A comprehensive search was carried out in mainstream bibliographic databases or Medical Subject Headings, including ScienDirect, PubMed, Scopus, and ISI Web of Science. The search was applied to the articles that were published between January 2020 and early 2023 with strict literature search and screening processes, it yielded 14 articles from 373 articles of initial literature database. Among 14 study results, there was acceptable for immunogenicity (both humoral and cellular immune responses (a key response for the development of a vaccination-induced immunogenicity and safety in 11 studies (78.57 %), whereas acceptable potent immunogenicity was found in patients aged more than 40 years with chronic diseases, particularly, chronic respiratory diseases and coronary artery diseases. Only potent T-cell response was identified in one study. No significant difference in vaccine safety compared with healthy subjects and effective neutralizing antibodies (two doses completion) against SARS-CoV-2 (COVID-19) in patients older than 60 years with diabetes and/or hypertension were demonstrated after completion of COVID-19 vaccination. Immunogenicity (both humoral and cellular) and safety in aged people and individuals living with various chronic diseases (both infectious and non-infectious) is highlighted in this study. In conclusion, specified local and systemic AEs and unsolicited AEs, AESI, and SAEs after each vaccination and after the second dose should be monitored. Recording the adverse events of special interest (AESI) and serious adverse events (SAEs) throughout the patients’ vaccination course should be performed and can decrease COVID-19 vaccination hesitancy in these persons.

Keywords: adverse reactions, covid-19, immunogenicity, neutralizing antibody, safety, vaccine, titer

AEs, adverse events; AESI, adverse events of special interest; BNT, Pfizer vaccine (BNT162b1, BNT162b2); ChAd, AstraZeneca vaccine (AZD1222 or ChAdOx-nCov19); CI, confidential interval, COVID-19 : coronavirus disease 2019, ELISA: enzyme-linked immunosorbent assay; GMR, geometric mean ratio; HIV, human immunodeficiency virus; IMIDs, immune-mediated inflammatory diseases; GMT, geometric mean titer; MNA, microneedle assay; PLWH, people living with human immunodeficiency virus; SAEs, serious adverse events; VLA, Valneva (VLA2001) vaccine

To identify immunogenicity and safety profiles of COVID-19 vaccination (two or three doses) among patients with various medical conditions, such hypertension, diabetes, endocrine diseases/disorders, neurological diseases/disorders, malignancies, organ transplantation, solid-organ transplantation, etc.

Several COVID-19 vaccines were developed to limit its ability to spread.¹ Currently, several studies support immunogenicity and safety of a third-dose-COVID-19 vaccination in healthy persons, patients with hematological malignancies, and solid-organ-transplant recipients, but are still questionable in patients with immune-mediated inflammatory diseases (IMIDs).^2–18

Search strategy and inclusion criteria

A comprehensive search was carried out in mainstream bibliographic databases or Medical Subject Headings, including ScienDirect, PubMed, Scopus, and ISI Web of Science, following the PRISMA guidelines. The search was applied to the articles that were published between January 2020 and early 2023 [Figure 1]. Our first involved performing searches of article abstract/keywords/title using strings of [(“ COVID-19 ” or “ SARS-CoV-2 ”, “ severe-acute-respiratory-syndrome-coronavirus-2 ”, “ coronavirus-disease 2019 ”, “ nCoV 2019 ”, “ SARS-CoV-2 vaccines ”, “ COVID-19 vaccines ”, SARS-CoV-2 vaccination ”, “ COVID-19 vaccination ”, “ efficacy ”, “ immunogenicity ”, “ safety ”, “ medical conditions ”, “ metabolic ”, “ immunocompromised ”, “ organ transplant “, “ solid-organ transplant ”, “ malignant or cancer ”, “ pulmonary ” or “ lung ”, “ renal ” or “ nephrological ”, “ endocrinological .”, “ diabetic ”, “ hypertension ”, “ hypertensive ”, “ obese ”, “ obesity ” ]. After a first approach of search, published articles focusing on medical conditions or diseases or disorders that related to SARS-CoV-2 or COVID-19 vaccine immunogenicity and safety were retained and the information on COVID-19-related medical conditions or diseases or disorders was extracted for having a crude knowledge involving their themes. Another round of publication search was conducted for adding the missing published articles that were not identified by the first round.

