Pros and Cons for COVID-19 Vaccination and Boost of Young Adults in Light of Recent Literature

Main Article Content

John Nemunaitis Paul V. Lehmann James Willey

Abstract

Many lives were saved in high-risk populations through the rapid development of COVID-19 vaccines.  However, further mutation of new viral variants has reduced vaccine efficacy.  Here we provide a review of the literature on pros and cons of vaccination and boost vs. naturally acquired immunity in young healthy adults.  Our research indicates (1) being vaccinated, even after booster shots, demonstrates limits to protection from infection and spreading of the COVID-19 variants.  (2) Young healthy adults predominantly develop mild or no symptoms after infection with SARS-CoV-2 variants, particularly Omicron, as such vaccination is not necessarily needed to protect young healthy adults.  (3) Sequential vaccination with booster injections has been associated with reports of autoimmune complications.  Complications not as commonly seen after natural infection.  (4) Numerous assessments have revealed immunity imprinted through natural infection and durable protection against COVID-19 variants thereby supporting choice to natural infection in some.  We conclude that for the young healthy adults, some of the risks and disadvantages afforded by vaccination prevail over the medical benefits.  Moreover, Omicron as was observed, caused mild upper respiratory tract infection, and appeared to act in young healthy adults as an ideal “natural vaccine” to induce herd immunity, which in effect will diminish new variant development and may reduce duration of future pandemics in combination with vaccination of elderly and immune compromised.

Article Details

How to Cite
NEMUNAITIS, John; LEHMANN, Paul V.; WILLEY, James. Pros and Cons for COVID-19 Vaccination and Boost of Young Adults in Light of Recent Literature. Medical Research Archives, [S.l.], v. 10, n. 8, aug. 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2943>. Date accessed: 28 sep. 2022. doi: https://doi.org/10.18103/mra.v10i8.2943.
Section
Articles

References

1. FDA Briefing Document: Application for Licensure of a Booster Dose for COMIRNATY (COVID-19 Vaccine, mRNA). In: Vaccines and Related Biological Products Advisory Committee Meeting: https://www.fda.gov/media/152176/download, 2021.
2. Atmar RL, Lyke KE, Deming ME, Jackson LA, Branche AR, El Sahly HM et al. Homologous and Heterologous Covid-19 Booster Vaccinations. N Engl J Med 2022; 386(11): 1046-1057.
3. Stawicki SP, Jeanmonod R, Miller AC, Paladino L, Gaieski DF, Yaffee AQ et al. The 2019-2020 Novel Coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2) Pandemic: A Joint American College of Academic International Medicine-World Academic Council of Emergency Medicine Multidisciplinary COVID-19 Working Group Consensus Paper. J Glob Infect Dis 2020; 12(2): 47-93.
4. Blackburn J, Yiannoutsos CT, Carroll AE, Halverson PK, Menachemi N. Infection Fatality Ratios for COVID-19 Among Noninstitutionalized Persons 12 and Older: Results of a Random-Sample Prevalence Study. Ann Intern Med 2021; 174(1): 135-136.
5. OpenVAERS. In: https://www.openvaers.com/.
6. Kostoff RN, Calina D, Kanduc D, Briggs MB, Vlachoyiannopoulos P, Svistunov AA et al. Why are we vaccinating children against COVID-19? Toxicol Rep 2021; 8: 1665-1684.
7. BLA Approavl Pfizer/BioNTech. In: U.S. Food & Drug Administration, 2021.
8. Pfizer and BioNTech Initiate Rolling Submission of Biologics License Application for U.S. FDA Approval of Their COVID-19 Vaccine. In. Germany: New York & Mainz, 2021.
9. Lopez-Leon S, Wegman-Ostrosky T, Perelman C, Sepulveda R, Rebolledo PA, Cuapio A et al. More than 50 long-term effects of COVID-19: a systematic review and meta-analysis. Sci Rep 2021; 11(1): 16144.
10. Oster ME, Shay DK, Su JR, Gee J, Creech CB, Broder KR et al. Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021. JAMA 2022; 327(4): 331-340.
11. Diaz GA, Parsons GT, Gering SK, Meier AR, Hutchinson IV, Robicsek A. Myocarditis and Pericarditis After Vaccination for COVID-19. JAMA 2021; 326(12): 1210-1212.
