World

Could a Covid vaccine bring back normality?

England is back in lockdown. It happened not a moment too soon. As of 2 November almost three-quarters of a million new cases have been officially counted since 21 September, when the government’s scientific advisory committee Sage advised lockdown. On that day, Britain had only had about 360,000 cases since Covid arrived. Now the figure is three times that. So many more cases mean it will take longer, and possibly require tougher social restrictions, to get numbers down by imposing lockdown than it would have in September, says James Naismith, head of the Rosalind Franklin Institute in Oxford.

Naismith calculates that we will have 500 deaths per day in two to three weeks because of the cases that occurred over the past week, compared with an average of 144 in the week ending 2 November. But it could be far worse. If we had done nothing for another two weeks, he says, we’d be looking at 1,000 deaths a day by Christmas – and more, if hospitals fill up and not everyone can get optimal treatment.

“No one is saying lockdowns are not harmful, they will cause misery and death,” says Naismith. “Being poorer as a country means we will be unhealthier. We know despair and isolation take lives. We know delays in treating some (non-Covid) diseases will increase deaths.” It is clear, however, that Covid-19 is far deadlier, he says.

But beating it back means people must follow the lockdown rules, and more closely than many did in spring. And that will be easier if there is a light at the end of this tunnel.

The brutal truth is that Boris Johnson’s pledge in July that Covid would be “over by Christmas” is as illusory as that promise proved back in the first world war. But we know that places that acted fast and forcefully enough to get infection down to low levels early on, then kept it there, with some distancing but also effective testing, tracing and quarantine, have been able to return to a degree of normality. Life is largely normal in New Zealand; the South Korean test and trace response is widely regarded as the benchmark; Taiwan recently celebrated 200 days without a case; Vietnam hasn’t added to its death count of 35 since 5 September, and China, source of the virus, has so far avoided a second wave.

But given that the UK’s test and trace system is so shambolic, we appear to be relying on a vaccine to bail us out. Sadly, it’s more complicated than that. Even once discovered, manufactured and distributed, it won’t banish the virus immediately, says Prof David Salisbury of Imperial College London, a former director of immunisation at the Department of Health. We will still need some distancing, and testing and quarantine to keep outbreaks under control. But we may not be condemned to the life we’re living now.

Vaccines

A vaccine may not be enough on its own, but it is necessary. It is the only proven way to reach “herd immunity” – when so many of the population (thought to be at least 60% for Covid-19) are immune to the virus that an infected person contacts very few non-immune people and, unable to find new hosts, the virus dies out.

Letting the virus rip through a population with less immunity – as advocated by the so-called Great Barrington Declaration and others – would kill thousands who would have been saved if we had slowed the spread of the virus before the vaccine arrived, overwhelm the NHS and leave many people dealing with the misery of “long Covid” for years to come.

We will know before the year’s end whether some of the 11 vaccines now in large-scale trials actually work. The US-based firm Pfizer and its partners are among the farthest along the track, partly because their vaccine is made of mRNA that codes for a virus protein, which is quick to produce.

Pfizer has nearly completed signing up 44,000 people for its vaccine, which requires two jabs four weeks apart. Half will receive a placebo. It hopes that by late November sufficient numbers of the participants will have caught Covid, and significantly fewer of them will have had the vaccine than a placebo. If there are so few that it shows the vaccine made people half as likely to get the disease, the vaccine will meet the minimum level of effectiveness set by the US regulatory agencies. If there are so few that it shows the vaccine protected 77% of recipients, the trial will stop, as it would not be ethical to keep giving people placebo – and approval can get under way.

In documents shared last week the head of the UK vaccine task force Katie Bingham revealed that the plan is to offer a vaccine to all adults over 50 by Easter next year.

Then what? Say the first vaccines protect 70% of the people who get them, and 70% of the population is vaccinated – and both of those are ambitious targets. That means 49% of the population will be protected, says David Salisbury. Herd immunity requires more than that. It may even be difficult to vaccinate that many, if side-effects such as fatigue, however mild or temporary, set in after the first jab and some refuse the second.

