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COVID-19 is noxious and constitutes a raft of adverse multiplier effects. As such, there is urgent need to understand the disease well and take action to mitigate its punitive pathologic & economic outcomes. Comprehending the conduct of the immune system during and after infection may provide fundamental leads to unraveling effective interventions. Some vaccines and drugs have since been validated and made available for emergency use among priority populations. However, these vaccines were developed at an accelerated pace and mainly on the basis of rudimentary immunological & molecular events. Therefore, there is need for continuous revelation of precise and more elaborate hallmarks in order to improve on, or develop more efficacious and safe interventions. Three scientific databases (PubMed, Cochrane and EMBASE) were searched between 1st December, 2020 and 15th January, 2021 for information about immune responses to SARS COV-2. Studies that utilized experimental designs, exhibited little to no likelihood of bias, published in highly refereed and peer reviewed journals were selected. A total of 10 papers were shortlisted for the final synthesis. A set of cytokines including: IL-2, IL-6, IL-7, IL-10, TNF, and GM-CSF are recovered in most cases. However, IL-6 is featured in most severe and fatal events. There wasn’t congruency by different studies on the precise conduct of T-cells during infection. Some studies reported elevated levels of both CD+4 & CD+8 T-cells among severe cases while others reported exhausted elevated levels of the same immunological parameters during mild disease. Higher levels of Natural Killer-cells (NK-cells) as well as Neutralizing Antibodies (Nabs) correlate with better disease outcomes. However, considering the role played by Abs in the production of cytokines (pro and anti-inflammatory), it may be crucial to profile the risk/benefit ratio of Abs during infection. Interventions that seek to: reverse high production of pro-inflammatory cytokines (IL-6), potentiate release and function of NK-cells, as well as Nabs and moderate exhaustion of CD+4 & CD+8 T-cells, may constitute promising outcomes.

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References

  1. Jeong, H.W., S.-M. Kim, H.-S. Kim, Y.-I. Kim, J.H. Kim, J.Y. Cho, S.-h. Kim, H. Kang, S.-G. Kim, and S.-J. Park. Viable SARS-CoV-2 in various specimens from COVID-19 patients. Clinical Microbiology and Infection, 2020. 26(11): p. 1520-1524.
    DOI  |   Google Scholar
  2. WHO. Weekly epidemiological update - 23 February 2021; Available from: https://www.who.int/publications/m/item/weekly-epidemiological-update---23-february-2021.
     Google Scholar
  3. Schiffrin, E.L., J.M. Flack, S. Ito, P. Muntner, and R.C. Webb. Hypertension and COVID-19. 2020, Oxford University Press US.
    DOI  |   Google Scholar
  4. Davidson, A.M., J. Wysocki, and D. Batlle, Interaction of SARS-CoV-2 and other Coronavirus with ACE (Angiotensin-Converting Enzyme)-2 as their main receptor: therapeutic implications. Hypertension, 2020. 76(5): p. 1339-1349.
    DOI  |   Google Scholar
  5. Mahmoud, I.S., Y.B. Jarrar, W. Alshaer, and S. Ismail, SARS-CoV-2 entry in host cells-multiple targets for treatment and prevention. Biochimie, 2020. 175: p. 93-98.
    DOI  |   Google Scholar
  6. Basit, A., T. Ali, and S.U. Rehman. Truncated human angiotensin converting enzyme 2; a potential inhibitor of SARS-CoV-2 spike glycoprotein and potent COVID-19 therapeutic agent. Journal of Biomolecular Structure and Dynamics, 2020: p. 1-10.
    DOI  |   Google Scholar
  7. Weisblum, Y., F. Schmidt, F. Zhang, J. DaSilva, D. Poston, J.C. Lorenzi, F. Muecksch, M. Rutkowska, H.-H. Hoffmann, and E. Michailidis. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. Elife, 2020. 9: p. e61312.
    DOI  |   Google Scholar
  8. Abbasi, A.Z., D.A. Kiyani, S.M. Hamid, M. Saalim, A. Fahim, and N. Jalal. Spiking dependence of SARS‐CoV‐2 pathogenicity on TMPRSS2. Journal of Medical Virology, 2021.
    DOI  |   Google Scholar
  9. Takeuchi, O. and S. Akira, Innate immunity to virus infection. Immunological reviews, 2009. 227(1): p. 75-86.
    DOI  |   Google Scholar
  10. Taefehshokr, N., B. Baradaran, A. Baghbanzadeh, and S. Taefehshokr. Promising approaches in cancer immunotherapy. Immunobiology, 2020. 225(2): p. 151875.
