptibility in Ireland, the UK and US.

Researchers asked participants about their attitude to a future coronavirus vaccine. They were also asked to rate the reliability of conspiratorial COVID-19 claims on a scale of one to seven.

On average, an increase by one-seventh in someone’s perceived reliability of misinformation is associated with a drop of almost a quarter – 23% – in the likelihood they will agree to get vaccinated.

Similarly, a one-point increase on the conspiracy reliability scale is linked, on average, to a 28% decrease in the odds of someone recommending vaccination to vulnerable friends and family.

Conversely, on average, a one-seventh increase in trust in scientists is associated with a 73% increase in the likelihood of getting vaccinated and a 79% increase in the odds of recommending vaccination to others.

The researchers controlled for many other factors – from age to politics – when modelling levels of ‘vaccine hesitancy’, and found the results to be consistent across all countries except Spain.

Jon Roozenbeek, Claudia R Schneider, Sarah Dryhurst, John Kerr, Alexandra LJ Freeman, Gabriel Recchia, Anne Marthe van der Bles, Sander van der Linden.
Susceptibility to misinformation about COVID-19 around the world.
R. Soc. Open Sci., 2020, doi: 10.1098/rsos.201199

Stuart Cohen, chief of the Division of Infectious Diseases and director of Hospital Epidemiology and Infection Prevention at UC Davis Health, will oversee the clinical trial and help recruit participants. “We at UC Davis Health are very excited to be part of this clinical trial and to study antibodies which have been used in the past to prevent many viral infections, such as hepatitis B, after exposure,” Cohen said. “We will test the ability of REGN-COV2 to prevent COVID-19 infection in people who have had close exposure to a diagnosed patient, such as a household member.”

The trial, sponsored by Regeneron Pharmaceuticals, is in Phase III to evaluate the efficacy, tolerability and safety of REGN-COV2 in adults with no history of SAR-Cov-2 infection but who live with someone who has COVID-19. Study participants will be randomly assigned to either an experimental group receiving the active medication or to the control group taking the placebo. As a double-blinded study, both the participants and the researchers will not know the group assignments.

The participants must have been in close contact with the infected person for no more than 96 hours before receiving either REGN-CoV-2 or the placebo. The trial seeks to determine whether it can prevent infection for one month following the drug administration.

On Oct. 6, the UC Davis Health team enrolled its first patient.

The antibody cocktail as a potential preventive measure for COVID-19

Regeneron developed the REGN-COV2 antibodies (a combination of REGN10933 + REGN10987 antibodies) to bind to the SARS-CoV-2 spike protein and block its interaction with the host receptor. The trial builds on encouraging findings from a set of studies that showed the neutralizing impact of REGN10933 and REGN10987. In addition to this clinical trial, UC Davis Health is involved in testing this antibody combination as a treatment for patients with COVID-19.

According to Regeneron, antibody approaches could serve as an important ‘bridge’ until a vaccine is widely available.

The clinical study (#NCT04452318) is titled “A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Assessing Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies in Preventing SARS-Cov-2 Infection in Household Contacts of Individuals Infected w/ SARS-CoV-2.”

A type of anti-bacterial T cells, so-called MAIT cells, are strongly activated in people with moderate to severe COVID-19 disease, according to a study by researchers at Karolinska Institutet in Sweden that is published in the journal Science Immunology. The findings contribute to increased understanding about how our immune system responds against COVID-19 infection. “To find potential treatments against COVID-19, it is important to understand in detail how our immune system reacts and, in some cases, perhaps contribute to worsening the disease,” says Johan Sandberg, professor at the Department of Medicine, Huddinge, at Karolinska Institutet and the study’s corresponding author.

T cells are a type of white blood cells that are specialized in recognizing infected cells, and are an essential part of the immune system. About 1 to 5 percent of T cells in the blood of healthy people consist of so-called MAIT cells (mucosa-associated invariant T cells), which are primarily important for controlling bacteria but can also be recruited by the immune system to fight some viral infections.

