July 10 (Reuters) - As scientists question whether the presence, or absence, of antibodies to the novel coronavirus can reliably determine immunity, some are looking to a different component of the immune system, known as T cells, for their role in protecting people in the pandemic.
Recent studies show that some recovered patients who tested negative for coronavirus antibodies did develop T cells in response to their COVID-19 infection. While the studies are small and have yet to be reviewed by outside experts, some scientists now say that people who experience a mild illness, or no symptoms at all, from the new coronavirus, may be eliminating the infection through this T cell response.
The findings add to the evidence that an effective COVID-19 vaccine will need to prompt T cells to work in addition to producing antibodies, and may have implications for several treatments in development. They may also shed light on how immunity to new exposure to infection could work.
"There is mounting evidence that people exposed to the virus have a transient (short-lived) antibody response, or have a T cell response in spite of a minor or absent antibody response," Dr Alessandro Sette, professor and member of the La Jolla Institute’s Infectious Disease and Vaccine Center in California, told Reuters.
When a virus gets past the body's initial defenses - which include infection-fighting white blood cells - a more specific "adaptive" response kicks in, triggering production of cells that target the invader. These include antibodies that can recognize a virus and lock onto it, preventing its entry into a person's cells, as well as T cells that can kill both invaders and the cells they have infected.
Six months into a global COVID-19 pandemic that has infected more than 12 million people, questions remain about whether the antibody response to this virus is robust and lasts over time. That could mean T cells have a more important role in offering protection against the illness.
"T cells are often important in controlling viral infections. We are seeing evidence of that," John Wherry, director of the University of Pennsylvania's Institute for Immunology, told Reuters.
A recent small French study https://www.medrxiv.org/content/10.1101/2020.06.21.20132449v1, not yet reviewed by experts, found that six out of eight family members in close contact with relatives who had COVID-19 developed a T cell response, but did not test positive for antibodies.
A Swedish study https://www.biorxiv.org/content/10.1101/2020.06.29.174888v1.full.pdf of 200 people found a strong T cell response in most individuals who had mild illness or no symptoms following coronavirus infection, regardless of whether they showed an antibody response. The finding suggests that coronavirus infection rates may be higher than what has been studied using antibody tests alone, the researchers said.
MEMORIES OF CORONAVIRUS
The focus on T cell responses could also shed light on the prospect for longer-term immunity.
There is some evidence that T cells developed after exposure to other coronaviruses that cause the common cold could help fight off the new virus, known as SARS-CoV-2.
A study led by the La Jolla Institute detected T cells that reacted to SARS-CoV-2 in about half of stored blood samples collected between 2015 and 2018, suggesting that the immune system cells developed after previous infection with circulating common cold coronaviruses, and that they might help protect against the new virus.
"It is a potentially encouraging piece of evidence," Wherry said.
Vaccine candidates against COVID-19 currently in the works aim to generate antibody and T cell responses, and the recent findings highlight the importance of gauging the T cell response seen in human clinical trials.
"We believe that the optimal vaccine design would be one that induces both an antibody and T cell response," Sette said.
After an infection or vaccination, the immune system retains a number of "memory" cells that are already primed to quickly attack the same virus in case of a future infection.
Many countries are using blood tests that look for antibodies to estimate how many people have been infected with the new virus even if they never showed symptoms. But scientists still do not know how antibody levels correlate to exposure to the virus or how long they may last. There are also questions about exactly which combination of immune-system cells will result in significant protection.
Measuring the level of memory T cells is much more complicated, especially if the cells are in lymph nodes or other hard-to-access areas of the body. In addition, T-cell responses are highly variable.
"It is a lot easier to collect antibody data," said Dr Daniela Weiskopf, an assistant professor at the La Jolla Institute.
