Skip to main content Accessibility help
×
Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-10T05:48:36.874Z Has data issue: false hasContentIssue false

Chapter 2 - Immunology of COVID-19 and Ineffective Immunity

Published online by Cambridge University Press:  06 January 2024

Steven C. Schachter
Affiliation:
Harvard Medical School
Wade E. Bolton
Affiliation:
VentureWell/Rapid Acceleration of Diagnostics (RADx)
Get access

Summary

For the purpose of this chapter, we are going to frame the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through a targeted and simplistic approach. SARS-CoV-2 invades and infects host cells via interaction of its spike protein with mucosal membrane receptor angiotensin-converting enzyme 2 (ACE2). The immune system response can be quite variable and depends on multiple factors, some specific to the virus and others specific to the patient’s immune competence or clinical comorbidities. SARS-CoV-2 can also be unusually effective at evading the triggering of early innate immune responses, such as type 1 interferons and related molecules. It is possible that much of the nature of COVID-19 as an illness is a consequence of this one evasion trick of SARS-CoV-2. In this chapter, we will describe this immune response and discuss mechanisms by which the virus actively seeks to evade our immune system. We will also discuss how we dissect the body’s immune response to assist us in identifying therapeutic and prophylactic targets and with the development of vaccines, and we will look at the effectiveness of these targets on morbidity and mortality and their adverse reaction profiles.

Type
Chapter
Information
Accelerating Diagnostics in a Time of Crisis
The Response to COVID-19 and a Roadmap for Future Pandemics
, pp. 31 - 49
Publisher: Cambridge University Press
Print publication year: 2024

