Insights into Editorial: T cell immune responses seen a year after infection

Introduction:

Like in most countries where the Omicron variant had become dominant and caused a high spike in daily cases, the third wave in India propelled by Omicron caused a large number of reinfections in unvaccinated people and breakthrough infections even among the fully vaccinated.

However, across the world, the Omicron variant was found to cause only mild disease in fully vaccinated people and in those with previous infection.

This was real-world proof that previous infection and/or full vaccination with two doses provide protection against progression of disease to a severe form.

The Adaptive Immune System:

1. Our adaptive immune system saves us from certain death by infection. An infant born with a severely defective adaptive immune system will soon die unless extraordinary measures are taken to isolate it from a host of infectious agents, including bacteria, viruses, fungi, and parasites.
2. Indeed, all multicellular organisms need to defend themselves against infection by such potentially harmful invaders, collectively called pathogens.
3. Invertebrates use relatively simple defense strategies that rely chiefly on protective barriers, toxic molecules, and phagocytic cells that ingest and destroy invading microorganisms (microbes) and larger parasites (such as worms).
4. Vertebrates, too, depend on such innate immune responses as a first line of defense, but they can also mount much more sophisticated defenses, called adaptive immune responses.
5. The innate responses call the adaptive immune responses into play, and both works together to eliminate the pathogens.

Protective effect due to Full Vaccination:

1. Laboratory studies undertaken in all countries have only studied the neutralisation ability of sera of people who have recovered from COVID-19 and people who have been fully vaccinated.
2. This could only shed light on the ability of past infection and/or vaccination to prevent infection by highly transmissive variants with immune escape.
3. But no studies have been done to evaluate the protective effect of memory T cell immune responses against severe disease 12 months after primary infection.
4. A new study from Wuhan addresses this gap. The results were published in the journal The Lancet Microbe.

Independent of severity:

1. The researchers found that neutralising antibodies were detectable even 12 months after infection in “most individuals”, and it remained stable 6-12 months after initial infection in people younger than 60 years.
2. The researchers found that “multifunctional T cell responses were detected for all SARS-CoV-2 viral proteins tested”.
3. And most importantly, the magnitude of T cell responses did not show any difference immaterial of how severe the disease was.
4. While the ability of antibodies to neutralise was nearly absent against the Beta variant, it was reduced in the case of the Delta variant.
5. In contrast, the T cell immune responses were detectable in all the 141 individuals tested 12 months after infection and even when they had lost the neutralising antibody response.
6. And the T cell responses were responding against the Beta variant in most of the 141 individuals.

Neutralising antibodies:

1. SARS-CoV-2-specific neutralising antibody and T cell responses were retained 12 months after initial infection.
2. Neutralising antibodies to the D614G, Beta, and Delta were reduced compared with those for the original strain, and were diminished in general.
3. Memory T cell responses to the original strain were not disrupted by new variants.
4. Findings show that robust antibody and T cell immunity against SARS-CoV-2 is present in majority of recovered patients 12 months after moderate-to-critical infection.

What are T cells and why are they important?

T cells are a part of the immune system that focuses on specific foreign particles.

T cells circulate until they encounter their specific antigen and play a critical part in immunity to foreign substances.

T cells can act as “killer cells”, attacking cells which have been infected with a virus or another kind of pathogen.

They can also act as “helper cells” by supporting B cells to produce antibodies.

Robustness of T cells:

1. The study reveals the durability and robustness of the T cell responses against variants, including Delta, even after one year of infection.
2. Most importantly, the robust and longstanding T cell responses were seen in people who have not been reinfected or vaccinated.
3. This would mean even in the absence of vaccination, a person who has been infected by the virus even one year ago would have robust immune responses, which would offer protection against disease progressing to a severe form requiring hospitalisation.
4. But the neutralising antibodies were found to diminish at the end of 12 months.
5. It might be recalled that except the Oxford vaccine (AstraZeneca), none of the trials evaluated the ability of the vaccines to prevent infection.
6. The endpoint of all vaccine efficacy studies was to evaluate if vaccinated people developed symptomatic disease or not.

Response to strains:

A year after infection, 115 of 141 (82%) individuals had neutralising antibodies against the original strain from Wuhan, China.

In contrast, only 68 (48%) had neutralising antibodies against D614G, 32 (23%) had neutralising antibodies against the Beta variant, and 69 (49%) had neutralising antibody responses against the Delta variant.

Conclusion:

This review aim at providing most recent knowledge on the aberrant cell-mediated immunity in host against SARS-CoV-2 and potential immunotherapies for COVID-19.

Researchers should still pay much attention to solve the main problem of immunotherapy in COVID-19, the application of different treatments according to the infectious stages and severity, to increase efficiency and to reduce side effects, such as excessive activation or cytokine storm.