But current UK vaccination plans don’t aim for herd immunity at first. The most recent advice calls for “targeted” vaccination of people most at risk: frontline workers such as medical staff, and people who are older or have medical conditions such as diabetes, who are most likely to contract severe disease. Vaccinating those people would cut severe cases, deaths and hospital demand, but they don’t number enough to reach herd immunity. “The virus will continue to circulate among younger healthy people, especially if they ignore social distancing and won’t wear masks,” says Salisbury – at least until more people are vaccinated. We will need what he calls “Vaccine Plus”, masks and some distancing, to keep this circulation in check – and stop it reaching the 30% of vaccinated, high-risk people who aren’t protected by the vaccine.

Moreover, warns Peter Hotez of Baylor College of Medicine in Texas, the first vaccines might stop vaccinated people getting sick, but not prevent them catching and transmitting the virus. “In that case we’ll still require masks and social distancing, until better vaccines come along,” he says.

Some immunologists think that is not all bad. If young children – who do not usually get so sick from Covid as adults – start catching the virus every winter we may develop enough immunity, if not to stop the virus circulating then at least to limit its impact. In a generation, everyone will have had it as children, and Covid will be mild. That may be what happened with the four coronaviruses that now cause common colds in winter. Genetic analysis shows one, OC43, left cattle and entered humans around 1890. It may be what really caused a pandemic that year of what we thought was severe flu, says Nicholas Christakis of Yale University, but which we now realise had Covid-like symptoms.

Drugs

In any case, the immediate effect of the vaccine should be fewer people dying but the virus still circulating at some level. This could be easier to face with some effective drugs to tame the sporadic cases.

Monoclonal antibodies are artificially made proteins similar to the ones our own immune systems make, but usually too late in the disease to save us. Several are under development, and the monoclonal made by US firm Eli Lilly was used to treat President Trump. Results have been mixed. Trials of the drug in hospitalised Covid patients ended in late October, when no improvements were seen. It is still being tested in less severe cases. One severe-case trial of a cocktail of two monoclonals made by US firm Regeneron has also been halted, although that drug is still being tested in the UK Recovery trial.

Recovery has so far mostly tested “re-purposed” drugs already approved to treat other conditions. As these have passed safety trials, they are a fast way to treat a new disease if they turn out to work for that too. So far, Recovery has found that two such hopefuls do not work on Covid: the hydroxychloroquine championed by the White House, and a mix called lopinavir/ritonavir, at least in severe disease.

A long-used anti-inflammatory drug, dexamethasone, did turn out to help in late Covid, when most damage is done by runaway inflammation, a reaction of the immune system. Recovery also plans to test tocilizumab, a monoclonal that blocks inflammation. University College London is similarly testing existing antiviral drugs favipiravir and lopinavir/ritonavir early in the disease.

Recovery is also testing blood serum containing antibodies to Covid from people who have survived it. Paul Morgan of the University of Cardiff has high hopes for drugs that block the over-activation of an immune system called complement, a feature of severe Covid. Preliminary small-scale trials of existing anti-complement drugs in the Netherlands have been promising.

There were several specific anti-coronavirus drugs in the works after the first Sars virus in 2003 that block bits of viral machinery. But Sars was eradicated with tracing and quarantine – it spread more clumsily than Covid. With no market for coronavirus drugs, research funding stopped despite warnings from scientists that the viruses remained a threat. Some researchers are trying to revive these efforts. “We need to develop countermeasures that can keep people from getting severely ill,” says Amesh Adalja of Johns Hopkins University. “I don’t think things will get completely back to normal, if that means to a pre-pandemic level,” he adds. “There will be some social distancing that will have to continue,” at least until a second-generation of vaccines arrives that prevents all transmission.

Testing

We also need better diagnostics. Some countries, notably South Korea, used widespread testing early in the pandemic to contain the virus and keep case numbers low. You need low case numbers to track and quarantine everyone infected, and UK numbers are currently too high. But vaccination should drive case numbers down to where containment becomes practicable. “We need to all become South Korea as quickly as possible,” says Joshua Gans of the University of Toronto, author of Economics in the Age of Covid-19.

Lockdown does economic damage, but he insists there is no trade-off between that and deaths. “There is no point where we can keep the economy humming while people are getting sick in large numbers.” The faster we stop that, the less expensive it will be – and testing can both help contain the virus and allow us to do things like resume work.

