Covid-19, immunotherapy, prospects


COVID-19 pandemic is a real threat for the people worldwide. Currently there is no specific treatment to eliminate SARS-CoV2 from the infected humans. In this review we describe and analyze several therapeutical preparations, which target immune system, used in the clinical trials to treat COVID-19. We discuss immune system modulation in two main aspects: first, achievement of passive immunity as prophylactic of severe and critical disease in SARS-CoV-2 infected people with concomitant risks; and, second, inhibition of cytokine storm, which is main cause of severe and critical disease. Finally, according to the USA NIH guidelines, monoclonal antibodies for passive immunity and dexamethasone for cytokine storm are discussed with emphasis on the timing of administration concerning COVID-19 patients’ stage of disease.


Download data is not yet available.


Amanat F, Krammer F. SARS-CoV-2 vaccines: status report. Immunity. (2020) 52:583–9.

Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. (2020) 581:215–20.

Stephens DS, McElrath MJ. COVID-19 and the Path to Immunity. JAMA. 2020 Oct 6; 324(13):1279-1281.

Lynch KL, Whitman JD, Lacanienta NP, Beckerdite EW, Kastner SA, Shy BR, et al. Magnitude and kinetics of anti-SARS-CoV-2 antibody responses and their relationship to disease severity. Clin Infect Dis. (2020) 72:301–8.

Kuri-Cervantes L, Pampena MB, Meng W, et al. Comprehensive mapping of immune perturbations associated with severe COVID-19. Sci Immunol. 2020;5(49) : eabd7114.4

Wang X, Guo X, Xin Q, et al. Neutralizing antibodies responses to SARS-CoV-2 in COVID-19 inpatients and convalescent patients. Clin Infect Dis. 2020.

Keller MA, Stiehm ER Passive immunity in prevention and treatment of infectious diseases. Clin Microbiol Rev. 2000 Oct; 13(4):602-14.

Bozzo J., Jorquera J.I. Use of human immunoglobulins as an anti-infective treatment: the experience so far and their possible re-emerging role. Expert Rev Anti Infect Ther. 2017;15:585–604.

Luke T.C., Kilbane E.M., Jackson J.L., Hoffman S.L. Meta-Analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med. 2006;145:599.

Marano G, Vaglio S, Pupella S, et al. Convalescent plasma: new evidence for an old therapeutic tool? Blood Transfus. 2016;14(2):152-157. doi:10.2450/2015.0131-15

van Griensven J., Edwards T., de Lamballerie X., Semple M.G., Gallian P., Baize S. Evaluation of convalescent plasma for Ebola virus disease in Guinea. N Engl J Med. 2016;374:33–42.

Shen C., Wang Z., Zhao F., Yang Y., Li J., Yuan J.,etal. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA. 2020;323(16):1582–1589.

Duan K., Liu B., Li C., Zhang H. et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc. Natl. Acad. Sci. USA. 2020;117(17):9490–9496.

Tanne J.H. Covid-19: FDA approves use of convalescent plasma to treat critically ill patients. BMJ. 2020;368:m1256.

Clinical trial NCT04427501

Chen P, Nirula A, Heller B, et al. SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with COVID-19. N Engl J Med. 2020.

Weinreich DM, Sivapalasingam S, Norton T, et al. REGN-COV2, a neutralizing antibody cocktail, in outpatients with COVID-19. N Engl J Med. 2020

Nile S.H., Nile A., Qiu J., Li L., Jia X., Kai G. COVID-19: pathogenesis, cytokine storm and therapeutic potential of interferons. Cytokine Growth Factor Rev. 2020;53:66–70.

Zolfaghari Emameh R., Nosrati H., Eftekhari M., Falak R., Khoshmirsafa M. Expansion of single cell transcriptomics data of SARS-CoV infection in human bronchial epithelial cells to COVID-19. Biol. Proced. Online. 2020;22:16.

Meduri GU, Bridges L, Shih MC, Marik PE, Siemieniuk RAC, Kocak M. Prolonged glucocorticoid treatment is associated with improved ARDS outcomes: analysis of individual patients' data from four randomized trials and trial-level meta-analysis of the updated literature. Intensive Care Med. 2016;42(5):829-840.

Meduri GU, Golden E, Freire AX, et al. Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial. Chest. 2007;131(4):954-963.

Steinberg KP, Hudson LD, Goodman RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med. 2006;354(16):1671-1684.

Mammen MJ, Aryal K, Alhazzani W, Alexander PE. Corticosteroids for patients with acute respiratory distress syndrome: a systematic review and meta-analysis of randomized trials. Pol Arch Intern Med. 2020;130(4):276-286.