12. Hause AM, Gee J, Baggs J, Abara WE, Marquez P, Thompson D et al. COVID-19 Vaccine Safety in Adolescents Aged 12-17 Years - United States, December 14, 2020-July 16, 2021. MMWR Morb Mortal Wkly Rep 2021; 70(31): 1053-1058.
13. Marshall M, Ferguson ID, Lewis P, Jaggi P, Gagliardo C, Collins JS et al. Symptomatic Acute Myocarditis in 7 Adolescents After Pfizer-BioNTech COVID-19 Vaccination. Pediatrics 2021; 148(3).
14. Snapiri O, Rosenberg Danziger C, Shirman N, Weissbach A, Lowenthal A, Ayalon I et al. Transient Cardiac Injury in Adolescents Receiving the BNT162b2 mRNA COVID-19 Vaccine. Pediatr Infect Dis J 2021; 40(10): e360-e363.
15. Montgomery J, Ryan M, Engler R, Hoffman D, McClenathan B, Collins L et al. Myocarditis Following Immunization With mRNA COVID-19 Vaccines in Members of the US Military. JAMA Cardiol 2021.
16. Kim HW, Jenista ER, Wendell DC, Azevedo CF, Campbell MJ, Darty SN et al. Patients With Acute Myocarditis Following mRNA COVID-19 Vaccination. JAMA Cardiol 2021.
17. Bautista Garcia J, Pena Ortega P, Bonilla Fernandez JA, Cardenes Leon A, Ramirez Burgos L, Caballero Dorta E. [Acute myocarditis after administration of the BNT162b2 vaccine against COVID-19]. Rev Esp Cardiol 2021; 74(9): 812-814.
18. Rosner CM, Genovese L, Tehrani BN, Atkins M, Bakhshi H, Chaudhri S et al. Myocarditis Temporally Associated With COVID-19 Vaccination. Circulation 2021; 144(6): 502-505.
19. Solomon MD, Tirupsur A, Hytopoulos E, Beggs M, Harrington DS, French C et al. Clinical utility of a novel coronary heart disease risk-assessment test to further classify intermediate-risk patients. Clin Cardiol 2013; 36(10): 621-7.
20. Gundry SR. Abstract 10712: Mrna COVID Vaccines Dramatically Increase Endothelial Inflammatory Markers and ACS Risk as Measured by the PULS Cardiac Test: a Warning. Circulation 2021; 144(Suppl_1): A10712-A10712.
21. Tamaki S, Mano T, Sakata Y, Ohtani T, Takeda Y, Kamimura D et al. Interleukin-16 promotes cardiac fibrosis and myocardial stiffening in heart failure with preserved ejection fraction. PLoS One 2013; 8(7): e68893.
22. Yamada A, Arakaki R, Saito M, Kudo Y, Ishimaru N. Dual Role of Fas/FasL-Mediated Signal in Peripheral Immune Tolerance. Front Immunol 2017; 8: 403.
23. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004; 203(2): 631-7.
24. Chen L, Li X, Chen M, Feng Y, Xiong C. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res 2020; 116(6): 1097-1100.
25. Lei Y, Zhang J, Schiavon CR, He M, Chen L, Shen H et al. SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2. Circ Res 2021; 128(9): 1323-1326.
26. Raghavan S, Kenchappa DB, Leo MD. SARS-CoV-2 Spike Protein Induces Degradation of Junctional Proteins That Maintain Endothelial Barrier Integrity. Front Cardiovasc Med 2021; 8: 687783.
27. Nuovo GJ, Magro C, Shaffer T, Awad H, Suster D, Mikhail S et al. Endothelial cell damage is the central part of COVID-19 and a mouse model induced by injection of the S1 subunit of the spike protein. Ann Diagn Pathol 2021; 51: 151682.
28. Cohen AN, Kessel B, Milgroom MG. Diagnosing SARS-CoV-2 infection: the danger of over-reliance on positive test results. medRxiv 2020: 2020.04.26.20080911.
29. Ogata AF, Cheng CA, Desjardins M, Senussi Y, Sherman AC, Powell M et al. Circulating SARS-CoV-2 Vaccine Antigen Detected in the Plasma of mRNA-1273 Vaccine Recipients. Clin Infect Dis 2021.
30. Rhea EM, Logsdon AF, Hansen KM, Williams LM, Reed MJ, Baumann KK et al. The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice. Nat Neurosci 2021; 24(3): 368-378.
