Table Info

Table 1.

Vaccines for treatment of COVID-19

Developer	Name of vaccine	Type of vaccine	Target antigen
Sinopharm	BBIBP-CorV	Inactivated virus	Whole virus
Sinovac Biotech	CoronaVac	Inactivated virus	Whole virus
Bharat Biotech	Covaxin	Inactivated virus	Whole virus
University of Oxford and AstraZeneca	AZD1222	Chimpanzee adenoviral vector	S protein
Janssen and Johnson & Johnson	Ad26.CoV2.S	Human adenoviral vector	S protein
Gamaleya	Sputnik V	Human adenoviral vectors (two serotypes)	S protein
Moderna and NIAD	mRNA-1273	mRNA	S protein
Pfizer and BioNTech	BNT162b2	mRNA	S protein
Novavax and CEPI	NVX-CoV-2373	Protein subunit	S protein
Bharat Biotech	BBV154 (1st intranasal vaccine)	Recombinant adenoviral vector	S protein

Declarations

Acknowledgments

SD, TS, AB, and RKS acknowledge the Department of Biotechnology, AIIMS, New Delhi, India for providing infrastructural facilities. AB thanks ICMR for the research fellowship. Figures are created with the help of Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license (https://smart.servier.com).

Author contributions

SD and TS equally contributed to: Writing—original draft. AB: Writing—review & editing. RKS: Conceptualization, Writing—review & editing, Supervision. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This work was financially supported by projects: DBT [BT-2189], Govt. of India, and an intramural grant [AC-21] sanctioned to RKS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

References

Bhardwaj A, Sapra L, Saini C, Azam Z, Mishra PK, Verma B, et al. COVID-19: immunology, immunopathogenesis and potential therapies. Int Rev Immunol. 2022;41:171–206. [DOI] [PubMed] [PMC]

Khadka RB, Bhandari R, Gyawali R, Neupane B, Pant D. Epidemiology and pathogenesis of coronavirus disease (COVID-19). Nov Res Microbiol J. 2020;4:675–87. [DOI]

Parasher A. COVID-19: current understanding of its pathophysiology, clinical presentation and treatment. Postgrad Med J. 2021;97:312–20. [DOI] [PubMed] [PMC]

Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal. 2020;10:102–8. [DOI] [PubMed] [PMC]

Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579:265–9. Erratum in: Nature. 2020;580:E7. [DOI] [PubMed] [PMC]

Zheng J, Miao J, Guo R, Guo J, Fan Z, Kong X, et al. Mechanism of COVID-19 Causing ARDS: exploring the possibility of preventing and treating SARS-CoV-2. Front Cell Infect Microbiol. 2022;12:931061. [DOI] [PubMed] [PMC]

Batah SS, Fabro AT. Pulmonary pathology of ARDS in COVID-19: a pathological review for clinicians. Respir Med. 2021;17:106239. [DOI] [PubMed] [PMC]

Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: a review. Clin Immunol. 2020;215:108427. [DOI] [PubMed] [PMC]

Matthay MA, Thompson BT, Ware LB. The Berlin definition of acute respiratory distress syndrome: should patients receiving high-flow nasal oxygen be included? Lancet Respir Med. 2021;9:933–6. [DOI] [PubMed] [PMC]

10.

Santos RS, Silva PL, Pelosi P, Rocco PR. Recruitment maneuvers in acute respiratory distress syndrome: the safe way is the best way. World J Crit Care Med. 2015;4:278–86. [DOI] [PubMed] [PMC]

11.

Jones JH, Minshall RD. Endothelial transcytosis in acute lung injury: emerging mechanisms and therapeutic approaches. Front Physiol. 2022;13:828093. [DOI] [PubMed] [PMC]

12.

Choudhary S, Sharma K, Silakari O. The interplay between inflammatory pathways and COVID-19: a critical review on pathogenesis and therapeutic options. Microb Pathog. 2021;150:104673. [DOI] [PubMed] [PMC]

13.

Chowdhury MA, Hossain N, Kashem MA, Shahid MA, Alam A. Immune response in COVID-19: a review. J Infect Public Health. 2020;13:1619–29. [DOI] [PubMed] [PMC]

14.

