|Ahead of print publication
Patterns of antibody response, adverse effects, and knowledge regarding COVID-19 vaccine: Findings of a serosurvey among vaccinated individuals in north-western India
Kuntal Bandyopadhyay1, Lakshmi Geetha Nair2, Deepshikha Mishra2, S Shashivadhanan2
1 48 FHO, Bathinda, Punjab, India
2 174 MH, Bathinda, Punjab, India
|Date of Submission||08-Jun-2021|
|Date of Decision||28-Jul-2021|
|Date of Acceptance||06-Jul-2021|
|Date of Web Publication||25-Sep-2021|
Gd Spl, Surgery, 174 MH, Bathinda - 151 004, Punjab
Source of Support: None, Conflict of Interest: None
Background: With reference to the National vaccination drive against COVID-19 disease (rolled out on January 16, 2021 by Government of India), this study was undertaken to analyze the patterns of antibody response among fully vaccinated adult individuals, to find the spectrum of adverse events following immunizations and knowledge component of the participants regarding the COVID-19 vaccines as well as its side effects. Materials and Methods: A total of 500 vaccinated individuals (with two doses of Government approved Covishield vaccine) were studied over a period of 9 weeks following the second dose of their vaccine. They were tested for the development of antibodies against SARS-CoV-2 spike protein, using an immunoglobulin G ELISA kit on three occasions, and the seroconversion pattern was analyzed. Results: A postvaccination seroconversion rate of 63.8% (at 2–3 weeks), 83.2% (at 4–5 weeks), and 93.2% (overall seroconversion rate at 8–9 weeks) was found. While 77.4% participants (at 4 weeks) and 65.9% participants (at 8 weeks) showed rise in optical density (OD) values, 7.4% showed a declining in OD values (at 8 weeks) and 6.8% remained seronegative throughout the study period. Sixty-two percent had experienced at least one form of adverse effect postvaccination, which were mostly mild in nature not requiring hospitalization. Conclusion: This study found that the timeline for seroconversion postvaccination by COVISHIELD varies between individuals, with few showing decline in the OD values as well and that majority of the adverse reactions observed in this population were only mild and manageable not requiring hospitalization.
Keywords: Adverse events following immunization, COVID-19 vaccine, knowledge, seroconversion
|How to cite this URL:|
Bandyopadhyay K, Nair LG, Mishra D, Shashivadhanan S. Patterns of antibody response, adverse effects, and knowledge regarding COVID-19 vaccine: Findings of a serosurvey among vaccinated individuals in north-western India. J Mar Med Soc [Epub ahead of print] [cited 2022 May 16]. Available from: https://www.marinemedicalsociety.in/preprintarticle.asp?id=326739
| Introduction|| |
COVID-19 disease has presently engulfed the entire globe. Since the time it was declared a pandemic by the World Health Organization (WHO) in Mar 2020, this virus has come a long way and is continuing its lethal journey by outsmarting all possible interventions against it., The usual response to the introduction of COVID-19 virus in our body (either by natural history of disease progression or by vaccination) is to produce protective antibodies. The immunoglobulin (Ig) M antibodies develop within 7–9 days and IgG antibodies develop within 2 weeks of contracting the virus on an average.,
The National Vaccination Campaign against COVID-19 disease was rolled out on January 16, 2021 by Government of India, with an initial intent to cover the entire adult population of our country in a phased manner (phase one for health-care workers [HCWs] and frontline workers (FLWs), phase two for people aged more than 60 years and more than 45 years with comorbidities, and phase three for the rest of the adult population more than 18 years). Initially, Government of India had approved only two vaccines for emergency use in the country, i.e., ChAdOx1 nCoV-19 coronavirus vaccine (recombinant) Covishield (a brand of the Oxford–AstraZeneca vaccine manufactured by the Serum Institute of India) and BBV-152 Covaxin (developed by Bharat Biotech). In April 2021, Sputnik V (distributed by Dr. Reddy's Laboratories) was approved as a third vaccine, which was deployed by May 2021.,
The purpose of this vaccination campaign was to cover maximum population of the country as early as possible with two doses of the vaccine and thus reduce the morbidity and mortality by providing immunity against severity and complications of COVID-19 disease. While a traditional vaccine development timeline is approximately 4 to 5 years (encompassing all phases of the clinical trials), the same was completed within 1 year of the occurrence of the pandemic, due to the pressing need for accelerated vaccine development leading to reduction in timeline required for approval under Emergency Use Authorization by the Government of India in keeping with the recommendation of the WHO. Moreover, with the phase four of this vaccine clinical trial (postmarketing surveillance phase) still underway, the adverse events following immunization (AEFI) are yet to be established statistically and scientifically.
