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Sunday, July 12, 2020

Filling middle seats nearly doubles airline passenger Covid risk

Tens of thousands of Americans are getting back on planes, at least for domestic travel, and their risk of catching COVID-19 could be dramatically higher than it needs to be in the case of airlines that let people use the middle seat rather than leaving it empty, according to a research paper from Massachusetts Institute of Technology.
The risk of dying from COVID-19 by flying, as a result, is higher than the risk of dying in a plane crash, according to a statistical model compiled by Arnold Barnett, the George Eastman Professor of Management Science at MIT’s Sloan School of Management.
Not letting anyone use the middle seat would still mean a higher risk of death by COVID-19 than the risk of death by a plane crash, but it would cut the risk in half, he estimates. That could mean 20 lives saved just in the next three months.
“The airlines are setting their own policies but the airlines and the public should know about the risk implications of their choices,” said Barnett in a telephone interview with ZDNet.
Barnett’s statistical hypothesis is going up against some resistance among airlines to give up the revenue from middle seats. United Airlines, for one, claims social distancing is impossible in an airplane cabin, a claim Barnett rejects as fairly disingenuous on the airline’s part.
What’s more, an examination of airlines’ public statements about their plans for a post-COVID-19 world suggests their fleets of planes will increasingly be composed of the narrow-body type, suggesting flights may become even more crowded, on average.

Gauging the risk of infection

Barnett posted his paper on the medRxiv pre-print server this past weekend. The paper has not yet been peer-reviewed, and so its findings must be taken with a degree of caution.
The middle seat refers to the seat between an aisle seat and a window seat in a row of three seats on a plane. A Boeing 737 or an Airbus 320, both narrow-body aircraft in wide use, have economy or coach sections of the cabin that feature three seats together on either side of a central aisle.
Barnett’s work is based on a simple equation one could almost do in one’s head with basic arithmetic. Using known statistics for infection rates of travelers coming from different parts of the US, the estimated effects of mask-wearing, and the distance a person is sitting from an infected individual in a row, Barnett calculated the risk of a passenger contracting COVID-19.
The average risk of catching COVID-19 from flying on a plane is 1 in 4,300, according to Barnett’s model. That rate is roughly double the risk if airlines were to leave the middle seat open, 1 in 7,700, Barnett estimates. Using a relatively low fatality rate of 1% of all people who contract COVID-19, he estimates, means that the 1-in-4,300 risks of catching COVID-19 turns into a risk of dying from the disease of 1 in 430,000. That is much more likely than the standard measure of risk of dying by an airplane crash, which is 1 in 34 million.
Barnett’s hypothesis draws upon a comprehensive review of the statistics known about COVID-19 that was published in the medical journal The Lancet on June 27 by researcher Derek Chu and colleagues at McMaster University in Hamilton, Ontario, Canada.
The reaction by the airlines to the idea of enforcing social distancing has been mixed.
Delta Airlines, the US’ biggest carrier by revenue, has a policy not to sell any middle seats through Sept. 30. However, American Airlines, the second biggest, originally limited bookings to half of all middle seats, but is now making available all seats for booking. And United Airlines, the third-biggest carrier, is maintaining the option of middle seat booking.
United’s chief executive, J. Scott Kirby, has dismissed distancing on planes as impossible. During an investor conference on May 28th with Sanford Bernstein analyst David Scott Vernon, Kirby remarked, “if you look at an airplane, airplanes don’t have social distancing.”
“You can’t be six feet apart on an airplane, middle seat or not,” said Kirby, referring to the recommended span between people generally referred to as social distancing, and the fact that a window and an aisle seat are closer together than that.

How distant can you be on a plane? 