Yuan R, Yu J, Jiao Z, Li J, Wu F, Yan R, et al. The roles of tissue-resident memory T cells in lung diseases. Front Immunol. 2021;12:710375. [DOI] [PubMed] [PMC]

15.

Tao H, Xu Y, Zhang S. The role of macrophages and alveolar epithelial cells in the development of ARDS. Inflammation. 2023;46:47–55. [DOI] [PubMed] [PMC]

16.

Wong JJM, Leong JY, Lee JH, Albani S, Yeo JG. Insights into the immuno-pathogenesis of acute respiratory distress syndrome. Ann Transl Med. 2019;7:504. [DOI] [PubMed] [PMC]

17.

Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020;75:1730–41. [DOI] [PubMed]

18.

Lv D, Hu B, Lin X, Wang R, Wu D, Long R, et al. Immunopathogenesis of patients with COVID-19: from the perspective of immune system ‘evolution’ and ‘revolution’. Expert Rev Mol Med. 2022;24:e19. [DOI] [PubMed] [PMC]

19.

Jiménez D, Torres Arias M. Immunouniverse of SARS-CoV-2. Immunol Med. 2022;45:186–224. [DOI] [PubMed]

20.

Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The cytokine storm in COVID-19: an overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev. 2020;53:25–32. [DOI] [PubMed] [PMC]

21.

Gentilotti E, Savoldi A, Compri M, Górska A, De Nardo P, Visentin A, et al. Assessment of COVID-19 progression on day 5 from symptoms onset. BMC Infect Dis. 2021;21:883. [DOI] [PubMed] [PMC]

22.

Nickel CH, Rueegg M, Pargger H, Bingisser R. Age, comorbidity, frailty status: effects on disposition and resource allocation during the COVID-19 pandemic. Swiss Med Wkly. 2020;150:w20269. [DOI] [PubMed]

23.

Finelli C. Obesity, COVID-19 and immunotherapy: the complex relationship! Immunotherapy. 2020;12:1105–9. [DOI] [PubMed] [PMC]

24.

Velotti F, Costantini L, Merendino N. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) for immunomodulation in COVID-19 related acute respiratory distress syndrome (ARDS). J Clin Med. 2022;12:304. [DOI] [PubMed] [PMC]

25.

Peyneau M, Granger V, Wicky PH, Khelifi-Touhami D, Timsit JF, Lescure FX, et al. Innate immune deficiencies are associated with severity and poor prognosis in patients with COVID-19. Sci Rep. 2022;12:638. [DOI] [PubMed] [PMC]

26.

Blot M, Bour JB, Quenot JP, Bourredjem A, Nguyen M, Guy J, et al.; LYMPHONIE study group. The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome. J Transl Med. 2020;18:457. Erratum in: J Transl Med. 2021;19:100. [DOI] [PubMed] [PMC]

27.

Lowery SA, Sariol A, Perlman S. Innate immune and inflammatory responses to SARS-CoV-2: implications for COVID-19. Cell Host Microbe. 2021;29:1052–62. [DOI] [PubMed] [PMC]

28.

Acharya D, Liu G, Gack MU. Dysregulation of type I interferon responses in COVID-19. Nat Rev Immunol. 2020;20:397–8. [DOI] [PubMed] [PMC]

29.

Hadjadj J, Yatim N, Barnabei L, Corneau A, Boussier J, Smith N, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020;369:718–24. [DOI] [PubMed] [PMC]

30.

Liu L, Wei Q, Nishiura K, Peng J, Wang H, Midkiff C, et al. Spatiotemporal interplay of severe acute respiratory syndrome coronavirus and respiratory mucosal cells drives viral dissemination in rhesus macaques. Mucosal Immunol. 2016;9:1089–101. [DOI] [PubMed] [PMC]

31.

Ebbo M, Crinier A, Vély F, Vivier E. Innate lymphoid cells: major players in inflammatory diseases. Nat Rev Immunol. 2017;17:665–78. [DOI] [PubMed]

32.

van Eeden C, Khan L, Osman MS, Cohen Tervaert JW. Natural killer cell dysfunction and its role in COVID-19. Int J Mol Sci. 2020;21:6351. [DOI] [PubMed] [PMC]

33.

