Researchers in Canada have shown that the long-lasting immunity that develops following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by different T cell responses than those observed for influenza A virus-specific immune memory.
The SARS-CoV-2 virus is the agent responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic that has caused more than 176 million infections and more than 3.8 million deaths since the outbreak first began in late December 2019.
It is still unclear whether the T cell, B cell, and antibody responses triggered by an infection with SARS-CoV-2 resemble those triggered by a typical respiratory virus.
All successful viruses must suppress the host’s innate immune response to some extent, but how the unique features of the early response to SARS-CoV-2 impact long-term immunity to SARS-CoV-2 compared with other respiratory viruses remains unknown, says the team from Sinai Health System in Toronto and the University of Toronto in Oregon.
Now, Tania Watts and colleagues have shown that among 24 recovered individuals, SARS-CoV-2-specific T cell responses were distinct from those typically observed for influenza A virus (IAV).
The T cell responses to SARS-CoV-2 exhibited a lower CD8+: CD4+ T cell ratio and a higher proportion of interleukin 2- (IL-2) and IL-6-producing cells, as well as an altered cytotoxic profile, compared with IAV-specific memory responses.
These T cell responses and altered phenotype lasted for about nine months following symptom onset.
“These data suggest that the memory T-cell phenotype after a single infection with SARS-CoV-2 persists over time, with an altered cytokine and cytotoxic profile compared to long term memory to IAV within the same subjects,” writes the team.
A pre-print version of the research paper is available on the medRxiv* server, while the article undergoes peer review.
A large proportion of the global population needs to acquire immunity to SARS-CoV-2
The SARS-CoV-2 virus continues to circulate in many regions of the world and controlling the COVID-19 pandemic will require immunity among a large proportion of the global population.
Although vaccine-induced immunity is a key component in acquiring SARS-CoV-2 immunity, a substantial number of people have recovered from COVID-19. It is crucial to understand how these individuals maintain and develop immunity to the virus.
While all successful viruses suppress the host’s innate immune response to some degree, SARS-CoV-2 is particularly adept at evading type I and III interferon (IFN) responses, and people with defects in IFN signaling are overrepresented among severe COVID-19 cases.
“Whether these unique features of the early response to SARS-CoV-2 impact long-term immunity to SARS-CoV-2 compared to other respiratory viruses remains unknown,” writes Watts and colleagues.
What did the study involve?
The researchers assessed the persistence and phenotype of T cell and antibody responses to SARS-CoV-2 among 24 recovered individuals at a median of 45 days and 145 days post-symptom onset. The majority (75%) of participants had recovered from mild disease that did not require hospitalization.
Antibody responses to SARS-CoV-2 were detected in 95% of participants.
A strong correlation was observed between plasma and salivary levels of immunoglobulin G (IgG) directed at the viral spike protein and its receptor-binding domain (RBD). The spike RBD mediates the initial stage of the infection process by binding to the host cell receptor angiotensin-converting enzyme 2 (ACE2).
A correlation was also observed between circulating T follicular helper cells and the SARS-CoV-2-specific IgG response.
All individuals had CD4+ T cell responses to SARS-CoV-2 that decayed with a half-life of five to six months for spike-specific IL-2-producing cells.
T cell memory phenotype differed between SARS-CoV-2 and IAV
The phenotype of the SARS-CoV-2-specific T cells differed from that of T cell memory responses to IAV within the same individuals.
The response to SARS-CoV-2 was characterized by a lower ratio of CD8+: CD4+ T cell and a lower ratio of IFN-g-: IL-2-producing cells, compared with IAV-specific memory responses.
The analysis also revealed a decreased IFN-g: IL-6 ratio and an altered profile of cytotoxic molecules compared with IAV-specific responses.
These T cell responses and altered phenotype persisted for about nine months following symptom onset.
The responses to IAV were about two to three times more stable than the responses to SARS-CoV-2.
The researchers say that since boosting is known to increase the duration of T cell immunity, this finding likely reflects the IAV-specific memory being boosted over a lifetime of exposure or vaccination.
“The response to SARS-CoV-2 represents a primary infection; whether this will change upon boosting remains to be determined,” they add.
What did the authors conclude?
The researchers say the findings demonstrate that most individuals in a cohort of recovered, mainly mild cases have detectable T and antibody responses to SARS-CoV-2 for around nine months post-infection.
“Although a limitation of our study is that the IAV-specific responses measured here represent a lifetime of exposure to IAV, whereas SARS-CoV-2-specific responses represent the response to a new infection… the data suggest that SARS-CoV-2 specific T cell responses are distinct from the typical response to the respiratory pathogen IAV,” concludes the team.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.