“Rapid testing should have been brought in months ago,” agrees epidemiologist Tim Sly of Ryerson University in Toronto. “Anyone who deals with the public, from medical staff to taxi drivers, could be required to take a rapid test once a week,” and quarantined with financial support if the test is positive.

The PCR (polymerase chain reaction) tests that we currently use are extremely accurate but slow. Rapid tests are less accurate but give almost instantaneous results. One kind (antigen) detects viral proteins, another (Lamp) detects viral RNA. The UK government plans to use all three kinds of tests to screen the half-million people of Liverpool, starting this weekend. The hope is to identify those infected, even without symptoms, and stop them spreading the virus. If it works, the plan is to deploy millions of the rapid tests before Christmas, in what was originally dubbed Operation Moonshot.

Slovakia and Chinese cities including Wuhan have already demonstrated that it is possible to conduct such mass testing. It will have little impact on the spread of the virus, however, if those who test positive do not isolate themselves. The rate at which people who test positive isolate in England is as low as 20%.

For now, the plan is to use the tests to snuff out the spread of the virus and get numbers down to manageable levels. But eventually, disease experts envisage using them to enable a return of normal activities, despite the continued low-level circulation of the virus. There is a risk that with many tests, even a small false positive rate could disrupt too many lives needlessly. However, Sly says tests can be nested to improve accuracy. A test that is 90% sensitive will miss 10% of positives. “But two tests five to seven days apart are 99% sensitive at finding you positive – if you actually are.”

This might enable us to begin carefree air travel again. Sly pictures taking a test when you buy the ticket a week before you fly. Then you get tested at the airport, a procedure not much more difficult than some now demanded in airport security. If both are negative, he says, “you board the plane and relax, because you know everyone else has been tested twice in the past week”. That means no catching Covid on the plane, and no quarantine at your destination. Airports in Italy, France and elsewhere are already using rapid tests to detect Covid in arriving passengers.

Another sign of a return to normality would be to hug Gran without fear. Well, Gran will be vaccinated, but that might not mean she is 100% protected. And we might be unknowingly carrying the virus even if we are also vaccinated. Gran might even be carrying it. The chances are lower, but still there. Again, the key is testing.

The sensitivity of rapid tests might be less than the slow lab tests used now, but rapid tests detect people who are actually transmitting the virus, says Michael Mina of Harvard University. He would like them used widely. “Frequent rapid antigen tests can help stop Covid-19 while we await vaccines,” he tweeted last week. “These will help society regain normalcy.”

Including a trip to the pub. Indoor gatherings might not be maskless for the foreseeable future, and some spacing might remain advisable. But even that may not be needed with widespread, self-administered rapid antigen tests, which will enable us to check if we pose a risk. Gans argues that trusting people to be truthful about these is no riskier than trusting people to monitor their symptoms, as we do now. Others may look at some individuals’ attitudes to masks and distancing and be less convinced.

Anthony Fauci told the BBC last week: “With a successful vaccine, and the continuation of some form of public health measures, as we progress through the months of 2021, getting towards the third and fourth quarter, we will see a considerable approach towards some form of normality.”

Meanwhile, what we are learning while fighting Covid, adds Johns Hopkins’s Adalja, “could make us much more resilient to the next pandemic threat we face.”. Disease experts don’t think Covid-19 is a one-off, or that it will be long before we see another pandemic. A flu pandemic is an ever-present threat, and other viruses in wild animals worry researchers. If nothing else, there are other coronaviruses in bats that could jump species, that could be more lethal than Covid-19, and different enough to present us with a whole new fight.

It is a fight we will be far more ready for if we don’t forget the lessons we are learning now. If wearing masks a bit longer helps drive those lessons home, that may not be a bad thing.

But humans are highly adaptable, and normality is a movable feast. This time next year you may be having dreams about having somehow, inexplicably, left home without a mask – and everyone is pointing and staring. You make sure you grab one as you do your daily home test for Covid and a few other viruses, and head out to meet Gran down the pub, to give her the sherry you brought her from Spain.

Source:

www.theguardian.com

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