SARS-CoV-2 infection induces both specific viral immunity (antibody responses induced by B cells) and cellular immunity (T-cell responses stimulated by antigen). However, further clarification of their independent roles on viral control and disease pathogenesis is needed.
Reduction of disease has been associated with specific T-cell responses to SARS-CoV-2 virus and / or antibodies. However, most of this data comes from studies analyzing patients during the recovery period and not due to active infection.
The researchers at the Duke-University of Singapore National Medical School (NUS) followed 12 patients with SARS-CoV-2 infection from the onset of symptoms to relapse or death. They measured viral loads of SARS-CoV-2 in the upper respiratory tract and specific antibodies of SARS-CoV-2 and T cells at several time points.
“We found that patients controlling SARS-Cov-2 infection with only mild symptoms characterized by early entry of IFN-γ produced SARS-CoV-2-specific T cells The level of humoral response, however, does not predict the level of COVID-19 disease severity, “said co-author Anthony Tanoto Tan, PhD, senior researcher at the Infectious Infectious Diseases program Duke-NUS (EID), in a statement.
T-cell responses are not associated with more severe COVID-19 infection
Using an enzyme-linked immunospot assay (IFN) -γ (ELISPOT), the researchers evaluated T-cell responses in epitopes across the spike protein, including the whole nucleoprotein (NP) ), membrane (M), the open reading frames (ORF) 7ab, ORF8, ORF3a, the unstructured protein (NSP) 7, and the NSP13 of ORF1ab.
They argued that the total size of SARS-CoV-2-specific T cells was not commensurate with the severity of the disease. Higher frequency of IFN-γ-secreting cells in all early stages (day one-15) and late stages (days 15-30) were present in mild COVID-19 patients but not in moderate / severe patients.
They also found a statistically significant direct correlation between early appearance of SARS-CoV-2 peptide-reactive cells (specific for NP, ORF7 / 8, ORF3a, M, and the spike protein) and shorter duration of infection.
“Our data support the notion that SARS-CoV-2-specific T cells play an important role in rapid control of viral infection and eventual clearing of the disease,” said co-author Martin Linster , PhD, senior researcher with the Duke- NUS EID Program.
“There is a time when T cell analysis should be considered in providing a broad understanding of the immune response against SARS-CoV-2. This would also mean that the vaccine will be more effective if complete induction of both antibodies and T. cells will occur, “said lead author Antonio Bertoletti, PhD, a professor at the Duke-NUS EID program.
Antibody responses associated with COVID-19 infection are more severe
In the study, the hardest cases of COVID-19 showed the fastest and strongest ability to neutralize the virus and thus the highest total amounts of SARS-CoV-2-specific antibodies. The researchers identified virus neutralization using a substitution virus neutralization test that measured the ability of serum antibodies to inhibit the binding of the spike-binding domain to the angiotensin-converting enzyme receptor 2 (ACE2) in vitro.
The highest neutral activity in patients was achieved within nine-15 days after the onset of the symptom. Patients with moderate / severe symptoms showed stronger specific antibody responses to viruses than those with mild infection. Most peptide-sensitive T cells were CD4 cells, whereas CD8 T cells specific to NP peptide pools were detected. As the frequency of SARS-CoV-2-specific T cells decreased sharply after SARS-CoV-2 clearance, the authors noted that the duration of T-cell analysis may have a significant effect on the size of the detected T-cell response.
ORF7 / 8-specific T cells were detected favorably at the acute stage of the disease, which corresponded to an increase in ORF8-specific antibodies in the early stages of SARS-CoV-2 disease. This triggered a strong IFN-γ response favorably in the early stages of the disease but only in patients with mild disease. In addition, these patients with mild symptoms cleared the virus early in the progression of the disease.
“This important study strengthens our understanding of the immune response against SARS-CoV-2. It has far-reaching implications including the design of the COVID-19 vaccine and the subsequent study of vaccine response,” said Patrick. Casey, PhD, senior associate dean for research at Duke-NUS.
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