Pre-existing memory T cells may reduce COVID-19 severity, but do not prevent infection

Pre-existing memory T cells that cross-react with SARS-CoV-2 may only reduce COVID-19 severity cannot prevent infection. The memory T cells are extremely unlikely to prevent SARS-CoV-2 infections. That is just not what T cells generally do. Hence, herd immunity cannot be achieved when only low percentage of the population is infected.

At least five papers published in reputable journals have found that 20-50% people who have not been infected with novel coronavirus (SARS-CoV-2) still harbour memory T cells derived from previous exposures to common cold coronaviruses. The memory T cells were found to cross-react with SARS-CoV-2. A team of researchers from La Jolla Institute for Immunology, La Jolla, California alone has published three papers that established the presence of memory T cells from common cold coronaviruses in people who have not been exposed to SARS-CoV-2 virus and found the memory T cells cross-reacting with novel coronavirus.

The five papers on memory T cells that cross-react with novel coronavirus were published in the journals Cell, Nature (here and here), Science, and Science Immunology.

With Mumbai, Delhi, London and New York witnessing a peak weeks after the coronavirus blazed through the cities, people have wrongly assumed that pre-existing memory T cells have been providing the much-needed protection from SARS-CoV-2 virus infection. This has led to the mistaken assumption that herd immunity can be achieved when just 20-30% of the population is infected by the virus, as against 60-70% that scientists say is needed.

“Pre-existing T cell immunity to SARS-CoV-2 could be relevant because it could influence COVID-19 disease severity. It is plausible that people with a high level of pre-existing memory CD4+ T cells that recognise novel coronavirus could mount a faster and stronger immune response upon exposure to the virus and thereby limit disease severity,” Alessandro Sette and Shane Crotty from La Jolla Institute for Immunology, La Jolla, California say in a Comment published in Nature Reviews Immunology.

“The memory T cells are extremely unlikely to prevent SARS-CoV-2 infections. That is just not what T cells generally do. We (Dr Sette and I) speculate that they may reduce COVID-19 disease severity and prevent deaths,” Dr Crotty says in an email.

Clarifying the role of memory T cells

But in a paper published in Cell, a team led by Dr Marcus Buggert from Karolinska Institutet, Stockholm, Sweden found robust memory T cells responses in COVID-19 patients and in healthy people. Based on this they noted that memory T cells indicates a “previously unanticipated degree of population-level immunity against COVID-19”, which contradicts the observation by others. In an email, Dr Buggert clarifies: “I completely agree with Prof. Crotty and Prof. Sette that T cells are not going to protect against reinfection by SARS-CoV-2, but may prevent from recurrent severe COVID-19. That’s what T cell immunity is all about.” 

In a communication to me, Dr Gagandeep Kang, Professor of Microbiology, Division of Gastrointestinal Sciences at CMC Vellore, echoed the views of Dr Crotty. “Memory T cells generated by seasonal coronavirus alone are very unlikely to prevent [SARS-CoV-2] infection. It is plausible that they play a role in reducing [COVID-19 disease] severity,” Dr Kang says.

In a series of tweets, Dr Crotty further clarified the misconstrued role of memory T cells in achieving herd immunity. “Even if our most optimistic speculations about cross-reactive T cell memory were found to be correct, it would mean that just as many people would get infected with SARS-CoV-2, but fewer would become severely ill and die from COVID-19,” Prof. Crotty says.

Role of memory T cells

Explaining how the memory T cells may help reduce the severity of the disease, virologist Dr Shahid Jameel, CEO of DBT-Wellcome Trust India Alliance, says: “The cross-reactive memory T cells on activation would help in the development of plasma cells and thus antibody production, and in the development of killer T cells that would kill virus infected cells. The latter reduces the reservoirs of infection. This would most likely reduce disease severity. Though a low probability event (if at all), we don’t yet know if such cross-reactive activation would have effects on the cytokine storm that causes most of the pathology and mortality in severe COVID-19 cases.”

Dr Jameel says that the adaptive immune system works at two fronts — humoral (produce antibodies) and cellular (T cells) immunity. “Antibodies protect against extracellular pathogens. But since antibodies cannot enter cells, these are unable to destroy cellular reservoirs of infection. For this, we need T cells that can seek and destroy infected cells and thus eliminate infection,” he explains.

Misconception about herd immunity

A few researchers have also been mistaking pre-existing cross-reactive memory T cells to be playing a part in achieving herd immunity even when only a small percentage of the population is infected. In a tweet, ophthalmologist Dr James Mathew Todaro at Columbia University said: “There is growing evidence that T-cell immunity allows populations to reach herd immunity once only 10-20% are infected with SARS-CoV-2. This would explain why a highly transmissible virus in densely populated areas peaked at 10-20% infected regardless of lockdowns or masks.”

In a bid to clear the misconception regarding cross-reactive memory T cells and herd immunity, Dr Crotty commented that “there are various tweets misinterpreting COVID-19 ‘pre-existing immunity’ and making dangerous claims about herd immunity”. He says cross-reactive immune memory, which avoids the word immunity, may sometimes get misinterpreted as “protective immunity”.

Dismissing the possibility of cross-reactive memory T cells producing herd immunity when only a small percentage of the population is infected, Dr Jameel says: “The [cross-reactive memory T cells] would not provide protective immunity from infection but may mitigate or reduce severity of disease. In fact, most vaccines also don’t prevent infection. They reduce or eliminate disease. How successful this is would depend upon the cross-reactivity at the T cell level.”

“Herd immunity is complicated, and most models have used calculations only for antibodies (and only stable antibodies at that). Hard to predict how much of a difference T cells would make,” Dr Kang adds.

“T cell immunity will not generate herd immunity, but I truly believe that there could be an “unanticipated” degree of immunity against more severe forms of COVID-19 in the population… and maybe T cells play a role here, but so far this is based on associations,” Dr Buggert says.

Published in The Hindu on August 29, 2020