There have now been over 12 million cases of COVID-19 infection globally, and half a million deaths. Researchers are constantly looking for new and better information to reduce the uncertainty around the virus.

Faced with ‘the largest public health crisis in the last century’, as Nature magazine calls it, experts from around the world have worked hard to better understand COVID-19. Their efforts have only been partly repaid: while they have discovered valuable information about the ways in which the virus enters the body, and reasonably effective treatments for severe cases, many questions remain unanswered.

Nature magazine has analysed one of the key aspects which researchers have not been able to satisfactorily unravel.

What we still don’t know about COVID-19

Different reactions to SARS-CoV-2

It is not yet clear why some people infected with SARS-CoV-2 develop severe or even lethal forms of pneumonia, even if they are apparently healthy—while others are asymptomatic. In Great Britain, for instance, only 22% of the people who tested positive for COVID-19 reported symptoms on the day of the test.

An international research team who analysed the genome of 4 000 people in Italy and Spain, identified two genetic mutations associated with the severe forms of the illness. One of these is located in that area of the genome which determines the blood type. The first study, which showed a possible association between a patient’s blood type and COVID-19, was published in March by Chinese researchers. They pointed out that people with blood type-A have higher risk of contracting the disease, while people with blood type-O have the lowest risk.

However, the genetic mutations identified so far do not play an important role in the evolution of the disease, according to immunologist Jean-Laurent Casanova, who is searching for other mutations which may have a more significant role. To this end, his team is analysing the genome of healthy persons under 50 who have developed severe forms of the illness, as is the case of “the one who ran a marathon in October, and now, five months later, is at the ICU, being intubated and ventilated.”

SARS-CoV-2 immunity

According to the studies carried out so far, the neutralising antibodies which fight the new coronavirus are strong for only a few weeks after the infection, but their efficiency drops after this period.

Immunologist George Kassiotis says antibodies are stronger and last for a longer period of time in cases with more severe forms of the illness.  There’s a model which has been identified also in the case of severe acute respiratory syndrome (SARS). Patients who recovered from a severe form of the illness still had antibodies 12 months later.

Immunity may, however, also be generated by factors such as T-cells. “People associate antibodies with immunity, but the immune system is an extraordinary mechanism. It is much more complex than antibodies”, says virologist Andres Finzi. Researchers have not yet found another measurable marker which correlates with long-term immunity.

The mutations of the virus and the effectiveness of a vaccine

Researchers believe that most SARS-CoV-2 mutations do not give reason for concern, because they do not modify its virulence or contagiousness.

Though some mutations might seem lethal (as is the case with the ones identified in Lombardia, for instance), this does not mean that there is cause for panic, says epidemiologist William Hanage. Hanage explains that in the initial, out of control phases of the epidemic, the probability of identifying more severe cases is higher.

A vaccine “would be the only way out of this pandemic”, according to the article in Nature, reminding the reader that 200 vaccines, around the world, are already in the development process. Tests performed on monkeys have suggested that vaccines might be able to prevent pulmonary infections, but could not stop the infection located in other parts of the body. This means that we might have a vaccine which safeguards against severe forms of the disease, but none to stop the virus from spreading. It is also unclear whether the antibodies generated by the anti-COVID-19 vaccines will be enough to stop new infections.

Herd immunity, an increasingly distant goal

Only 5% of Spain’s population has developed antibodies against the new coronavirus, a large-scale study, recently published in The Lancet, has shown. The study was conducted with a sample of more than 61 000 people. The results of the study suggest that herd immunity is “unattainable”.

Researchers have discovered that 14% of the people who tested positive for antibodies, tested negative in the second test, which was administered only a few weeks after the first test. These results converge with data from previous research, which suggested short-term immunity for asymptomatics, or for people with mild symptoms of COVID-19.

Lack of symptoms means a superficial infection which does not really stimulate the immune system in order for it to develop an immunological memory”, explained virology professor Ian Jones. One third of the participants in the study who have been infected remained asymptomatic.

The lethalness of the virus

Estimating the fatality rate of the infection as accurately as possible would be useful in determining the possible number of deaths if the virus could no longer be kept under control. It would also offer information about the size of the losses which would be registered as the pandemic unfolds in densely populated countries. It would also provide the governments of poor countries, battling malaria or measles, with a guideline, helping them decide how to break down costs—ventilators or mosquito nets?—as pointed out by a comprehensive analysis published in The New York Times.

Two indicators which can outline the magnitude of the danger posed by COVID-19 are the infection fatality rate (IFR) and the case fatality rate (CFR). While the CFR represents the proportion of deaths caused by COVID-19 compared to the total number of diagnosed people, the IFR represents the proportion of deaths among all the infected persons, including asymptomatic infection cases, and undiagnosed ones.

