Evaluation of SARS-Cov-2 neutralizing antibody among Sinopharm Vero Cell (BBIBP-CorV) vaccinated medical students

Abstract

BACKGROUND:

Information regarding seropositivity and vaccine efficacy among medical students is scarce. This study aims to detect the status of SARS-CoV-2 neutralizing antibodies among the Sinopharm’s Vero Cell (BBIBP-CorV) vaccinated medical students.

MATERIALS AND METHODS:

A prospective, cross-sectional study was carried out among medical students of Gandaki Medical College Teaching Hospital, Pokhara, Nepal from March through August 2022. The level of SARS-CoV-2 serum- neutralizing IgG antibody was measured and its relation with participants’ age and sex, duration of vaccination, and any comorbid condition was determined.

RESULTS:

A total of 110 medical students were included in the final analysis, the majority being females (65.5%) and the mean age is 23.1 $\pm$ 3.2 years. Most of the students (96.4%) had neutralizing antibodies against SARS-CoV-2. Among the 29 (26.36%) students who received a booster dose, the positivity rate was 100%. The mean IgG levels were 9.57 $\pm$ 9.58 $\mu$ g/ml and 2.91 $\pm$ 2.47 $\mu$ g/ml among students receiving an additional booster dose and among those not receiving it, respectively. In the cohort receiving a booster dose of the vaccine, the average value of neutralizing IgG antibodies was high. In contrast, the ones not receiving it, the titers were low and showed a declining trend.

CONCLUSION:

Though the dose strategy of the Sinopharm vaccine is effective, booster vaccination may be an important strategy to ensure protection among medical students, who are at high risk of COVID-19 due to constant patient exposure during their training. Further studies should assess vaccine efficacy among individuals who received other vaccines as well.

Keywords

Medical students neutralizing antibody seropositive sinopharm vaccine

1. Introduction

Assumed to be transmitted from pangolin to humans, the first case of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) was described on November 17, 2019, in Wuhan, China. The World Health Organization (WHO) proclaimed the pandemic on March 11, 2020, which has become the largest pandemic of the twenty-first century [1, 2]. Since January, shortly after the discovery of the virus, real-time reverse transcription polymerase chain reaction (RT-PCR) has been used to diagnose infections since it is sensitive and effective at detecting viral infection [3, 4]. To date, there is no specific treatment for this illness, and vaccination remains the best population-based measure to prevent the infection and decrease the disease severity [5].

The BBIBP-CorV vaccine, popularly known by the name of Sinopharm, is an inactivated whole virus vaccine manufactured by the Beijing Institute of Biological Products Co., Limited (BIBP). This vaccine delivers SARS-CoV-2 antigens to the body through two or three intramuscular injections, to produce antibodies that boosts the immune system to combat subsequent COVID-19 viral attacks [6] Nepal began the COVID-19 immunization campaign on January 27, 2021, to combat the pandemic [7]. On March 29, 2021, China supplied the Vero Cell vaccine created by China’s BIBP under Sinopharm for emergency usage in Nepal after it was approved by the Department of Drug Administration on February 17 [8]. The Ministry of Health and Population reports that more than 9 million people have received the Vero cell vaccination in two doses, and more than 400,000 have received a third dose, as of August 24 2022 [9].

Following vaccination or virus infection, COVID-19 antibodies develop over a few days to a few weeks [10]. These antibodies include specific anti-S protein antibodies that target the spike’s S1 protein subunit and receptor-binding domains (RBD) [11]. Antibody testing among the vaccinated cohort will help ascertain the immune response following vaccination. Medical students are at high risk of getting infected. Still there is lack of information pertinent to medical students regarding the level of protection against SARS-CoV-2, even at the global stage. This study will assess the level of IgG- neutralizing antibodies produced on vaccinated medical students to evaluate the level of SARS-CoV-2 immunity, and in turn, the effectiveness of the Sinopharm vaccine.