With the introduction of COVID-19 vaccine in our country, the cases were speculated to decline and a rise in immunity was foreseen after a complete vaccination schedule. However, few studies have reported that not all individuals infected with the virus (asymptomatic or symptomatic) develop protective antibodies (IgG/IgM) in them due to various reasons. Therefore, it becomes pertinent to find if an individual responds in a similar way when vaccinated, and thus, this study was undertaken to study the patterns of antibody response among fully vaccinated adult individuals and also to find the spectrum of AEFIs and the knowledge component of the participants regarding the COVID-19 vaccines as well as its side effects.
| Materials and Methods|| |
This was a longitudinal observational study, conducted among the population residing at a military station in North-Western India between February and May 2021. In the absence of any previous literature on this subject and by assuming the prevalence in the environment to be 50%, keeping a margin of error at 5% and alpha-error at 5% with 95% confidence interval, the minimum calculated sample size came out to be 385. However, for the study, a sample size of 500 was taken. The inclusion criteria consisted of all consenting adults more than 18 years of age HCWs/FLWs who received complete schedule of Covishield vaccine (two doses, at least 4 weeks apart) and agreed to be available in the place of study for the entire duration of its conduct while the exclusion criteria were any individual who did not complete the stipulated two doses of vaccine, were unavailable during the study period, those who had been diagnosed as a confirmed COVID-19 case (symptomatic/asymptomatic) by reverse transcription-polymerase chain reaction test/rapid antibody test in the past 4 months, those individuals with antibodies to whole-cell antigen (due to natural infection) against SARS-CoV-2 (detected by IgG ELISA kit [COVID Kavach ELISA]) at day 0, and those unwilling to participate in the study. HCWs were defined as any doctor, nurse, paramedical staff, or supporting staff working in a health-care establishment. FLWs were defined as all Officers, Junior Commissioned Officers, and Other Ranks serving in the Armed Forces, other than HCWs.
The process of participant's enrolment is depicted in [Figure 1]. A sampling frame comprising of all individuals fitting into the inclusion criteria was prepared and participants were selected using simple random sampling method. At a time, 90 participants were contacted and subjected to blood sample “zero” to check for the presence of any previous demonstrable antibodies to whole-cell antigen (due to natural infection) against SARS-CoV-2 (with IgG ELISA kit [COVID Kavach ELISA]) and only those negative for antibodies to SARS-CoV2 at this stage were included. This process was repeated till the stipulated sample size of 500 was reached. The blood sample was collected by a sample collection team (comprising of a team leader, a trained phlebotomist, and two supporting members) which observed all universal precautions for COVID-19 prevention during sample collection. Participants were considered seropositive if the absorption value of their test sample was more than the “cut off” value. The “cut off” value was calculated as per the kit instructions (average optical density [OD] negative control + 0.2).
The enrolled 500 participants were further subjected to three additional blood samples, collected at specific intervals (blood sample-1 collected at 2–3 weeks, blood sample-2 collected at 4–5 weeks, and blood sample-3 collected at 8–9 weeks following the date of individual's second dose of vaccine, respectively). During collection of blood sample-0, the team briefed the participants about the study and obtained a written informed consent from the study participants, a questionnaire was given (separate ID and form for each subject) and thereafter 3–5 ml of venous blood was collected and labeled (same ID as on form). The venous samples were centrifuged at the designated health-care facility, and thereafter, serum was obtained and stored. For the next three sample collections, only blood sample was collected from the participants. Participants were also observed for the development of any fresh symptoms of COVID-19 infection during follow-up period.
These three blood samples were tested for seroconversion (presence of specific antibodies against spike protein [S1]), using S-1 spike protein containing receptor binding domain ELISA kits (ELISafe19™ by HIMEDIA), at the designated health-care establishment. Participants were considered seropositive if the test sample OD value obtained by ELISA was more than the “cut off” value. The “cut off” value was calculated as per the kit's instructions as 0.2+ average of negative control OD value. Index value of the test samples was estimated by means of OD values being represented as multiples of “cut off” value. The “index values” were then plotted to look for the pattern of increase in OD values in the series of collected blood samples from the study participants representing a quasi-quantitative estimation of the level of antibodies developed against the S1 spike protein. Blood sample-1 index value for each participant was taken as “baseline value,” and further, rise/fall in the index values in the next two periodic blood samples was calculated as multiples of “baseline value.” The data generated were compiled, collated, and analyzed using software IBM SPSS version 20 and Epi info 7 by Centres for Disease Control and Prevention, Atlanta. The results were tabulated and subjected to appropriate statistical tests. Institutional ethical committee of the principal investigator's institution processed the protocol and provided the clearance.
| Results|| |
A total of 500 participants were studied with a mean age of 41 ± 2.1 years. The study included 442 (88.4%) male and 58 (11.6%) female participants. Majority of the participants 270 (54.0%) were HCWs while 230 (46.0%) of them were FLWs. A total of 330 (66.0%) had education up to standard XII, while 130 (26.0%) had completed graduation and 40 (8.0%) had a postgraduate or higher qualification. Comorbidities were absent in 464 (92.8%) participants and 36 (7.2%) had some comorbidity in them. The details are depicted in [Table 1].