Barnett, while circumspect in his report, was more adamant when asked about Kirby’s remarks by ZDNet.
“United asserts that there are no such implications, that middle-seat-empty is a PR measure and not a safety measure,” said Barnett. “That simply isn’t true.”
Barnett points out that social distancing is not an either-or matter, not a question of either two meters or nothing. The report by Chu et al. in The Lancet, he notes, indicates a continuum, where risk declines increasingly with distance so that any distance that can be imposed can be helpful.
“The basic formula says that for every additional meter, the risk goes down by a factor of two,” he explained. “So in that sense, two meters is only half as risky as one meter and three meters is only half as risky as two.”
When approached by ZDNet about Barnett’s research, United emphasized the safety measures it is taking other than blocking the middle seat. Through a spokesperson, the company stated in an email that it is “committed to delivering a new level of cleanliness.” That involves a “multi-layered approach” that includes filtered air, hospital-grade disinfectant sprayers used on the plane before each flight, and requiring all passengers and crew to wear a face mask. United says the Cleveland Clinic judges that approach “a safer environment than any one precaution alone.”
“I imagine the various things they’re doing are a sincere attempt to make things safer, but that doesn’t contradict the point that it would be safer still if you kept a middle seat open,” Barnett told ZDNet.
Given the prospect of death, Barnett leans toward implementing measures that he argues could save lives.
With 200,000 passengers per day being carried by the major US airlines over the next three months, a total of perhaps 18 million passengers will be carried in the US at the current rate of bookings, he explained. Going from the 1 in 7,700 COVID-19 risks per passenger with the middle seat filled to just 1 in 4,300 with it empty would avert 1,800 Covid-19 infections, he argues, and 18 potential deaths at a fatality rate of 1%.
Using a value of $9 million for a human life, which is a figure described by Boston University researcher Austin Frakt as roughly the value US government agencies use, the dollar equivalent of the 18 lost lives would be about $173 million.
“It is hard to imagine that the cost to American Airlines and United of averting those deaths would be anywhere near $173 million in the coming months,” Barnett told ZDNet.
It’s not just United and American that are hesitant about distancing. The International Air Transport Association, which counts 290 airlines as members, including large international carriers such as British Airways, has advised against social distancing on planes.
“IATA does not recommend restricting the use of the ‘middle seat’ to create social distancing while on board aircraft,” the organization said in early May. The IATA’s reasons for discouraging the practice include research reports this year that show there has been no COVID-19 transmission onboard flights, which the IATA ascribes to the effectiveness of air filters.

Studies show on-board transmission is real

Despite the airlines’ defense of air filters, there is data from over forty years’ worth of epidemiological studies that show that diseases including influenza can be transmitted from passenger to passenger on planes.
Such studies are compiled by interviewing passengers after the flight and investigating their contacts before, during, and post-flight, rather like a detective story.
One such study, performed in 2003 by scientists at the Centers for Disease Control, found that the original SARS virus was spread from one sick passenger to 22 passengers on board a 120-person flight traveling for three hours from Hong Kong to Beijing.
Comprehensive literature reviews of such studies demonstrate that infections may be rare but they are real. A 2017 survey by scientists at Emory University found in the literature “over a dozen cases of inflight transmission.” Moreover, “studies of severe acute respiratory syndrome (SARS) and pandemic Influenza (H1N1p) transmission on airplanes indicate that air travel can serve as a conduit for the rapid spread of newly emerging infections and pandemics,” the report states.
At the same time, it’s hard to scientifically account for exactly how the virus is transmitted. There is a “complex transmission dynamic” that happens with airborne diseases on planes, particularly influenza, noted a 2016 study by scientists at the European Centre for Disease Prevention and Control, based on an extensive review of decades of epidemiological studies.
The Emory study in 2017 noted that “the movement of aerosols over long periods of time in an empty cabin” is “extremely difficult to simulate with the fastest supercomputers.”
“According to Boeing engineers, airflow in an empty cabin lies on the ‘boundary of turbulence’,” the authors wrote, “which is the hardest cabin airflow regime to simulate over long time periods.”

Droplets or aerosols?