In this study, the researchers wanted to find out which role MAIT cells play in COVID-19 disease pathogenesis. They examined the presence and character of MAIT cells in blood samples from 24 patients admitted to Karolinska University Hospital with moderate to severe COVID-19 disease and compared these with blood samples from 14 healthy controls and 45 individuals who had recovered from COVID-19. Four of the patients died in the hospital.

The results show that the number of MAIT cells in the blood decline sharply in patients with moderate or severe COVID-19 and that the remaining cells in circulation are highly activated, which suggests they are engaged in the immune response against SARS-CoV-2. This pattern of reduced number and activation in the blood is stronger for MAIT cells than for other T cells. The researchers also noted that pro-inflammatory MAIT cells accumulated in the airways of COVID-19 patients to a larger degree than in healthy people.

“Taken together, these analyses indicate that the reduced number of MAIT cells in the blood of COVID-19 patients is at least partly due increased accumulation in the airways,” Johan Sandberg says.

In convalescent patients, the number of MAIT cells in the blood recovered at least partially in the weeks after disease, which can be important for managing bacterial infections in individuals who have had COVID-19, according to the researchers. In the patients who died, the researchers noted that the MAIT cells tended to be extremely activated with lower expression of the receptor CXCR3 than in those who survived.

“The findings of our study show that the MAIT cells are highly engaged in the immunological response against COVID-19,” Johan Sandberg says. “A likely interpretation is that the characteristics of MAIT cells make them engaged early on in both the systemic immune response and in the local immune response in the airways to which they are recruited from the blood by inflammatory signals. There, they are likely to contribute to the fast, innate immune response against the virus. In some people with COVID-19, the activation of MAIT cells becomes excessive and this correlates with severe disease.”

Parrot T, Gorin JB, Ponzetta A, Maleki KT, Kammann T, Emgård J, Perez-Potti A, Sekine T, Rivera-Ballesteros O, the Karolinska COVID-19 Study Group, Gredmark-Russ S, Rooyackers O, Folkesson, E, Eriksson LI, Norrby-Teglund A, Ljunggren HG, Björkström NK, Aleman S, Buggert M, Klingström J, Strålin K, Sandberg JK.
MAIT cell activation and dynamics associated with COVID-19 disease severity.
Science Immunology, 2020. doi: 10.1126/sciimmunol.abe1670

64 higher income economies have joined the COVAX Facility, a global initiative that brings together governments and manufacturers to ensure eventual COVID-19 vaccines reach those in greatest need, whoever they are and wherever they live. These 64 economies include commitments from 35 economies as well as the European Commission which will procure doses on behalf of 27 EU member states plus Norway and Iceland. By pooling financial and scientific resources, these participating economies will be able to insure themselves against the failure of any individual vaccine candidate and secure successful vaccines in a cost-effective, targeted way.

The 64 members of the Facility will be joined by 92 low- and middle-income economies eligible for support for the procurement of vaccines through the Gavi COVAX Advance Market Commitment (AMC), a financing instrument aimed at supporting the procurement of vaccines for these countries. This means that 156 economies, representing roughly 64% of the global population in total, are now either committed to or eligible for the COVAX Facility, with more to follow.

With the Commitment Agreements secured, the COVAX Facility will now start signing formal agreements with vaccine manufacturers and developers, which are partners in the COVAX effort, to secure the doses needed to end the acute phase of the pandemic by the end of 2021. This is in addition to an ongoing effort to raise funding for both R&D and for the procurement of vaccines for lower-income countries via the Gavi COVAX AMC.

“COVAX is now in business: governments from every continent have chosen to work together, not only to secure vaccines for their own populations, but also to help ensure that vaccines are available to the most vulnerable everywhere,” said Dr Seth Berkley, CEO of Gavi, the Vaccine Alliance, which is coordinating the COVAX Facility. “With the commitments we’re announcing today for the COVAX Facility, as well as the historic partnership we are forging with industry, we now stand a far better chance of ending the acute phase of this pandemic once safe, effective vaccines become available.”

