Introduction
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a major global public health challenge. The host response to SARS-CoV-2 involves both cellular and humoral immune mechanisms, with the production of virus-specific antibodies forming an important component of acquired immunity. Immunoglobulin G (IgG) antibodies can persist following natural infection and contribute to protection against subsequent exposure, although the magnitude and duration of the antibody response vary among individuals [1][2].
Vaccination has been one of the principal strategies for reducing the morbidity and mortality associated with COVID-19. India initiated its COVID-19 vaccination programme in January 2021 with the introduction of Covishield and Covaxin [3]. Covishield, also known as ChAdOx1-nCoV-19 or AZD1222, is a replication-deficient chimpanzee adenovirus-vectored vaccine encoding the SARS-CoV-2 spike protein. Clinical studies have demonstrated that ChAdOx1-nCoV-19 induces both humoral and cellular immune responses following vaccination [4][5].
Healthcare personnel constituted one of the priority groups for COVID-19 vaccination because of their frequent occupational exposure to patients with confirmed or suspected SARS-CoV-2 infection. Evaluation of post-vaccination antibody responses among healthcare workers is therefore particularly relevant. Studies conducted among healthcare personnel have demonstrated a substantial rise in SARS-CoV-2 antibody titres following ChAdOx1-nCoV-19 vaccination, although the magnitude of response may be influenced by previous SARS-CoV-2 infection and baseline antibody status [6][7]. In individuals with prior infection, vaccination may act as a potent immune booster, producing higher post-vaccination antibody levels than those observed in infection-naïve individuals [7].
The immune response generated following vaccination is not necessarily sustained at its initial magnitude. Longitudinal studies among healthcare workers have demonstrated that antibody levels rise rapidly following vaccination but subsequently decline over the following months [7][8]. Assessment at multiple time points is therefore important for understanding the kinetics and durability of the vaccine-induced humoral immune response.
Despite the development of a measurable antibody response, breakthrough SARS-CoV-2 infections may occur after vaccination. Studies among vaccinated healthcare personnel have documented post-vaccination infections following both the first and second doses [9]. Safety is another important component of vaccine evaluation. ChAdOx1-nCoV-19 vaccination is commonly associated with transient local and systemic adverse events such as injection-site pain, tenderness, fever, headache, malaise, and myalgia [10].
Although several studies have evaluated the immune response following COVID-19 vaccination, longitudinal data assessing antibody levels from the pre-vaccination period through multiple post-vaccination time points remain valuable, particularly among frontline healthcare personnel in Indian healthcare settings. The present study was therefore undertaken to assess the pre- and post-vaccination IgG antibody response to ChAdOx1-nCoV-19 (Covishield) among frontline healthcare personnel of a tertiary care hospital in Haryana, India, with serial assessment up to six months, together with evaluation of breakthrough COVID-19 infections and adverse events following vaccination.
Aim and Objectives
Aim
To assess the humoral IgG antibody response following ChAdOx1-nCoV-19 (Covishield) vaccination among frontline healthcare personnel of a tertiary care hospital in Haryana, India.
Objectives
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To assess quantitative SARS-CoV-2 antibody levels before Covishield vaccination and at one month, two months, and six months following vaccination.
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To evaluate the change and persistence of antibody levels at different follow-up intervals after vaccination.
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To assess the occurrence of breakthrough COVID-19 infection following the first and second doses of Covishield.
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To document the frequency and pattern of adverse events following the first and second doses of Covishield vaccination.
Materials and Methods
Study design and setting
The present interventional longitudinal study was conducted among frontline healthcare personnel of a tertiary care hospital in Haryana, India, from January 2021 to December 2021. A total of 120 frontline healthcare personnel were included in the study.
Study participants and sampling
Frontline healthcare personnel who volunteered to receive ChAdOx1-nCoV-19 (Covishield) vaccination and participate in serial SARS-CoV-2 antibody assessment were enrolled using simple random sampling. The study population comprised doctors, nursing personnel, paramedical staff, and support staff.
Inclusion criteria
Frontline healthcare personnel of the institute who were willing to receive Covishield vaccination, undergo serial antibody testing, and provide written informed consent were eligible for participation.
Exclusion criteria
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Pregnant women.
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Participants with a history of drug or food allergy.
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Participants receiving immunosuppressive drugs or systemic steroids.
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Eligible personnel unwilling to participate or undergo the planned follow-up.
Data collection
Baseline demographic and clinical variables including age, sex, type of healthcare personnel, weight, body mass index, dietary status, smoking status, and alcohol use were recorded. Information regarding previous COVID-19 infection, COVID-19 infection among family members, and pre-vaccination antibody status was documented. Administration of the first and second doses of Covishield was recorded, and participants were followed for occurrence of COVID-19 infection after each dose.