Alhazzani W, Moller MH, Arabi YM, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit Care Med. 2020;48(6):e440-e469.

Recovery Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in hospitalized patients with COVID-19 - preliminary report. N Engl J Med. 2020.

Zhang W, Zhao Y, Zhang F, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the perspectives of clinical immunologists from China. Clin Immunol. 2020;214:108393.

"Summary of opinion for Olumiant" (PDF). European Medicines Agency (EMA). 15 December 2016.

Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus remdesivir for hospitalized adults with COVID-19. N Engl J Med. 2020;

Cao Y, Wei J, Zou L, et al. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial. J Allergy Clin Immunol. 2020 Jul;146(1):137-146.e3.

Yoshikawa T, Hill T, Li K, Peters CJ, Tseng CT. Severe acute respiratory syndrome (SARS) coronavirus-induced lung epithelial cytokines exacerbate SARS pathogenesis by modulating intrinsic functions of monocyte-derived macrophages and dendritic cells. J Virol. 2009;83(7):3039-3048.

Giuseppe Gritti, Federico Raimondi, Alessandro Rambaldi et al., Use of siltuximab in patients with COVID-19 pneumonia requiring ventilatory support. medRxiv 2020.04.01.20048561

Luo P., Liu Y., Qiu L., Liu X., Liu D., Li J. Tocilizumab treatment in COVID‐19: a single center experience. J. Med. Virol. 2020;92(7):814–818.

Bouillon R, Marcocci C, Carmeliet G, et al. Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions. Endocr Rev. 2019;40(4):1109–1151. doi: 10.1210/er.2018-00126.

Zhou Y, Chi J, Lv W, Wang Y. Obesity and diabetes as high-risk factors for severe coronavirus disease 2019 (Covid-19) Diabetes Metab Res Rev. 2021;37(2):e3377. doi: 10.1002/dmrr.3377.

Favre G, Legueult K, Pradier C, et al. Visceral fat is associated to the severity of COVID-19. Metabolism. 2021; 115:154440. doi: 10.1016/j.metabol.2020.154440.

Giustina A, Formenti AM (2020) Does hypovitaminosis D play a role in the high impact of COVID infection in Italy? British Medical Journal Available at:

Liu N, Sun J, Wang X, Zhang T, Zhao M, Li H. Low vitamin D status is associated with coronavirus disease 2019 outcomes: a systematic review and meta-analysis. Int J Infect Dis. 2021;104:58–64. doi: 10.1016/j.ijid.2020.12.077.

Munshi R, Hussein MH, Toraih EA, et al. Vitamin D insufficiency as a potential culprit in critical COVID-19 patients. J Med Virol. 2021;93(2):733–740. doi: 10.1002/jmv.26360

Yisak H, Ewunetei A, Kefale B, et al. Effects of Vitamin D on COVID-19 infection and prognosis: a systematic review. Risk Manag Healthc Policy. 2021;14:31–38. Published 2021 Jan 7. 10.2147/RMHP.S291584.

Ulivieri FM, Banfi G, Camozzi V, et al. Vitamin D in the Covid-19 era: a review with recommendations from a G.I.O.S.E.G. expert panel. Endocrine. 2021;72(3):597–603. 10.1007/s12020-021-02749-3.

Nogues X, Ovejero D, Pineda-Moncusí M, et al. Calcifediol Treatment and COVID-19-Related Outcomes. J Clin Endocrinol Metab. 2021;106(10):e4017–e4027. doi: 10.1210/clinem/dgab405.

Murai IH, Fernandes AL, Sales LP, et al. Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial. JAMA. 2021;325(11):1053–1060. doi: 10.1001/jama.2020.26848.

di Filippo L, Doga M, Frara S, Giustina A. Hypocalcemia in COVID-19: prevalence, clinical significance and therapeutic implications [published online ahead of print, 2021 Apr 13]. Rev Endocr Metab Disord. 2021;1–10. 10.1007/s11154-021-09655-z.

Martha JW, Wibowo A, Pranata R. Hypocalcemia is associated with severe COVID-19: A systematic review and meta-analysis. Diabetes Metab Syndr. 2021;15(1):337–342. doi: 10.1016/j.dsx.2021.01.003.

Alemzadeh E, Alemzadeh E, Ziaee M, Abedi A, Salehiniya H. The effect of low serum calcium level on the severity and mortality of Covid patients: A systematic review and meta-analysis [published online ahead of print, 2021 Sep 17]. Immun Inflamm Dis. 2021. 10.1002/iid3.528. 10.1002/iid3.528.




How to Cite





Similar Articles

1 2 3 4 5 6 7 > >> 

You may also start an advanced similarity search for this article.