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Shang, J., Ye, G., Shi, K., et al., Structural basis of receptor recognition by SARS-CoV-2. Nature, 581, 7807 (2020), 221224.Google Scholar
Shereen, M.A., Khan, S., Kazmi, A., Bashir, N., and Siddique, R., COVID-19 infection: origin, transmission, and characteristics of human coronaviruses. J Adv Res, 24 (2020), 9198.Google Scholar
Shang, J., Wan, Y., Luo, C., et al., Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci USA, 117, 21 (2020), 1172711734.Google Scholar
Amor, S., Fernandez Blanco, L., and Baker, D., Innate immunity during SARS-CoV-2: evasion strategies and activation trigger hypoxia and vascular damage. Clin Exp Immunol, 202, 2 (2020), 193209.CrossRefGoogle ScholarPubMed
Onomoto, K., Onoguchi, K., and Yoneyama, M., Regulation of RIG-I-like receptor-mediated signaling: interaction between host and viral factors. Cell Mol Immunol, 18, 3 (2021), 539555.Google Scholar
Stravalaci, M., Pagani, I., and Paraboschi, E. M., et al., Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules. Nat Immunol, 23, 2 (2022), 275286.CrossRefGoogle ScholarPubMed
Busnadiego, I., Fernbach, S., Pohl, M. O., et al., Antiviral activity of type I, II, and III interferon counterbalances ACE2 inducibility restricts SARS-CoV-2. mBio, 11, 5 (2020), e01928–20.Google Scholar
Eyndhoven, L. C., Singh, A., and Tel, J., Decoding the dynamics of multilayered stochastic antiviral IFN-I responses. Trends Immunol, 42, 9 (2021), 824839.Google Scholar
Iwasaki, A., A virological view of innate immune recognition. Annu Rev Microbiol, 66, 1 (2012), 177196.CrossRefGoogle ScholarPubMed
Ma, Y., Zhang, Y., and Zhu, L., Role of neutrophils in acute viral infection. Immun Inflamm Dis, 9, 4 (2021), 11861196.CrossRefGoogle ScholarPubMed
Bjorkstrom, N. K., Strunz, B., and Ljunggren, H. G., Natural killer cells in antiviral immunity. Nat Rev Immunol, 22, 2 (2022), 112123.CrossRefGoogle ScholarPubMed
Fuchs, Y. and Steller, H., Programmed cell death in animal development and disease. Cell, 147, 4 (2011), 742758.CrossRefGoogle ScholarPubMed
Gu, W., Gan, H., Ma, Y., et al., The molecular mechanism of SARS-CoV-2 evading host antiviral innate immunity. Virol J, 19, 1 (2022), 49.Google Scholar
Cuapio, A., Boulouis, C., Filipovic, I., et al., NK cell frequencies, function and correlates to vaccine outcome in BNT162b2 mRNA anti-SARS-CoV-2 vaccinated healthy and immunocompromised individuals. Mol Med, 28, 1 (2022), 20.CrossRefGoogle ScholarPubMed
Majumdar, S. and Murphy, P. M., Chemokine regulation during epidemic coronavirus infection. Front Pharmacol, 11 (2020), 600369.Google ScholarPubMed
Gorse, G. J., Patel, G. B., Vitale, J. N., and O’Connor, T. Z., Prevalence of antibodies to four human coronaviruses is lower in nasal secretions than in serum. Clin Vaccine Immunol, 17 (2010), 18751880.Google Scholar
Edridge, A. W. D., Seasonal coronavirus protective immunity is short-lasting. Nat Med, 26 (2020), 16911693.CrossRefGoogle ScholarPubMed
Saletti, G., Older adults lack SARS CoV-2 cross-reactive T lymphocytes directed to human coronaviruses OC43 and NL63. Sci Rep, 10, (2020), 21447.Google Scholar
Tang, F., Lack of peripheral memory B cell responses in recovered patients with severe acute respiratory syndrome: a six-year follow-up study. J Immunol, 186 (2011), 72647268.CrossRefGoogle ScholarPubMed
Wu, L. P., Duration of antibody responses after severe acute respiratory syndrome. Emerg Infect Dis, 13 (2021), 15621564.CrossRefGoogle Scholar
Le Bert, N., Tan, A. T., Kunasegaran, K., et al., SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature, 584 (2020), 457462.Google Scholar
Röltgen, K. and Boyd, S. D., Antibody and B cell responses to SARS-CoV-2 infection and vaccination. Cell Host Microbe, 29 (2021), 10631075.CrossRefGoogle Scholar
SARS-CoV-2-specific antibody and T-cell responses 1 year after infection in people recovered from COVID-19: a longitudinal cohort study Li Guo, Geng Wang, Yeming Wang, Qiao Zhang, et al. Lancet Microbe. 2022 May;3(5):e348-e356.CrossRefGoogle Scholar
Jo, D. H., Minn, D., Lim, J., et al., Rapidly declining SARS-CoV-2 antibody titers within 4 months after BNT162b2 vaccination. Vaccines (Basel), 9, 10 (2021), 1145.Google ScholarPubMed
Verma, S., Saksena, S., and Sadri-Ardekani, H., ACE2 receptor expression in testes: implications in coronavirus disease 2019 pathogenesis. Biol Reprod, 103, 3 (2020), 449451.CrossRefGoogle ScholarPubMed
Poma, A. M., Bonuccelli, D., Giannini, R., et al., COVID-19 autopsy cases: detection of virus in endocrine tissues. J Endocrinol Invest, 45, 1 (2022), 209214.CrossRefGoogle ScholarPubMed
Bryce, C., Grimes, Z., Pujadas, E., et al., Pathophysiology of SARS-CoV-2: the Mount Sinai COVID-19 autopsy experience. Mod Pathol, 34, 8 (2021), 14561467.Google Scholar
Chen, N., Zhou, M., Dong, X., et al., Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 395, 10223 (2020), 507513.CrossRefGoogle Scholar
Paranjpe, I., Russak, A. J., Freitas, J. K., et al., Retrospective cohort study of clinical characteristics of 2199 hospitalised patients with COVID-19 in New York City. BMJ Open, 10, 11 (2020), 040736.Google Scholar
Raza, R. Z. and Abbasi, S.W., An evolutionary insight into the heterogeneous severity pattern of the SARS-CoV-2 infection. Front Genet, 13 (2022), 859508.CrossRefGoogle ScholarPubMed
World Health Organization, Clinical Management of COVID-19: Interim Guidance, May 27, 2020 (2020).Google Scholar
World Health Organization, Laboratory Testing for Coronavirus Disease (COVID-19) in Suspected Human Cases: Interim Guidance, March 19, 2020 (2020), https://apps.who.int/iris/handle/10665/331501.Google Scholar
NIH, NIH to launch public-private partnership to speed COVID-19 vaccine and treatment options (April 17, 2020), https://tinyurl.com/dpve3adr.Google Scholar
FNIH, Accelerating COVID-19 Therapeutic Interventions & Vaccines (ACTIV), https://tinyurl.com/2uz7amzc.Google Scholar
Li, M., Wang, H., Tian, L., et al., COVID-19 vaccine development: milestones, lessons and prospects. Signal Transduct Target Ther, 7, 1 (2022), 146.Google ScholarPubMed
Link-Gelles, R., Ciesla, A. A., Fleming-Dutra, K. E., et al., Effectiveness of bivalent mRNA vaccines in preventing symptomatic SARS-CoV-2 infection – increasing community access to testing program, United States, September–November 2022. MMWR Morb Mortal Wkly Rep, 71, 48 (2022), 15261530.Google Scholar
National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases. Selected Adverse Events Reported after COVID-19 Vaccination (2023), https://tinyurl.com/aucame4v.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×