The Covid conundrum

How and when will the pandemic end?

Sep 18, 2021

Sarah Gilbert (bottom right in red) receives a standing ovation on the first day of Wimbledon in recognition of her work on the Oxford / Astra-Zeneca vaccine

On the first day of the 2021 All-England Lawn Tennis Championships on June 28, Dame Sarah Gilbert Professor of Vaccinology at Oxford’s Jenner Institute, was treated to a standing ovation from grateful spectators on a packed centre court at Wimbledon. Together with her Oxford colleagues, Gilbert had succeeded in delivering the AstraZeneca vaccine against Covid-19 in record time and tennis fans - enjoying a rare day in the stands without face masks - were keen to show their appreciation.

On the other side of the world in Sydney and Perth, however, it was a different story as Australian authorities revived stay-at-home orders a bid to suppress a surge in infections sparked by the Delta variant. Meanwhile, in countries across Southeast Asia and Africa armed police were enforcing Covid curfews, while in Portugal residents of Lisbon and Porto found themselves facing the return of night-time restrictions thanks to an increase in infections sparked, in part, by the decision to allow thousands of English football fans to attend the UEFA Champions League final in Porto without having to quarantine.

It was a sobering reminder of how the coronavirus has divided our world (in Australia only six percent of the population has been immunised against Covid versus 60 percent in the UK and 40 percent in Portugal), and how, until populations reach herd immunity, the only solution is to employ quarantines and other measures dating from the Dark Ages.

As a historian of medicine I’m often asked, how and when will the pandemic end? There are no easy answers to this question but herd immunity – and thus the end of the pandemic – can be reached in one of two ways. The first, and infinitely more humane method, is vaccination. The second is to allow the coronavirus to run through a population so that people develop antibodies naturally, albeit it with firebreaks to prevent too many people becoming ill at the same time and potentially overwhelming hospitals. But between these extremes lie myriad intermediary scenarios employing a combination of vaccination, social distancing and other “non-pharmaceutical interventions”, such as mask wearing. The crucial question is should we rely vaccines alone to do this job or should we employ a mix of measures?

This question has been with us since the beginning of the pandemic but has been brought into sharper relief by the roll-out of the AstraZeneca, Pfizer and other vaccines and the unlocking of societies that has followed. Neither method is without risks – even with complete vaccine coverage, some people will continue to fall ill, risking complications such as long Covid, and some will die. And as long as social distancing measures remain in place, the economy and peoples’ mental health will be adversely impacted. Little wonder that many politicians, seeking to steer a course between this Scylla and Charybdis, are saying that sooner or later we are going to have to learn to live with Covid.

In 1918 these questions did not arise. With the exception of the smallpox vaccine, there were no vaccines against viral diseases and, although scientists attempted to make a vaccine against Spanish flu, their efforts proved unsuccessful. While some countries, such as Australia, employed quarantines to delay the introduction of the virus by troops returning from the war in Europe, and while some US cities mandated face mask and bans on public gatherings in an effort to “flatten the curve”, such measures were by and large considered impractical in European nations caught up in the military conflict. Instead, prioritising the wartime economy, people were left to find their own accommodation with the virus as infections spread through the population. “When epidemics occur, death always happens,” stated the British Medical Journal. “Fear is the mother of infection,” advised The Times’s medical correspondent. “To go about expecting influenza is to invite it.”

Even when it became possible to manufacture vaccines against influenza, as was the case during the 1957 and 1968 influenza pandemics, it was thought there was little possibility of developing vaccines against the new pandemic strains in time. Instead, calculating that, at most, one quarter of the population would be infected, the viruses were allowed to run their course.

Today, whether we realise it or not, descendants of the H1N1 Spanish flu and other pandemic viruses continue to circulate. Sure, every season they mutate a little and vaccines have to be updated, but while some people, mostly the elderly, continue die, the rest of us have learned to live with the threats. The viruses are no longer epidemic but endemic. This is the endgame most scientists envisage for Covid, hence the talk of “booster vaccines” and follow-on jabs to address mutations in the coronavirus. In the meantime, however, given the uneven global distribution of vaccines and on-going supply bottlenecks, the need for social distancing and quarantines has not gone away. This is particularly the case in low- and middle-income countries in Africa, Asia and Latin America, where despite the World Health Organization’s COVAX initiative, vaccine supplies fall well short of what is required to reach the Elysian fields of herd immunity. Instead, as I write, those counties have become fertile breeding grounds for the Delta and other variants. The problem is that as long as the virus continues to run wild anywhere in the world, there is a risk of someone becoming infected with an emerging variant resistant to vaccines and unknowingly introducing it to another country, potentially undermining the effectiveness of that country’s vaccination programme. As Tedros Ghebreyesus, the director of the WHO, puts it: “No one is safe, until we are all safe”. The tragedy is that it has taken far too long for the world to wake up to this fundamental biological fact.