The whole matter is made more complex by the disagreement over how COVID-19 spreads. The World Health Organization contends that it spreads by relatively heavy droplets that quickly fall to the ground once they are shed from someone’s mouth or nose.
Some scholarly studies reinforce the primacy of droplets. In one study, cited by the IATA, published in April in the Canadian Journal of Medicine, there was no transmission of COVID-19 on a flight from China to Canada even though a COVID-19-positive individual was onboard. The study concluded that “the lack of secondary cases after prolonged air travel exposure supports droplet transmission, not airborne, as the likely route of spread of the COVID-19.”
As a result of the droplet theory, the guiding principle for airlines has been what’s known as the “2-row rule,” meaning, the risk is mostly confined to the row in which the infected person is sitting, and two rows in front of them and two rows behind.
But the role of droplets has been questioned of late. Over 200 scientists this week sent a letter to the WHO arguing that COVID-19 is not limited to droplet transmission but can conceivably be carried on finer aerosol particles. If so, that could mean that in the complex airflow of the cabin, the disease particles could travel farther.
Again, the scholarly record is unclear. The two principal authors of the 2017 Emory University study, Vicki Stover Hertzberg and Howard Weiss, had noted in a prior study in 2016 that multiple incidences of SARS and influenza infection on planes happened outside the two-row range. In the 2017 study, they sought to explain that apparent disparity by closely studying movements of passengers and cabin crew on multiple flights, looking for evidence that heavy droplets were spread by sick people moving about the cabin.
Even that study, however, concluded that fine, airborne aerosols might still be involved. “Our model assumes that droplets are the main transmission route for influenza and SARS,” they wrote. “This assumption is based on general public health agency guidance to health care providers, but it may not be true: Significant transmission may also occur via smaller virus-laden particles (the smallest being aerosols), which have larger dispersion distances.”
For his purposes, Barnett initially modeled only risk to people in the row of the infected person; he revised upward his assessment of risk in a second version of the paper after taking into account adjacent rows. While there may be further risk beyond those three rows, Barnett concedes, he is willing to leave that out of his model for the time being.
“I totally agree that it’s complex,” said Barnett of the various factors at play. “The temptation is to throw up one’s hands, but I think it’s better to make a serious attempt to put the clues together than not to make any attempt at all and just have conjectures clashing.”

Dr. Fauci is not happy 

Despite the various uncertainties, Barnett is not the only one sounding concerned. The experts on COVID-19 have publicly voiced worries about the airlines’ reluctance to distance.
During Senate testimony on June 30th, Anthony Fauci, director of the National Institute Of Allergy And Infectious Diseases at the National Institutes of Health, was asked by Senator Bernie Sanders whether it is a good idea to have airlines cramming people together on cross-country flights.
“American Airlines announced that they were going to fill up all of their planes and other airlines have done the same,” said Sanders. “So you’re going to have people going from New York to California, five, six hours sitting inches apart from each other.”
“That is something that is of concern,” Fauci responded. “I think in the confines of an airplane that becomes even more problematic.”CDC director Robert Redfield, who testified alongside Fauci, said American’s decision to book any middle seats at all was “disappointing.”
For his part, Barnett is hardly an airline critic generally speaking. He has done fundamental work on the statistics demonstrating the rising trend of airline safety. He has been quoted in popular articles saying airline travel is dramatically safer than most people believe.
“Generally, they do a fabulous job with safety,” said Barnett. He is mindful, too, of how the airlines are struggling amidst unprecedented circumstances, the “deepest and sharpest decline of demand the airline industry has ever seen,” as United’s Kirby has put it.
“Obviously, this is a horrible time for them,” Barnett said of the airlines. “For all the airlines, they never imagined anything like this could happen.”
At the same time, he’s critical of the dismissiveness of United and others, noting the lack of evidence on their side.
“If one really were able to establish with actual data that transmission is not happening, then I think that would obviously have to replace any of these estimates, but I don’t think at the moment we have that information,” he told ZDNet. “Believe me, if United had it more convincingly, I think they would be presenting it.”
The airlines all talk to one another about best practices, noted Barnett. If special kinds of cleaning really rid the cabin of a virus, why would Delta be going ahead with its policy of keeping the middle seat open, he asked.
“It’s not a matter that that these high-speed electrostatic sprays really are believed to eliminate the incremental risk,” he said.