Antibody assessment
Quantitative SARS-CoV-2 IgG antibody levels were assessed using the VIDAS platform at serial study time points: VIDAS-1 before vaccination, VIDAS-2 approximately one month after the first dose, VIDAS-3 approximately two months after the first dose, and VIDAS-4 approximately six months after the first dose. Serial measurements were used to evaluate the early post-vaccination rise, persistence, and subsequent waning of the humoral antibody response.
Assessment of adverse events
Adverse events following both doses of Covishield were documented within 48 hours and after 48 hours. Recorded events included local-site pain/tenderness/soreness, fever with chills and headache, malaise, breathlessness with chest heaviness, loss of smell and taste, cold and congestion, and myalgia. Paracetamol use following vaccination was also recorded.
Ethical considerations
The study protocol was approved by the Institutional Ethics Committee Maharaja Agrasen Medical College, Agroha, Hisar, Haryana. Written informed consent was obtained from each participant before enrolment and confidentiality of participant information was maintained throughout the study.
Statistical analysis
Data were compiled and analyzed using SPSS software. Continuous variables were expressed as mean ± standard deviation, while categorical variables were summarized as frequencies and percentages. Successive paired quantitative antibody measurements were compared using paired statistical analysis. A two-sided p-value <0.05 was considered statistically significant.
Results
A total of 120 frontline healthcare personnel were included in the study. Baseline characteristics, previous COVID-19 infection status, antibody response at different time points, and post-vaccination adverse events were assessed. The findings are presented in the following tables.
| Variable | n (%) / Mean ± SD |
| Age (years), mean ± SD | 34.58 ± 9.67 |
| Sex | |
| Male | 78 (65.0) |
| Female | 42 (35.0) |
| Type of healthcare personnel | |
| Doctor | 81 (67.5) |
| Support staff | 18 (15.0) |
| Paramedical staff | 17 (14.2) |
| Nursing | 4 (3.3) |
| Weight (kg), mean ± SD | 71.12 ± 9.74 |
| BMI (kg/m²), mean ± SD | 24.52 ± 3.91 |
| Dietary status | |
| Vegetarian | 99 (82.5) |
| Non-vegetarian | 21 (17.5) |
| Current smoker | 0 (0.0) |
| Current alcoholic | 21 (17.5) |
The study included 120 healthcare personnel with a mean age of 34.58 ± 9.67 years. Males constituted 65.0% of the study population. Doctors represented the largest healthcare personnel category (67.5%). The mean weight was 71.12 ± 9.74 kg and the mean BMI was 24.52 ± 3.91 kg/m². Most participants were vegetarian (82.5%), while 17.5% were non-vegetarian. Current alcohol use was reported by 17.5% of participants, whereas none were current smokers.
| Variable | n (%) |
| Previous COVID-19 infection before vaccination | |
| Yes | 111 (92.5) |
| No | 9 (7.5) |
| COVID-19 infection in family | |
| Yes | 16 (13.3) |
| No | 104 (86.7) |
| Pre-vaccination antibody status | |
| Positive | 50 (41.7) |
| Not available | 70 (58.3) |
| Received 1st dose of Covishield | 120 (100) |
| Received 2nd dose of Covishield | 120 (100) |
| COVID-19 infection after 1st dose | |
| Yes | 7 (5.8) |
| No | 113 (94.2) |
| COVID-19 infection after 2nd dose | |
| Yes | 5 (4.2) |
| No | 115 (95.8) |
A previous history of COVID-19 infection before vaccination was reported in 111 (92.5%) participants, while 9 (7.5%) had no previous infection. COVID-19 infection in a family member was reported by 16 (13.3%) participants. Pre-vaccination antibody results were positive in 50 (41.7%) participants, while results were unavailable for 70 (58.3%). All participants received both doses of Covishield. COVID-19 infection occurred in 7 (5.8%) participants after the first dose and in 5 (4.2%) after the second dose.
| Antibody assessment | Participants with result (n) | Antibody level, Mean ± SD |
| VIDAS-1: Pre-vaccination | 50 | 6.79 ± 5.96 |
| VIDAS-2: 1 month after 1st dose | 112 | 18.86 ± 14.15 |
| VIDAS-3: 2 months after 1st dose | 110 | 18.26 ± 11.94 |
| VIDAS-4: 6 months after 1st dose | 110 | 14.66 ± 14.62 |
Among participants with available antibody results, the mean antibody level was 6.79 ± 5.96 before vaccination and increased to 18.86 ± 14.15 one month after the first dose. The mean antibody level remained relatively stable at two months (18.26 ± 11.94) and subsequently declined to 14.66 ± 14.62 at six months.