31. Sellaturay P, Nasser S, Islam S, Gurugama P, Ewan PW. Polyethylene glycol (PEG) is a cause of anaphylaxis to the Pfizer/BioNTech mRNA COVID-19 vaccine. Clin Exp Allergy 2021; 51(6): 861-863.
32. Igyarto BZ, Jacobsen S, Ndeupen S. Future considerations for the mRNA-lipid nanoparticle vaccine platform. Curr Opin Virol 2021; 48: 65-72.
33. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 2020; 367(6483): 1260-1263.
34. Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN et al. An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. N Engl J Med 2020; 383(20): 1920-1931.
35. Vojdani A, Kharrazian D. Potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases. Clin Immunol 2020; 217: 108480.
36. Vojdani A, Vojdani E, Kharrazian D. Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases. Front Immunol 2020; 11: 617089.
37. Seneff S, Nigh G. Worse Than the Disease? Reviewing Some Possible Unintended Consequences of the mRNA Vaccines Against COVID-19. International Journal of Vaccine Theory, Practice, and Research 2021; 2(1): 38-79.
38. Lyons-Weiler J. Pathogenic priming likely contributes to serious and critical illness and mortality in COVID-19 via autoimmunity. J Transl Autoimmun 2020; 3: 100051.
39. Ehrenfeld M, Tincani A, Andreoli L, Cattalini M, Greenbaum A, Kanduc D et al. Covid-19 and autoimmunity. Autoimmun Rev 2020; 19(8): 102597.
40. Vera-Lastra O, Ordinola Navarro A, Cruz Domiguez MP, Medina G, Sanchez Valadez TI, Jara LJ. Two Cases of Graves' Disease Following SARS-CoV-2 Vaccination: An Autoimmune/Inflammatory Syndrome Induced by Adjuvants. Thyroid 2021; 31(9): 1436-1439.
41. Iremli BG, Sendur SN, Unluturk U. Three Cases of Subacute Thyroiditis Following SARS-CoV-2 Vaccine: Postvaccination ASIA Syndrome. J Clin Endocrinol Metab 2021; 106(9): 2600-2605.
42. Buzhdygan TP, DeOre BJ, Baldwin-Leclair A, Bullock TA, McGary HM, Khan JA et al. The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood-brain barrier. Neurobiol Dis 2020; 146: 105131.

43. Achua JK, Chu KY, Ibrahim E, Khodamoradi K, Delma KS, Iakymenko OA et al. Histopathology and Ultrastructural Findings of Fatal COVID-19 Infections on Testis. World J Mens Health 2021; 39(1): 65-74.
44. Navarra A, Albani E, Castellano S, Arruzzolo L, Levi-Setti PE. Coronavirus Disease-19 Infection: Implications on Male Fertility and Reproduction. Front Physiol 2020; 11: 574761.
45. Verma S, Saksena S, Sadri-Ardekani H. ACE2 receptor expression in testes: implications in coronavirus disease 2019 pathogenesisdagger. Biol Reprod 2020; 103(3): 449-451.
46. Wang Z, Xu X. scRNA-seq Profiling of Human Testes Reveals the Presence of the ACE2 Receptor, A Target for SARS-CoV-2 Infection in Spermatogonia, Leydig and Sertoli Cells. Cells 2020; 9(4).
47. Classen JB. Review of COVID-19 Vaccines and the Risk of Chronic Adverse Events Including Neurological Degeneration. Journal of Medical-Clinical Research and Reviews 2021; 5(3): 1-7.
48. Kirkcaldy RD, King BA, Brooks JT. COVID-19 and Postinfection Immunity: Limited Evidence, Many Remaining Questions. JAMA 2020; 323(22): 2245-2246.
49. Sekine T, Perez-Potti A, Rivera-Ballesteros O, Stralin K, Gorin JB, Olsson A et al. Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19. Cell 2020; 183(1): 158-168 e14.
50. Saxena SK, Kumar S, Ansari S, Paweska JT, Maurya VK, Tripathi AK et al. Characterization of the novel SARS-CoV-2 Omicron (B.1.1.529) variant of concern and its global perspective. J Med Virol 2021.
51. Liu Y, Liu J, Johnson BA, Xia H, Ku Z, Schindewolf C et al. Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant. bioRxiv 2021: 2021.08.12.456173.
52. Brown CM, Vostok J, Johnson H, Burns M, Gharpure R, Sami S et al. Outbreak of SARS-CoV-2 Infections, Including COVID-19 Vaccine Breakthrough Infections, Associated with Large Public Gatherings - Barnstable County, Massachusetts, July 2021. MMWR Morb Mortal Wkly Rep 2021; 70(31): 1059-1062.
