Effect of vaccine dose on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibody levels in a vaccinated community in Gowa Regency, Indonesia

Abstract

BACKGROUND:

The administration of the coronavirus disease 2019 (COVID-19) vaccine aims to stimulate the production of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies. This leads to an enhanced production of neutralizing antibodies (Nabs), which naturally neutralize the virus within the body, thereby reducing the risk of COVID-19 infection. This study determined the analysis of factors affecting SARS-CoV-2 antibody levels in vaccinated individuals using data from the COVID-19 Seroepidemiological Survey of Gowa Regency.

METHODS AND MATERIAL:

This was an analytic observational study with a cross-sectional design. The COVID-19 Seroepidemiology Survey data as a whole were 851 individuals, and in this study, the number of samples was 804 individuals from all COVID-19 Seroepidemiology Survey samples who had performed the COVID-19 vaccine in Gowa Regency, selected through purposive sampling.

STATISTICAL ANALYSIS USED:

Data analysis was conducted using various statistical tests, including the independent-samples t-test, Mann–Whitney test, Kruskal–Wallis test, and multiple logistic regression. Furthermore, the analysis was performed through the STATA program version 14.0.

RESULTS:

There was a significant influence between the history of COVID-19 infection (P = 0.0006) and dose of vaccine (P = 0.0001) with SARS-CoV-2 antibody levels in vaccinated individuals. Meanwhile, vitamin consumption and comorbid history did not affect SARS-CoV-2 antibody levels. Multivariate analysis showed that vaccine dose was the most influential variable on antibody levels (P = 0.046; Odds Ratio (OR) 0.19; 95% Confidence Interval (CI): 0.036–0.968).

CONCLUSIONS:

The most influential factor was the vaccine dose on SARS-CoV-2 antibody levels in community in Gowa Regency.

Introduction

Coronavirus disease 2019 (COVID-19) is a disease caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).[1] Common signs and symptoms of infection include fever, cough, and shortness of breath. Furthermore, the average incubation period is 5–6 days with the longest incubation period being 14 days. Severe cases can also lead to pneumonia, acute respiratory syndrome, kidney failure, and death.[2] Clinical manifestations found that most patients with SARS-CoV-2 infection have clinical features ranging from mild to severe respiratory illness. Compelling evidence also supports the occurrence of asymptomatic transmission of this infection, which has resulted in the inadequacy of current public health strategies to effectively control the spread.[3]

This virus was first detected in Wuhan City (Capital of Hubei Province, China) in late 2019. This virus was detected as SARS-CoV-2, a continuation of the SARS virus, which had an outbreak in early 2002 but did not cause a global pandemic, while SARS-CoV-2 quickly spreads around the world.[4]

According to the World Health Organization (WHO)’s cumulative COVID-19 data as of June 7, 2023, a total of 767,750,853 confirmed cases have been recorded, with 6,941,095 deaths (0.9%). In the Southeast Asia region, Vietnam stands as the country with the highest number of confirmed cases at 11,590,617 individuals, followed by Indonesia and Malaysia.[5]

The confirmed cases in Indonesia amounted to 6,810,599 with 161,832 death cases (2.4%). South Sulawesi is the 11^th province with the most confirmed cases in Indonesia,[2] while Gowa Regency is in second place after Makassar City with 11,427 cases and 136 deaths.

The increasing transmission, especially in Indonesia, requires control that can reduce the morbidity rate of the disease. One of the transmission controls is by vaccinating the entire community to form an SARS-CoV-2 antibody. The main objective of vaccination is the achievement of immunogenicity, namely the ability of vaccine to stimulate the emergence of neutralizing antibody (Nab) to reduce the risk of infection or experiencing infection with severe symptoms when compared to the non-vaccinated group.[6]

There are also intrinsic factors such as comorbid history and behavior, including maintaining body immunity by taking vitamin, which can affect the magnitude and persistence of antibody responses. The data showed that individuals who had SARS-CoV-2 infection before vaccination increased SARS-CoV-2 antibody levels.[7]

Research conducted by Elizabeth Fraley et al.[7] (2022) stated that many intrinsic and behavioral factors can affect the magnitude and persistence of antibody responses. The data obtained showed that individuals who had SARS-CoV-2 infection before vaccination or younger individuals had significantly higher antibody levels after primary immunization with the SARS-CoV-2 Mesenger Ribonukleat Acid (mRNA) vaccine and had a significantly longer antibody half-life measured at 7 months after vaccination.