2. Materials and methods

2.1 Study design and study population

A cross-sectional study was carried out among medical students of Gandaki Medical College Teaching Hospital and Research Center (GMCTHRC), Pokhara, Nepal from March through August 2022. All the medical students enrolled in the Bachelor of Medicine and Bachelor of Surgery (MBBS) program at GMCTHRC were invited to participate.

Cochran’s formula was used to estimate the sample size: $N=Z^{2}\times p\times(1-p)/d^{2}$ .

The level of SARS CoV-2 serum neutralizing IgG antibody is unknown ( $P=$ 0.5). Based on the degree of evidence that can be achieved on 95% confidence interval ( $Z=$ 1.96) and 10% margin of error ( $e=$ 0.10), the sample size was determined to be 96. Considering 10% ( $n=$ 10) data to be incomplete or invalid, the total sample size was estimated to be around 110.

A total of 110 medical students who received at least two doses of Sinopharm’s Vero Cell (BBIBP-CorV) vaccine against SARS-CoV-2 and crossed 21 days of vaccination were included. We excluded the participants who did not receive any vaccine or tested positive for COVID-19 and those who didn’t receive both doses of Sinopharm vaccine. We also excluded people who were cross-vaccinated or under immunosuppressive drug therapy.

2.2 Executive methodology

Five milliliters of blood sample were collected from the study participants using venipuncture of the median cubital vein. A code number identified the sample and different details like age, sex, and any comorbidities were noted. The samples were then brought to the Microbiology laboratory of GMCTHRC to detect neutralizing antibodies. Antibody level was measured using MAGLUMI^® SARS-CoV-2 Neutralizing Antibody detection kit. The assay was fully automated Chemoluminescence immunoassay (CLIA) run in a closed system, Maglumi 2000 CLIA analyzer. Positive results were defined by neutralizing antibody levels greater than 0.300 $\mu$ g/ml.

2.3 Statistical methods

The collected data were all entered into MS Excel and checked for accuracy. After data cleaning, it was imported and analyzed by using SPSS (Statistical Package for Social Sciences) 20. Descriptive statistics and Chi-square test was used for analysis. The p-value for statistical significance was set as less than 0.05.

2.4 Ethical consideration

This study was approved by the Institutional Review Committee of GMCTHRC (Ref no: 165/079/080). Written informed consent was obtained from the study participants after the objectives and procedure in detail. The anonymity of the study participants was maintained throughout.

3. Results

Table 1
Demographic information

Individuals not receiving a booster dose of Sinopharm vaccine:
Demographic variables	Frequency (N)	Percentage
Sex:
Male	38	34.5
Female	72	65.5
Total	110
Male	28	34.6
Female	53	65.4
Total	81
Individuals receiving a booster dose of Sinopharm vaccine:
Male	10	34.5
Female	19	65.5
Total	29
IgG positivity:
Yes	106	96.3
No	4	3.7
Total	110

The demographic and general characteristics of our study population is summarized in Table 1. A total of 110 medical students were included in the final analysis. The mean age was 23.1 $\pm$ 3.2 years, ranging from 18 through 28 years. Majority (72, 65.5%) of the study participants were females.

Table 2

Assessment of SARS-CoV-2 IgG antibody positivity

Items	Gender	Positive	Negative	IgG antibody level ( $\mu$ g/ml)
				Min	Max	Median
Individuals not receiving a booster dose of vaccine ( $n=$ 81)
	Male	27 (96.43%)	1 (3.57%)	0.2	9.17	2.19
	Female	50 (94.34%)	3 (5.66%)	0.15	9.5	1.93
	Total	77 (95.06%)	4 (4.94%)
Individuals receiving a booster dose of vaccine ( $n=$ 29)
	Male	10 (100%)	0	1.16	30	2.53
	Female	19 (100%)	0	1.15	30	6.55
	Total	29 (100%)	0

In our study, 81 (73.64%) people had not received booster doses of the Sinopharm vaccine. In this cohort, males had more significant positivity rate than females (27/28, 96.43% vs. 50/53, 94.34%). Among the 29 (26.36%) participants who had received booster doses of the Sinopharm vaccine, both males (10/29) and females (19/29) had a 100% positivity rate as shown in Table 2.