53. Uriu K, Kimura I, Shirakawa K, Takaori-Kondo A, Nakada T-a, Kaneda A et al. Ineffective neutralization of the SARS-CoV-2 Mu variant by convalescent and vaccine sera. bioRxiv 2021: 2021.09.06.459005.
54. Mathew D, Giles JR, Baxter AE, Oldridge DA, Greenplate AR, Wu JE et al. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science 2020; 369(6508).
55. Ruopp MD, Strymish J, Dryjowicz-Burek J, Creedon K, Gupta K. Durability of SARS-CoV-2 IgG Antibody Among Residents in a Long-Term Care Community. J Am Med Dir Assoc 2021; 22(3): 510-511.
56. Seow J, Graham C, Merrick B, Acors S, Pickering S, Steel KJA et al. Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans. Nat Microbiol 2020; 5(12): 1598-1607.
57. Shrotri M, Navaratnam AMD, Nguyen V, Byrne T, Geismar C, Fragaszy E et al. Spike-antibody waning after second dose of BNT162b2 or ChAdOx1. Lancet 2021; 398(10298): 385-387.
58. Planas D, Veyer D, Baidaliuk A, Staropoli I, Guivel-Benhassine F, Rajah MM et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature 2021; 596(7871): 276-280.
59. Mizrahi B, Lotan R, Kalkstein N, Peretz A, Perez G, Ben-Tov A et al. Correlation of SARS-CoV-2-breakthrough infections to time-from-vaccine. Nat Commun 2021; 12(1): 6379.
60. Rella SA, Kulikova YA, Dermitzakis ET, Kondrashov FA. Rates of SARS-CoV-2 transmission and vaccination impact the fate of vaccine-resistant strains. Sci Rep 2021; 11(1): 15729.
61. Liu Y, Arase N, Kishikawa J-i, Hirose M, Li S, Tada A et al. The SARS-CoV-2 Delta variant is poised to acquire complete resistance to wild-type spike vaccines. bioRxiv 2021: 2021.08.22.457114.
62. Yahi N, Chahinian H, Fantini J. Infection-enhancing anti-SARS-CoV-2 antibodies recognize both the original Wuhan/D614G strain and Delta variants. A potential risk for mass vaccination? J Infect 2021; 83(5): 607-635.
63. Suthar MS, Arunachalam PS, Hu M, Reis N, Trisal M, Raeber O et al. Durability of immune responses to the BNT162b2 mRNA vaccine. bioRxiv 2021: 2021.09.30.462488.
64. Nordstrom P, Ballin M, Nordstrom A. Risk of infection, hospitalisation, and death up to 9 months after a second dose of COVID-19 vaccine: a retrospective, total population cohort study in Sweden. Lancet 2022; 399(10327): 814-823.
65. Shitrit P, Zuckerman NS, Mor O, Gottesman BS, Chowers M. Nosocomial outbreak caused by the SARS-CoV-2 Delta variant in a highly vaccinated population, Israel, July 2021. Euro Surveill 2021; 26(39).
66. Riemersma KK, Grogan BE, Kita-Yarbro A, Halfmann PJ, Segaloff HE, Kocharian A et al. Shedding of Infectious SARS-CoV-2 Despite Vaccination. medRxiv 2021: 2021.07.31.21261387.
67. Subramanian SV, Kumar A. Increases in COVID-19 are unrelated to levels of vaccination across 68 countries and 2947 counties in the United States. Eur J Epidemiol 2021.
68. Lyngse FP, Mortensen LH, Denwood MJ, Christiansen LE, Møller CH, Skov RL et al. SARS-CoV-2 Omicron VOC Transmission in Danish Households. medRxiv 2021: 2021.12.27.21268278.
69. Kimura I, Kosugi Y, Wu J, Yamasoba D, Butlertanaka EP, Tanaka YL et al. SARS-CoV-2 Lambda variant exhibits higher infectivity and immune resistance. bioRxiv 2021: 2021.07.28.454085.
70. Grenfell BT, Pybus OG, Gog JR, Wood JL, Daly JM, Mumford JA et al. Unifying the epidemiological and evolutionary dynamics of pathogens. Science 2004; 303(5656): 327-32.