All keywords combinations from medical conditions or disease types and SARS-CoV-2 (COVID-19) vaccine efficacy (immunogenicity and safety) variables to bind the population of cases under consideration. Search string for disease groups include [“ SARS-CoV-2 vaccines (vaccination)” or “ COVID-19 vaccines (vaccination) ” or “ medical conditions ” or “ medical diseases ” or “ immunocompromised ” or “ organ transplant “ or “ solid-organ transplant ” or “ malignant or cancer ” or “ pulmonary ” or “ lung ” or “ endocrinological ” or “ diabetic ” or “ renal ” or “ nephrological ” or “ hypertension ” or “ hypertensive ” or “ obese ” or “ obesity ”]. The initial literature databases were further manually screened with the following rules : 1) non-SARS-CoV-2 (COVID-19)-related articles were excluded; 2) articles that did not report immunogenicity and safety related to SARS-CoV-2 (COVID-19) vaccines (vaccination) were not considered, such as commentary articles, or editorial; 3) non-peer reviewed articles were not considered to be of a scholarly trustworthy validity; and 4) duplicated and non-English articles were removed. The articles were carefully selected to guarantee the literature quality, which is a trade-off for quantity (Figure 1).

SARS-CoV-2 (COVID-19)-immunogenicity-and-safety-efficacy-related medical conditions or medical diseases or medical disorders on human health

Figure 1 Literature search and screening flow.

With strict literature search and screening processes, it yielded 14 articles (Table 1) from 373 articles of initial literature database. Needed article information was extracted from each article by : 1) direct information including journal, title, authors, abstract, full text documents of candidate studies, publishing year; 2) place name of the study area; 3) study period; 4) research method used; 5) type of variables studied; 6) types of SARS-CoV-2 (COVID-19)-immunogenicity- and-safety-efficacy-related medical conditions or diseases or disorders studied; and 7) the conclusions made about the impacts of SARS-CoV-2 (COVID-19)-immunogenicity-and-safety-efficacy-related medical conditions or medical diseases or medical disorders on human health.

Among 14 study results,^19–32 there was acceptable for immunogenicity, a key response for the development of a vaccination-induced immunogenicity both humoral and cellular immunity 2 or 3 doses of vaccination)¹⁹ and acceptable safety in 11 studies (78.57 %). Acceptable potent immunogenicity was found in patients aged more than 40 years with chronic diseases, particularly, chronic respiratory diseases and coronary artery diseases.²⁶ Only potent T-cell response was identified in one study,²⁷ and there was no significant difference in vaccine safety compared with healthy subjects.²⁴ Effective neutralizing antibodies (two doses completion) against SARS-CoV-2 (COVID-19) in patients older than 60 years with diabetes and/or hypertension²⁴ were demonstrated after completion of COVID-19 vaccination. After completion of COVID-19 vaccination, females revealed higher immune response than males.²⁴ SII-NVX-CoV2373-vaccine-related-adverse-events (AEs) incidence was higher, compared to the healthy controls.²⁰ In India, among adults, SII-NVX-CoV2373 vaccine revealed well tolerated, safe, and immunogenic.²⁰ Pooled seroconversion rate in people living with HIV (PLWH) after the first and second doses were 67.51 and 96.65 %, respectively.²¹ In lung-cancer patients, number of doses (third dose, etc.) and intervals of mRNA-COVID-19 vaccination are suggested to maintain effective immunity.²² In young children, after full vaccination with WIBP-CorV, antibody response was characterized up to 180 days.²³ In COVID-19-vaccination safety control, actively monitoring for specified local and systemic AEs and unsolicited AEs for 7 days after each vaccination and for 2 weeks after the second dose, respectively, by using structures diary cards or online-platform cards.²⁰ Adverse events of special interest (AESI) and serious adverse events (SAEs) should be recorded throughout the patients’ vaccination course.²⁰ To our knowledge, age, an important factor that has been documented in other COVID-19 vaccines (Corona Vac, BNT162b2 and an adenovirus-vectored COVID-19 vaccine) in influencing vaccine responses.²³ Inducing antibody response was higher in children and adolescent than in adults and aged people.²³

Immunogenicity (both humoral and cellular) and safety in aged people and individuals living with various chronic diseases (both infectious and non-infectious) is highlighted in this study. Specified local and systemic AEs and unsolicited AEs, AESI, and SAEs after each vaccination and after the second dose should be monitored. Recording the adverse events of special interest (AESI) and serious adverse events (SAEs) throughout the patients’ vaccination course should be performed and can decrease COVID-19 vaccination hesitancy in these persons.