It all comes down to economics

At the end of the day, it may be mostly a matter of economics for the airlines.
The IATA, in its announcement casting cold water on distancing, made the case that giving up middle seats would drive up plane fares because the number of passengers would fall below the number needed to make each flight profitable.
“Calls for social distancing measures on aircraft would fundamentally shift the economics of aviation by slashing the maximum load factor to 62%,” said the IATA. “That is well below the average industry breakeven load factor of 77%.”
The organization offers examples of the kinds of fare increases that might happen as a result, such as a 43% jump in the average North American fare, to $289 from $202. The “era of affordable travel will come to an end,” warns the IATA. Either that or “airlines will go bust.”
The focus on load, however, seems to ignore the extraordinary stimulus given to airlines this year. US carriers are running on billions of dollars in grants and loans from the US government’s CARES bailout enacted in response to COVID-19.
United, for example, is receiving a $3.5 billion grant and a $1.5 billion low-interest loan. As a condition, they are continuing to keep their staff employed. Given those subsidies, with a full staff, argues Barnett, airlines could afford to take lower yield to save lives. They have spare fleet capacity given lower overall volumes, and fuel is relatively cheap.
“What is the marginal cost to fly?” asked Barnett rhetorically. “You’ve got to pay the employees whether they fly or not; the planes are sitting idle; fuel prices are near a low,” he observed.
“If you’re going to talk about economics, the marginal cost of flying the plane is just so low that even at low fares, and even with seats kept empty, you could say the flight is profitable.”
Given that business travel, the bulk of revenue for airlines, may not rebound in a hurry, added Barnett, the argument can be made that airlines should stoke demand for leisure travel by reassuring nervous consumers.
“When you hear on the national news that Anthony Fauci is disappointed in American Airlines, some of this will deter some flying at the margin,” he said. “You could argue that, even from a purely economic standpoint, middle-seat-empty might make a lot of sense.”

A new normal?

There is another concern, however, one hinted at by Wall Street’s questions posed to airline management: What if changes during COVID-19 become a new normal?
That is a somewhat disturbing prospect for analysts used to the steady economics of tighter and tighter unit costs as a result of crowded coach cabins.
During American’s first-quarter earnings conference call with Wall Street analysts, on April 30th, an analyst from UBS investment bank asked American’s CEO, William Parker, regarding emptying the middle seat, “How long do you think something like that lasts if customers get used to it?”
“I mean, is it potentially that you’re putting it in there and it has to stay through the vaccine development next year?” asked the analyst, Myles Walton.
“I can’t really answer your question other than to tell you it will continue to evolve over time,” replied Parker.
In another investor talk in mid-May run by equity research firm Wolfe Research, analyst Hunter Keay asked United’s head of commercial aerospace & defense, Andrew Nocella, whether he thought the airline might permanently change layouts of plains for more distancing.
“Is there some sort of scenario that you envision to where you would actually modify the interiors of your aircraft to accommodate social distancing in the event that, say, regulators mandate you leave middle seats unsold?” asked Keay.
Nocella dismissed the prospect. Such changes “would take years to enact,” replied Nocella. Moreover, they “would be, I think, a pretty significant restructuring of the business model that we just don’t think there’s any reason to believe is necessary at this point.”
Asked about these concerns, Barnett replied that the right way to think about things in his view is to assume temporary measures. “If we were talking about this as a policy that’s going to go on for five years, then, of course, I think the kinds of long-term economic arguments would start to carry weight,” he said.
“But I think the hope is that if there isn’t a second wave in the fall if they make great progress with a vaccine, then maybe the time will come when everyone will agree that we’re close to the all-clear.”
Prepare to be crammed even more
Perhaps, but United and American are already contemplating a post-COVID-19 world, and their vision is a world that implies lower investment, leaner facilities, and possibly even more seats crammed together.
American plans to come out of the crisis “more efficient,” CEO Parker told analyst Vernon at the same Bernstein conference in May, meaning, a smaller staff, ultimately, but also a slimmed-down fleet of planes.
The crisis is an opportunity, Parker suggested. “And when we’re able to use this crisis to figure out things that we can do more efficiently, we simply won’t add back some things that we had in the past.”
One of American’s big future projects is “putting the seats together,” American chief financial officer Derek Kerr said at the same conference. “That will help cost structure because we’re putting a few more seats on those aircraft.”
During the Wolfe conference, analyst Keay, assessing the post-COVID-19 plans, asked American’s head of network strategy, Vasu Raja, “what about the idea of using more wide-bodies in the domestic market? You can facilitate distance between passengers.”
“Actually, it’s kind of the converse of that,” said Raja. “I think you’ll see a lot less wide-bodies in domestic, in part because the trip costs are so high, right?” American has “no plans over the next 3 or 4 years to grow that wide-body fleet any bigger,” added CFO Kerr.
Regardless of what happens with a vaccine, a second wave, mask-wearing, or anything else relating to the pandemic, airline passengers may have to expect to be closer than ever, not more distant, in years to come.