71. Pulliam JRC, van Schalkwyk C, Govender N, von Gottberg A, Cohen C, Groome MJ et al. Increased risk of SARS-CoV-2 reinfection associated with emergence of Omicron in South Africa. Science 2022; 376(6593): eabn4947.
72. Liu L, Iketani S, Guo Y, Chan JF, Wang M, Liu L et al. Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2. Nature 2022; 602(7898): 676-681.
73. Servellita V, Morris MK, Sotomayor-Gonzalez A, Gliwa AS, Torres E, Brazer N et al. Predominance of antibody-resistant SARS-CoV-2 variants in vaccine breakthrough cases from the San Francisco Bay Area, California. Nat Microbiol 2022.
74. Avanzato VA, Matson MJ, Seifert SN, Pryce R, Williamson BN, Anzick SL et al. Case Study: Prolonged Infectious SARS-CoV-2 Shedding from an Asymptomatic Immunocompromised Individual with Cancer. Cell 2020; 183(7): 1901-1912 e9.
75. Choi B, Choudhary MC, Regan J, Sparks JA, Padera RF, Qiu X et al. Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host. N Engl J Med 2020; 383(23): 2291-2293.
76. Lumley SF, O'Donnell D, Stoesser NE, Matthews PC, Howarth A, Hatch SB et al. Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers. N Engl J Med 2021; 384(6): 533-540.
77. Sheehan MM, Reddy AJ, Rothberg MB. Reinfection Rates among Patients who Previously Tested Positive for COVID-19: a Retrospective Cohort Study. Clin Infect Dis 2021.
78. Pilz S, Chakeri A, Ioannidis JP, Richter L, Theiler-Schwetz V, Trummer C et al. SARS-CoV-2 re-infection risk in Austria. Eur J Clin Invest 2021; 51(4): e13520.
79. Sen P, Yamana TK, Kandula S, Galanti M, Shaman J. Burden and characteristics of COVID-19 in the United States during 2020. Nature 2021; 598(7880): 338-341.
80. Shrestha NK, Burke PC, Nowacki AS, Terpeluk P, Gordon SM. Necessity of COVID-19 Vaccination in Persons Who Have Already Had COVID-19. Clin Infect Dis 2022.
81. O. ME, Byrne P, Carty PG, De Gascun C, Keogan M, O'Neill M et al. Quantifying the risk of SARS-CoV-2 reinfection over time. Rev Med Virol 2021: e2260.
82. Abu-Raddad LJ, Chemaitelly H, Coyle P, Malek JA, Ahmed AA, Mohamoud YA et al. SARS-CoV-2 antibody-positivity protects against reinfection for at least seven months with 95% efficacy. EClinicalMedicine 2021; 35: 100861.
83. Kojima N, Klausner JD. Protective immunity after recovery from SARS-CoV-2 infection. Lancet Infect Dis 2022; 22(1): 12-14.
84. Gazit S, Shlezinger R, Perez G, Lotan R, Peretz A, Ben-Tov A et al. SARS-CoV-2 Naturally Acquired Immunity vs. Vaccine-induced Immunity, Reinfections versus Breakthrough Infections: a Retrospective Cohort Study. Clin Infect Dis 2022.
85. Perez G, Banon T, Gazit S, Moshe SB, Wortsman J, Grupel D et al. A 1 to 1000 SARS-CoV-2 reinfection proportion in members of a large healthcare provider in Israel: a preliminary report. medRxiv 2021: 2021.03.06.21253051.
86. Turner JS, Kim W, Kalaidina E, Goss CW, Rauseo AM, Schmitz AJ et al. SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans. Nature 2021; 595(7867): 421-425.
87. Alfego D, Sullivan A, Poirier B, Williams J, Adcock D, Letovsky S. A population-based analysis of the longevity of SARS-CoV-2 antibody seropositivity in the United States. EClinicalMedicine 2021; 36: 100902.
88. Wang Z, Muecksch F, Schaefer-Babajew D, Finkin S, Viant C, Gaebler C et al. Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection. Nature 2021; 595(7867): 426-431.
89. Martiszus I. COVID-19 Natural Immunity vs Vaccine Immunity. In: Cure-Hub LLC, 2021.
90. Haveri A, Ekstrom N, Solastie A, Virta C, Osterlund P, Isosaari E et al. Persistence of neutralizing antibodies a year after SARS-CoV-2 infection in humans. Eur J Immunol 2021.

91. Ye Q, West AMV, Silletti S, Corbett KD. Architecture and self-assembly of the SARS-CoV-2 nucleocapsid protein. Protein Sci 2020; 29(9): 1890-1901.
