The pandemic has reached a grim milestone: one million people have died, according to COVID-19 Worldometer.
January 13th we have published “Mystery China pneumonia outbreak likely caused by new human coronavirus” by Connor Bamford, a virologist at Queen’s University Belfast. Since then, we have published more than 3,500 articles about the no longer so new coronavirus, officially called Sars-CoV-2. Despite the tremendous accomplishment of the world’s leading experts, we’ve just skimmed the surface of everything there is to know about this confusing pathogen. That much remains a mystery.
At this important point, we asked several experts from different fields what their burning question about the coronavirus is. This is what they said:
Connor Bamford, Research Associate, Virology, Queen’s University Belfast
- 1 How did Sars-CoV-2 get into the human population?
- 2 How can we tell if someone is protected from Sars-CoV-2?
- 3 How can we explain the extreme geographic differences in COVID-19 death rates?
- 4 What is the success of a vaccine in the short or long term?
- 5 How can COVID-safe behavior be embedded in people’s lives?
- 6 What is the full spectrum of health consequences of COVID-19 infection?
How did Sars-CoV-2 get into the human population?
We need to understand how Sars-CoV-2-like viruses invade humans if we are to stop the next pandemic, as we do with influenza. Although it was originally believed to have appeared in the Huanan Seafood Wholesale Market in December 2019, the earliest patient had No connection to the market This suggests that the virus had appeared before. How did it happen?
Since the original research into the beginnings of Sars coronavirus in 2002, horseshoe bats have been identified in Southeast Asia as the Reservoir hostsand a virus (RmYN02) very similar to Sars-CoV-2 has already been found in bats. However, similar viruses were also produced found in psoriasisThis increases the possibility that Sars-CoV-2 did not jump directly from a bat.
Sars-CoV-2 has also already spread Cats, dogs, tiger and minkand civets and raccoon dogs bred for Sars-CoV-1 (the virus that caused the 2002-04 Sars epidemic) acted as intermediate hostsand bring a bat virus into the vicinity of humans. It is possible that Sars-CoV-2 is a generalist virus that can spread through a variety of species.
With the increasing contact between humans and animals, zoonoses are becoming a growing threat. We have to be vigilant. An important step now is to find out the events that resulted in Sars-CoV-2 going from bat to human.
Sarah Caddy, Clinical Research Fellow, Viral Immunology, Cambridge University
How can we tell if someone is protected from Sars-CoV-2?
The immune response to Sars CoV-2 infection is aimed at clearing the virus from the body. Many studies have carefully described the various stages of the immune response after the initial infection, but we do not know which aspects of immunity are essential to preventing recurrence. What relative roles do different types of antibodies play or what is the significance of different T cell subsets?
An important goal of Sars-CoV-2 immunological research is therefore to identify which immune component (or which immune components) can show that a person is protected from future infections. Such a marker would be called “Correlate of Protection”.
The ability to measure an accurate correlate of protection would be valuable for two reasons. First, it could tell us if someone who has recovered from COVID-19 is likely to get infected again. Second, identifying an easily measurable correlate of protection for vaccine trials would be helpful – this could speed up assessments of the vaccine’s effectiveness.
Identifying good correlates of protection for other coronaviruses has proven notoriously difficult. So far, useful results have only been achieved when volunteers have been infected with viruses experimentally. The first human Sars-Cov-2 challenge studies are now to begin early next year, so it is hoped that this will enable correlates of protection to be found more quickly.
Derek Gatherer, Lecturer and Fellow of the Institute for Social Futures at Lancaster University
How can we explain the extreme geographic differences in COVID-19 death rates?
The cumulative deaths from COVID-19 per million population (dpm) are very unevenly distributed across Europe (see map below) and range from 7 p.m. in Slovakia to 856 a.m. in Belgium. A wedge of relatively lightly affected countries extends from Finland south to the northern Balkans.
Other continents, particularly Southeast Asian countries, have similar areas of low COVID-19 mortality. Could populations from low mortality countries have some cross-immunity to Sars-CoV-2 caused by recent exposure to another coronavirus – the obvious candidates are the milder “cold” coronaviruses: 229E, NL63, or OC43 HKU1?
An indication that this could be the case is the observation that antibodies from the original Sars patients from 2003 have some binding to coronaviruses 229E, NL63 and especially OC43. Seasonal coronaviruses, but seasonal respiratory infections without flu in general, have received so little attention that relevant clinical field data are extremely sparse and often old (e.g. A third of Hamburgers had antibodies against the coronavirus OC43 in 1975 or 58% of Hungarians were interviewed five years later).
