The pandemic has reached a grim milestone: a million individuals have now died of COVID-19, in accordance with Worldometers.

On January 13, we revealed “Thriller China pneumonia outbreak doubtless attributable to new human coronavirus” by Connor Bamford, a virologist at Queen’s College Belfast. Since then, now we have revealed greater than 3,500 articles on the now not-so-novel coronavirus, formally named Sars-CoV-2. Regardless of this large output from the world’s main consultants, now we have merely skimmed the floor of all there may be to find out about this perplexing pathogen. A lot stays a thriller.

At this essential juncture, we requested a number of consultants from completely different fields what their burning query in regards to the coronavirus is. Here’s what they stated:

Connor Bamford, Analysis Fellow, Virology, Queen’s College Belfast

How did Sars-CoV-2 enter the human inhabitants?

We should perceive how Sars-CoV-2-like viruses leap into people if we’re to cease the subsequent pandemic, as we do for influenza. Though initially thought to have emerged within the Huanan Seafood Wholesale Market in December 2019, the earliest affected person had no hyperlink to the market suggesting the virus had emerged earlier than then. How did this occur?

Learn extra:

Thriller China pneumonia outbreak doubtless attributable to new human coronavirus

Because the unique investigations into the beginnings of Sars coronaviruses in 2002, horseshoe bats in south-east Asia have been implicated because the reservoir hosts, and a virus (RmYN02) that’s extraordinarily just like Sars-CoV-2 has already been present in bats. Nonetheless, related viruses have additionally been present in pangolins, elevating the likelihood that Sars-CoV-2 might not have jumped straight from a bat.

Additionally, Sars-CoV-2 has already unfold to cats, canines, tigers and mink, and for Sars-CoV-1 (the virus that prompted the 2002-04 Sars epidemic), farmed civet cats and raccoon canines acted as intermediate hosts, bringing a bat virus into proximity to people. It’s potential that Sars-CoV-2 is a generalist virus, able to spreading via a variety of species.

With the rise involved between people and wildlife, zoonoses have gotten an ever-growing risk. We should be vigilant. An essential step now’s to determine the occasions that led Sars-CoV-2 to go from bat to human.

Related viruses have been present in pangolins.

Arief Budi Kusuma/Shutterstock

Sarah Caddy, Scientific Analysis Fellow, Viral Immunology, College of Cambridge

How can we inform if somebody is protected against Sars-CoV-2?

The immune response to Sars-CoV-2 an infection goals to get rid of the virus from the physique. Many research have fastidiously described the varied phases of the immune response after preliminary an infection, however we have no idea which features of immunity are important for stopping repeat infections. What are the relative roles of various kinds of antibodies, or the significance of various T cell subsets?

An essential purpose of Sars-CoV-2 immunological analysis is, due to this fact, to establish which immune element (or parts) can present an individual is protected against future an infection. Such a marker can be termed a “correlate of safety”.

The power to measure an correct correlate of safety can be beneficial for 2 causes. First, it might inform us whether or not somebody who has recovered from COVID-19 is more likely to get re-infected. Second, figuring out an simply measurable correlate of safety can be useful for vaccine trials – it might pace up the analysis of vaccine efficacy.

Nonetheless, figuring out good correlates of safety for different coronaviruses has confirmed notoriously troublesome. Helpful outcomes have beforehand solely been generated when volunteers have been experimentally contaminated with viruses. The primary human Sars-Cov-2 problem research at the moment are because of start early subsequent yr, so it’s hoped that this can allow correlates of safety to be discovered extra quickly.

Learn extra:

Coronavirus: why I help the world’s first COVID vaccine problem trial

Derek Gatherer, Lecturer and Fellow of the Institute for Social Futures, Lancaster College

How can we clarify the intense geographical variation in COVID-19 mortality charges?

Cumulative deaths from COVID-19 per million of inhabitants (dpm), are very inconsistently distributed throughout Europe (see map under) starting from 7dpm in Slovakia to 856dpm in Belgium. A wedge of comparatively frivolously affected nations extends from Finland southwards to the northern Balkans.

There are related pockets of low COVID-19 mortality on different continents, notably south-east Asian nations. May the populations of low mortality nations have some cross-immunity to Sars-CoV-2 generated by current publicity to a different coronavirus – the apparent candidates being the milder “frequent chilly” coronaviruses: 229E, NL63, OC43 or HKU1?

A touch that this can be the case is offered by the remark that antibodies from the unique 2003 Sars sufferers have some binding to coronaviruses 229E, NL63 and notably OC43. However so little consideration has been paid to seasonal coronaviruses, certainly, to seasonal non-flu respiratory infections, basically, that related medical discipline information is extraordinarily sparse and sometimes outdated (as an example, one-third of residents of Hamburg had antibodies to coronavirus OC43 in 1975 or 58% of Hungarians sampled 5 years later).

We urgently want extra lab research to grasp how a lot cross-immunity coronaviruses confer on one another, whereas inhabitants research are wanted to find out the prevalence of coronavirus antibodies, not simply to Sars-CoV-2 but additionally its milder but probably vital cousins.

Serology – the examine of antibody prevalence – has lengthy been the Cinderella of virology in contrast with the extra glamorous world of genome sequencing, however its significance and the results of its neglect at the moment are turning into obvious.