92. Long QX, Tang XJ, Shi QL, Li Q, Deng HJ, Yuan J et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med 2020; 26(8): 1200-1204.
93. Mallapaty S. Will antibody tests for the coronavirus really change everything? Nature 2020; 580(7805): 571-572.
94. Woloshin S, Patel N, Kesselheim AS. False Negative Tests for SARS-CoV-2 Infection - Challenges and Implications. N Engl J Med 2020; 383(6): e38.
95. Channappanavar R, Fett C, Zhao J, Meyerholz DK, Perlman S. Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection. J Virol 2014; 88(19): 11034-44.
96. Tang F, Quan Y, Xin ZT, Wrammert J, Ma MJ, Lv H et al. Lack of peripheral memory B cell responses in recovered patients with severe acute respiratory syndrome: a six-year follow-up study. J Immunol 2011; 186(12): 7264-8.
97. Peiris JS, Chu CM, Cheng VC, Chan KS, Hung IF, Poon LL et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet 2003; 361(9371): 1767-72.
98. Liu L, Wei Q, Lin Q, Fang J, Wang H, Kwok H et al. Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI Insight 2019; 4(4).
99. Ho MS, Chen WJ, Chen HY, Lin SF, Wang MC, Di J et al. Neutralizing antibody response and SARS severity. Emerg Infect Dis 2005; 11(11): 1730-7.
100. Lee WS, Wheatley AK, Kent SJ, DeKosky BJ. Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies. Nat Microbiol 2020; 5(10): 1185-1191.
101. Bolles M, Deming D, Long K, Agnihothram S, Whitmore A, Ferris M et al. A double-inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge. J Virol 2011; 85(23): 12201-15.
102. Deming D, Sheahan T, Heise M, Yount B, Davis N, Sims A et al. Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants. PLoS Med 2006; 3(12): e525.
103. Tseng CT, Sbrana E, Iwata-Yoshikawa N, Newman PC, Garron T, Atmar RL et al. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS One 2012; 7(4): e35421.
104. Yasui F, Kai C, Kitabatake M, Inoue S, Yoneda M, Yokochi S et al. Prior immunization with severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein causes severe pneumonia in mice infected with SARS-CoV. J Immunol 2008; 181(9): 6337-48.
105. Agrawal AS, Tao X, Algaissi A, Garron T, Narayanan K, Peng BH et al. Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus. Hum Vaccin Immunother 2016; 12(9): 2351-6.
106. Weingartl H, Czub M, Czub S, Neufeld J, Marszal P, Gren J et al. Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets. J Virol 2004; 78(22): 12672-6.
107. Czub M, Weingartl H, Czub S, He R, Cao J. Evaluation of modified vaccinia virus Ankara based recombinant SARS vaccine in ferrets. Vaccine 2005; 23(17-18): 2273-9.
108. Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S et al. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 2003; 348(20): 1953-66.
109. Hohdatsu T, Yamada M, Tominaga R, Makino K, Kida K, Koyama H. Antibody-dependent enhancement of feline infectious peritonitis virus infection in feline alveolar macrophages and human monocyte cell line U937 by serum of cats experimentally or naturally infected with feline coronavirus. J Vet Med Sci 1998; 60(1): 49-55.
110. Takada A, Kawaoka Y. Antibody-dependent enhancement of viral infection: molecular mechanisms and in vivo implications. Rev Med Virol 2003; 13(6): 387-98.
111. Barrett AD, Gould EA. Antibody-mediated early death in vivo after infection with yellow fever virus. J Gen Virol 1986; 67 ( Pt 11): 2539-42.
112. 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(7): 1489-1501 e15.
113. Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y et al. Antibody Responses to SARS-CoV-2 in Patients With Novel Coronavirus Disease 2019. Clin Infect Dis 2020; 71(16): 2027-2034.
114. Braun J, Loyal L, Frentsch M, Wendisch D, Georg P, Kurth F et al. SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19. Nature 2020; 587(7833): 270-274.
115. Chandrashekar A, Liu J, Martinot AJ, McMahan K, Mercado NB, Peter L et al. SARS-CoV-2 infection protects against rechallenge in rhesus macaques. Science 2020; 369(6505): 812-817.
116. Ni L, Ye F, Cheng ML, Feng Y, Deng YQ, Zhao H et al. Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals. Immunity 2020; 52(6): 971-977 e3.