We urgently need more laboratory studies to understand how much coronaviruses lend one another across immunity, while population studies are needed to determine the prevalence of coronavirus antibodies, not just to Sars-CoV-2 but its milder ones as well but potentially significant cousins.
Serology – the study of antibody prevalence – has long been the Cinderella of virology compared to the more glamorous world of genome sequencing, but its importance and the consequences of neglecting it are now becoming apparent.
From San Jose – own map, based on the Generic Mapping Tools and ETOPO2 (annotated by DG). Data from the WHO epidemiological update., CC BY-SA
Anne Moore, Lecturer in Biochemistry and Cell Biology at University College Cork
What is the success of a vaccine in the short or long term?
The endgame of the COVID-19 pandemic requires the identification and manufacture of a safe and effective vaccine and a subsequent global vaccination campaign.
Candidate Sars CoV-2 vaccines were rapidly developed due to years of vaccine development efforts. The unprecedented and significant contribution of global funding to this pandemic vaccine effort can only buy so much time for studies to succeed or fail. For a study to be successful, the virus needs to be circulating in the community so we can see how many people who have been vaccinated will be infected (compared to those who are given a placebo).
Short term success will show that vaccine will be a safer one offer at least 50% protection. And when we see short-term success, what does long-term success look like?
The biggest question is how long does the protection last? If it is short lived, then how can we restore immunity to a protective level? How can we find out without relying on a traditional empirical approach? If there is no short-term success, then how can we ensure global commitment is sustained to prevent Sars-CoV-2 vaccines from falling into the same predicament as abandoned Sars vaccination efforts? There will be another pandemic; We need a long-term vision and commitment in order to be successful in the short term in the future.
Susan Michie and Robert West, Professors in Health Psychology, UCL
How can COVID-safe behavior be embedded in people’s lives?
It looks like COVID-19 will be with us for the foreseeable future. We’ll all have to adopt a range of behaviors to keep us from getting infected or infecting others. We know what that is: the question is how they can be embedded in our lives.
Behaviors include keeping a greater physical distance from others; Wearing a COVID kit (face mask, hand sanitizer and tissues) when we are outside the home; Wear a face mask properly in indoor public places and store or dispose of it safely. Disinfection of hands and surfaces after possible contamination; Catching coughs and sneezes in tissues; Never touch our eyes, nose, or mouth unless we know our hands are clean. Avoiding or leaving unsafe situations such as poorly ventilated indoor areas that are crowded; to be vaccinated; and stay home and get tested when we have symptoms.
The challenge is how these can be adopted on a large scale and maintained over time, i.e. as routines and habits embedded in people’s lives. This requires an understanding of what maintains and changes human behavior. We need to equip people with the skills to develop routines that can become habits over time, provide the time and social and environmental support to achieve this, and motivate them to take advantage of these opportunities.
David Hunter, Richard Doll Professor of Epidemiology and Medicine, Oxford University
What is the full spectrum of health consequences of COVID-19 infection?
We now have good data on deaths from COVID-19 infection, showing a staggering increase in the risk of death with age. This contrasts with the 2009 H1N1 flu epidemic, which left the elderly relatively less affected, and reminds us that we still have a lot more to learn about this virus.
While the main focus has been on deaths, small studies of COVID-19 survivors who have been discharged from hospital suggest that many are not returning to their baseline. We know little about “long COVID” among those who did not need hospitalization, despite many individual reports of recurrent attacks of fever, fatigue and a wide range of other symptoms.
Follow-up of COVID-19 patients suggests damage to the heart, lungs, and other organs that may cause problems in the future, and there is evidence that this may also be the case in those with mild symptoms . Many viral infections can cause undiagnosed pathology, but serious long-term effects are relatively rare. However, if these effects are more common in COVID-19, an exclusive focus on deaths means we will not be considering the full cost of failing to control the epidemic, or the full benefits of it.
Studies have started in patients after they have been discharged from the hospital. We urgently need well-controlled studies in the majority of those infected who did not need hospitalization, in case we only see the tip of the COVID iceberg.
Sarah L Caddy, Clinical Research Fellow for Virus Immunology and Veterinarian, Cambridge University;; Anne Moore, Lecturer in biochemistry and cell biology, University College Cork;; Connor Bamford, Research Associate, Virology, Queen’s University Belfast;; David HunterRichard Doll Professor of Epidemiology and Medicine, Oxford University;; Derek Gatherer, Lecturer, Lancaster University;; Robert West, Professor of Health Psychology and Director of Tobacco Studies, UCL, and Susan Michie, Professor of Health Psychology and Director of the UCL Center for Behavioral Change, UCL