Osmotica Pharma’s Eye-Opening Surge

Osmotica Pharmaceuticals OSMT 25.29% surged Friday, ending the day up 25.3% to close at $8.77 per share.
What Happened? On Thursday afternoon, Osmotica reported the FDA approved their flagship drug Upneeq. This approval sent shares up as high as $9.37 on Friday.
Upneeq is now the only FDA approved treatment for acquired blepharoptosis.
Why It’s Important: Upneeq is used as a treatment for those with ptosis. Ptosis is associated with droopy eyelids and affecting the full field of vision.
It’s estimated ptosis affects over 11% of adults over the age of 50 in the United States and countless others in other countries around the world. Osmotica hopes to sell Upneeq commercially in the next month.
Osmotica also produces methylphenidate, which is used to treat ADD, but sales of methylphenidate were down 60% year-over-year in the first quarter. Revenue totals for Osmotica was a reported total of $48.6 million, a decrease from $57.1 million from the first quarter of 2019.
What’s Next? Upneeq is Osmotica’s competitive advantage on the market right now and its market share is currently uncapped as the only FDA approved drug. They continue to work with partners outside the U.S. for international distribution.

Biotech week ahead, July 13

Biotech stocks advanced in the week ended July 10 amid mixed news flow emerging out of the sector.
FDA approved a few drugs, including Endo International PLC’s ENDP 2.38% cellulite treatment, while Merck & Co., Inc. MRK 0.04%Eisai Co., Ltd’s ESALY 2.04% combo therapy was rejected by the FDA as a first-line treatment option for liver cancer.
Unum Therapeutics Inc UMRX 10.3% was the biggest gainer for the week, with the shares reacting to an acquisition and fund buying. In major COVID-19 updates, Novavax, Inc. NVAX 2.01% announced $1.6 billion federal funding for its coronavirus vaccine program.
The week also saw three biotechs testing the IPO waters. The three issues raised a combined $583.7 million from the offerings.
Here are the key catalysts for the unfolding week.

Conferences

Annual Biomarkers for Alzheimer’s Disease Summit (digital event): July 15

PDUFA Dates

The FDA is set to rule on Verrica Pharmaceuticals Inc’s VRCA 8.9% NDA for VP-102, a topical solution, being reviewed as a potential treatment option for molluscum contagiosum. Updating on the regulatory review, the company said in late June it received a letter from the FDA stating there are deficiencies that preclude discussion of labeling and post-marketing requirements/commitments at this time. The PDUFA date is set for Monday.

Adcom Meetings

FDA’s Oncologic Drugs Advisory Committee will discuss GlaxoSmithKline plc’s GSK 1.07% biologic license application for belantamab mafodotin for the treatment of adults with relapsed or refractory multiple myeloma who have received at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. The drug linker technology for the product candidate was licensed from Seattle Genetics, Inc. SGEN 3.76%. (Tuesday)
The Cardiovascular and Renal Drugs Advisory Committee is scheduled to discuss Mallinckrodt PLC’s MNK 8.58% new drug application for terlipressin, lyophilized powder for solution for injection, for the proposed indication of treatment of hepatorenal syndrome Type 1. (Wednesday)

Clinical Readouts/Presentations

Gritstone Oncology Inc GRTS 14.1% is scheduled to present data from the ongoing Phase 1 studies of its immunotherapy product candidates GRANITE and SLATE. The company also said it would discuss Phase 2 study plans. (Monday)
INmune Bio Inc INMB 12.9% will report interim data from its Phase Ib clinical study of XPro1595 in Alzheimer’s disease. (Tuesday)
Cassava Sciences Inc SAVA 8.99% said its lead neuroscientist, Lindsay Burns will give a keynote presentation at the Biomarkers for Alzheimer’s Disease Summit, with the presentation focusing on SavaDx, the company’s investigational diagnostic to detect Alzheimer’s disease with a simple blood test. (Wednesday)

Earnings

  • Abbott Laboratories ABT 0.69% (Thursday, before the market open)
  • AngioDynamics, Inc. ANGO 4.02% (Thursday, before the market open)
  • Johnson & Johnson JNJ 0.02% (Thursday, before the market open)

IPOs

Cambridge, Massachusetts-based Relay Therapeutics has filed with the SEC for offering 14.7 million shares to be priced between $16 and $18. Repare is a clinical-stage precision medicine company transforming the drug discovery process with an initial focus on enhancing small molecule therapeutic discovery in targeted oncology. The company has applied for listing its shares on the Nasdaq under the ticker symbol RLAY.