Market M, Angka L, Martel AB, Bastin D, Olanubi O, Tennakoon G, et al. Flattening the COVID-19 curve with natural killer cell based immunotherapies. Front Immunol. 2020;11:1512. [DOI] [PubMed] [PMC]

34.

Xie Z, Chen J, Zheng C, Wu J, Cheng Y, Zhu S, et al. 1,25‐Dihydroxyvitamin D₃-induced dendritic cells suppress experimental autoimmune encephalomyelitis by increasing proportions of the regulatory lymphocytes and reducing T helper type 1 and type 17 cells. Immunology. 2017;152:414–24. [DOI] [PubMed] [PMC]

35.

Kosyreva A, Dzhalilova D, Lokhonina A, Vishnyakova P, Fatkhudinov T. The role of macrophages in the pathogenesis of SARS-CoV-2-associated acute respiratory distress syndrome. Front Immunol. 2021;12:682871. [DOI] [PubMed] [PMC]

36.

Roy RK, Sharma U, Wasson MK, Jain A, Hassan MI, Prakash H. Macrophage activation syndrome and COVID 19: impact of MAPK driven immune-epigenetic programming by SARS-Cov-2. Front Immunol. 2021;12:763313. [DOI] [PubMed] [PMC]

37.

Lee JW, Chun W, Lee HJ, Min JH, Kim SM, Seo JY, et al. The role of macrophages in the development of acute and chronic inflammatory lung diseases. Cells. 2021;10:897. [DOI] [PubMed] [PMC]

38.

Schulte-Schrepping J, Reusch N, Paclik D, Baßler K, Schlickeiser S, Zhang B, et al.; Deutsche COVID-19 OMICS Initiative (DeCOI). Severe COVID-19 is marked by a dysregulated myeloid cell compartment. Cell. 2020;182:1419–40.E23. [DOI] [PubMed] [PMC]

39.

Knoll R, Schultze JL, Schulte-Schrepping J. Monocytes and macrophages in COVID-19. Front Immunol. 2021;12:720109. [DOI] [PubMed] [PMC]

40.

Chen H, Liu W, Wang Y, Liu D, Zhao L, Yu J. SARS-CoV-2 activates lung epithelial cell proinflammatory signaling and leads to immune dysregulation in COVID-19 patients. EBioMedicine. 2021;70:103500. [DOI] [PubMed] [PMC]

41.

Gómez-Rial J, Rivero-Calle I, Salas A, Martinón-Torres F. Role of monocytes/macrophages in Covid-19 pathogenesis: implications for therapy. Infect Drug Resist. 2020;13:2485–93. [DOI] [PubMed] [PMC]

42.

Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol. 2020;20:355–62. Erratum in: Nat Rev Immunol. 2020;20:448. [DOI] [PubMed] [PMC]

43.

Sefik E, Qu R, Junqueira C, Kaffe E, Mirza H, Zhao J, et al. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature. 2022;606:585–93. [DOI] [PubMed] [PMC]

44.

Campana P, Parisi V, Leosco D, Bencivenga D, Della Ragione F, Borriello A. Dendritic cells and SARS-CoV-2 infection: still an unclarified connection. Cells. 2020;9:2046. [DOI] [PubMed] [PMC]

45.

Marongiu L, Valache M, Facchini FA, Granucci F. How dendritic cells sense and respond to viral infections. Clin Sci (Lond). 2021;135:2217–42. [DOI] [PubMed]

46.

Xiong Y, Liu Y, Cao L, Wang D, Guo M, Jiang A, et al. Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients. Emerg Microbes Infect. 2020;9:761–70. [DOI] [PubMed] [PMC]

47.

Vivier E, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G. Innate lymphoid cells: 10 years on. Cell. 2018;174:1054–66. [DOI] [PubMed]

48.

Kumar A, Cao W, Endrias K, Kuchipudi SV, Mittal SK, Sambhara S. Innate lymphoid cells (ILC) in SARS-CoV-2 infection. Mol Aspects Med. 2021;80:101008. [DOI] [PubMed] [PMC]

49.

