What Are the Main Research Gaps for Lifting Confinement Measures?

This is the third document of a series of discussion notes adressing fundamental questions about the COVID-19 crisis and response strategies. Written by ISGlobal immunologist and science writer Adelaida Sarukhan, the text addresses the main research gaps for lifting confinement mesures.

The diversity of viruses on this planet is immense. Mammals are estimated to harbor some 320,000 different viruses that we do not yet know. The new coronavirus (SARS-CoV-2) was one of them, until at the end of last year it acquired the ability to jump from some animal species (probably the pangolin) to humans, and from there transmit it from person to person, causing a outbreak of pneumonia of unknown origin in Wuhan City.

What percentage of the population has been infected with the coronavirus?

Among confirmed cases, 80% of people are known to have mild to moderate symptoms, 15% have severe symptoms, and 6% are considered critical. However, it is believed that a significant percentage do not have symptoms or present them in such a mild way that they often escape detection.

Some studies suggest that between 17% and 30% of infected people do not develop symptoms, but may contribute to virus transmission. Knowing the real percentage of people infected by the virus (symptomatic or not) is vital for two reasons:

1. Better estimate the virus fatality rate (the so-called infection fatality rate).
2. Have a better idea of ​​the percentage of people who could have immunity against the virus.

This question can only be answered by conducting serological studies (to detect antibodies against the virus) at the population level.

To carry out these studies in Spain, it is required:

• Identify / develop a valid test in terms of specificity and sensitivity.
• Acquire or produce a sufficient number of said tests.
• Plan a sampling strategy both in the population at risk and in the general population, in order to obtain statistically significant data.

Do infected people develop immunity to the virus?

Several studies indicate that patients with COVID-19 develop antibodies against the IgM-type virus about six days after infection, followed by IgG-type antibodies.

However, it is still not known with certainty whether:

• All infected people (including asymptomatic people) generate sufficient levels of antibodies.
• Whether these antibodies are protective (that is, whether they are capable of effectively neutralizing SARS-CoV-2).

Therefore, it is not only enough to know how many people have developed antibodies against the virus, but it is also necessary to make sure that these antibodies will protect them against future infections.

How long does immunity last?

Once the population susceptible to having protective antibodies against the virus has been identified / estimated, it is important to determine how long this immunity will last. It could be a few months (as is the case with immunity against coronaviruses that cause common colds), or it could be a couple of years (as observed with SARS). To answer, it is necessary to carry out longitudinal serological studies.

How fast is the virus mutating?

At the moment, genetic analysis carried out on samples obtained at different times and places indicate that the virus is mutating little.

However, over time, selective pressure on the virus (exerted by increasing immunity in the population) could facilitate the emergence of strains that escape this immunity.

To answer this question, it is essential to establish genetic virus surveillance mechanisms that consist of regularly sequencing viruses obtained from patients from different geographical areas and publishing them on an open platform for analysis.

Why is the child population less susceptible to the disease and what role does it play in the transmission of the infection?

Boys and girls are much less susceptible to developing severe forms of the disease, although they do appear to become infected. The reasons for this are not yet known and deserve to be investigated. However, an even more pressing issue at the moment is understanding what role they play in virus transmission. This information will be essential to guide decisions related to the reopening of schools and recommendations on the coexistence of minors with older adults.