IPO Quiet Period Expirations


Almost 470 kids have tested positive for coronavirus in Fla. county

An additional 136 children in Manatee County have tested positive for COVID-19, according to the Florida Department of Health.
In a report dated Friday, the health department said a total of 468 children have tested positive for the novel coronavirus responsible for the COVID-19 respiratory disease. A week earlier, 332 people 17 and younger had tested positive, according to the health department.
A total of 1,070 children have been tested in Manatee since the start of the pandemic, for a positivity rate of 43.7%, up from 35.7%, a week earlier.
By comparison, the county’s overall positivity rate as of Saturday was 9%. The county has a total of 4,632 cases, as of Sunday, meaning 10.1% of those who have tested positive in Manatee County were children.
Statewide, a total of 17,073 children have been infected with the coronavirus, or 24.2% of those tested. In Florida, 6.7% of those who have tested positive are children.
Four children have died.
In Sarasota County, a total of 155 children had tested positive, as of a Friday, up from 103 a week earlier. A total of 547 children have been tested, for a positivity rate of 28.3%
Miami-Dade County has the most children who have tested positive for COVID-19 — 3,076 or 39.7% of those who have been tested.

Robust T cell immunity in convalescents with asymptomatic or mild COVID-19

Takuya Sekine1,13, André Perez-Potti1,13, Olga Rivera-Ballesteros1,13, Kristoffer Strålin2, Jean-Baptiste Gorin1, Annika Olsson2, Sian Llewellyn-Lacey3, Habiba Kamal2, Gordana Bogdanovic4, Sandra Muschiol4, David J. Wullimann1, Tobias Kammann1, Johanna Emgård1, Tiphaine Parrot1, Elin Folkesson2, Olav Rooyackers5,6, Lars I. Eriksson6,7, Anders Sönnerborg2,8, Tobias Allander4,9, Jan Albert4,9, Morten Nielsen10,11, Jonas Klingström1, Sara Gredmark-Russ1,2, Niklas K. Björkström1, Johan K. Sandberg1, David A. Price3,12, Hans-Gustaf Ljunggren1,13, Soo Aleman2,13, Marcus Buggert1,13,14; Karolinska COVID-19 Study Group
1Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. 2Division of Infectious Diseases, Karolinska University Hospital and Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden. 3Division of Infection and Immunity, Cardiff University School of Medicine, University Hospital of Wales, Cardiff, UK 5Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden. 5Department of Clinical Interventions and Technology, Karolinska Institutet, Stockholm, Sweden. 6Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden. 7Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. 8Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden. 9Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. 10Department of Health Technology, Technical University of Denmark, DK-2800 Lyngby, Denmark. 11Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, San Martín, Argentina.
12Systems Immunity Research Institute, Cardiff University School of Medicine, University Hospital of Wales, Cardiff, UK
13Equal contribution
14Lead contact
Lead contact: Marcus Buggert, PhD, Karolinska Institutet, Alfred Nobels Allé 8, 141 52 Stockholm, Sweden. Email: marcus.buggert@ki.se. Tel: +46-739245224.
One sentence summary SARS-CoV-2 induces robust memory T cell responses in antibody-seronegative and antibody-seropositive individuals with asymptomatic or mild COVID-19.
ABSTRACT SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. We systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in a large cohort of unexposed individuals as well as exposed family members and individuals with acute or convalescent COVID-19. Acute phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV2-specific T cells were detectable in antibody-seronegative family members and individuals with a history of asymptomatic or mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits robust memory T cell responses akin to those observed in the context of successful vaccines, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19 also in seronegative individuals.

https://www.biorxiv.org/content/10.1101/2020.06.29.174888v1.full.pdf