| Comparison | Paired participants (n) | Antibody level, Mean ± SD | p-value |
| VIDAS-1 vs VIDAS-2 | 48 | 6.80 ± 6.05 vs 31.58 ± 10.89 | <0.001 |
| VIDAS-2 vs VIDAS-3 | 103 | 18.69 ± 14.22 vs 17.97 ± 12.00 | 0.059 |
| VIDAS-3 vs VIDAS-4 | 104 | 18.66 ± 12.01 vs 14.43 ± 14.46 | <0.001 |
Antibody levels increased significantly from pre-vaccination to one month after the first dose (p<0.001). The difference between one and two months was not statistically significant (p=0.059). A significant decline in antibody levels was observed between two and six months (p<0.001).
| Variable | 1st dose, n (%) | 2nd dose, n (%) |
| Adverse event reported within 48 h | 117 (97.5) | 109 (90.8) |
| No adverse event reported within 48 h | 3 (2.5) | 11 (9.2) |
| Paracetamol use | 61 (50.8) | 59 (49.2) |
Adverse events were commonly reported following both doses of Covishield. Within 48 hours, adverse events were reported by 117 (97.5%) participants after the first dose and 109 (90.8%) after the second dose. Paracetamol use was reported by 61 (50.8%) and 59 (49.2%) participants following the first and second doses, respectively.
| Adverse event | 1st dose ≤48 h n (%) | 1st dose >48 h n (%) | 2nd dose ≤48 h n (%) | 2nd dose >48 h n (%) |
| Local-site pain/tenderness/soreness | 66 (55.0) | 40 (33.3) | 47 (39.2) | 46 (38.3) |
| Fever with chills and headache | 37 (30.8) | 35 (29.2) | 24 (20.0) | 35 (29.2) |
| Malaise | 10 (8.3) | 4 (3.3) | 7 (5.8) | 8 (6.7) |
| Breathlessness with chest heaviness | 4 (3.3) | — | — | 20 (16.7) |
| Loss of smell and taste | — | 23 (19.2) | — | — |
| Cold and congestion | — | 7 (5.8) | 13 (10.8) | — |
| Myalgia | — | — | 18 (15.0) | — |
| No reaction reported/Nil* | 3 (2.5) | 11 (9.2) | 11 (9.2) | 11 (9.2) |
Local-site pain/tenderness/soreness was the most frequently reported adverse event following both doses of Covishield. It was reported in 66 (55.0%) participants within 48 hours and 40 (33.3%) after 48 hours following the first dose, compared with 47 (39.2%) and 46 (38.3%), respectively, following the second dose. Fever with chills and headache was reported in 37 (30.8%), 35 (29.2%), 24 (20.0%) and 35 (29.2%) participants across the four assessment periods, respectively. Other reported adverse events included malaise, breathlessness with chest heaviness, loss of smell and taste, cold and congestion, and myalgia.
Discussion
This study assessed the longitudinal IgG antibody response, breakthrough COVID-19 infection, and short-term adverse events following two doses of ChAdOx1-nCoV-19 (Covishield) among 120 frontline healthcare personnel. The principal finding was a marked early rise in antibody levels after vaccination, relative stability during the early follow-up period, and a significant decline by six months. Breakthrough infections were uncommon, while post-vaccination reactions were frequently reported but were predominantly transient local and systemic events.
The mean age of participants was 34.58 ± 9.67 years, and 65.0% were male. Singh et al. reported a higher mean age of 44.8 years, although the proportion of males was broadly comparable (59.2%) [11]. Faizal et al. studied a comparatively younger group of healthcare workers, with a median age of 31.5 years, and also reported male predominance [6]. Differences in demographic profiles across studies may reflect variations in the composition of healthcare personnel recruited at different centres.
A previous history of COVID-19 infection was reported by 92.5% of participants in the present study. Among participants with an available pre-vaccination antibody result, the recorded results were positive. This high prevalence of previous exposure is important when interpreting post-vaccination antibody levels, because prior SARS-CoV-2 infection may augment the immune response to vaccination. Verma et al. reported higher antibody titres among Covishield-vaccinated healthcare workers with pre-existing antibodies, supporting the contribution of previous infection to a stronger post-vaccination response [7].
The quantitative antibody response demonstrated a clear early rise after vaccination. Mean antibody levels increased from 6.79 ± 5.96 before vaccination to 18.86 ± 14.15 at one month after the first dose. In paired participants, the increase from 6.80 ± 6.05 to 31.58 ± 10.89 was statistically significant (p<0.001). Devi et al. similarly reported a marked increase in antibody response following Covishield vaccination [12], while Faizal et al. also documented a consistent early rise in SARS-CoV-2 antibody titres among healthcare workers after ChAdOx1 vaccination [6]. These findings collectively support the strong early humoral immunogenicity of Covishield.