García M, Kokkinou E, Carrasco García A, Parrot T, Palma Medina LM, Maleki KT, et al.; Karolinska KI/K COVID-19 Study Group. Innate lymphoid cell composition associates with COVID-19 disease severity. Clin Transl Immunology. 2020;9:e1224. [DOI] [PubMed] [PMC]

50.

Silverstein NJ, Wang Y, Manickas-Hill Z, Carbone C, Dauphin A, Boribong BP, et al.; COVID-19 Collection & Processing Team; Meyer NJ, Betts MR, Li JZ, Walker BD, Yu XG, Yonker LM, et al. Innate lymphoid cells and COVID-19 severity in SARS-CoV-2 infection. Elife. 2022;11:e74681. [DOI] [PubMed] [PMC]

51.

Gomez-Cadena A, Spehner L, Kroemer M, Khelil MB, Bouiller K, Verdeil G, et al. Severe COVID-19 patients exhibit an ILC2 NKG2D⁺ population in their impaired ILC compartment. Cell Mol Immunol. 2021;18:484–6. [DOI] [PubMed] [PMC]

52.

Scozzi D, Liao F, Krupnick AS, Kreisel D, Gelman AE. The role of neutrophil extracellular traps in acute lung injury. Front Immunol. 2022;13:953195. [DOI] [PubMed] [PMC]

53.

Yang SC, Tsai YF, Pan YL, Hwang TL. Understanding the role of neutrophils in acute respiratory distress syndrome. Biomed J. 2021;44:439–46. [DOI] [PubMed] [PMC]

54.

Zhao J, Zhang G, Cui W, Tian B. Progress of neutrophil extracellular traps in airway inflammation of acute lung injury/acute respiratory distress syndrome: review. J Cell Mol Immunol. 2020;36:664–70. Chinese. [PubMed]

55.

Dosanjh A. Eosinophil-derived neurotoxin and respiratory tract infection and inflammation: implications for COVID-19 management. J Interferon Cytokine Res. 2020;40:443–5. [DOI] [PubMed]

56.

Al Duhailib Z, Farooqi M, Piticaru J, Alhazzani W, Nair P. The role of eosinophils in sepsis and acute respiratory distress syndrome: a scoping review. Can J Anaesth. 2021;68:715–26. [DOI] [PubMed] [PMC]

57.

Fong SW, Yeo NK, Chan YH, Goh YS, Amrun SN, Ang N, et al. Robust virus-specific adaptive immunity in COVID-19 patients with SARS-CoV-2 Δ382 variant infection. J Clin Immunol. 2022;42:214–29. Erratum in: J Clin Immunol. 2021;42:230–1. [DOI] [PubMed] [PMC]

58.

Sette A, Crotty S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell. 2021;184:861–80. [DOI] [PubMed] [PMC]

59.

Chen ST, Park MD, Del Valle DM, Buckup M, Tabachnikova A, Thompson RC, et al. A shift in lung macrophage composition is associated with COVID-19 severity and recovery. Sci Transl Med. 2022;14:eabn5168. [DOI] [PubMed] [PMC]

60.

Quast I, Tarlinton D. B cell memory: understanding COVID-19. Immunity. 2021;54:205–10. [DOI] [PubMed] [PMC]

61.

Rodda LB, Netland J, Shehata L, Pruner KB, Morawski PA, Thouvenel CD, et al. Functional SARS-CoV-2-specific immune memory persists after mild COVID-19. Cell. 2021;184:169–83.E17. [DOI] [PubMed] [PMC]

62.

Lee E, Oh JE. Humoral immunity against SARS-CoV-2 and the impact on COVID-19 pathogenesis. Mol Cells. 2021;44:392–400. [DOI] [PubMed] [PMC]

63.

Wang F, Nie J, Wang H, Zhao Q, Xiong Y, Deng L, et al. Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia. J Infect Dis. 2020;221:1762–9. [DOI] [PubMed] [PMC]

64.

Chen Z, John Wherry E. T cell responses in patients with COVID-19. Nat Rev Immunol. 2020;20:529–36. [DOI] [PubMed] [PMC]

65.