The results of research conducted by Watanabe et al.[8] (2022) mentioned that the multivariate analysis showed that a history of comorbidities in respondents with the second vaccine was associated with lower Ab titers, while research related to vaccine doses by Lias Bensouna et al.[9] (2022) mentioned that the third dose of BNT162b2 vaccine substantially increased antibody levels in patients receiving maintenance dialysis and appeared to be as well tolerated as the second dose.

The information pertains to COVID-19 cases and strategies for their containment through the augmentation of SARS-CoV-2 antibody levels within the human body. Consequently, considerable interest has been shown in conducting studies about the analysis of factors that influence levels of SARS-CoV-2 antibody in individuals vaccinated in Gowa Regency. The primary objective is to comprehend and examine the factors that impact levels of SARS-CoV-2 antibody in vaccinated individuals.

Materials and Methods

Study design and setting

This study was conducted using an analytical observational approach through a cross-sectional design in Gowa Regency, South Sulawesi Province.

Study participants and sample

The number of samples was 804 respondents, in the form of SARS-CoV-2 serology data and questionnaire data. The sampling technique employed was purposive sampling, employing specific inclusion criteria. These criteria encompassed all participants in the seroepidemiological survey who had received at least one dose of COVID-19 vaccine in Gowa Regency. Additionally, the samples included individuals with complete data, encompassing questionnaire responses and serology data in the form of laboratory results.

These 804 individuals come from all seroepidemiological survey samples who have performed the COVID-19 vaccine in Gowa Regency at least the first dose vaccine and samples that have complete data, both questionnaire data and serology data in the form of laboratory results. So, of the 851 samples with complete data, 804 samples who have performed the vaccine were obtained.

Data collection tools and technique

This study used secondary data from the results of the implementation of the COVID-19 Seroepidemiological Survey conducted in March 2022. Data in the form of SARS-CoV-2 serology results and questionnaires were related to the variables studied.

Ethical consideration

Permission to conduct further analysis was obtained through a certificate from the Department of Epidemiology, Faculty of Public Health, Hasanuddin University with Number: 13355/UN4.14.7.1/PT.01.00/2022, and ethical approval from the Faculty of Public Health, Hasanuddin University with Number 3008/UN4.14.1/TP. 01.02/2023.

Data analysis

Data processing and analysis were performed using the STATA version 14.0 program. The bivariate analysis employed an independent-samples t-test, Mann–Whitney, and Kruskal–Wallis to determine which variables had a significant influence on SARS-CoV-2 antibody levels and multivariate analysis. Meanwhile, multiple logistic regression tests with the backward method were used to determine the variables most associated with SARS-CoV-2 antibody levels in a vaccinated community in Gowa Regency.

Results

Table 1 shows that the total sample consisted of 804 respondents, who were mostly females with a proportion of 52.49% and men by 47.51%. Based on age group, most respondents were in the age group of 30–49 years, consisting of 393 individuals (48.88%), while the least was in 1–14 years comprising 45 individuals (5.60%).

Table 1.

Distribution based on respondent characteristics

Respondent characteristics	Total (n=804)	Percentage (%)
Gender
Male	382	47.51
Female	422	52.49
Age (year)
1–14	45	5.60
15–29	163	20.27
30–49	393	48.88
≥50	203	25.25
SARS-CoV-2 antibody levels (AU/ml)
<50	5	0.62
50–1000	50	6.22
1001–10000	419	52.11
>10000	330	41.04
Categorical antibody levels
Nonreactive	5	0.62
Reactive	799	99.38

Source: COVID-19 Seroepidemiology Survey Data of Gowa Regency, 2022

A significant proportion of the respondents, specifically 799 individuals (99.38%), exhibited the presence of SARS-CoV-2 antibody or showed reactivity. Among these respondents, the highest percentage was observed in the category of SARS-CoV-2 antibody levels ranging from 1001 to 10000 AU/ml, accounting for 52.11%. In contrast, a mere five respondents (0.62%) did not possess antibody or reported non-reactivity.

Table 2 shows that the highest average antibody level obtained in respondents who took vitamin was 12,524.201 AU/ml. This was higher than those who did not take vitamin at 11,380.488 AU/ml. For the comorbid history variable, the average antibody level in respondents who had a history of comorbidities was 12,225.399 AU/ml. Meanwhile, in respondents who did not have a history of comorbidities the average antibody level was 11,649.568 AU/ml.

Table 2.