The other thing that has hampered our response – and which continues to hamper it – is the inability, or unwillingness, to accept the necessity of quarantines and the continued need for social distancing. Derived from the Italian word quarantena, meaning 40 days, quarantines are a supremely rational, tried-and-tested means of separating those suspected of harbouring a potentially deadly pathogen from the well. Ever since Dubrovnik banned travellers from plague-infested areas during the Black Death that swept Europe in the fourteenth century, quarantines have been used to buy societies time. By delaying our contact with a potentially deadly pathogen against which we have no immunity, quarantines act as what the historians Geoff Manaugh and Nicola Twilley call “a buffer between the known and the unknown”. [1] And there was so much that was unknown at the start of the pandemic, from the virus’s true infection fatality rate, variously estimated at anywhere from 0.7 percent to 3-4 percent; to the percentage of people who were asymptomatic but contagious; to whether a first attack of Covid conferred immunity against a second attack and how long the immunity lasted.

Similar miscalculations, coupled with the mistaken belief that the coronavirus would behave like a common flu, informed America’s initially complacent response to the alarming reports from China in the first weeks of 2020. This was a mistake: whereas flu has a two- to four-day incubation period, on average it takes five to six days and in some cases as long as 14 days for someone infected with SARS-CoV-2 to develop symptoms. That gives authorities a one- to two-week window in which to test, trace and isolate infectious individuals and shut down the infection chains before they spiral out of control. But whereas countries such as Taiwan, South Korea and Hong Kong, where the experience of the 2003 SARS outbreak was fresh in memory and where politicians had a healthy distrust China, aggressively employed test, trace and isolate, the US and most European countries, with the exception of Germany and Greece, failed to employ these proven public health techniques in time. Why this was the case will keep historians and committees of inquiry occupied for years, but certainly a key factor was the refusal of government officials to abandon or adjust pandemic plans modelled on influenza, coupled with political complacency and scientific group-think. As one senior British conservative politician told Reuters: “We had in our minds that Covid-19 was a nasty flu and needed to be treated as such. The implication was it was a disease that could not be stopped and that it was ultimately not that deadly.” [2]

Another reason for high mortality suffered by countries like the UK during the initial phase of the pandemic was the inability of politicians, and the scientists who advised them, to believe that the citizens of London and other European cities would accept similar restrictions on their freedom of movement as the citizens of Wuhan. That imaginative failure arguably lay at the heart of Britain’s decision to pursue a herd immunity strategy during the initial phase of the pandemic by letting the virus run through the population, rather than locking society down tightly in an effort to suppress infections and prevent hospitals being inundated with severely ill patients. According to Jeremy Farrar, the director of the Wellcome Trust medical charity and a prominent member of one of the key scientific committees that advised Boris Johnson’s government on its options, the idea that any European government could tell people “You can’t leave your house” was met at the time with “disbelief, including from me”. [3]

Today, we know better. As I write this in July 2021, Britain is emerging from its third national lockdown in 18 months. Like the previous two lockdowns, it has met with widespread compliance – sure, there have been fines here and there for breaches of stay-at-home orders and occasional protests, but by and large Britons have gone along with the measures with remarkable grace. And the same has been true of other Western democracies, such as Italy and Portugal, where lockdowns have been punctuated by balcony singing and applause for frontline health workers. As Cicero and the founders of the ancient Roman republic observed, Salus populi suprema lex esto - “the health and welfare of the people is the highest law”.

The result is that even as people have learnt to distance themselves from friends and neighbours in case they might be unwitting harbourers of the virus, so the lockdowns have also seen an explosion in virtual social connections and a reaffirmation of our common humanity. Never before, it could be argued, have we been so isolated and so connected all at the same time. In this way, twenty-first century technology has enabled the reinvention of quarantines. Even Americans have discovered that the instruction to “shelter-in-place” is not as big an imposition on their cherished freedoms as it might have been in times gone by. Nor, despite claims on social media that the virus is being spread by 5G mobile phone masts and that Covid-19 is a hoax, do most believe that lockdowns and vaccines are a conspiracy to rob them of their liberty. On the contrary, since Joe Biden became the president, the speed of the vaccine roll-out and the uptake of vaccines in the US has been impressive.

