|Year : 2022 | Volume
| Issue : 3 | Page : 153-155
Immune system diversity against SARS-CoV-2 infection and vaccines
Esmaeil Mortaz1, Ian M Adcock2
1 Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Department of Respiratory Cell & Molecular Biology and Head of the Molecular Cell Biology Group, National Heart and Lung Institute, Imperial College, London, England, United Kingdom
|Date of Submission||17-May-2022|
|Date of Decision||10-Jul-2022|
|Date of Acceptance||05-Aug-2022|
|Date of Web Publication||18-Sep-2022|
Dr. Esmaeil Mortaz
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Mortaz E, Adcock IM. Immune system diversity against SARS-CoV-2 infection and vaccines. J Prev Diagn Treat Strategies Med 2022;1:153-5
|How to cite this URL:|
Mortaz E, Adcock IM. Immune system diversity against SARS-CoV-2 infection and vaccines. J Prev Diagn Treat Strategies Med [serial online] 2022 [cited 2022 Oct 1];1:153-5. Available from: http://www.jpdtsm.com/text.asp?2022/1/3/153/356290
The coronavirus disease-2019 (COVID-19) pandemic that has been with us for more than 2 years is caused by infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Exposure to the many mutant strains or variants of SARS-COV-2 has resulted in severe global health problems. Both cellular and humoral immunity is involved in the host defense against SARS-CoV-2 and activation of these pathways is able to control the infection resulting in a mild form of the disease. However, when comorbidities such as diabetes, heart disease, or some genetic defects of the immune system are present, a moderate or severe form of the disease may be developed. Virus-specific CD8 + T cells play a crucial role for the elimination of the virus in infected cells. The action of CD8 T cells during SARS-CoV-2 infection is rapid and only lasts for a short while before disappearing equally rapidly. Virus-specific antibodies produced by B- and plasma cells are insufficient alone to effectively protect against infection in most cases. The unprecedentedly quick introduction of COVID-19 vaccines in 2020 gave hope toward effective control of the disease.
These vaccines were highly effective for the symptomatic, critical disease, and fatal outcomes caused by the original strain of SARS-CoV-2 as well as the Alpha (B.1.1.7) variant which was major in early 2021. However, modest reductions in vaccine effectiveness against viral infection and mild disease have been reported with the Beta (B.1.351) and Delta variants, although effectiveness against critical and severe disease has remained high for at least 6 months after first immunization with two COVID-19 vaccine doses., Third (booster) doses induce a rapid and additional substantial increase in protection against both mild and critical diseases.,
Several questions remain to be answered however (i) what is the diversity of the immune response associated with severe, moderate, and mild forms of the disease and (ii) how long will the immunity triggered by vaccination, and immune protection against SARS-CoV-2 viruses last? To address these two important questions, we need to fully understand the response of the immune system against SARS-CoV-2 infection. The immunopathogenesis of SARS-COV-2 infection/COVID-19 is extremely similar to that of not just other coronaviruses but of other intracellular viruses. Therefore, understanding what made this virus capable of driving a pandemic needs to be considered. What is clear is that an intact and properly activated immune system can control the degree of infection while defects in primary (genetic defects) or secondary (underlying disorders) immune function prevents early resolution of the infection and affect the severity of disease. Differences in long-term COVID-19 immunity, whether induced naturally or by vaccination, need to be studied in these different cohorts of patients.
Studies of SARS-CoV-2 infection show that differences in viral dosages, transmission pathways, severity of infection, and date of infection could influence immunity duration. Due to our lack of knowledge of the biological and genetic risk factors associated with SARS-CoV-2 severity, it is challenging to assess the long-term induction of humoral immunity. However, it is evident that the innate immune system is critical in securing long-term protection from COVID-19.
Moreover, as with other infectious diseases, SARS-CoV-2 induces long-lived memory T-cells that provide long-term protective immunity. Upon reexposure to the virus, they are able to generate a rapid response against the virus. While some infections result in robust and long-lasting T-cell memory, others fail to do so and this may account for the diversity of mild, moderate, and severe diseases. This is an area that requires greater study, especially in the lungs of patients with different disease severities. Along similar lines, the type and levels of antibodies and immune cells play a key role in modulating COVID-19 severity. For example, the levels of neutralizing Abs are higher in patients with severe COVID-19 than in mild or asymptomatic patients for up to 1-year post-COVID-19 infection. Furthermore, there is a strong positive correlation between the severity of past COVID-19 infections and the humoral- and cell-mediated responses in individuals.