Effect of study variables on SARS-CoV-2 antibody levels in community

Determinants of SARS-CoV-2 antibody levels	SARS-CoV-2 antibody levels (AU/ml)					P
	n (804)	Min	Max	Mean	SD
Vitamin consumption status
Yes	239	0	40001	12524.201	10955.08
No	565	0	40001	11380.488	10497.3
Comorbid history status
Yes	99	408	40001	12225.399	9744.606	0.6144*
No	705	0	40001	11649.568	10765.94
History of COVID-19 infection
Yes	60	172	40001	16366.068	12368.77	0.0006**
No	744	0	40001	11345.828	10409.29
Vaccine dose
One dose	86	0	40001	9389.545	9956.076	0.0001***
Two doses	576	0	40001	10922.143	10074.98
Three doses	142	76	40001	16370.455	11979.99

Source: COVID-19 Seroepidemiology Survey Data of Gowa Regency, 2022. *Independent t-test. **Mann–Whitney test. ***Kruskal–Wallis test

Regarding the variable of COVID-19 infection history, the average high antibody level obtained in respondents who had a history of COVID infection was 16,366.068 AU/ml compared with respondents who did not have any history at 11,345.828 AU/ml. Regarding the variable of vaccine dose, respondents who received three doses had the highest average antibody levels, reaching 16,370.455 AU/ml. Conversely, those who only received one dose exhibited the lowest average antibody levels, measuring at 9,389.545 AU/ml.

The results of statistical analysis using Mann–Whitney and Kruskal–Wallis showed that variables with a significant effect on SARS-CoV-2 antibody levels included a history of COVID-19 infection (P = 0.0006) and vaccine dose (P = 0.0001). The variables that did not influence antibody levels using the independent-samples t-test were vitamin consumption (P = 0.1638) and comorbid history (P = 0.6144).

Table 3 shows that there were two models in the multivariate analysis. Furthermore, three variables had a P value below <0.25 included in the multivariate test, namely vitamin consumption, infection history, and vaccine dose. After multivariate analysis with a logistic regression test, the variable most associated with SARS-CoV-2 antibody levels was vaccine dose (P = 0.043; OR 0.19; 95% CI: 0.038–0.949) after excluding the time interval of the last vaccination and adverse effect. There were no confounders or interacting variables in the multivariate test.

Table 3.

Results of multivariate analysis between independent variables and SARS-CoV-2 antibody levels

Study variables	Model 1		Model 2
	P	OR (95% CI)	P	OR (95% CI)	Coef.	Cons.
Vitamin consumption status	0.895	0.86 (0.093-7.923)
History of COVID-19 infection		1
Vaccine dose	0.059	0,20 (0.038-1.062)	0.043	0.19 (0.038-0.949)	-1.668	7.010

OR : Odds ratio, CI : Confidence interval

Discussion

This study discusses the factors that influence SARS-CoV-2 antibody levels in vaccinated individuals in Gowa District, where the independent variables studied are vitamin consumption, comorbid history status, COVID-19 infection history status, and vaccine dose. From the results of the bivariate analysis, there are two variables associated with antibody levels, namely COVID-19 infection history and vaccine dose [Table 2]. The multivariate analysis found that the most influential factor was the vaccine dose variable [Table 3].

In the results of the study, it was found that there was no influence between vitamin consumption variables and SARS-CoV-2 antibody levels in people who had been vaccinated in Gowa Regency with P value = 0.163. The results of the analysis showed that the average antibody level in respondents who took vitamin was 12,524.201 AU/ml higher than the average antibody level in respondents who did not take vitamin, which was 11,380.488 AU/ml.

The results of research conducted by Yani et al.[10] (2021) explained that taking vitamin regularly can be beneficial during the new normal era. Another study, the benefits of taking vitamin D conducted by Utami and Yasmon (2022), explained that the active form of vitamin D provides activity in innate and acquired immune responses and endothelial membrane stability. Another study describing the benefits of taking vitamin D conducted by Utami and Yasmon (2022) explained that the active form of vitamin D provides activity on innate and acquired immune responses and endothelial membrane stability[11] and can modulate the immune system, so it is recommended to be consumed to reduce the transmission of SARS-CoV-2 by increasing antiviral immunity.[12]

The results of bivariate analysis of comorbid history status variables on the formation SARS-CoV-2 antibody levels in people who have vaccinated the P value = 0.614, which means that there is no influence between comorbid history status and SARS-CoV-2 antibody levels in people who have vaccinated. From the results of the average antibody levels obtained, respondents who have a history of comorbidities have high average antibody levels compared with respondents who do not have a history of comorbidities. This happens because all respondents with comorbidities have antibody levels in their bodies, while for those without a history of comorbidities several respondents do not have SARS-CoV-2 antibody levels in their bodies (nonreactive).