The COVAX Facility is part of COVAX, the vaccines pillar of the Access to COVID-19 Tools (ACT) Accelerator, which is co-led by the Coalition for Epidemic Preparedness Innovations (CEPI), Gavi, the Vaccine Alliance, and the World Health Organization (WHO) – working in partnership with developed and developing country vaccine manufacturers, UNICEF, the World Bank, Civil Society Organisations and others.

The allocation of vaccines, once licensed and approved, will be guided by an Allocation Framework released today by WHO following the principle of fair and equitable access, ensuring no participating economy will be left behind. Policies determining the prioritization of vaccine rollout within economies will be guided by recommendations from the WHO Strategic Advisory Group of Experts on Immunization (SAGE), which has recently released a Values Framework laying the groundwork for subsequent guidance on target populations and policies on vaccine use.

“COVID-19 is an unprecedented global crisis that demands an unprecedented global response,” said WHO Director-General, Dr Tedros Adhanom Ghebreyesus. “Vaccine nationalism will only perpetuate the disease and prolong the global recovery. Working together through the COVAX Facility is not charity, it’s in every country’s own best interests to control the pandemic and accelerate the global economic recovery.”

The commitment of fully self-financing economies will now unlock vital funding and the security of demand needed to scale up manufacturing and secure the doses needed for the Facility. CEPI is leading COVAX vaccine research and development work, which aims to develop at least three safe and effective vaccines which can be made available to economies participating in the COVAX Facility. Nine candidate vaccines are currently being supported by CEPI; eight of which are currently in clinical trials.

“This is a landmark moment in the history of public health with the international community coming together to tackle this pandemic. The global spread of COVID-19 means that it is only through equitable and simultaneous access to new lifesaving COVID-19 vaccines that we can hope to end this pandemic,” said Dr Richard Hatchett, CEO of CEPI. “Countries coming together in this way shows a unity of purpose and resolve to end the acute phase of this pandemic, and we must now work closely with vaccine manufacturers – who play an integral part in the global response – to put in place the agreements needed to fulfil COVAX’s core aim: to have two billion vaccine doses available by the end of 2021. Today, we have taken a great leap towards that goal, for the benefit of all.”

The success of COVAX hinges not only on economies signing up to the COVAX Facility and commitments from vaccine manufacturers, but also filling key funding gaps for both COVAX research and development (R&D) work and the Gavi COVAX AMC to support participation of lower income economies in the COVAX Facility.

Governments, vaccine manufacturers (in addition to their own R&D), organisations and individuals have committed US$ 1.4 billion towards vaccine R&D so far, but a further US$ 700-800 million is urgently needed to continue to move the portfolio forward in addition to US$ 300 million to fund WHO’s SOLIDARITY trial.

The Gavi COVAX AMC has raised around US$ 700 million from sovereign donors as well as philanthropy and the private sector, against an initial target of US$ 2 billion in seed funding needed by the end of 2020. Funding the Gavi COVAX AMC will be critical to ensuring ability to pay is not a barrier to accessing COVID-19 vaccines, a situation which would leave the majority of the world unprotected, with the pandemic and its impact continuing unabated.

The Commitment Agreements also commit higher income governments to provide an upfront payment to reserve doses by 9 October 2020. These funds will be used to accelerate the scale-up of vaccine manufacturing to secure two billion doses of vaccine, enough to vaccinate one billion people assuming the vaccine requires a two-dose regimen. Further details on these upfront payments are available in Gavi’s COVAX Facility Explainer.

As well as procuring doses for participating economies, the COVAX Facility will also maintain a buffer of doses for emergency and humanitarian use.

About Gavi, the Vaccine Alliance

Gavi, the Vaccine Alliance is a public-private partnership that helps vaccinate half the world’s children against some of the world’s deadliest diseases. Since its inception in 2000, Gavi has helped to immunise a whole generation – over 760 million children – and prevented more than 13 million deaths, helping to halve child mortality in 73 developing countries. Gavi also plays a key role in improving global health security by supporting health systems as well as funding global stockpiles for Ebola, cholera, meningitis and yellow fever vaccines. After two decades of progress, Gavi is now focused on protecting the next generation and reaching the unvaccinated children still being left behind, employing innovative finance and the latest technology – from drones to biometrics – to save millions more lives, prevent outbreaks before they can spread and help countries on the road to self-sufficiency.