Toor SM, Saleh R, Sasidharan Nair V, Taha RZ, Elkord E. T-cell responses and therapies against SARS-CoV-2 infection. Immunology. 2021;162:30–43. [DOI] [PubMed] [PMC]

66.

Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM, Moderbacher CR, et al. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell. 2020;181:1489–501.E15. [DOI] [PubMed] [PMC]

67.

Weiskopf D, Schmitz KS, Raadsen MP, Grifoni A, Okba NMA, Endeman H, et al. Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome. Sci Immunol. 2020;5:eabd2071. [DOI] [PubMed] [PMC]

68.

de Candia P, Prattichizzo F, Garavelli S, Matarese G. T cells: warriors of SARS-CoV-2 infection. Trends Immunol. 2021;42:18–30. [DOI] [PubMed]

69.

Anft M, Paniskaki K, Blazquez-Navarro A, Doevelaar A, Seibert FS, Hölzer B, et al. COVID-19-induced ARDS is associated with decreased frequency of activated memory/effector T cells expressing CD11a⁺⁺. Mol Ther. 2020;28:2691–702. [DOI] [PubMed] [PMC]

70.

Zhao L, Mao Y, Yu H, Liu H, Wang C, Liu J, et al. The preventive effects of Lactobacillus casei on acute lung injury induced by lipopolysaccharide. Indian J Microbiol. 2021;61:370–82. [DOI] [PubMed] [PMC]

71.

Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017;9:eaal3653. [DOI] [PubMed] [PMC]

72.

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30:269–71. [DOI] [PubMed] [PMC]

73.

Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020;395:1569–78. Erratum in: Lancet. 2020;395:1694. [DOI] [PubMed] [PMC]

74.

Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al.; ACTT-1 Study Group Members. Remdesivir for the treatment of Covid-19 — final report. N Engl J Med. 2020;383:1813–26. [DOI] [PubMed] [PMC]

75.

Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad. 2017;93:449–63. [DOI] [PubMed] [PMC]

76.

Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, et al. Experimental treatment with favipiravir for COVID-19: an open-label control study. Engineering (Beijing). 2020;6:1192–8. [DOI] [PubMed] [PMC]

77.

Takahashi H, Iwasaki Y, Watanabe T, Ichinose N, Okada Y, Oiwa A, et al. Case studies of SARS-CoV-2 treated with favipiravir among patients in critical or severe condition. Int J Infect Dis. 2020;100:283–5. [DOI] [PubMed] [PMC]

78.

Zhou D, Dai SM, Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother. 2020;75:1667–70. [DOI] [PubMed] [PMC]

79.

Yan Y, Zou Z, Sun Y, Li X, Xu KF, Wei Y, et al. Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model. Cell Res. 2013;23:300–2. [DOI] [PubMed] [PMC]

80.

Réa-Neto Á, Bernardelli RS, Câmara BMD, Reese FB, Queiroga MVO, Oliveira MC. An open-label randomized controlled trial evaluating the efficacy of chloroquine/hydroxychloroquine in severe COVID-19 patients. Sci Rep. 2021;11:9023. [DOI] [PubMed] [PMC]

81.

Eze P, Mezue KN, Nduka CU, Obianyo I, Egbuche O. Efficacy and safety of chloroquine and hydroxychloroquine for treatment of COVID-19 patients-a systematic review and meta-analysis of randomized controlled trials. Am J Cardiovasc Dis. 2021;11:93–107. [PubMed] [PMC]

82.

So C, Ro S, Murakami M, Imai R, Jinta T. High-dose, short-term corticosteroids for ARDS caused by COVID-19: a case series. Respirol Case Rep. 2020;8:e00596. [DOI] [PubMed] [PMC]

83.

Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, Veiga VC, et al.; COALITION COVID-19 Brazil III Investigators. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: the CoDEX randomized clinical trial. JAMA. 2020;324:1307–16. [DOI] [PubMed] [PMC]

84.

Villar J, Ferrando C, Martínez D, Ambrós A, Muñoz T, Soler JA, et al.; dexamethasone in ARDS network. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 2020;8:267–76. [DOI] [PubMed]

85.

Raju R, V P, Biatris PS, J SJUC. Therapeutic role of corticosteroids in COVID-19: a systematic review of registered clinical trials. Futur J Pharm Sci. 2021;7:67. [DOI] [PubMed] [PMC]

86.