The IgG level was generally distributed among individuals receiving booster dose ( $p=$ 0.167) and non- normally distributed among individuals not receiving a booster dose ( $p=$ 0.046) as analyzed by the Kolmogorov Smirnov test. Among individuals receiving a booster dose, the mean IgG level was 9.57 $\pm$ 9.58 $\mu$ g/ml. Amongst participants not receiving the same, the mean IgG level was 2.91 $\pm$ 2.47 $\mu$ g/ml. The median and Inter quartile range of IgG levels was 6.55 and 10.92 respectively. Among individuals not receiving booster doses, the median and inter-quartile range of IgG levels were 2.06 and 3.86 respectively.

Table 3

Assessment of SARS-CoV-2 IgG antibody level in relation to time

Items vaccination (weeks)	Time since	IgG positive $N$ (%)	IgG negative $N$ (%)	IgG level mean $\pm$ S.D
Individuals not receiving a booster dose of vaccine ( $n=$ 81)
	1–4	5 (100%)	0	2.42 $\pm$ 2.27
	5–8	0	0	–
	9–12	0	0	–
	13–16	0	0	–
	17–20	1 (100%)	0	1.35
	21–24	4 (80%)	1 (20%)	1.96 $\pm$ 1.23
	25–28	6 (100%)	0	2.2 $\pm$ 2.18
	29–32	6 (100%)	0	3.89 $\pm$ 2.69
	33–36	11 (100%)	0	3.58 $\pm$ 2.64
	$>$ 36	44 (93.62%)	3 (6.38%)	2.91 $\pm$ 2.59
	Total	77 (95.06%)	4 (4.94%)	2.91 $\pm$ 2.47
Individuals receiving a booster dose of vaccine ( $n=$ 29)
	1–4	0	0	–
	5–8	1 (100%)	0	3.9
	9–12	0	0	–
	13–16	4 (100%)	0	6.27 $\pm$ 3.44
	17–20	5 (100%)	0	7.86 $\pm$ 7.06
	21–24	12 (100%)	0	10.17 $\pm$ 10.52
	25–28	7 (100%)	0	12.46 $\pm$ 12.67
	Total	29 (100%)	0	9.57 $\pm$ 9.58

Further analysis of the study data was done in relation to the duration since recent immunization. The average time since the last vaccination was 37.46 $\pm$ 13.07 weeks for individuals who didn’t receive a booster dose and 20.90 $\pm$ 4.87 weeks for those who did. In the cohort not receiving booster dose, the antibody level peaked at 29–32 weeks after which a declining trend was appreciated In three participants, neutralizing antibodies could not be detected after 36 weeks. In one case, the antibody was undetectable at 24 weeks following vaccination. In the cohort receiving a booster dose of the vaccine, the average value of neutralizing IgG antibody was high, peaked relatively early (at 25–28 weeks) and the antibody levels were yet to show a decreasing trend (Table 3).

4. Discussion

Since the discovery of SARS-CoV-2 in 2019, vaccination is regarded as the most reliable method of virus prevention and a global vaccination campaign is underway to combat this epidemic [12]. There are several vaccines available to defend against SARS-CoV-2, including inactivated virus vaccines, protein-based vaccines, RNA and DNA vaccines and viral vector-based vaccines [13]. The BBIBP-CorV vaccine, an inactivated vaccine, was developed in 2020 by the Beijing Institute of Biological Products Co. and China National Pharmaceutical Group Co., Ltd. [14]. The vaccine’s phase III clinical trials indicated 79% efficacy [15]. However, an interim study from the UAE found that it was 86% effective against the COVID-19 virus [16]. It is given intramuscularly in two doses four weeks apart. A booster dose may be given four to six months after the original vaccine series [16].

In this study, the majority, 65.5% ( $n=$ 72) of participants were females and about a quarter, 26.36% ( $n=$ 29) had received a booster dose of the Sinopharm vaccine. The efficacy of the Sinopharm vaccine is highly variable in the existing literature, varying from 56 to 95 % [17]. Also, it has been found that the majority of students (96.4%) had neutralizing antibodies against SARS-CoV-2.