    DOI  |   Google Scholar
  11. Koay, H.-F., T.S. Fulford, and D.I. Godfrey. An unconventional view of COVID-19 T cell immunity. Journal of Experimental Medicine, 2020. 217(12).
    DOI  |   Google Scholar
  12. Rao, K.-S., V. Suryaprakash, R. Senthilkumar, S. Preethy, S. Katoh, N. Ikewaki, and S.J. Abraham. Role of immune dysregulation in increased mortality among a specific subset of COVID-19 patients and immune-enhancement strategies for combatting through nutritional supplements. Frontiers in Immunology, 2020. 11: p. 1548.
    DOI  |   Google Scholar
  13. Ahmadpoor, P. and L. Rostaing. Why the immune system fails to mount an adaptive immune response to a Covid‐19 infection. Transplant International, 2020. 33(7): p. 824-825.
    DOI  |   Google Scholar
  14. Xia, H., Z. Cao, X. Xie, X. Zhang, J.Y.-C. Chen, H. Wang, V.D. Menachery, R. Rajsbaum, and P.-Y. Shi. Evasion of type I interferon by SARS-CoV-2. Cell Reports, 2020. 33(1): p. 108234.
    DOI  |   Google Scholar
  15. Pairo-Castineira, E., S. Clohisey, L. Klaric, A.D. Bretherick, K. Rawlik, D. Pasko, S. Walker, N. Parkinson, M.H. Fourman, and C.D. Russell. Genetic mechanisms of critical illness in Covid-19. Nature, 2021. 591(7848): p. 92-98.
    DOI  |   Google Scholar
  16. Copaescu, A., O. Smibert, A. Gibson, E.J. Phillips, and J.A. Trubiano. The role of IL-6 and other mediators in the cytokine storm associated with SARS-CoV-2 infection. Journal of Allergy and Clinical Immunology, 2020. 146(3): p. 518-534. e1.
    DOI  |   Google Scholar
  17. Le Bert, N., A.T. Tan, K. Kunasegaran, C.Y. Tham, M. Hafezi, A. Chia, M.H.Y. Chng, M. Lin, N. Tan, and M. Linster. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature, 2020. 584(7821): p. 457-462.
    DOI  |   Google Scholar
  18. Vabret, N. Antibody responses to SARS-CoV-2 short-lived. Nature Reviews Immunology, 2020. 20(9): p. 519-519.
    DOI  |   Google Scholar
  19. Le, T.T., J.P. Cramer, R. Chen, and S. Mayhew. Evolution of the COVID-19 vaccine development landscape. Nat Rev Drug Discov, 2020. 19(10): p. 667-8.
    DOI  |   Google Scholar
  20. WHO. mRNA vaccines against COVID-19: Pfizer-BioNTech COVID-19 vaccine BNT162b2: prepared by the Strategic Advisory Group of Experts (SAGE) on immunization working group on COVID-19 vaccines, 22 December 2020. 2020, World Health Organization.
     Google Scholar
  21. Mark Vrabel, M. Preferred reporting items for systematic reviews and meta-analyses. in Oncology nursing forum. 2015. Oncology Nursing Society.
    DOI  |   Google Scholar
  22. Guyatt, G., A.D. Oxman, E.A. Akl, R. Kunz, G. Vist, J. Brozek, S. Norris, Y. Falck-Ytter, P. Glasziou, and H. DeBeer, GRADE guidelines: 1. Introduction—GRADE evidence profiles and summary of findings tables. Journal of clinical epidemiology, 2011. 64(4): p. 383-394.
    DOI  |   Google Scholar
  23. Pierce, C.A., P. Preston-Hurlburt, Y. Dai, C.B. Aschner, N. Cheshenko, B. Galen, S.J. Garforth, N.G. Herrera, R.K. Jangra, and N.C. Morano. Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients. Science translational medicine, 2020. 12(564).
    DOI  |   Google Scholar
  24. Zhang, F., R. Gan, Z. Zhen, X. Hu, X. Li, F. Zhou, Y. Liu, C. Chen, S. Xie, and B. Zhang. Adaptive immune responses to SARS-CoV-2 infection in severe versus mild individuals. Signal transduction and targeted therapy, 2020. 5(1): p. 1-11.
    DOI  |   Google Scholar
  25. Henss, L., T. Scholz, C. von Rhein, I. Wieters, F. Borgans, F.J. Eberhardt, K. Zacharowski, S. Ciesek, G. Rohde, and M. Vehreschild. Analysis of humoral immune responses in SARS-CoV-2 infected patients. The Journal of Infectious Diseases, 2020.