One conspiracy has not been so easy to quash, however: namely, the proposition that the coronavirus was manufactured in or accidentally escaped from a Chinese laboratory. Most reputable scientists initially dismissed the theory that the SARS-CoV-2 might have been the product of an experiment in which researchers deliberately add or subtract genes in an effort to make a virus more transmissible to humans. Such “gain of function” experiments are usually justified on the grounds that if you know your enemy beforehand then you can design medical countermeasures before such mutations have a chance to occur naturally. The fact that the Huanan seafood market, where the virus was first identified, is located in same city as the Wuhan Institute of Virology (WIV), a high security lab which is also home to an unrivalled collection of bat viruses, initially leant these claims plausibility. Little wonder then that when it was reported that SARS-Cov-2 was 96 percent identical to a bat coronavirus that had been retrieved from a cave in Yunnan in 2013, and that the virus, dubbed RaTG13, was stored at WIV, Donald Trump suggested the Chinese might be engaged in a cover-up.

Although the Chinese authorities strenuously denied Trump’s claims, their refusal to allow independent researchers to scrutinize WIV’s records only fuelled speculation and many scientists who initially dismissed the theory now say they are unable to definitively rule it out, hence the calls for both the lab-leak and natural spillover theories to be taken seriously.[4] However, SARS-Cov-2 does not appear to be derived from any of the standard genetic backbones commonly used in laboratory experimentation on SARS-like viruses and on the balance of probabilities experts such as Farrar, a veteran of the SARs and bird flu outbreaks in Southeast Asia, subscribe to the more parsimonious explanation that the coronavirus probably acquired its mutations naturally, most likely when it jumped to a pangolin or some other farmed animal. We know that such “spillover events” occur all the time in nature and that each time they result in the acquisition of new mutations. According to Farrar, all it would take is for “natural selection to hit a sweet spot, conjuring up a form of the virus able to clinch a foothold in a human host”. However, Farrar also acknowledges that “nobody is yet in a position to rule out an alternative”.[5]

If the beginnings of the pandemic are still uncertain so is the question of when and how the pandemic might end. As I write, the European Union are in the process of relaxing travel restrictions to allow anyone who can demonstrate they have had two jabs of an approved vaccine to enter Europe without the need to quarantine or present a negative PCR test. What has made it possible to contemplate a return to normality is the stunning success of the new vaccines against Covid. When scientists first began work on vaccines targetting the coronavirus’s spike protein shortly after the publication of its genetic sequence in January 2020, the WHO declared that anything better than 50 percent efficacy would be considered a success. To have two vaccines – Pfizer and Moderna – with 95 percent efficacy against severe Covid disease – exceeded all expectations. And when you consider that since its roll out in the UK, the AstraZeneca vaccine has also been shown to be as effective Pfizer in reducing severe disease in real world populations – and a fourth vaccine manufactured by Johnson and Johnson has demonstrated 85 efficacy after just one jab – then science has provided an embarrassment of riches. The problem is these riches are not evenly distributed or available on the same terms to everyone anywhere in the world. At time of writing, the WHO has shipped 90 million doses to 130 low- and middle- income countries under its COVAX initiative, but billions of doses will be needed if Africa and Asia are to enjoy the same immunisation levels as populations in Europe and North America.

To date, only a handful of countries have succeeded in vaccinating in excess of half their populations. Some, like the United Kingdom and Israel, are on course to achieve herd immunity. Based on current estimates of the virus’s reproductive number, this should kick in when about two thirds of a population are immunised. But depending on the emergence of new variants and changes in the transmissibility of the virus, the required threshold could be as high as 90 percent (the more contagious a virus, the more people needed to be vaccinated to suppress the basic reproduction number below one).

Unfortunately, because of the alarming increase in transmission due to the emergence of the Delta virus, no one can presently say when we will reach herd immunity. Adding to the uncertainty is the wide variation in social distancing measures and regulations on face masks and the ventilation of public spaces. In the US and France, for instance, face masks are no longer mandatory on public transport and in other public settings; by contrast in Greece and Portugal face coverings continue to be required in restaurants and congested outdoor spaces. And while restrictions for Britons ended on July 19 – a date which the country’s tabloid newspapers dubbed “freedom day” – in other countries freedom from the virus remains a remote prospect.

Depressingly, all that can be said with any certainty is that the pandemic still has some way to run.

The above text is adapted from the Afterword from the Portuguese edition of my book, The Pandemic Century: One Hundred Years of Panic, Hysteria, and Hubris.

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