Covid: 3 key facts that we still do not know after two years of pandemic (and why it is important to find out)

“The more questions we answer, the bigger new questions arise,” says Dr. Seema Lakdawala, professor of microbiology and molecular genetics at the University of Pittsburgh.

Lakdawala refers to the impetuous race scientists like her have embarked on since December 2019 to decipher the SARS-CoV-2, which by then was just beginning to expand.

More than two years later, researchers have made great strides, enabling the development of vaccines and treatments to combat covid-19.

However, as the expert indicates, there are still fundamental issues that remain a unknown.

Solving these mysteries, experts say, would strengthen the fight the pandemic.

These are 3 key facts SARS-CoV-2 for which there is still no definitive answer.

1. The precise origin of the virus

“The source of the original outbreak has yet to be determined,” states the UK Health Security Agency on its website.

In February 2021, a WHO team tasked with investigating the origins of covid traveled to China and concluded that the virus probably arose from bats, but that more research was needed.

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Tedros Adhanom Ghebreyesus, WHO director-general, said the investigation had been hampered by the fhigh data and transparency from China.

One of the conclusions of the WHO investigation was that it was “extremely unlikely” that the virus had reached humans due to an incident in a laboratory.

Tedros, however, later said that that conclusion was “premature” and in an editorial published in the magazine Science in october said that “a laboratory accident cannot be ruled out until there is enough evidence. “

That same month, WHO assembled a team of experts who joined the Scientific Advisory Group on the Origins of New Pathogens (SAGO).

SAGO’s mission is to investigate whether the virus passed from animals to humans in the Wuhan markets or if it was leaked in a laboratory accident.

The SAGO group had its first meeting in November 2021.

Tedros explains that the findings of groups like SAGO can be useful in developing policies that reduce the possibility that animal viruses jump to humans.

At the end of October, intelligence agencies The United States declassified a report saying they may never be able to identify the origins of the SARS-CoV-2 virus.

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The document rules out that the virus was created as biological weapon, and considers animal-to-human transmission and a laboratory leak as the most plausible hypotheses.

The report, however, warns that it did not reach a final conclusion.

China has vigorously rejected the theory that the virus was leaked in a laboratory accident.

In an article published in November 2021 on the portal Stat News, John P. Moore, professor of microbiology and immunology at Cornell University, states that “We may never know the origin of covid-19.”

Moore adds that other more “outlandish” theories, which can be discarded and that the debate today centers between the natural transmission of the virus and the filtration of a laboratory.

2. The infectious dose of the virus

The infectious dose is the amount of virus necessary for infection to occur.

In the case of SARS-CoV-2, this dose is not known, that is, it is not clear how much of inhaled virus particles they are enough for a person to become infected.

“The infectious dose of SARS-CoV-2 required to transmit the infection“, indicate the Centers for Disease Control and Prevention of the United States (CDC, for its acronym in English).

The CDC also indicates that animal studies and epidemiological investigations show that inhaling the virus can cause infection, but that the contribution of inhaling the virus or its contact with mucous membranes (such as the eyes) “It remains unquantified and will be difficult to establish.”

“The infectious dose of SARS-CoV-2 in humans is a very difficult amount to measure without infect experimentally to humans, “Dr. Lakdawala, a specialist in respiratory viruses with pandemic potential, tells BBC Mundo.

With some viruses, such as those that cause influenza, it is enough for the person to be exposed to 10 virus particles to become infected, while for other viruses, such as MERS, thousands of particles are needed to cause infection.

In the case of SARS-CoV-2, that amount is not known.

Lakdawala explains that the closest they know comes from the 229e virus, a type of coronavirus that causes the common cold and has a influenza-like infectious dose.

“But it is not clear if the same thing happens with SARS-CoV-2 “, says the expert.

“In the case of the variant omicronIt is not clear if it is more infectious because fewer particles are needed to become infected. “

“We don’t know if it takes a hundred particles, a thousand particles, or 10,000 particles to become infected.”

Covid-19 is clearly very contagious, but this may be because few particles are needed for infection (the infectious dose is low), or because infected people release a large amount of virus in their environment, says the expert.

Currently, much of the information about the infectious potential of a person and the isolation measures they are based on how long the person continues to shed viruses.

Therefore, Lakdawala explains, knowing more about the infectious dose of the virus could serve to better assess risks in spaces such as restaurants or schools, and depending on how long people are in certain places.

“Right now only we are being cautious and trying to avoid transmission, but knowing the amount of virus needed could help improve some measures, “says the expert.

And he concludes that although the infectious dose is not known, “With vaccines the amount of virus it takes to become infected is probably higher.”

“With the vaccine you need to breathe in more virus to start the infection,” Lakdawala explains.

Several studies are currently under development in which volunteers are exposed to different doses of the virus in a controlled environment, from which it is expected to have more information on the infectious dose.

3. The level of antibodies needed to prevent infection

Currently it is not known what amount of antibodies You must have a person to be considered protected against COVID-19.

To that extent it is known as “correlate of protection”, because they are indicators that the human body is protected against disease or infection.

Several experts agree that that amount of antibodies with which someone can be considered protected, is a key piece of information in the fight against covid-19.

“It is needed with urgency a correlate of protection for vaccines against SARS-CoV-2, “he wrote in the journal Science in July 2021 Florian Krammer, a professor in the Department of Microbiology at the Icahn School of Medicine at Mount Sinai Hospital in New York.

In his article, Krammer explains the importance of successfully establishing a level of antibodies as a correlate of protection, that is, to be able to identify the minimum amount of antibodies that offer protection.

One reason is that the approval of new vaccines could be accelerated based on the reading the amount of immunity they offer, without the need for lengthy and extensive phase 3 trials, says Krammer.

Knowing the correlate of protection would also allow administering the vaccination of immunosuppressed people more efficiently, for example, applying booster doses if it is observed that a sufficient amount of antibodies was not generated, explains the expert.

In addition, Krammer says, the protection correlate could be an indicator used by health authorities to determine what percentage of their population is protected.

Krammer, however, cautions that it is unlikely It is possible to identify a correlate that can be applied to all vaccines, to all variants and to all populations, but which would still be “extremely useful” in the fight against covid-19.

In the case of omicron, for example, vaccines generate fewer antibodies that neutralize the virus, explains Lakdawala.

“But that does not mean that we are not protected”, clarifies the expert.

“The data consistently shows that vaccines prevent serious illness compared to the unvaccinated. “

The expert adds that the appearance of new variants they can cause the infectious dose and protection correlate data to change.

“Every time the virus is transmitted it can mutate, and every time it mutates it can impact these variables, so you have to avoid transmission “says Lakdawala.

To do this, while the researchers try to answer these and other unknowns, it recommends continuing to maintain the measures of “common sense”: wear masks, get vaccinated and keep your distance.