Ranjbar K, Moghadami M, Mirahmadizadeh A, Fallahi MJ, Khaloo V, Shahriarirad R, et al. Correction to: Methylprednisolone or dexamethasone, which one is superior corticosteroid in the treatment of hospitalized COVID-19 patients: a triple-blinded randomized controlled trial. BMC Infect Dis. 2021;21:436. Erratum for: BMC Infect Dis. 2021;21:337. [DOI] [PubMed] [PMC]

87.

Robbiani DF, Gaebler C, Muecksch F, Lorenzi JCC, Wang Z, Cho A, et al. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature. 2020;584:437–42. [DOI] [PubMed] [PMC]

88.

Stebbing J, Phelan A, Griffin I, Tucker C, Oechsle O, Smith D, et al. COVID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect Dis. 2020;20:400–2. [DOI] [PubMed] [PMC]

89.

Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271–80.E8. [DOI] [PubMed] [PMC]

90.

Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA. 2020;323:1582–9. [DOI] [PubMed] [PMC]

91.

Allahyari A, Seddigh-Shamsi M, Mahmoudi M, Amel Jamehdar S, Amini M, Mozdourian M, et al. Efficacy and safety of convalescent plasma therapy in severe COVID-19 patients with acute respiratory distress syndrome. Int Immunopharmacol. 2021;93:107239. [DOI] [PubMed] [PMC]

92.

Chan MC, Kuok DI, Leung CY, Hui KP, Valkenburg SA, Lau EH, et al. Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo. Proc Natl Acad Sci U S A. 2016;113:3621–6. [DOI] [PubMed] [PMC]

93.

Lanzoni G, Linetsky E, Correa D, Messinger Cayetano S, Alvarez RA, Kouroupis D, et al. Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: a double-blind, phase 1/2a, randomized controlled trial. Stem Cells Transl Med. 2021;10:660–73. [DOI] [PubMed] [PMC]

94.

Shi L, Huang H, Lu X, Yan X, Jiang X, Xu R, et al. Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomized, double-blind, placebo-controlled phase 2 trial. Signal Transduct Target Ther. 2021;6:58. [DOI] [PubMed] [PMC]

95.

Buonaguro FM, Puzanov I, Ascierto PA. Anti-IL6R role in treatment of COVID-19-related ARDS. J Transl Med. 2020;18:165. [DOI] [PubMed] [PMC]

96.

Zhu H, Shi X, Ju D, Huang H, Wei W, Dong X. Anti-inflammatory effect of thalidomide on H1N1 influenza virus-induced pulmonary injury in mice. Inflammation. 2014;37:2091–8. [DOI] [PubMed]

97.

Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020;117:10970–5. [DOI] [PubMed] [PMC]

98.

Toniati P, Piva S, Cattalini M, Garrafa E, Regola F, Castelli F, et al. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: a single center study of 100 patients in Brescia, Italy. Autoimmun Rev. 2020;19:102568. [DOI] [PubMed] [PMC]

99.

Rilinger J, Kern WV, Duerschmied D, Supady A, Bode C, Staudacher DL, et al. A prospective, randomised, double blind placebo-controlled trial to evaluate the efficacy and safety of tocilizumab in patients with severe COVID-19 pneumonia (TOC-COVID): a structured summary of a study protocol for a randomised controlled trial. Trials. 2020;21:470. [DOI] [PubMed] [PMC]

100.

Pinzon RT, Wijaya VO, Buana RB. Interleukin-6 (IL-6) inhibitors as therapeutic agents for coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis. J Infect Public Health. 2021;14:1001–9. [DOI] [PubMed] [PMC]

101.

Lee KY. Pneumonia, acute respiratory distress syndrome, and early immune-modulator therapy. Int J Mol Sci. 2017;18:388. [DOI] [PubMed] [PMC]

102.

Gharebaghi N, Nejadrahim R, Mousavi SJ, Sadat-Ebrahimi SR, Hajizadeh R. Correction to: The use of intravenous immunoglobulin gamma for the treatment of severe coronavirus disease 2019: a randomized placebo-controlled double-blind clinical trial. BMC Infect Dis. 2020;20:895. Erratum for: BMC Infect Dis. 2020;20:786. [DOI] [PubMed] [PMC]

103.