The participants were studied for the development of antispike protein antibodies against SARS-CoV-2 postcomplete vaccination (two doses) with Covishield vaccine. Out of 500 selected participants, 319 (63.8%) became seropositive and the rest 181 (36.2%) remained seronegative at 2–3 weeks. Between weeks 4 and 5, 97 more participants had seroconversion, bringing the total seropositive cases at this stage to 416 (83.2%) and 84 (16.8%) remained seronegative. Among the 319 seropositive participants (who were positive between 2 and 3 weeks as well), 247 (77.4%) participants showed an increase in index values, while 72 (22.6%) had no change in index values and none of the initial seropositive participants showed any decreasing trend of index values at this stage. Between 8 and 9 weeks, 50 more participants had seroconversion while 37 previously seropositive participants became seronegative, bringing the overall seroconversion rate to be 466 (93.2%) but net seropositive cases at this stage to be 429 (85.8%). Among the 416 seropositive participants (at 4–5-week stage), 274 (65.9%) participants showed an increase in index values, while 105 (25.2%) had no change in index values and 37 (8.9%) participants showed a decrease in index values at this stage. At the end of the study period, a total of 34 (6.8%) participants remained seronegative throughout, while 37 previously seropositive participants turned negative at third sampling, thus, making the total seronegative at the end of study period to be 71 (14.2%) participants [Figure 1] and [Table 2].
The participants were studied for any AEFI experienced due to the vaccine and it was found that 310 (62.0%) had some or the other form of AEFI postvaccination while 190 (38.0%) had no such experience. Out of these 310 participants, majority 104 (33.5%) experienced pain at the site of injection only, 90 (29.0%) experienced chills only and 42 (13.5%) experienced fever only. Only 2 (0.6%) participants required hospitalization for AEFI [Figure 2]. Among the 310 participants who suffered any form of AEFI, 209 (67.4%) had seroconversion at 2–3 weeks, a further 52 had seroconversion at 4–5 weeks making the total seroconversion to be 261 (84.2%) and another 45 became seropositive at 8–9 weeks making the total tally to be 306 (98.7%), while 4 (1.3%) remained seronegative even at 8–9-week postcompleted two doses of vaccine. The percentage of satisfactory response for the knowledge component of the participants with respect to HCWs, FLWs, and total response combining the two categories is depicted in [Figure 3]. In addition to the knowledge component, when asked for the reasons to take a vaccine, 283 (56.6%) participants revealed that they were self-motivated, 193 (38.6%) were motivated by others, and the rest 24 (4.8%) had no specific reasons for the same. Furthermore, the source of information for vaccine and its side effects was found to be social media for 268 (53.6%) participants, family and friends for 132 (26.4%) participants, through doctors or their webinars for 52 (10.4%) participants, and other means for rest 48 (9.6%) participants.
|Figure 2: Spectrum of adverse events following immunization experienced among participants|
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|Figure 3: Percentage of correct responses for knowledge on COVID-19 vaccine among participants (N = 500, n1 [health-care worker] =270 and n2 [frontline worker] =230)|
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[Table 3] shows the association of various parameters such as age, gender, category (HCW/FLW), associated comorbidities and education levels of the participants with seroconversion (at any time postvaccination), any increase in antibody titers among seropositive participants, and any AEFIs experienced by them. A statistically significant association was found between the absence of comorbidities and seroconversion as well as rise in antibody titers (P < 0.001) among the study participants. Furthermore, the association of being an HCW with seropositivity was found to be significant (P < 0.05).
|Table 3: Association of various variables in the study with study parameters|
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| Discussion|| |
With limited literature available on this subject and more so on this subset of population, this study is probably one of the first in this domain. At present, with no similar studies available on antibody response to two doses of Covishield vaccine in India, this study compared its findings with comparable studies across the globe. The mean age of participants in this study was found to be 41 ± 2.1 years, which is comparable to the studies done by Gobbi et al. (median age: 44.5 years) and Thiruvengadam et al. (median age: 44.0 years).
