“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 SARS-CoV-2, which was just beginning to spread by then.
More than two years later, researchers have made great strides, enabling the development of vaccines and treatments to combat the COVID-19, according to BBC.
However, as the expert indicates, there are still fundamental issues that remain unknown.
Solving those mysteries, experts say, would strengthen the fight against the pandemic.
These are 3 key data from 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 not yet been 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 likely arose from bats, but that more research was needed.
Tedros Adhanom Ghebreyesus, WHO director-general, said the investigation had been hampered by a lack of 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 journal Science in October, said that “a laboratory accident cannot be ruled out until there is sufficient 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 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 of animal viruses jumping to humans.
In late October, US intelligence agencies declassified a report saying they may never be able to identify the origins of the SARS-CoV-2 virus.
The document rules out that the virus was created as a 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 definitive 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 Stat News portal, 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 have emerged, which can be discarded, and that the debate today centers between natural transmission of the virus and filtration from a laboratory.
2. The infectious dose of the virus
The infectious dose is the amount of virus necessary for an infection to occur.
In the case of SARS-CoV-2, that dose is not known, that is, it is not clear how many inhaled virus particles are enough for a person to become infected.
“The infectious dose of SARS-CoV-2 necessary to transmit the infection has not been established,” indicates 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 inhalation of the virus or its contact with mucous membranes (such as the eyes) “remains unquantified and will be difficult to establish. ”.
“The infectious dose of SARS-CoV-2 in humans is a very difficult quantity to measure without experimentally infecting humans,” Dr. Lakdawala, a specialist in respiratory viruses with pandemic potential, tells BBC Mundo.
With some viruses, such as those that cause influenza, it takes a person to be exposed to 10 particles of the virus 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 an infectious dose similar to influenza.
“But it is not clear if the same thing happens with SARS-CoV-2,” says the expert.
“In the case of the omicron variant, it 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 a person’s infectious potential and isolation measures are based on how long the person continues to shed viruses.
For this reason, Lakdawala explains, knowing more about the infectious dose of the virus could serve to better assess the risks in spaces such as restaurants or schools, and depending on how long people are in certain places.
“Right now we are just 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 that is needed to become infected is probably higher.”
“With the vaccine you need to breathe in more virus to start the infection,” explains Lakdawala.
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
It is currently not known how many antibodies a person must have to be considered protected against covid-19.
This measure is known as a “correlate of protection”, because they are indicators that the human body is protected against disease or infection.
Several experts agree that the amount of antibodies with which someone can be considered protected is a key piece of information in the fight against covid-19.
“A protective correlate is urgently needed for vaccines against SARS-CoV-2,” wrote in the journal Science in July 2021 Florian Krammer, a professor in the Department of Microbiology at Mount Sinai Hospital’s Icahn School of Medicine, In New York.
In his article, Krammer explains the importance of being able to establish an antibody level as a correlate of protection, that is, to be able to identify the minimum amount of antibodies that offer protection.
One reason is that approval of new vaccines could be sped up based on reading the amount of immunity they offer, without requiring long and extensive phase 3 trials, Krammer says.
Knowing the correlate of protection would also make it possible to administer 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 that health authorities use to determine what percentage of their population is protected.
Krammer, however, warns that it is unlikely that it will be possible to identify a correlate that can be applied to all vaccines, to all variants and to all populations, but that even so, it would 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 severe disease compared to unvaccinated.”
The expert adds that the appearance of new variants may 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 researchers try to answer these and other unknowns, he recommends continuing to maintain “common sense” measures: wearing masks, getting vaccinated and keeping your distance.
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