Shao Z, Feng Y, Zhong L, Xie Q, Lei M, Liu Z, et al. Clinical efficacy of intravenous immunoglobulin therapy in critical ill patients with COVID-19: a multicenter retrospective cohort study. Clin Transl Immunology. 2020;9:e1192. [DOI] [PubMed] [PMC]

104.

Chen RE, Winkler ES, Case JB, Aziati ID, Bricker TL, Joshi A, et al. In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains. Nature. 2021;596:103–8. [DOI] [PubMed] [PMC]

105.

Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020;18:1094–9. [DOI] [PubMed] [PMC]

106.

Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033–4. [DOI] [PubMed] [PMC]

107.

Su M, Jia Y, Li Y, Zhou D, Jia J. Probiotics for the prevention of ventilator-associated pneumonia: a meta-analysis of randomized controlled trials. Respir Care. 2020;65:673–85. [DOI] [PubMed]

108.

Kumova OK, Fike AJ, Thayer JL, Nguyen LT, Mell JC, Pascasio J, et al. Lung transcriptional unresponsiveness and loss of early influenza virus control in infected neonates is prevented by intranasal Lactobacillus rhamnosus GG. PLoS Pathog. 2019;15:e1008072. [DOI] [PubMed] [PMC]

109.

Jung YJ, Lee YT, Ngo VL, Cho YH, Ko EJ, Hong SM, et al. Heat-killed Lactobacillus casei confers broad protection against influenza A virus primary infection and develops heterosubtypic immunity against future secondary infection. Sci Rep. 2017;7:17360. [DOI] [PubMed] [PMC]

110.

Park MK, Ngo V, Kwon YM, Lee YT, Yoo S, Cho YH, et al. Lactobacillus plantarum DK119 as a probiotic confers protection against influenza virus by modulating innate immunity. PLoS One. 2013;8:e75368. [DOI] [PubMed] [PMC]

111.

Liu Y, Tran DQ, Rhoads JM. Probiotics in disease prevention and treatment. J Clin Pharmacol. 2018;58:S164–79. [DOI] [PubMed] [PMC]

112.

Olimpio F, da Silva JRM, Vieira RP, Oliveira CR, Aimbire F. Lacticaseibacillus rhamnosus modulates the inflammatory response and the subsequent lung damage in a murine model of acute lung inflammation. Clinics (Sao Paulo). 2022;77:100021. [DOI] [PubMed] [PMC]

113.

Raheem A, Liang L, Zhang G, Cui S. Modulatory effects of probiotics during pathogenic infections with emphasis on immune regulation. Front Immunol. 2021;12:616713. [DOI] [PubMed] [PMC]

114.

Li Q, Wang Y, Sun Q, Knopf J, Herrmann M, Lin L, et al. Immune response in COVID-19: what is next? Cell Death Differ. 2022;29:1107–22. [DOI] [PubMed] [PMC]

115.

Moreno-Nunez P, Bueno-Cavanillas A, San Jose-Saras D, Vicente-Guijarro J, Fernández Chávez AC, Aranaz-Andrés JM, et al. How does vaccination against SARS-CoV-2 affect hospitalized patients with COVID-19? Clin Med. 2022;11:3905. [DOI] [PubMed] [PMC]

116.

Djuricic I, Calder PC. Beneficial outcomes of omega-6 and omega-3 polyunsaturated fatty acids on human health: an update for 2021. Nutrients. 2021;13:2421. [DOI] [PubMed] [PMC]

117.

Szabó Z, Marosvölgyi T, Szabó É, Bai P, Figler M, Verzár Z. The potential beneficial effect of EPA and DHA supplementation managing cytokine storm in coronavirus disease. Front Physiol. 2020;11:752. [DOI] [PubMed] [PMC]

118.

Mazidimoradi A, Alemzadeh E, Alemzadeh E, Salehiniya H. The effect of polyunsaturated fatty acids on the severity and mortality of COVID patients: a systematic review. Life Sci. 2022;299:120489. [DOI] [PubMed] [PMC]