     Google Scholar
  26. Carsetti, R., S. Zaffina, E. Piano Mortari, S. Terreri, F. Corrente, C. Capponi, P. Palomba, M. Mirabella, S. Cascioli, and P. Palange. Different Innate and Adaptive Immune Responses to SARS-CoV-2 Infection of Asymptomatic, Mild, and Severe Cases. Frontiers in immunology, 2020. 11: p. 3365.
    DOI  |   Google Scholar
  27. Long, Q.-X., X.-J. Tang, Q.-L. Shi, Q. Li, H.-J. Deng, J. Yuan, J.-L. Hu, W. Xu, Y. Zhang, and F.-J. Lv. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nature medicine, 2020. 26(8): p. 1200-1204.
    DOI  |   Google Scholar
  28. Moderbacher, C.R., S.I. Ramirez, J.M. Dan, A. Grifoni, K.M. Hastie, D. Weiskopf, S. Belanger, R.K. Abbott, C. Kim, and J. Choi. Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity. Cell, 2020. 183(4): p. 996-1012. e19.
    DOI  |   Google Scholar
  29. Sekine, T., A. Perez-Potti, O. Rivera-Ballesteros, K. Strålin, J.-B. Gorin, A. Olsson, S. Llewellyn-Lacey, H. Kamal, G. Bogdanovic, and S. Muschiol. Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19. Cell, 2020. 183(1): p. 158-168. e14.
    DOI  |   Google Scholar
  30. Thieme, C.J., M. Anft, K. Paniskaki, A. Blazquez-Navarro, A. Doevelaar, F.S. Seibert, B. Hoelzer, M.J. Konik, M.M. Berger, and T. Brenner. Robust T Cell response toward spike, membrane, and nucleocapsid SARS-CoV-2 proteins is not associated with recovery in critical COVID-19 patients. Cell Reports Medicine, 2020. 1(6): p. 100092.
    DOI  |   Google Scholar
  31. Suthar, M.S., M.G. Zimmerman, R.C. Kauffman, G. Mantus, S.L. Linderman, W.H. Hudson, A. Vanderheiden, L. Nyhoff, C.W. Davis, and O. Adekunle. Rapid generation of neutralizing antibody responses in COVID-19 patients. Cell Reports Medicine, 2020. 1(3): p. 100040.
    DOI  |   Google Scholar
  32. Gudbjartsson, D.F., G.L. Norddahl, P. Melsted, K. Gunnarsdottir, H. Holm, E. Eythorsson, A.O. Arnthorsson, D. Helgason, K. Bjarnadottir, and R.F. Ingvarsson. Humoral immune response to SARS-CoV-2 in Iceland. New England Journal of Medicine, 2020. 383(18): p. 1724-1734.
    DOI  |   Google Scholar
  33. Hojyo, S., M. Uchida, K. Tanaka, R. Hasebe, Y. Tanaka, M. Murakami, and T. Hirano. How COVID-19 induces cytokine storm with high mortality. Inflammation and Regeneration, 2020. 40(1): p. 1-7.
    DOI  |   Google Scholar
  34. Chen, R., L. Sang, M. Jiang, Z. Yang, N. Jia, W. Fu, J. Xie, W. Guan, W. Liang, and Z. Ni. Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China. Journal of Allergy and Clinical Immunology, 2020. 146(1): p. 89-100.
    DOI  |   Google Scholar
  35. Yi, J.S., M.A. Cox, and A.J. Zajac. T‐cell exhaustion: characteristics, causes and conversion. Immunology, 2010. 129(4): p. 474-481.
    DOI  |   Google Scholar
  36. van Eeden, C., L. Khan, M.S. Osman, and J.W. Cohen Tervaert. Natural killer cell dysfunction and its role in COVID-19. International Journal of Molecular Sciences, 2020. 21(17): p. 6351.
    DOI  |   Google Scholar
  37. Freund-Brown, J., L. Chirino, and T. Kambayashi. Strategies to enhance NK cell function for the treatment of tumors and infections. Critical Reviews™ in Immunology, 2018. 38(2).
    DOI  |   Google Scholar
  38. Assadiasl, S., Y. Fatahi, M. Zavvar, and M.H. Nicknam. COVID-19: Significance of antibodies. Human Antibodies, 2020(Preprint): p. 1-11.
    DOI  |   Google Scholar
  39. Polycarpou, A., M. Howard, C.A. Farrar, R. Greenlaw, G. Fanelli, R. Wallis, L.S. Klavinskis, and S. Sacks. Rationale for targeting complement in COVID‐19. EMBO molecular medicine, 2020. 12(8): p. e12642.
    DOI  |   Google Scholar