This study reported a postvaccination seroconversion rate of 63.8% (at 2–3 weeks), 83.2% (at 4–5 weeks), and 93.2% (overall seroconversion rate at 8–9 weeks). A similar study done by Salvagno et al. for antibody response post two doses of Pfizer COVID-19 mRNA BNT162b2 vaccine among baseline seronegative individuals showed a seroconversion rate of 0% (at 7 days), 98.7% (at 21 days), and 100% (at 50 days), while a similar study done by Thiruvengadam et al. showed it to be 46% (at 1 week), 84.7% (between 10 and 28 days), and 85.3% (at 6–10 weeks). The difference in seroconversion rates may be attributed to the different make and dosage schedule of the vaccines administered as well as the population characteristics.
This study found a rise in index values, calculated by expressing the OD values obtained by ELISA as multiples of cut off value, in 77.4% participants (in comparison of index values at 4–5 weeks with baseline values at 2–3 weeks) and in 65.9% participants (on comparison of index values at 8–9 weeks with Index values at 4–5 weeks). This was comparable to a study done by Mazzoni et al., which found an increase in antibody titers in 63.8% participants (at day 14 sample compared to day 7 sample) and in 78% participants (at day 28 sample as compared to day 14 sample), while another study by Salvagno et al. found that the increase in antibody titers was 11 folds among baseline seronegative individuals (no prior antibodies before the start of the study) and only 1.3 folds among baseline seropositive individuals (with prior antibodies before the start of the study). Our study also reported that 37 previously seropositive participants became seronegative and also showed a decrease in index values, more studies with similar findings could not be found. However, the study done by Gobbi et al. found that although antibody levels might progressively decline in few individuals postinfection or vaccination, the immune memory persists for months. This can be taken as a possible explanation for the above finding in our study.
Our study did not find any significant association between seroconversion and rise in index values with age or gender but found a significant association with the absence of comorbidities. A study done by Salvagno et al. contradicts our former finding but is in agreement to the latter finding. Studies done by Korth et al. and Wong et al. agree to our above findings. In our study, it was found that 62.0% had experienced some or the other form of AEFI postvaccination, which were mostly mild in nature not requiring hospitalization. This was similar to the findings of the study by Jayadevan et al., which found that 65.9% participants had developed some form of AEFI.
There are a few limitations in this study. First, this study was done on a selected population of HCWs and FLWs who were administered a Government approved vaccine Covishield, and thus, the results cannot be generalized to other population groups or other approved vaccines. Second, due to limited resources, the study was done for selected participants only and their seroconversion could be studied only for a period of 8–9-week postsecond dose of vaccine. A bigger study with a bigger sample size and extended follow-up period should be done to observe the actual duration of protection conferred by the antibodies. Third, again due to limited resources (absence of chemiluminescence immunoassay), exact numerical quantification of antibody titers was not done, and thus, effect of acquiring a fresh infection by a participant during the study period on overall antibody titers could not be ruled out. Fourth, despite the use of objective scales and efforts to accurately collect the data, the presence of bias inherent to the study design such as recall bias cannot be ruled out.
| Conclusion|| |
With the introduction of COVID-19 vaccines in our country, and HCWs/FLWs being the first recipients for the same, this study provides a brief insight regarding the protection conferred and adverse reactions to this Government approved vaccine COVISHIELD. To conclude, this study found that the timeline for seroconversion postvaccination by COVISHIELD varies between individuals, with few showing decline in the levels as well and that majority of the adverse reactions observed in this population were only mild and manageable without requiring hospitalization. Thus, it is recommended that all COVID-19 prevention measures such as mask, sanitization, and social distancing should be diligently followed even after being fully vaccinated. Moreover, there exists a considerable knowledge gap among the population (especially the FLWs) regarding the vaccine and its side effects, in spite of intensive Information, Education and Communication (IEC) activities by Government of India at all levels and through all modes of communication. It is recommended that there should be a target-oriented IEC activity for each individual just before and after the vaccination procedure to bridge the existing knowledge gap. Although more elaborate studies with different target population and bigger sample sizes and also follow-up studies with longer duration (4–6 months following the second dose of vaccine) are needed to concretely establish the actual duration of protection conferred by antibodies and to support the findings of the present study, the significance of the results of this study is also important to be kept in mind while making policies related to the subject at hand.
We sincerely thank Sub Maj KC Joshi, 48 FHO, Bathinda, Hav (BTA) Pradeep Kumar, 174 MH, Bathinda and Hav (BTA) Burhanuddin, 174 MH, Bathinda for their efforts and support in conducting this study.
Financial support and sponsorship
ELISA kits were provided within station and hospital resources.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]