117. Liu J, Li S, Liu J, Liang B, Wang X, Wang H et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 2020; 55: 102763.
118. He R, Lu Z, Zhang L, Fan T, Xiong R, Shen X et al. The clinical course and its correlated immune status in COVID-19 pneumonia. J Clin Virol 2020; 127: 104361.
119. Le Bert N, Tan AT, Kunasegaran K, Tham CYL, Hafezi M, Chia A et al. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature 2020; 584(7821): 457-462.
120. Yang LT, Peng H, Zhu ZL, Li G, Huang ZT, Zhao ZX et al. Long-lived effector/central memory T-cell responses to severe acute respiratory syndrome coronavirus (SARS-CoV) S antigen in recovered SARS patients. Clin Immunol 2006; 120(2): 171-8.
121. Blom K, Braun M, Ivarsson MA, Gonzalez VD, Falconer K, Moll M et al. Temporal dynamics of the primary human T cell response to yellow fever virus 17D as it matures from an effector- to a memory-type response. J Immunol 2013; 190(5): 2150-8.
122. Demkowicz WE, Jr., Littaua RA, Wang J, Ennis FA. Human cytotoxic T-cell memory: long-lived responses to vaccinia virus. J Virol 1996; 70(4): 2627-31.
123. Fuertes Marraco SA, Soneson C, Cagnon L, Gannon PO, Allard M, Abed Maillard S et al. Long-lasting stem cell-like memory CD8+ T cells with a naive-like profile upon yellow fever vaccination. Sci Transl Med 2015; 7(282): 282ra48.
124. Precopio ML, Betts MR, Parrino J, Price DA, Gostick E, Ambrozak DR et al. Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8(+) T cell responses. J Exp Med 2007; 204(6): 1405-16.
125. Li CK, Wu H, Yan H, Ma S, Wang L, Zhang M et al. T cell responses to whole SARS coronavirus in humans. J Immunol 2008; 181(8): 5490-500.
126. Zhao J, Zhao J, Mangalam AK, Channappanavar R, Fett C, Meyerholz DK et al. Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses. Immunity 2016; 44(6): 1379-91.
127. Zhao J, Alshukairi AN, Baharoon SA, Ahmed WA, Bokhari AA, Nehdi AM et al. Recovery from the Middle East respiratory syndrome is associated with antibody and T-cell responses. Sci Immunol 2017; 2(14).
128. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC et al. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med 2020; 383(19): 1813-1826.
129. McCullough PA, Kelly RJ, Ruocco G, Lerma E, Tumlin J, Wheelan KR et al. Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection. Am J Med 2021; 134(1): 16-22.
130. Halstead ES, Umstead TM, Davies ML, Kawasawa YI, Silveyra P, Howyrlak J et al. GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization. Respir Res 2018; 19(1): 3.
131. Sever-Chroneos Z, Murthy A, Davis J, Florence JM, Kurdowska A, Krupa A et al. GM-CSF modulates pulmonary resistance to influenza A infection. Antiviral Res 2011; 92(2): 319-28.
132. Unkel B, Hoegner K, Clausen BE, Lewe-Schlosser P, Bodner J, Gattenloehner S et al. Alveolar epithelial cells orchestrate DC function in murine viral pneumonia. J Clin Invest 2012; 122(10): 3652-64.
133. Huang FF, Barnes PF, Feng Y, Donis R, Chroneos ZC, Idell S et al. GM-CSF in the lung protects against lethal influenza infection. Am J Respir Crit Care Med 2011; 184(2): 259-68.
134. Kadir Z, Ma X, Li J, Zhang F. Granulocyte-macrophage colony-stimulating factor enhances the humoral immune responses of mouse zona pellucida 3 vaccine strategy based on DNA and protein coadministration in BALB/c mice. Reprod Sci 2013; 20(4): 400-7.
135. Zhao W, Zhou X, Zhao G, Lin Q, Wang X, Yu X et al. Enrichment of Ly6C(hi) monocytes by multiple GM-CSF injections with HBV vaccine contributes to viral clearance in a HBV mouse model. Hum Vaccin Immunother 2017; 13(12): 2872-2882.
136. Herold S, Hoegner K, Vadasz I, Gessler T, Wilhelm J, Mayer K et al. Inhaled granulocyte/macrophage colony-stimulating factor as treatment of pneumonia-associated acute respiratory distress syndrome. Am J Respir Crit Care Med 2014; 189(5): 609-11.