In those not taking booster doses of the Sinopharm vaccine, the positivity rate was slightly higher for males than for females, but this was not statistically significant. Among students who received the booster dose, both males and females had the same (100%) percent positivity rate. There is a variability of seropositivity in terms of gender throughout the literature [18]. In the Bahrainis cohort of 379 people who were doubly vaccinated with Sinopharm, seropositivity was slightly greater in males when compared to females but it was not a statistically significant difference ( $p=$ 0.507) [19]. A study by Di et al. reported a significantly greater seropositivity rate in females than in males [20]. These variations may be explained by the difference in sampling techniques and/or geographic variations. Several others factors like administration route and schedule, nutritional status, obesity and immune history may also affect it.

We looked at individuals who were not administrated with a booster dose of the Sinopharm vaccine, with a significant favorable outcome (approx. 95% seropositivity rate). Similar findings were reported in a study from Sri Lanka, wherein 95.07% of individuals had detectable SARS-CoV-2 specific total antibodies after three months following a twofold Sinopharm immunization protocol [21]. In Jordanian adults, 85.7% of those receiving two doses of the Sinopharm vaccine produced IgG [22]. It is established that the protection provided by the antibodies often lasts for a few months, but it is important to monitor their level so that booster doses can be administered over time [20]. In the cohort not receiving the booster dose in our study, it was found that the average neutralizing antibody titer was 2.91 $\pm$ 2.47 $\mu$ g/ml. This average was much higher among the students receiving the booster dose, the mean level being 9.57 $\pm$ 9.58 $\mu$ g/ml. In the study by Saeed et al among 2868 people receiving the Sinopharm vaccine, the average antibody titer after the first dose was 9.53 AU/ml, which increased to 158.63 AU/ml following the administration of the second dose. The antibody level showed a decline over time, but after the third/ booster dose, the antibody level considerably increased to $>$ 250 AU/ml [22]. Similar trends were observed in our study, where subjects who received an additional booster dose of the vaccination had high neutralizing antibody titers. Because medical students are at high risk of exposure to the virus, an additional booster dose could be beneficial for long-term protection.

In the cohort not receiving a booster dose, the antibody level peaked at 29–32 weeks after which a declining trend was appreciated while among those receiving a booster dose, the antibody titer was high and peaked relatively early, i.e. at 25–28 weeks and the antibody level showed a non-declining trend. Neutralizing antibodies could still be found in significant levels even after more than six months among people who received a booster dose. Other studies have also reported that antibody levels peak three to four weeks after the second and remain at a relatively high level for over three months after the booster injection [22, 23].

5. Conclusion

Medical students are constantly exposed to patients during their training and comprise a high-risk population for COVID-19. As such, assessing the response to available vaccination is clinically meaningful. Among students who were vaccinated with the Sinopharm vaccine, the level of neutralizing antibody decreased over time, justifying the need for a booster dose to confer increased benefits. Further studies should incorporate a broader audience and a variety of other available vaccines to provide more robust information. Longitudinal follow-up studies that assess the antibody levels in the vaccinated cohort over a long duration may provide additional information about vaccine efficacy and the need/effectiveness of booster doses to mitigate the risks of disease transmission and severity. This will also help derive more generalizable conclusions.

Footnotes

Acknowledgments

We would like to express our gratitude to the medical students who took part in this study as well as the medical lab technologists at GMCTH for supplying all the essential lab supplies and for their kind support.

Conflict of interest

There is no conflict of interest.

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Evaluation of SARS-Cov-2 neutralizing antibody among Sinopharm Vero Cell (BBIBP-CorV) vaccinated medical students

Abstract

BACKGROUND:

MATERIALS AND METHODS:

RESULTS:

CONCLUSION:

Keywords

1. Introduction

2. Materials and methods

2.1 Study design and study population

2.2 Executive methodology

2.3 Statistical methods

2.4 Ethical consideration

3. Results

Table 1 Demographic information

5. Conclusion

Footnotes

Acknowledgments

Conflict of interest

References

Table 1
Demographic information