The Vaccine Alliance brings together developing country and donor governments, the World Health Organization, UNICEF, the World Bank, the vaccine industry, technical agencies, civil society, the Bill & Melinda Gates Foundation and other private sector partners.

About CEPI

CEPI is an innovative partnership between public, private, philanthropic, and civil organisations, launched at Davos in 2017, to develop vaccines to stop future epidemics. CEPI has moved with great urgency and in coordination with WHO in response to the emergence of COVID-19. CEPI has initiated nine partnerships to develop vaccines against the novel coronavirus. The programmes are leveraging rapid response platforms already supported by CEPI as well as new partnerships.

Before the emergence of COVID-19, CEPI’s priority diseases included Ebola virus, Lassa virus, Middle East Respiratory Syndrome coronavirus, Nipah virus, Rift Valley Fever and Chikungunya virus. CEPI also invested in platform technologies that can be used for rapid vaccine and immunoprophylactic development against unknown pathogens (Disease X).

About WHO

The World Health Organization provides global leadership in public health within the United Nations system. Founded in 1948, WHO works with 194 Member States, across six regions and from more than 150 offices, to promote health, keep the world safe and serve the vulnerable. Our goal for 2019-2023 is to ensure that a billion more people have universal health coverage, to protect a billion more people from health emergencies, and provide a further billion people with better health and wellbeing.

About ACT-Accelerator

The Access to COVID-19 Tools ACT-Accelerator, is a new, ground-breaking global collaboration to accelerate the development, production, and equitable access to COVID-19 tests, treatments, and vaccines. It was set up in response to a call from G20 leaders in March and launched by the WHO, European Commission, France and The Bill & Melinda Gates Foundation in April 2020.

The ACT-Accelerator is not a decision-making body or a new organisation, but works to speed up collaborative efforts among existing organisations to end the pandemic. It is a framework for collaboration that has been designed to bring key players around the table with the goal of ending the pandemic as quickly as possible through the accelerated development, equitable allocation, and scaled up delivery of tests, treatments and vaccines, thereby protecting health systems and restoring societies and economies in the near term. It draws on the experience of leading global health organisations which are tackling the world’s toughest health challenges, and who, by working together, are able to unlock new and more ambitious results against COVID-19. Its members share a commitment to ensure all people have access to all the tools needed to defeat COVID-19 and to work with unprecedented levels of partnership to achieve it.

The ACT-Accelerator has four areas of work: diagnostics, therapeutics, vaccines and the health system connector. Cross-cutting all of these is the workstream on Access & Allocation.

People who survive serious COVID-19 infections have long-lasting immune responses against the virus, according to a new study led by researchers at Massachusetts General Hospital (MGH). The study, published in Science Immunology, offers hope that people infected with the virus will develop lasting protection against reinfection. The study also demonstrates that measuring antibodies can be an accurate tool for tracking the spread of the virus in the community.

The immune system produces proteins called antibodies in response to SARS-CoV-2, the virus that causes COVID-19. “But there is a big knowledge gap in terms of how long these antibody responses last,” says Richelle Charles, MD, an investigator in the Division of Infectious Diseases at MGH and a senior author of the paper. To find out, she and her colleagues obtained blood samples from 343 patients with COVID-19, most of whom had severe cases. The blood samples were taken up to four months after a patient’s symptoms emerged. The blood’s plasma was isolated and applied to laboratory plates coated with the receptor-binding domain (RBD) of the virus’s “spike” protein, which attaches to cells, leading to infection. The team studied how different types of antibodies in the plasma bound to RBD. The results were compared to blood samples obtained from more than 1,500 individuals prior to the pandemic.

The researchers found that measuring an antibody called immunoglobulin G (IgG) was highly accurate in identifying infected patients who had symptoms for at least 14 days. Since the standard PCR (nasal swab) test for SARS-CoV-2 loses sensitivity over time, augmenting it with a test for antibodies in patients who have had symptoms for at least eight days (at which time 50 percent are producing antibodies) will help identify some positive cases that might otherwise be missed, says Charles.