There is a greater proportion of memory B-cells that recognize and bind competitively to the ACE2 receptor-binding domain in severe COVID-19 patients compared to asymptomatic and mild patients. The higher levels of SARS-CoV-2 antigen-specific Ab titers in severe patients are possibly due to a higher viral load or excessive activation of T-cells., Neutralizing Abs can prevent reinfection while nonneutralizing Abs are unable to do this. Moreover, higher anti-nucleocapsid (NC) Ab levels were seen in severe patients. In addition, complement hyperactivation by NC is a key feature of severe COVID-19 pathogenesis., In severe COVID-19 patients, the antibody-dependent cell-mediated phagocytosis (ADCP) capacity of circulating Abs is higher than in mild and asymptomatic patients. Severe patients have pronounced anti-SARS-CoV-2 immunoglobulin A and immunoglobulin G responses that can activate scavenger receptors, such as Fcγ and Fcα receptors, in comparison to mild and asymptomatic groups.
Moreover, the levels of plasma Abs in the severe group were sufficient for phagocytosis and suggest a milder course of reinfection in patients with previous severe infection. However, a correlation between anti-SARS-CoV-2 Abs and complement hyperactivation has not yet been clearly identified. Recently, strong humoral and cellular immune responses against NC were reported in patients with severe disease compared to subjects with a mild or moderate disease which may explain the very low reinfection rate in the severe group.
Many questions remain concerning how SARS-CoV-2 infection and immunization might result in long-term protective immunity. We know that the immunity provided by vaccine and prior infection is both high but not complete. Importantly, antibody titers correlate with protection at a population level, but protective titers at the individual level remain unknown. The required frequency of booster immunizations (if any) in different age groups is also unclear. The absolute benefits of immunization may be far greater among immunocompromised and elderly individuals given the very steep age gradient of COVID-19 infection fatality rate.,
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Mortaz E, Tabarsi P, Varahram M, Folkerts G, Adcock IM. The immune response and immunopathology of COVID-19. Front Immunol 2020;11:2037.
Rezaei M, Mahmoudi S, Mortaz E, Marjani M. Immune cell profiling and antibody responses in patients with COVID-19. BMC Infect Dis 2021;21:646.
Abu-Raddad LJ, Chemaitelly H, Butt AA, National Study Group for COVID-19 Vaccination. Effectiveness of the BNT162b2 covid-19 vaccine against the B.1.1.7 and B.1.351 variants. N Engl J Med 2021;385:187-9.
Lopez Bernal J, Andrews N, Gower C, Gallagher E, Simmons R, Thelwall S, et al
. Effectiveness of covid-19 vaccines against the B.1.617.2 (Delta) variant. N Engl J Med 2021;385:585-94.
Andrews N, Tessier E, Stowe J, Gower C, Kirsebom F, Simmons R, et al
. Duration of protection against mild and severe disease by covid-19 vaccines. N Engl J Med 2022;386:340-50.
Choe PG, Kang CK, Kim KH, Yi J, Kim ES, Park SW, et al
. Persistence of neutralizing antibody response up to one year after asymptomatic or symptomatic SARS-CoV-2 infection. J Infect Dis 2021;224:1097-9.
Sun B, Feng Y, Mo X, Zheng P, Wang Q, Li P, et al
. Kinetics of SARS-CoV-2 specific IgM and IgG responses in COVID-19 patients. Emerg Microbes Infect 2020;9:940-8.
Liu Y, Yan LM, Wan L, Xiang TX, Le A, Liu JM, et al
. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis 2020;20:656-7.
Kang CK, Kim M, Lee S, Kim G, Choe PG, Park WB, et al
. Longitudinal analysis of human memory T-cell response according to the severity of illness up to 8 months after SARS-CoV-2 infection. J Infect Dis 2021;224:39-48.
Kang CK, Han GC, Kim M, Kim G, Shin HM, Song KH, et al
. Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity. Int J Infect Dis 2020;97:313-21.
Li D, Sempowski GD, Saunders KO, Acharya P, Haynes BF. SARS-CoV-2 neutralizing antibodies for COVID-19 prevention and treatment. Annu Rev Med 2022;73:1-16.
Ma L, Sahu SK, Cano M, Kuppuswamy V, Bajwa J, McPhatter J, et al
. Increased complement activation is a distinctive feature of severe SARS-CoV-2 infection. bioRxiv 2021;6:eabh2259.
Holter JC, Pischke SE, de Boer E, Lind A, Jenum S, Holten AR, et al
. Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients. Proc Natl Acad Sci U S A 2020;117:25018-25.
Skendros P, Mitsios A, Chrysanthopoulou A, Mastellos DC, Metallidis S, Rafailidis P, et al
. Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis. J Clin Invest 2020;130:6151-7.