Related: States reopen, relax guidelines to prevent coronavirus spread
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States reopen, relax guidelines to prevent coronavirus spread
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States reopen, relax guidelines to prevent coronavirus spread
NEW YORK, NEW YORK - MAY 06: An employee wearing a mask cleans the inside of the restaurant, Blue Stripes Cacao Shop as it prepares to reopen for takeaway and delivery orders after being closed for over a month amid the coronavirus pandemic on May 6, 2020 in New York City. Governor Andrew Cuomo made the announcement that all bars and restaurants must close by on March 16th unless it was takeout or delivery. COVID-19 has spread to most countries around the world, claiming over 263,000 lives with over 3.8 million cases. (Photo by Alexi Rosenfeld/Getty Images)
NEW YORK, NEW YORK - MAY 06: An employee wearing a mask cleans the inside of the restaurant, Blue Stripes Cacao Shop as it prepares to reopen for takeaway and delivery orders after being closed for over a month amid the coronavirus pandemic on May 6, 2020 in New York City. Governor Andrew Cuomo made the announcement that all bars and restaurants must close by on March 16th unless it was takeout or delivery. COVID-19 has spread to most countries around the world, claiming over 263,000 lives with over 3.8 million cases. (Photo by Alexi Rosenfeld/Getty Images)
THOUSAND OAKS, CA - MAY 06: A Cadillac Dealership displays a sign stating its reopened during the Coronavirus Pandemic on May 06, 2020 in Thousand Oaks, California. The coronavirus pandemic worldwide has claimed over 263,000 lives and infected over 3.7 million people. (Photo by Josh Lefkowitz/Getty Images)
HOUSTON, May 5, 2020 -- Customers shop at a shopping mall in Frisco, on the outskirts of Dallas, Texas, the United States, May 5, 2020. After closed for several weeks due to the outbreak of COVID-19 pandemic, the shopping mall reopened with shortened business hours on Tuesday. (Photo by Dan Tian/Xinhua via Getty) (Xinhua/ via Getty Images)
HOUSTON, May 5, 2020 -- Cars are parked in front of a shopping mall in Frisco, on the outskirts of Dallas, Texas, the United States, May 5, 2020. After closed for several weeks due to the outbreak of COVID-19 pandemic, the shopping mall reopened with shortened business hours on Tuesday. (Photo by Dan Tian/Xinhua via Getty) (Xinhua/ via Getty Images)
Dawson Padilla (L), owner of a protein shakes store, works behind the bar on May 5, 2020 in Stillwater, Oklahoma. - In the face of intimidation against employees and the threat of an armed attack by local residents wielding their individual liberties, the mayor of Stillwater had to give in: he gave up imposing the wearing of masks on customers in shops. This demand was included in a 21-page document that was supposed to accompany the gradual reopening of restaurants and shops from 1 May, as authorized by the state of Oklahoma. "About three and a half hours after the law came into effect" of the text, "we started receiving calls from stores claiming that employees were being threatened and insulted, and threatened with physical violence," said Norman McNickle, the city's director of services. (Photo by Johannes EISELE / AFP) (Photo by JOHANNES EISELE/AFP via Getty Images)
A worker of the Aspen Cafe wears a mask as she makes coffee on May 5, 2020 in Stillwater, Oklahoma. - In the face of intimidation against employees and the threat of an armed attack by local residents wielding their individual liberties, the mayor of Stillwater had to give in: he gave up imposing the wearing of masks on customers in shops. This demand was included in a 21-page document that was supposed to accompany the gradual reopening of restaurants and shops from 1 May, as authorized by the state of Oklahoma. "About three and a half hours after the law came into effect" of the text, "we started receiving calls from stores claiming that employees were being threatened and insulted, and threatened with physical violence," said Norman McNickle, the city's director of services. (Photo by Johannes EISELE / AFP) (Photo by JOHANNES EISELE/AFP via Getty Images)
Kelly Lyda, owner of the Aspen Cafe, stands in his Cafe on May 5, 2020 in Stillwater, Oklahoma. - In the face of intimidation against employees and the threat of an armed attack by local residents wielding their individual liberties, the mayor of Stillwater had to give in: he gave up imposing the wearing of masks on customers in shops. This demand was included in a 21-page document that was supposed to accompany the gradual reopening of restaurants and shops from 1 May, as authorized by the state of Oklahoma. "About three and a half hours after the law came into effect" of the text, "we started receiving calls from stores claiming that employees were being threatened and insulted, and threatened with physical violence," said Norman McNickle, the city's director of services. (Photo by Johannes EISELE / AFP) (Photo by JOHANNES EISELE/AFP via Getty Images)