The researchers found that IgG levels remained elevated in these patients for four months, and were associated with the presence of protective neutralizing antibodies, which also demonstrated little decrease in activity over time. “That means that people are very likely protected for that period of time,” says Charles. “We showed that key antibody responses to COVID-19 do persist.”

In another finding, Charles and her colleagues showed that people infected with SARS-CoV-2 had immunoglobulin A (IgA) and immunoglobulin M (IgM) responses that were relatively short-lived, declining to low levels within about two and a half months or less, on average. “We can say now that if a patient has IgA and IgM responses, they were likely infected with the virus within the last two months,” says Charles.

Knowing the duration of the immune response by IgA and IgM will help scientists obtain more accurate data about the spread of SARS-CoV-2, explains Jason Harris, MD, a pediatric infectious disease specialist at MGH and co-senior author of the study. “There are a lot of infections in the community that we do not pick up through PCR testing during acute infection, and this is especially true in areas where access to testing is limited,” he says. “Knowing how long antibody responses last is essential before we can use antibody testing to track the spread of COVID-19 and identify ‘hot spots’ of the disease.”

Anita S Iyer, Forrest K Jones, Ariana Nodoushani, Meagan Kelly, Margaret Becker, Damien Slater, Rachel Mills, Erica Teng, Investigation, Mohammad Kamruzzaman, Wilfredo F Garcia-Beltran, Michael Astudillo, Diane Yang, Tyler E. Miller, Elizabeth Oliver, Stephanie Fischinger, Caroline Atyeo, A John Iafrate, Stephen B Calderwood, Stephen A Lauer, Methodology, Supervision, Validation, Jingyou Yu, Zhenfeng Li, Jared Feldman, Blake M Hauser, Timothy M Caradonna, John A Branda, Sarah E Turbett, Regina C LaRocque, Guillaume Mellon, Dan H Barouch, Aaron G Schmidt, Andrew S Azman, Galit Alter, Edward T Ryan, Jason B Harris, Richelle C Charles.
Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients.
Science Immunology, 2020. doi: 10.1126/sciimmunol.abe0367

The Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines has authorised another Phase-1 clinical trial of a vaccine against COVID-19 in Germany. The new vaccine candidate is a so-called vector vaccine. Trials on vaccine candidates in humans are a significant step in the direction of authorising safe and efficacious vaccines against COVID-19. This new vaccine is a vector vaccine developed by the German Center for Infection Research (Deutsches Zentrum für Infektionsforschung, DZIF) and the IDT Biologika GmbH against SARS-CoV-2. In this vector vaccine, the genetic information for the spike surface protein of the SARS-CoV-2 virus is built into the smallpox vaccine virus MVA. The starting vaccine virus MVA was already developed more than 30 years ago at the Ludwig-Maximilians University (LMU) in Munich, and the authorised smallpox vaccine Imvanex was derived from it. The viral vector MVA equipped with the genetic information of SARS-CoV-2 cannot replicate in the body after injection. The genetic information (desoxyribonucleic acid, DNA) of the spike protein of the virus thus inserted is used in the body to form the spike protein. The immune system recognises the foreign spike protein and triggers an immune response. The aim is to generate antibodies, certain cytokines and immune cells (T cells) for lasting protection against SARS-CoV-2. Preclinical models at the universities of Marburg and Munich have already shown that the MVA vector vaccine against SARS-CoV-2 shows the desired immune responses and a protective effect.

The clinical trial authorised by the Paul-Ehrlich-Institut on 30 September 2020 is a phase 1 clinical trial with altogether 30 healthy subjects aged between 18 and 55 years. The participants receive two vaccinations at an interval of four weeks. The working group at the University Medical Center Hamburg-Eppendorf (UKE) and the DZIF partner in Marburg are simultaneously measuring the formation of antibodies and T cells in the body and comparing them with the immune response of recovered COVID-19 patients. The UKE is responsible for the clinical trial, which is carried out jointly with the contracted medical institute CTC North. The study is financed by public funds from the DZIF.