Between one and two months, the mean antibody levels were 18.86 ± 14.15 and 18.26 ± 11.94, respectively. In paired analysis, the difference between these time points was not statistically significant (p=0.059), suggesting relative stability of the antibody response during the early post-vaccination period. By six months, however, the mean antibody level had declined to 14.66 ± 14.62, and the paired decline from two to six months was statistically significant (p<0.001). Singh et al. reported a similar gradual decline in humoral antibody levels over six months among Indian healthcare workers after Covishield vaccination [8]. Verma et al. also observed waning antibody levels several months after vaccination, although participants with pre-existing antibodies tended to maintain higher titres [7]. Thus, the present findings are consistent with the expected pattern of an early antibody peak followed by progressive waning over time.
Breakthrough COVID-19 infection occurred in 7 (5.8%) participants after the first dose and 5 (4.2%) after the second dose. Ghanaie et al. reported post-vaccination infection rates of 3.7% after the first dose and 5.9% after the second dose among healthcare personnel [9]. Although direct comparison between studies should be made cautiously because of differences in circulating variants, exposure intensity, case detection, and follow-up periods, these findings indicate that breakthrough infection may occur despite vaccination.
Adverse events were commonly reported after both vaccine doses. Within 48 hours, 97.5% of participants reported an adverse event after the first dose and 90.8% after the second dose. Local-site pain, tenderness, or soreness was the most frequently reported reaction, followed by fever with chills and headache. Hoque et al. similarly reported local tenderness and fever among common reactions after ChAdOx1-nCoV-19 vaccination [10]. The pattern is also consistent with the reactogenicity profile described in clinical evaluation of ChAdOx1-nCoV-19, in which transient local and systemic reactions were commonly observed [4].
Overall, the present study demonstrates a strong early IgG antibody response following Covishield vaccination, persistence of the response during the initial two months, and significant waning by six months. The concurrent assessment of breakthrough infections and adverse events provides a broader real-world perspective on vaccine response among frontline healthcare personnel. These findings reinforce the value of longitudinal follow-up when interpreting post-vaccination humoral immunity, particularly in populations with substantial previous SARS-CoV-2 exposure.
Limitations of the Study
The study has several limitations. First, it was conducted at a single tertiary care centre and included a relatively young healthcare-worker population, which may limit generalizability to the wider population, particularly older adults and individuals with major comorbidities. Second, pre-vaccination quantitative antibody results were unavailable for a substantial proportion of participants, and the number of paired observations varied across follow-up time points. Third, 92.5% of participants reported previous COVID-19 infection, making it difficult to separate vaccine-induced antibody responses from hybrid immunity due to prior infection. Fourth, the study did not include an unvaccinated control group and assessed humoral antibody levels without evaluation of neutralizing antibody activity or cellular immune responses. Fifth, breakthrough infections and adverse events were based on recorded clinical history and follow-up, and the study did not account for circulating SARS-CoV-2 variants or quantify exposure intensity. Finally, follow-up was limited to six months; therefore, longer-term antibody persistence and the effect of subsequent booster doses could not be evaluated.
Conclusion
Covishield vaccination produced a strong early IgG antibody response among frontline healthcare personnel, with antibody levels remaining relatively stable during the first two months and showing a significant decline by six months. Breakthrough infections were uncommon, while adverse events were predominantly transient local and systemic reactions. The findings demonstrate effective early humoral immunogenicity of ChAdOx1-nCoV-19 and highlight the progressive waning of antibody levels over time, supporting the importance of longitudinal assessment of vaccine-induced immunity.
Declarations
Conflict of Interest
The authors declare no conflict of interest.
Funding
This work was supported by Maharaja Agrasen Medical College, Agroha, Hisar, Haryana, India.
Acknowledgements
The authors express their gratitude to Maharaja Agrasen Medical College, Agroha, Hisar, Haryana, India, for providing the institutional support and resources required for carrying out the study.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request and subject to institutional approval.
Authors' Contribution Statement
All authors have read and agreed to the published version of the manuscript:
Conceptualization: Dr. Sneh Kumari, Dr. Salil Dube; Methodology: Dr. Ashutosh Sharma, Dr. Diksha; Validation: Dr. Aman Goyal, Dr Kawalpreet Kaur; Formal Analysis: Dr. Sunil Kumar Dahiya, Dr. Raghavendra R Huchchannavar; Investigation: Dr Sneh Kumari, Dr. Diksha; Resources: Dr Sneh Kumari; Data Curation: Dr. Diksha; Writing (Original Draft): Dr. Sneh Kumari; Writing (Review and Editing): Dr Salil Dube, Dr. Sunil Kumar Dahiya.