Most newly discharged patients who recently recovered from COVID-19 produce varying virus-specific antibodies and T cells, according to a study that has implications for designing an effective vaccine against the deadly disease. Fourteen patients examined in the study, published in the journal Immunity, showed wide-ranging immune responses. However, the results from six of them that were assessed at two weeks after discharge suggest that antibodies were maintained for at least that long.
The study also indicates which parts of the virus are most effective at triggering these immune responses, and should, therefore, be targeted by potential vaccines. The researchers, including those from Tsinghua University in China, noted that it is not clear why immune responses varied widely across the patients. This variability may be related to the initial quantities of virus that the patients encountered, their physical states, or their microbiota, they said.
Other open questions, the researchers said, include whether these immune responses protect against COVID-19 upon re-exposure to SARS-CoV-2, as well as which types of T cells are activated by infection with the virus. It is also important to note that the laboratory tests that are used to detect antibodies to SARS-CoV-2 in humans still need further validation to determine their accuracy and reliability, they said.
"These findings suggest both B and T cells participate in immune-mediated protection against the viral infection," said co-senior study author Chen Dong of Tsinghua University.
"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," Dong said.
Relatively little is known about the protective immune responses induced by the disease-causing virus, SARS-CoV-2, and addressing this gap in knowledge may accelerate the development of an effective vaccine, noted Cheng-Feng Qin of the Academy of Military Medical Sciences in China.
The researchers compared the immune responses of 14 COVID-19 patients who had recently become virus-free to those of six healthy donors. Eight of the patients were newly discharged, and the remaining six were follow-up patients who were discharged two weeks prior to the analyses.
The researchers collected blood samples and assessed the levels of immunoglobulin M (IgM) antibodies, which are the first to appear in response to an infection, as well as immunoglobulin G (IgG) antibodies -- the most common type found in blood circulation.
Compared to healthy controls, both newly discharged and follow-up patients showed higher levels of IgM and IgG antibodies that bind to the SARS-CoV-2 nucleocapsid protein -- which encapsulates the viral genomic RNA -- as well as the S protein's receptor-binding domain (S-RBD), which binds to receptors on host cells during the process of viral entry.
These findings show that COVID-19 patients can mount antibody responses to SARS-CoV-2 proteins and suggest that these antibodies are maintained for at least two weeks after discharge.
Five newly discharged patients had high concentrations of neutralising antibodies that bind to a pseudovirus expressing the SARS-CoV-2 S protein, the researchers said.
Neutralising antibodies prevents infectious particles from interacting with host cells, they said.
All except one follow-up patient had detectable neutralising antibodies against the pseudovirus, according to the researchers.
Compared to healthy controls, five newly discharged patients had higher concentrations of T cells that secrete interferon gamma (IFNγ) -- a signaling molecule that plays a critical role in immunity -- in response to the SARS-CoV-2 nucleocapsid protein, they said.
These are the same patients who had high concentrations of neutralising antibodies, the researchers said.
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