Dr. Attapon Cheepsattayakorn conducted the study framework and wrote the manuscript. Associate Professor Dr. Ruangrong Cheepsattayakorn and Professor Dr. Porntep Siriwanarangsun contributed to scientific content and assistance in manuscript writing. All authors read and approved the final version of the manuscript..

There are no conflicting interests declared by the authors.

None.

1. Keech C, Albert G, Cho I, et al. Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. N Engl J Med. 2020;383(24):2320–2332.  
2. Hall VG, Ferreira VH, Ku T, et al. Randomized trial of a third dose of mRNA-1273 vaccine in transplant recipients. N Engl J Med. 2021;385(13):1244–1246.  
3. Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA COVID-19 vaccine in solid-organ transplant recipients. N Engl J Med. 2021;385(7):661–662.  
4. Benotmane I, Gautier G, Perrin P, et al. Antibody response after a third dose of the mRNA-1273 SARS-CoV-2 vaccine in kidney-transplant recipients with minimal serologic response to 2 doses. JAMA. 2021;326(11):1063–1065.  
5. Saiag E, Grupper A, Avivi I, et al. The effect of a third-dose BNT162b2 vaccine on anti-SARS-CoV-2 antibody levels in immunosuppressed patients. Clin Microbiol Infect. 2022;28(5):735.e5–735.e8.  
6. Aikawa NE, Kupa LdeVK, Mediros Ribeiro AC, et al. Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases. Ann Rheum Dis. 2022;81(7):1036–1043.  
7. Azzolini E, Pozzi C, Germagnoli L, et al. mRNA COVID-19 vaccine booster fosters B- and T-cell responses in immunocompromised patients. Life Sci Alliance. 2022;5(6):e202201381.  
8. Tenforde MW, Patel MM, Gaglani M, et al. Effectiveness of a third dose of Pfizer-BioNTech and Moderna vaccines in preventing COVID-19 hospitalization among immunocompetent and immunocompromised adults-United States, August-December 2021. MMWR Morb Mortal Wkly Rep. 2021;71(4):118–124.  
9. Yue L, Zhou J, Zhou Y, et al. Antibody response elicited by a third boost dose of inactivated SARS-CoV-2 vaccine can neutralize SARS-CoV-2 variants of concern. Emerg Microbes Infect. 2021;10(1):2125–2127.  
10. Schmiedeberg K, Vuilleumler N, Pagano S, et al. Efficacy and tolerability of a third dose of an mRNA anti-SARS-CoV-2 vaccine in patients with rheumatoid arthritis with absent or minimal serological response to two previous doses. Lancet Rheumatol. 2022;4(1):e11–e13.  
11. Karaba All, Zhu X, Liang T, et al. A third dose of SARS-CoV-2 vaccine increases neutralizing antibodies against variants of concern in solid-organ transplant recipients. Am J Transplant. 2022;22(4):1253–1260.
12. Bar On YM, Goldberg Y, Mandel M, et al. Protection of BNT162b2 vaccine booster against COVID-19 in Israel. N Engl J Med. 2021;385(15):1393–1400.  
13. Bensouna I, Caudwell V, Kubab S, et al. SARS-CoV-2 antibody response after a third dose of the BNT162b2 vaccine in patients receiving maintenance hemodialysis or peritoneal dialysis. Am J Kidney Dis. 2022;79(2):185–192.  
14. Bertrand D, Hamzaoui M, Leme´e V, et al. Antibody and T-cell response to a third dose of SARS-CoV-2 mRNA BNT162b2 vaccine in kidney-transplant recipients. Kidney Int. 2021;100(6):1337–1340.  
15. Le Bougeois A, Coste Burel M, Guillaume T, et al. Interest of a third dose of BNT162b2 anti—SARS-CoV-2 messenger-RNA vaccine after allotransplant. Br J Haematol. 2022;196(5):e38–e40.  
16. Marlet J, Gatault P, Maakaroun Z, et al. Antibody responses after a third dose of COVID-19 vaccine in kidney-transplant recipients and patients treated for chronic lymphocytic leukemia. Vaccines. 2021;9(10):1055.  