137. Rosler B, Herold S. Lung epithelial GM-CSF improves host defense function and epithelial repair in influenza virus pneumonia-a new therapeutic strategy? Mol Cell Pediatr 2016; 3(1): 29.
138. Ohashi K, Sato A, Takada T, Arai T, Nei T, Kasahara Y et al. Direct evidence that GM-CSF inhalation improves lung clearance in pulmonary alveolar proteinosis. Respir Med 2012; 106(2): 284-93.
139. Peacock TP, Goldhill DH, Zhou J, Baillon L, Frise R, Swann OC et al. The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. Nat Microbiol 2021; 6(7): 899-909.
140. Cheng YW, Chao TL, Li CL, Chiu MF, Kao HC, Wang SH et al. Furin Inhibitors Block SARS-CoV-2 Spike Protein Cleavage to Suppress Virus Production and Cytopathic Effects. Cell Rep 2020; 33(2): 108254.
141. Hoffmann M, Kleine-Weber H, Pohlmann S. A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells. Mol Cell 2020; 78(4): 779-784 e5.
142. Coutard B, Valle C, de Lamballerie X, Canard B, Seidah NG, Decroly E. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antiviral Res 2020; 176: 104742.
143. Becker GL, Lu Y, Hardes K, Strehlow B, Levesque C, Lindberg I et al. Highly potent inhibitors of proprotein convertase furin as potential drugs for treatment of infectious diseases. J Biol Chem 2012; 287(26): 21992-2003.
144. Braun E, Sauter D. Furin-mediated protein processing in infectious diseases and cancer. Clin Transl Immunology 2019; 8(8): e1073.
145. Gagnon H, Beauchemin S, Kwiatkowska A, Couture F, D'Anjou F, Levesque C et al. Optimization of furin inhibitors to protect against the activation of influenza hemagglutinin H5 and Shiga toxin. J Med Chem 2014; 57(1): 29-41.
146. Xu Z, Peng C, Shi Y, Zhu Z, Mu K, Wang X et al. Nelfinavir was predicted to be a potential inhibitor of 2019-nCov main protease by an integrative approach combining homology modelling, molecular docking and binding free energy calculation. bioRxiv 2020: 2020.01.27.921627.
147. Hosogaya N, Miyazaki T, Fukushige Y, Takemori S, Morimoto S, Yamamoto H et al. Efficacy and safety of nelfinavir in asymptomatic and mild COVID-19 patients: a structured summary of a study protocol for a multicenter, randomized controlled trial. Trials 2021; 22(1): 309.
148. Ohashi H, Watashi K, Saso W, Shionoya K, Iwanami S, Hirokawa T et al. Potential anti-COVID-19 agents, cepharanthine and nelfinavir, and their usage for combination treatment. iScience 2021; 24(4): 102367.
149. Senzer N, Barve M, Nemunaitis J, Kuhn J, Melnyk A, Beitsch P et al. Long Term Follow Up: Phase I Trial of “bi-shRNA furin/GMCSF DNA/Autologous Tumor Cell” Immunotherapy (FANG™) in Advanced Cancer. Journal of Vaccines & Vaccination 2013; 4(8): 209.
150. Rocconi RP, Grosen EA, Ghamande SA, Chan JK, Barve MA, Oh J et al. Gemogenovatucel-T (Vigil) immunotherapy as maintenance in frontline stage III/IV ovarian cancer (VITAL): a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Oncol 2020; 21(12): 1661-1672.
151. Rocconi RP, Monk BJ, Walter A, Herzog TJ, Galanis E, Manning L et al. Gemogenovatucel-T (Vigil) immunotherapy demonstrates clinical benefit in homologous recombination proficient (HRP) ovarian cancer. Gynecol Oncol 2021; 161(3): 676-680.
152. Zhou W, Wang W, Wang H, Lu R, Tan W. First infection by all four non-severe acute respiratory syndrome human coronaviruses takes place during childhood. BMC Infect Dis 2013; 13: 433.
153. Lehmann AA, Kirchenbaum GA, Zhang T, Reche PA, Lehmann PV. Deconvoluting the T Cell Response to SARS-CoV-2: Specificity Versus Chance and Cognate Cross-Reactivity. Front Immunol 2021; 12: 635942.
154. Dan JM, Mateus J, Kato Y, Hastie KM, Yu ED, Faliti CE et al. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science 2021; 371(6529).