Different from the results of a study conducted by Farid et al.[13] (2022), which states that participants over 50 years old with comorbidities and have done a complete vaccine, have lower levels of Spike (S) antibodies, revealing that both age and the original health of a person disrupt the development of immune antibodies.

Another study that differs from the results of the study conducted by Watanabe et al.[8] (2022) states that, from multivariate analysis, a history of comorbidities in respondents with the second vaccine is associated with lower Ab titers.

The results showed that individuals with a history of infection influence antibody levels (P = 0.0006). Therefore, the occurrence of a history of COVID-19 infection in vaccinated individuals has high levels of SARS-CoV-2 antibody compared with those getting medication from vaccination without a history of previous infection. This is because someone who has a history of infection has been previously exposed to the pathogen. For individuals who are infected or sick, the next immune system to work is the adaptive immune or specific immune system, which is performed mainly by T lymphocytes, B lymphocytes, and dendritic cells.[14]

The cooperation of the three cells produces antibody that can eliminate the virus by various mechanisms and lead to an increased antibody response, with the achievement of immunoglobulin G (IgG) levels.[15]

The results are in line with a study conducted by Igawa et al.[16] (2022), where almost all health workers produced S-specific antibody after vaccination. However, health workers with COVID-19 produce higher titers of antibody than those who are unaffected by COVID-19. Furthermore, Busch et al.[17] (2022) found that seropositivity due to previous infection without vaccination decreased from 15.6% (15.2–16.0%) to 11.7% (11.4–12.0%) and increased from 0.7% (0.6–0.7%) to 18.9% (18.5–19.3%). The combined seroprevalence of infection, vaccination, or both increased from 19.8% (19.3–20.2%) to 94.5% (93.5–94.0%). However, a history of COVID-19 infection does not protect 100% against recurrent infection and offers the public the idea that vaccination can provide additional protection.[18]

The analysis of vaccine dose variables affects SARS-CoV-2 antibody levels (P = 0.0001) and is the most influential factor on antibody levels in Gowa Regency. The probability of antibody levels in vaccinated individuals with a complete vaccine dose is 99.5%.

In some cases, multi-dosing is essential to receive the highest levels of immunity.[15] Salvador et al.[19] 2019 reported that vaccine should be given in two or three injections to stimulate the formation of high antibody titers. In theory, the administration of a complete vaccine dose combined with a booster can increase levels of antibody. Administration of the third vaccine dose substantially increased anti-S1 antibody levels, with acceptable vaccine reactions and overall self-reported tolerance similar to the second dose.[9]

These results are in line with Tanaka et al.[20] (2020) who found that a total of 636 health workers participated in this study with the results. The peak anti-spike protein (SP) immunoglobulin G (IgG) titer after the third dose was approximately 4.1-fold higher than after the first and second doses. The rate of decline in anti-SP immunoglobulin G (IgG) titer after the third dose was significantly more gradual than after the second.Lam et al.[21] (2022) stated that vaccination is one of the effective ways to control SARS-CoV-2 transmission and reduce disease severity. Another study found that hesitation to vaccinate is an important cause of the incidence and prevalence of COVID-19 cases.[22] In some types of vaccine, several doses are given because not all individuals respond proportionally and sufficiently to a single dose.[23]

It is important to administer a booster dose since the COVID-19 vaccine loses its effect after the fifth month due to a decline in Ab levels. In addition, individuals with no prior history of infection should be prioritized in vaccination since antibody levels decline subsequently in those affected by the disease.[24] The administration of booster vaccinations combined with vaccine knowledge can increase antibody levels in the body and last for a long period of time.[25,26]

Limitations and recommendation

The utilization of secondary data was observed without adequate consideration for previous study, resulting in limited awareness of the current situation in the field.

For further studies with the same discussion, to conduct research with other variables related to factors that affect SARS-CoV-2 antibody levels, such as environmental factors, geography, behavioral factors, and nutritional intake factors.

Conclusions

In conclusion, the main source of COVID-19 vaccination in Gowa Regency was the formation of SARS-CoV-2 antibody levels among the community. Subsequently, it was strengthened by the administration of vaccine dose and the history of COVID-19 infection. This was because natural SARS-CoV-2 infection (infection-induced immunity) or vaccination (hybrid immunity) stimulated the immune response to form antibody and the most influential factor was the vaccine dose compared with other variables.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.