According to the World Health Organisation (WHO), as per 30 September 2020, the vaccine candidate is one of the 41 preventive specific COVID-19 vaccine candidates being evaluated in clinical trials. In Germany, it represents the first authorised phase 1 clinical trial for a vector-based COVID-19 vaccine. The increasing number of clinical trials worldwide is an important step toward authorising safe and efficacious COVID-19 vaccine products.

The Paul-Ehrlich-Institut, which is the competent authority for authorising clinical trials and the evaluation and marketing authorisation of vaccines in Germany, expects additional clinical trials for COVID-19 vaccine candidates to start in Germany in the next few months. The Paul-Ehrlich-Institut supports the worldwide COVID-19 vaccine development with top priority.

Background for Vector Vaccines

COVID-19 vector vaccines contain innocuous parts of the genome of SARS-CoV-2 in their genetic information, i.e. the blueprint for the spike protein or for a component of that spike protein. After this genetic information has entered a few body cells of the vaccinated subject, it is read (like the genetic information of the body cells itself) in the cells as messenger RNA, and the appropriate surface structures (proteins) of the virus are produced. The immune system reacts to the foreign protein thus formed and forms defences against it (among other things antibodies). If the person thus vaccinated comes into contact with SARS-CoV-2 later on, the immune system will recognise the surface structure with the aim to prevent or alleviate a serious course of a COVID-19 infection, and even to reduce the transmission of SARS-CoV-2 from human to human.

Four out of five people experiencing the recent loss of smell and/or taste tested positive for COVID-19 antibodies – and of those who tested positive, 40 percent did not have cough or fever, reports a new study in PLOS Medicine by Prof. Rachel Batterham at University College London and colleagues. COVID-19 can cause loss of taste and smell, but the prevalence of COVID-19 antibodies in people reporting these symptoms is unknown, and the significance of loss of smell and/or taste as a predictor of COVID-19 is not well understood. To estimate the seroprevalence of SARS-CoV-2 antibodies in people with acute loss of their sense of smell and/or taste, researchers enrolled 590 people self-reporting a loss of taste/smell in the previous month. Following verification of symptoms via a telemedicine consultation, 567 participants with smell and/or taste loss participants underwent a SARS-CoV-2 antibodies test.

78% had SARS-CoV-2 antibodies, and participants with loss of smell were almost 3 times more likely to have SARS-CoV-2 antibodies compared to those with loss of taste, suggesting that a loss of smell is a highly specific symptom of COVID-19. Of the 78% of participants testing positive for antibodies, 40% had neither cough nor fever. While the study had limitations, such as the self-reporting of smell/taste changes and the lack of a control group, the researchers believe the evidence indicates that loss of smell should be taken into greater consideration in COVID-19 public health measures such as testing, case isolation, and treatment strategies.

These findings also have significant implications for policy makers globally, as most countries do not recommend self-isolation and testing based on acute loss of smell/taste. This study suggests that an over-reliance on cough and fever as the main symptoms of COVID-19 may be flawed and that loss of smell needs to be urgently recognized globally as a key symptom of COVID-19.

Prof. Rachel Batterham, who led the study, said “Early self-recognition of COVID-19 symptoms by the members of the public, together with rapid self-isolation and PCR testing are vital in order to limit spread of the disease. Currently, most countries around the world do not recognize sudden loss of smell as a symptom of COVID-19.

78% of participants in our community-based study with sudden onset loss of smell or taste had SARS-CoV-2 antibodies. The vast majority had mild symptoms and 40% did not report having a fever or cough. Our findings suggest that people who notice a loss in their ability to smell every day house-hold odors such as garlic, coffee and perfumes should self-isolate and seek PCR testing. Loss of sense of smell needs to be recognized globally by policy makers as a key symptom of COVID-19.”

Makaronidis J, Mok J, Balogun N, Magee CG, Omar RZ, et al.
Seroprevalence of SARS-CoV-2 antibodies in people with an acute loss in their sense of smell and/or taste in a community-based population in London, UK: An observational cohort study.
PLOS Medicine 2020, doi: 10.1371/journal.pmed.1003358