Virus-specific antibodies are generated by many newly discharged COVID-19 patients

According to a research published on in the Immunity journal on May 3^rd, 2020, a majority of the recently discharged patients who have currently recovered from the COVID-19 infection create virus-specific T cells and antibodies but the responses of various patients are quite different.

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In the study, 14 patients were examined who displayed extremely different immune responses; however, the results obtained from six of these patients, who were evaluated at two weeks following discharge, indicate that antibodies were preserved for at least that long.

Further study results indicated the parts of the virus that are most effective at activating these immune responses, and should hence be targeted by promising vaccines.

It remained unclear as to why immune responses differed extensively from one patient to another. According to the authors, this difference may be associated with the initial quantities of viruses that were encountered by the patients and also their physical states or their microbiota.

There were also other open questions such as whether such immune responses guard against the COVID-19 infection when re-exposed to SARS-CoV-2 and the types of T cells that are triggered by the infection caused by the virus.

It is equally significant to observe that the laboratory tests used for detecting the SARS-CoV-2 antibodies in humans still have to be verified further to establish their reliability and accuracy.

These findings suggest both B and T cells participate in immune-mediated protection against the viral infection. Our work has provided a basis for further analysis of protective immunity and for understanding the mechanism underlying the development of COVID-19, especially in severe cases. It also has implications for designing an effective vaccine to protect against infection.”

Chen Dong, Study Senior Co-Author, Tsinghua University

Only limited knowledge is available about the protective immune responses caused by SARS-CoV-2, the disease-causing virus, and dealing with this knowledge gap may speed up the development of an effective vaccine, added Cheng-Feng Qin, the study’s co-senior author from the Academy of Military Medical Sciences in Beijing, China.

Keeping this aim in mind, the scientists compared the immune responses of 14 patients infected with the COVID-19 virus and who had lately become virus-free to those of the six healthy donors.

While eight of the patients were recently discharged, the remaining six were all follow-up patients who were discharged two weeks before the analyses. Particularly, the scientists obtained the blood samples and evaluated the concentrations of immunoglobulin M (IgM) antibodies, which appear first in response to an infection and also assessed the immunoglobulin G (IgG) antibodies, which are the most general type present in blood circulation.

The recently discharged as well as follow-up patients displayed higher levels of IgG and IgM antibodies when compared to healthy controls. These antibodies adhere to the SARS-CoV-2 nucleocapsid protein, which surrounds the viral genomic RNA and also the S protein’s receptor-binding domain (S-RBD), which adheres to the receptors on host cells during the process of viral entry.

Collectively, these findings demonstrate that patients infected with the COVID-19 virus can build up antibody responses to SARS-CoV-2 proteins, and indicate that these antibodies are preserved for a minimum of two weeks following discharge.

Furthermore, five recently discharged patients were found to have high levels of neutralizing antibodies that adhere to a pseudovirus that expresses the SARS-CoV-2 S protein. Neutralizing antibodies inhibit infectious particles from communicating with host cells.

Moreover, except for one patient, all the follow-up patients had perceptible neutralizing antibodies against the pseudovirus.

Five newly discharged patients had higher concentrations of T cells when compared to healthy controls. These T cells secrete interferon-gamma (IFNγ), a kind of signaling molecule that plays an important role in immunity, in reaction to the SARS-CoV-2 nucleocapsid protein.

These are the same patients who displayed high levels of neutralizing antibodies. Moreover, three recently discharged patients displayed perceptible levels of IFNγ-secreting T cells that were specific to the SARS-CoV-2 main protease, a protein that plays a crucial role in viral replication.

In the meantime, seven recently discharged patients displayed detectable levels of IFNγ-secreting T cells that were specific to the S-RBD of SARS-CoV-2.

On the other hand, a high concentration of IFNγ-secreting T cells was shown by only one follow-up patient and these cells appeared in response to the nucleocapsid protein, S-RBD, and the main protease.

One discovery that has possible clinical relevance is that the quantity of neutralizing antibodies was positively related to IgG antibodies against S-RBD, but not with those that adhere to the nucleocapsid protein. Furthermore, S-RBD caused both T cell and antibody responses.

Our results suggest that S-RBD is a promising target for SARS-CoV-2 vaccines. But our findings need further confirmation in a large cohort of COVID-19 patients.”

Fang Chen, Study Senior Co-Author, Tsinghua University