Deaths per million (dpm) of inhabitants in Europe and surrounding nations, as of mid-September 2020. Crimson: >200dpm; Blue: 100-200dpm; Black <100dpm.

By San Jose – personal map, based mostly on the Generic Mapping Instruments and ETOPO2 (annotated by DG). Knowledge from WHO Epidemiological Replace., CC BY-SA

Anne Moore, Senior Lecturer in Biochemistry and Cell Biology, College Faculty Cork

For a vaccine, what does success appear like within the quick versus long run?

The endgame to the COVID-19 pandemic requires the identification and manufacture of a protected and efficient vaccine and a subsequent international immunisation marketing campaign.

Candidate Sars-CoV-2 vaccines have been quickly developed based mostly on years of vaccine improvement efforts. The unprecedented and vital enter of worldwide funding into this pandemic vaccine effort can solely purchase a lot time for trials to succeed or fail. A profitable trial wants the virus to be circulating in the neighborhood so we are able to decide what number of vaccinated individuals (versus these receiving a placebo) develop into contaminated.

Quick-term success will present {that a} protected vaccine will present at the very least 50% safety. And if we see short-term success, what does long-term success appear like?

The largest query is, what’s the period of safety? Whether it is short-lived, then how can we increase immunity again to protecting ranges? How can we determine this out with out counting on a conventional empirical strategy? If there isn’t short-term success, then how can we be sure that international dedication is maintained to stop Sars-CoV-2 vaccines from ending up in the identical scenario as terminated vaccine efforts for Sars? There will likely be one other pandemic; we want a long-term imaginative and prescient and dedication to have short-term future success.

Susan Michie and Robert West, Professors of Well being Psychology, UCL

How can COVID-safe behaviour develop into embedded in individuals’s lives?

It seems to be as if COVID-19 will likely be with us for the foreseeable future. We’ll all must undertake a variety of behaviours to maintain ourselves from getting contaminated or infecting others. We all know what these are: the query is how they’ll develop into embedded in our lives?

The behaviours embrace preserving a larger bodily distance from others; carrying a COVID equipment (face masks, hand sanitiser and tissues) every time we’re outdoors the house; carrying a face masks correctly in indoor public areas and storing or disposing of it safely; disinfecting palms and surfaces after potential contamination; catching coughs and sneezes in tissues; by no means touching our eyes, nostril or mouth until we all know our palms are clear; avoiding or leaving unsafe conditions, corresponding to poorly ventilated indoor areas the place there are many individuals; getting vaccinated; and staying at dwelling and getting examined if now we have signs.

How can we get individuals to embed good behaviours of their lives.

Kzenon/Shutterstock

The problem is easy methods to get these adopted at scale and maintained over time, in different phrases, embedded in individuals’s lives as routines and habits. This requires an understanding of what maintains and modifications human behaviour. We have to equip individuals with the abilities to develop routines that may develop into habits over time, present the time and social and environmental help to realize this and inspire them to make use of these alternatives.

David Hunter, Richard Doll Professor of Epidemiology and Medication, College of Oxford

What’s the full spectrum of well being penalties of COVID-19 an infection?

We now have good information on deaths from COVID-19 an infection, displaying an astonishing improve in threat of loss of life with growing age. This contrasts with the 2009 H1N1 flu epidemic, wherein the aged have been comparatively much less affected, and reminds us that now we have an excellent deal extra to study this virus.

Whereas a lot of the focus has been on deaths, small research of COVID-19 survivors discharged from hospital counsel that many don’t return to their baseline well being standing. We all know little about “lengthy COVID” amongst those that didn’t require hospital admission, regardless of many particular person stories of recurrent bouts of fever, fatigue, and a variety of different signs.

Comply with-up of COVID-19 sufferers counsel proof of injury to the center, lungs and different organs which will trigger issues sooner or later, and there may be some proof that this can be true even amongst these with gentle signs. Many viral infections could cause undiagnosed pathology, however extreme long-term results are comparatively unusual. If these results are extra frequent for COVID-19, nevertheless, then an unique deal with deaths means that we are going to not be contemplating the complete prices of failing to manage the epidemic, nor the complete advantages of doing so.

Research have began amongst sufferers after discharge from hospital. We urgently want well-controlled research among the many majority of these contaminated who didn’t want hospitalisation in case we’re solely seeing the tip of the COVID iceberg.

Anne Moore has acquired funding from HRB and Enterprise Eire for vaccine analysis and from small and medium scale vaccine improvement firms within the EU and the USA.

Connor Bamford receives funding from Wellcome Belief and UKRI.

Derek Gatherer receives funding from the UK Financial & Social Analysis Council and the Ministry of Well being of the Kingdom of Saudi Arabia.

Robert West is a participant within the behavioural subgroup of England's Scientific Advisory Group on Emergencies and the Impartial Scientific Advisory Group on Emergencies. He’s an unpaid director of a not-for-profit firm that goals to help behaviour change for the general public good.

Susan Michie receives grant funding from varied analysis funding organisations

David Hunter and Sarah L Caddy don’t work for, seek the advice of, personal shares in or obtain funding from any firm or organisation that might profit from this text, and have disclosed no related affiliations past their educational appointment.