Study reveals immune response to SARS-CoV-2 peptides in COVID-19 convalescent patients
Study reveals immune response to SARS-CoV-2 peptides in COVID-19 convalescent patients

Study reveals immune response to SARS-CoV-2 peptides in COVID-19 convalescent patients

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) occurred as a “pneumonia of unknown etiology” in Wuhan, China in 2019. The disease caused by SARS-CoV-2 was designated as coronavirus disease 2019 (COVID-19) and was declared a pandemic by the World Health Organization (WHO). COVID-19 infections can range from asymptomatic to severe, which can eventually lead to the death of elderly people and people with comorbidities.

Examination: Antibody and T cell immune responses to SARS-CoV-2 peptides in COVID-19 convalescent patients. Image credit: Corona Borealis Studio / Shutterstock

Background

Previous studies of mild and severe SARS-CoV-2 infections have indicated that activation of antibody responses is required to recover from COVID-19. Higher IgG antibodies were identified in patients with severe infections compared to those with mild infections. Piggen (S) glycoprotein and nucleocapsid (N) proteins have been identified to be important immunogens. A study also showed that levels of S-specific or receptor-binding domain (RBD) -specific IgG antibodies were higher in patients not admitted to the intensive care unit (ICU), whereas levels of N-specific IgG were higher in patients admitted to the intensive care unit.

Several studies have also reported that IgG and IgM antibody titers peaked on day 18 of SARS-CoV-2 infection followed by a gradual decrease. The decrease in IgM occurred within the first month, while the levels of IgG remained high for several months and decreased approx. 7 months after SARS-CoV-2 infection. However, the cause of the drop in antibody titers is still unclear and requires further research.

Furthermore, several conserved epitopes have been identified on S and N proteins that could play a protective role against SARS-CoV-2 infection. Therefore, these epitopes can be used as a target for the development of vaccines. In addition, several epitopes were identified from serum samples obtained from the United States, Switzerland, Singapore, and China that could be used as markers of infection as well as disease severity.

A new study published in Limits in microbiology was intended to demonstrate the reactivity of COVID-19 serum obtained from patients in Tatarstan, Russia with the S and N peptides previously identified as immunogenic. The study also aimed to determine the correlations between S- and N-peptide reactivity with the severity of lung injury, clinical and demographic characteristics, duration of symptoms, and age along with the cross-reactivity of COVID-19 convalescent sera with human endemic coronavirus (eCoV). ) peptides.

About the study

The study involved the collection of convalescent serum samples from 138 COVID-19 patients and 39 controls between March and December 2020. In addition, 22 control serum samples collected during 2015-2016 were included in the study. Acute serum samples were collected from 14 COVID-19 patients. The serum samples were collected at different times after infection. Blood samples were also collected from 17 COVID-19 patients and 9 controls.

Then, S- and N-peptides from SARS-CoV-2 as well as other eCoVs such as NL63, OC43, HKU1 and 229E were synthesized followed by alignment of amino acid sequences of SARS-CoV-2 N- and S-peptides with each eCoV. SARS-CoV-2-specific antibody titers were measured by an enzyme-linked immunosorbent assay (ELISA) followed by peptide reactivity with serum antibodies from infected patients as well as controls. Finally, ELISpot analysis was performed using peripheral blood mononuclear cells (PBMCs) obtained from the blood samples.

Survey results

The results showed 105 mild COVID-19 cases, 43 moderate cases and 4 severe cases. 39 patients with moderate disease and 4 patients with serve disease required hospitalization. Lung injuries were found to be less than 20 percent, 20 to 40 percent, and greater than 40 percent in 117, 31, and 4 patients, respectively, while fever was reported in all patients.

Peptides essential for virus replication and binding to the ACE2 receptor were selected for the study. In addition, two mutations were identified in the S protein peptides and five mutations were identified in the N protein peptides from the newly circulating delta strain.

The results also reported that S1, S7, S18 and N6 peptides had higher reactivity with convalescent serum compared to serum collected from controls in 2020. However, several SARS-CoV-2 peptides from control samples collected in 2015 were found to have higher reactivity with convalescent serum. The results were also similar for acute serum.

Furthermore, peptides S1, S2, S7, S14, S19, and N6 were reported to have high reactivity in serum samples collected ≤ 3 months after recovery compared to 2020 controls, and most of them were reported to remain active 4-6 months after recovery. However, the reactivity of half of these peptides was lost ≥ 7 months after recovery, with only S7, S18 and N6 peptides remaining reactive.

An increased serum reactivity with peptides S1, S7, S18 and N6 was observed in male COVID-19 patients, while the reactivity for women was higher for peptides S7 and N6 compared to the respective controls. Also younger COVID-19 patients were found to have higher reactivity with more peptides compared to older patients. In addition, the severity of SARS-CoV-2 was positively correlated with lung damage, increasing age, high fever, and duration of fever. Out of all the peptides that showed reactivity, only S1 and S18 were reported to correlate with clinical parameters, where S1 was negatively correlated with the severity of the disease and S18 was positively correlated with fever.

It showed the results too T-cell reactivity to S6, N6 and N19 was higher in COVID-19 patients compared to controls. The reactivity to S4 and S15 was also observed to be higher in older patients compared to younger patients. In addition, the highest degree of similarity between SARS-CoV-2 S protein was found with NL63.S1 alphacoronavirus, while for other eCoVs it was less than 65b percent. Analysis of antibody reactivity with other eCoVs indicated that previous infection with them could not protect against severe COVID-19.

Therefore, the present study demonstrated early activation and circulation of anti-SARS-CoV-2 antibodies, which gradually decreased with time after infection. Several S- and N-peptides were identified which were immunogenic and could indicate the severity of the disease. The study also highlighted that COVID-19 serum had limited cross-reactivity with other eCoV peptides. Thus, this study is important in identifying T cell epitopes that can be used to develop prophylactic and therapeutic measures.

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