17. Reindl Schwaighofer R, Heinzel A, Mayrdorfer M, et al. Comparison of SARS-CoV-2 antibody response 4 weeks after homologous vs heterologous third vaccine dose in kidney-transplant recipients: a randomized clinical trial. JAMA Intern Med. 2022;182(2):165–171.  
18. Mair MJ, Berger JM, Mitterer M, et al. Third dose of SARS-CoV-2 vaccination in hemato-oncological patients and healthcare workers : immune responses and adverse events-a retrospective cohort study. Eur J Cancer. 2022;165:184–194.  
19. Kartnig F, Mrak D, Simader E, et al. Safty and immunogenicity of a third COVID-19 vaccination in patients with immune-mediated inflammatory diseases compared with healthy controls. Ann Rheum Dis. 2023;82(2):292–300.  
20. Kulkarni PS, Kadam A, Godbole S, et al. Safety and immunogenicity of SII-NVX-CoV2373 (COVID-19 vaccine) in adults in a phase 2/3, observer-blind, randomized controlled study. Lancet Reg Health Southeast Asia. 2023;10:100139.
21. Kang L, Shang W, Gao P, et al. Immunogenicity and safety of COVID-19 vaccines among people living with HIV : a systematic review and meta-analysis. Vaccines. 2022;10(9):1569.  
22. Hibino M, Uryu K, Takeda T, et al. Safety and immunogenicity of mRNA vaccines against severe acute respiratory syndrome coronavirus 2 in patients with lung cancer receiving immune checkpoint inhibitors : a multicenter observational study in Japan. J Thorac Oncol. 2022;17 (8):1002–1013.  
23. Xia S, Duan K, Zhang Y, et al. Safety and immunogenicity of an inactivated COVID-19 vaccine, WIBP-CorV, in healthy children : interim analysis of a randomized, double-blind, controlled, phase ½ trial. Front Immunol. 2022;13:898151.  
24. Huang R, Liu X, Xie F, et al. Safety and immunogenicity of inactivated SARS_CoV-2 vaccine (BBIBP-CorV) in hypertensive and/or diabetic people aged over 60 years: a prospective open-label study. Diabetes Ther. 2023;14(1):139–151.  
25. Yang B, Huang X, Gao H, et al. Immunogenicity, efficacy, and safety of SARS-CoV-2 vaccine dose fractionation : a systematic review and meta-analysis. BMC Med. 2022;20(1):409.  
26. Li C, Bi H, Fu Z, et al. Retrospective study of the CoronaVac SARS-CoV-2 vaccine in people with underlying medical conditions. Commun Med. 2022;2(1):151.
27. Song JW, Hu W, Shen L, et al. Safety and immunogenicity of COVID-19 vaccination in immunocompromised patients. Chin Med J. 2022;135(22):2656–2666.
28. Zakarya K, Kutumbetov L, Orynbayev M, et al. Safety and immunogenicity of a QazCovid-in® inactivated whole-virion vaccine against COVID-19 in healthy adults : a single-centre, randomized, single-blind, placebo-controlled phase 1 and open-label phase 2 clinical trials with a 6 months follow-up in Kazakhstan. EClinicalMedicine. 2021;39:101078.  
29. French RW Jr, Klein NP, Kitchin N, et al. Safety, immunogenicity, and efficacy of the BNT162b2 COVID-19 vaccine in adolescents. N Engl J Med. 2021;385(3):239–250.
30. Munro APS, Janani L, Cornelius V, et al. Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCoV-19 or BNT162b2 in the UK (COV-BOOST) : a blinded, multicentre, randomized, controlled, phase 2 trial. Lancet. 2021;398(10318):2258–2276.  
31. Xia S, Duan K, Zhang Y, et al. Effect of an inactivated vaccine against SARS-CoV-2 on safety and immunogenicity outcomes: interim analysis of 2 randomized clinical trials. JAMA. 2020;324(10):951–960.
32. Walsh EE, French RW, Falsey AR, et al. Safety and immunogenicity of two RNA-based COVID-19 vaccine candidates. N Engl J Med. 2020;383(25):2439–2450.