Last week, after the World Health Organization had summoned a meeting with 1 300 experts from around the world, Dr Soumya Swaminathan, chief researcher of the organisation, declared that they had reached a consensus on the infection fatality rate (IFR)—it will be approximately 0,6%.

Although the small percentage appears to be reassuring, 0,6% of the global population means no less than 47 million people, writes The New York Times.

The case fatality rate (CFR) varies a lot from country to country: less than 1% in Iceland, below 2% percent in both Israel and New Zealand, 5% in China, 4,6% in the US, 14% in Italy and Great Britain, and 16% in Belgium.

The global fatality rates may, however, change—as various analyses show. The pandemic initially hit developed countries, with good medical systems, but it is now spreading to and within heavily populated countries with precarious medical systems such as India, Mexico, and Nigeria. Furthermore, the U.S. and Europe may be confronted with an increase in the number of ‘hotbeds’, as the winter approaches. These hotbed regions do not yet have the experience of battling COVID-19 in wintertime.

The direction the pandemic will go is not yet known, but the information we have on the eight flu pandemics the U.S. has faced since 1763 show a repeated pattern: a light wave was followed, after a few months, by a deadlier one.

It’s possible that this pattern will not apply to the current situation, believes Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy, at the University of Minnesota. It is a coronavirus, not a flu, but since the contagion rate is much higher in the case of the coronavirus, “the numbers will go up in the next 12 to 18 months”, says Osterholm.

More than just a flu

The New York Times has compared this coronavirus crisis with other deadly events which took place in the last century, using the numbers of deaths caused by COVID-19 from 25 cities and regions. Although it has not killed as many people as the Spanish Flu did, few other infections rival COVID-19 when it comes to the mortality it generates, conclude the authors of the analysis.

Any disaster in which the usual number of deaths is doubled should be considered a state of emergency, according to the recommendation of the United Nations High Commissioner for Refugees.

During the initial stages of the COVID-19 pandemic, mortality rates grew far past that: 4.5 times more in Madrid, from mid-March to mid-April; over 5 times more in Guyas, Ecuador; almost 6 times more in New York, in April; and 6.6 times more in Bergamo, Northern Italy.

If you look at the total impact of the pandemic in a country, it might not strike you as big. But, if you truly wish to know what is going on, you must look at each state, city and local area”, said Robert Anderson, chief of the Mortality Statistics Branch from the National Center for Health Statistics, Centers for Disease Control and Prevention.

The certainty at the core of uncertainty

New research shows that we do not even know everything about the ways in which the new coronavirus spreads. Recently, 239 researchers from 32 countries asked the WHO, in an open letter, to update their recommendation guide, after they presented new evidence on the airborne transmission of the virus. The World Health Organization confirmed emergent proof that tiny particles exhaled by infected persons may float in the air for a longer period than announced, and that the possibility of infection in this way will be analysed. The WHO will publish a scientific communiqué on the confirmed ways in which COVID-19 is transmitted.

What we currently know shows that social distancing remains the best approach at this time (I wrote more on the role of distancing, at the beginning of the pandemic, in the article “COVID-19: Social distancing, new ways to love amidst the pandemic”).

Prevention is all the more important. Collected data from most countries shows that the health status of 20% of patients who tested positive deteriorated enough for them to need oxygen or advanced medical care, as Janet Diaz says, the Head of Clinical Care within the WHO Emergencies Program.

On the other hand, not only is herd immunity very hard to attain (and in some ways unethical), but a stable Western country’s decision to not implement distancing measures seems to have shown troubling signs of failure. In Sweden, restaurants, shops, gyms and most schools remained opened during the initial stages of the pandemic. “They literally gained nothing. It’s a self-inflicted wound and they did not get any economic advantage”, says Jacob F. Kirkegaard at the end of this dangerous experiment.

Sweden is approaching 5 500 deaths caused by COVID-19. The country has suffered 40% more deaths than the USA, and 12 times more deaths than Norway. Not even the economic projections went as predicted. The unemployment rate grew to 9 percent, almost 2 percent more than in March, and it is estimated that the economy will contract by 4.5%. The Swedish experiment has shown that the virus itself, and not the safety measures, have brought about the economic crisis, writes economic journalist Peter Goodman.

The larger number of deaths and economic losses, similar to those suffered by countries who imposed restrictions, “suggests that the alleged choice between saved lives and a healthy economy is a fake one: The failure to impose social distancing may cost lives and jobs simultaneously”.

Although the volume of information we have on COVID-19 is far from satisfactory, what we do know is enough to outline, however vaguely, the scale of the global challenge we are facing. But it also works to help us understand the value of protective measures. Because, try as we might to distort things, it’s not about how scared or brave we are in the face of the epidemic, or how swiftly we navigate new territories we are unequipped to verify. It is about how much we cherish life—even when it comes to the lives of those who, as cynics might say, “would have died anyway”.

Carmen Lăiu is a writer for ST Network and Semnele timpului.