Computer specialist Toby Angel drinks his coffee on May 5, 2020 in Stillwater, Oklahoma. - In the face of intimidation against employees and the threat of an armed attack by local residents wielding their individual liberties, the mayor of Stillwater had to give in: he gave up imposing the wearing of masks on customers in shops. This demand was included in a 21-page document that was supposed to accompany the gradual reopening of restaurants and shops from 1 May, as authorized by the state of Oklahoma. "About three and a half hours after the law came into effect" of the text, "we started receiving calls from stores claiming that employees were being threatened and insulted, and threatened with physical violence," said Norman McNickle, the city's director of services. (Photo by Johannes EISELE / AFP) (Photo by JOHANNES EISELE/AFP via Getty Images)
WESTPORT, CONNECTICUT - MAY 05: A cafe along a shopping street in the affluent community remains mostly empty of pedestrians and open stores on May 05, 2020 in Westport, Connecticut. A growing number of states have begun reopening parts of the economy amid demonstrations like the one yesterday that targeted the Connecticut state capital and the governor's mansion in Hartford. (Photo by Spencer Platt/Getty Images)
WESTPORT, CONNECTICUT - MAY 05: A cafe along a shopping street in the affluent community remains mostly empty of pedestrians and open stores on May 05, 2020 in Westport, Connecticut. A growing number of states have begun reopening parts of the economy amid demonstrations like the one yesterday that targeted the Connecticut state capital and the governor's mansion in Hartford. (Photo by Spencer Platt/Getty Images)
LAGUNA HILLS, CA - MAY 05: Customers maintain safety protocols at The BarberHood in Laguna Hills, CA, on Tuesday, May 5, 2020. The shop is one of the first to re-open and defy the state"u2019s stay-at-home order during the COVID-19 (coronavirus) lockdown. (Photo by Paul Bersebach/MediaNews Group/Orange County Register via Getty Images)
SAN CLEMENTE, CA - MAY 05: Visitors walk on the beach south of the pier in San Clemente, CA on Tuesday, May 5, 2020. The city opened its beaches for daily active use after coordinating with Gov. Gavin Newsom"u2019s office to maintain social distancing during the COVID-19 (coronavirus) lockdown. (Photo by Paul Bersebach/MediaNews Group/Orange County Register via Getty Images)
SAN CLEMENTE, CA - MAY 05: Surfers were back on the waves at T Street in San Clemente, CA on Tuesday, May 5, 2020. The city opened its beaches for daily active use after coordinating with Gov. Gavin Newsom"u2019s office to maintain social distancing during the COVID-19 (coronavirus) lockdown. (Photo by Paul Bersebach/MediaNews Group/Orange County Register via Getty Images)
KENMORE, WA - MAY 05: Lynette Fisher-Charles and her dog Gracie, a two-year-old springer spaniel, go for a hike in Saint Edward State Park on May 5, 2020 in Kenmore, Washington. The first phase to reopen the state begins today easing some restrictions including opening some parks, that were put in place during Governor Jay Inslees Stay Home, Stay Healthy order last March to help reduce the spread of COVID-19. Kenmore, WA is located northeast of Seattle. (Photo by Karen Ducey/Getty Images)
KENMORE, WA - MAY 05: Daryl Kline, a park ranger at Saint Edward State Park removes a sign saying the park is closed on May 5, 2020 in Kenmore, Washington. The first phase to reopen the state begins today easing some restrictions that were put in place during Governor Jay Inslees Stay Home, Stay Healthy order last March to help reduce the spread of COVID-19. Kenmore, WA is located northeast of Seattle. (Photo by Karen Ducey/Getty Images)
LAGUNA BEACH, CA - MAY 05: Lifeguards keep a lookout at Laguna Beach, CA after officials reopened access to the sand on Tuesday, May 5, 2020. The beach has been closed since March 23, 2020 due to the COVID-19 (coronavirus) outbreak. City parks along the beach are still closed and people cannot sit or linger on the sand. (Photo by Paul Bersebach/MediaNews Group/Orange County Register via Getty Images)
NEW YORK, May 4, 2020 -- Photo taken on May 4, 2020 shows Times Square in New York, the United States.
Amid the ongoing COVID-19 pandemic, New York Governnor Andrew Cuomo on Monday outlined additional guidelines regarding when regions can reopen.
According to the Governor's Press Office, the state will monitor four core factors to determine if a region can reopen: number of new infections, health care capacity, diagnostic testing capacity and contact tracing capacity. (Photo by Wang Ying/Xinhua via Getty) (Xinhua/Wang Ying via Getty Images)
NEW YORK, May 4, 2020 -- A worker cleans a cafe's signboard at Times Square in New York, the United States, May 4, 2020.
Amid the ongoing COVID-19 pandemic, New York Governnor Andrew Cuomo on Monday outlined additional guidelines regarding when regions can reopen.
According to the Governor's Press Office, the state will monitor four core factors to determine if a region can reopen: number of new infections, health care capacity, diagnostic testing capacity and contact tracing capacity. (Photo by Wang Ying/Xinhua via Getty) (Xinhua/Wang Ying via Getty Images)
ASBURY PARK, NJ - MAY 4: People walk near the closed boardwalk due to the outbreak of COVID-19 in the state on May 4, 2020 in the Jersey Shore in New Jersey. Some towns at Jersey Shore expect the reopening of beaches soon. (Photo by Eduardo MunozAlvarez/VIEWpress/Corbis via Getty Images)
NORTH ANDOVER, MA - MAY 4: Although all golf courses in Massachusetts are still ordered to stay closed by governor Charlie Baker, workers at the North Andover Country Club in North Andover, MA work on the grass on May 4, 2020, getting the course ready for when they eventually are allowed to re-open. (Photo by Jim Davis/The Boston Globe via Getty Images)
LOS ANGELES, CA - MAY 04: Gov. Gavin Newsom announced select retail businesses will be allowed to reopen starting Friday in California during the coronavirus pandemic on Monday, May 4, 2020 in Los Angeles, CA. (Jason Armond / Los Angeles Times via Getty Images)
SANFORD, UNITED STATES - MAY 04, 2020: Customers enjoy a meal at Racks Billiards Sports Bar and Grill on the first day that retail stores and restaurants in all Florida counties except Palm Beach, Broward, and Miami Dade were permitted to reopen as COVID-19 restrictions are eased. Under phase one of the plan to reopen the state, stores and restaurants are limited to 25 percent of their indoor capacity.- PHOTOGRAPH BY Paul Hennessy / Echoes Wire/ Barcroft Studios / Future Publishing (Photo credit should read Paul Hennessy / Echoes Wire/Barcroft Media via Getty Images)
SANFORD, UNITED STATES - MAY 04, 2020: A customer leaves a Books-A-Million store on the first day that retail stores and restaurants in all Florida counties except Palm Beach, Broward, and Miami Dade were permitted to reopen as COVID-19 restrictions are eased. Under phase one of the plan to reopen the state, stores and restaurants are limited to 25 percent of their indoor capacity.- PHOTOGRAPH BY Paul Hennessy / Echoes Wire/ Barcroft Studios / Future Publishing (Photo credit should read Paul Hennessy / Echoes Wire/Barcroft Media via Getty Images)
BOZEMAN, MT - MAY 04: Sales staff wear masks at the reopened Schnee's Boots, Shoes and Outdoors on Main Street on May 4, 2020 in Bozeman, Montana. Wyoming health officials today reported that the state's confirmed coronavirus cases grew by nine to a total of 444. (Photo by William Campbell/Getty Images)
BOZEMAN, MT - MAY 04: Signs for restaurants and stores announce their reopenings on Main Street on May 4, 2020 in Bozeman, Montana. Wyoming health officials today reported that the state's confirmed coronavirus cases grew by nine to a total of 444. (Photo by William Campbell/Getty Images)
JENSEN BEACH, FLORIDA - MAY 04: Cole Hunter carries Harper Hunter, 1, as Holly Hunter,4, follows along as they arrive at the beach on May 04, 2020 in Jensen Beach, Florida. Restaurants, retailers, as well as beaches and some state parks reopened today with caveats, as the state continues to ease restrictions put in place to contain COVID-19. The counties of Palm Beach, Broward and Miami Dade continue to maintain restrictions. (Photo by Joe Raedle/Getty Images)
JACKSONVILLE BEACH, FLORIDA - MAY 04: People are seen dining outside at Cruisers Grill as the state of Florida enters phase one of the plan to reopen the state on May 04, 2020 in Jacksonville Beach, Florida. Restaurants, retailers, beaches and some state parks reopen today with caveats, as the state continues to ease restrictions put in place to contain the coronavirus (COVID-19). (Photo by Sam Greenwood/Getty Images)
JACKSONVILLE BEACH, FLORIDA - MAY 04: People are seen at a department store as the state of Florida enters phase one of the plan to reopen the state on May 04, 2020 in Jacksonville Beach, Florida. Restaurants, retailers, beaches and some state parks reopen today with caveats, as the state continues to ease restrictions put in place to contain the coronavirus (COVID-19). (Photo by Sam Greenwood/Getty Images)
SAINT AUGUSTINE, FLORIDA - MAY 04: A mask is seen on the statue of Henry M. Flagler as the state of Florida enters phase one of the plan to reopen the state on May 04, 2020 in Saint Augustine, Florida. Restaurants, retailers, beaches and some state parks reopen today with caveats, as the state continues to ease restrictions put in place to contain the coronavirus (COVID-19). (Photo by Sam Greenwood/Getty Images)
A man works on power lines in Los Angeles, California on May 4, 2020, amid the coronavirus pandemic. - California governor Gavin Newsom earlier today announced the gradual reopening of the state later this week as dismal US employment figures are expected with the release of figures Friday May 8 for April's US jobs report, as 30 million Americans filed for unemployment in the last six weeks. (Photo by Frederic J. BROWN / AFP) (Photo by FREDERIC J. BROWN/AFP via Getty Images)
