ORIGINAL ARTICLE |
https://doi.org/10.5005/jacm-11020-0002 |
Severe Acute Respiratory Syndrome Coronavirus 2 Breakthrough Infections among Fully Vaccinated Undergraduate Medical Students at a Teaching Hospital in Puducherry
1,2Department of Microbiology, Pondicherry Institute of Medical Sciences, Puducherry, India
Corresponding Author: Shashikala Nair, Department of Microbiology, Pondicherry Institute of Medical Sciences, Puducherry, India, Phone: +91 9443265947, e-mail: shashikalanair2@gmail.com
Received: 10 May 2024; Accepted: 18 June 2024; Published on: 26 July 2024
ABSTRACT
Context: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a significant pandemic, claiming many lives. Controlling the infection posed a great challenge, which was addressed by the development of vaccines against the virus. However, the disease continued to spread, resulting in breakthrough infections. Consequently, understanding the risk factors and severity of breakthrough infections became a major concern.
Aims: (1) To measure the incidence of SARS-CoV-2 breakthrough infection among fully vaccinated medical students; (2) to determine the risk factors for breakthrough SARS-CoV-2 infection in vaccinated medical students; (3) to find out the severity of illness among students with breakthrough infection.
Settings and design: This was a cross-sectional study carried out on undergraduate medical students at a teaching hospital in Puducherry. Study subjects were identified by simple random sampling.
Materials and methods: A total of 215 undergraduate medical students vaccinated with two doses of the coronavirus disease 2019 (COVID-19) vaccine were included in the study. The questionnaire consisted of demographic details, COVID vaccination details, COVID infection history, risk factors, and severity of illness.
Statistical analysis: Data has been summarized using frequency and percentage.
Results: Among 215 fully vaccinated medical students, 57 (26%) breakthrough cases were detected, including 21 males (36%) and 36 females (64%) between the ages of 18 and 23 years. Among these, 9 (16%) had received Covaxin and 47 (84%) had received Covishield. The major risk factor for breakthrough infection was close contact with confirmed cases. Among symptomatic students, the majority had only mild symptoms. The predominant symptoms in infected cases were fever, cough, body ache, and sore throat. The majority (51.8%) had their symptoms resolved within 1 week.
Conclusion: Identifying the occurrence, severity, and factors responsible for breakthrough infections with SARS-CoV-2 is important, as it may inform the choice of response by healthcare authorities. Asymptomatic cases of breakthrough infections may pose a threat to vulnerable populations.
Keywords: Breakthrough infection, Coronavirus disease vaccine, Severe Acute Respiratory Syndrome Coronavirus 2, Severity, Symptoms
How to cite this article: Raveendran P V A, Nair S. Severe Acute Respiratory Syndrome Coronavirus 2 Breakthrough Infections among Fully Vaccinated Undergraduate Medical Students at a Teaching Hospital in Puducherry. J Acad Clin Microbiol 2024;26(1):7–12.
Source of support: Nil
Conflict of interest: None
INTRODUCTION
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in December 2019 in Wuhan, China, is a major health concern due to the rapid spread of the disease. The World Health Organization declared it a public health emergency in March 2020. According to data from 12 September 2022, globally there have been 60,59,12,418 confirmed cases of COVID-19, including 64,91,649 deaths, reported to World Health Organization (WHO). In India, 5,28,165 people have died because of this infection.1 Due to the high mortality caused by the virus, it is essential to control the infection. SARS-CoV-2 infection presents a spectrum of disease severity ranging from asymptomatic to fatal.
Coronavirus disease 2019 vaccines have played a critical role in controlling this pandemic. Various types of vaccines have been developed. Covishield, a viral vector vaccine, is manufactured by the Serum Institute of India under license from AstraZeneca. Covaxin, an inactivated vaccine, is developed by Bharat Biotech. On January 1 and 2, 2021, the National Health Regulatory Authority of India granted emergency use authorization to the viral vector vaccine Covishield and the inactivated vaccine Covaxin, respectively.2 Subsequently, Sputnik V received emergency use authorization on 13 April 2021. The national COVID-19 vaccination program in India was launched on 16 January 2021.2 However, no vaccine is perfectly effective and protection is expected to decline with time, after vaccination.
Breakthrough COVID-19 infection has been defined as an individual testing positive for SARS-CoV-2 ribonucleic acid (RNA) or antigen in a specimen collected any time after 14 days of receiving all doses of any of the licensed COVID-19 vaccines.3 Being an RNA virus, mutations have been observed in SARS-CoV-2, with the first major mutation seen in its spike protein (D614G). New variants have led to breakthrough COVID-19 infections in individuals immunized with two doses. Identifying the frequency, severity, and causes of breakthrough infections is important as it will provide information on whether additional vaccine doses or changes in vaccine formulations are needed to reduce the incidence of infection.
Various studies have been conducted to identify risk factors for breakthrough infections. Immunocompromised individuals are at the highest risk for developing infections.4 Contact with infected persons is one of the risk factors for developing a breakthrough infection.5 Healthcare workers and frontline workers had an independent risk of developing infection.6 Obesity, diabetes mellitus, cardiovascular disease, chronic kidney disease, and liver disease were associated with increased COVID-19 infection and mortality.7 Some individuals had asymptomatic infections. Among those who developed symptoms, the main complaints were fever, headache, body ache, cough, sore throat, and loss of taste and smell.2 Most of these symptoms resolved within a week, but a few individuals experienced persistent symptoms, lasting >6 weeks.5,8-14 Vaccination was associated with lower risk of developing severe disease.15-19 Rate of admission to hospital was more among those with underlying comorbidities.2 Severity of infection was less in breakthrough infection compared to infection occurring in unvaccinated persons.
The purpose of the study was to measure the incidence of breakthrough infections among fully vaccinated medical students and to identify various risk factors associated with breakthrough infection. If any breakthrough infection was observed, its severity based on signs, symptoms, hospital admission, and duration of symptoms was also identified. Thus, the efficacy of vaccines against SARS-CoV-2 can be correlated with breakthrough infections, as they may indicate reduced vaccine effectiveness.
MATERIALS AND METHODS
We conducted a cross-sectional study among undergraduate medical students between August and September 2022 at a teaching hospital in Puducherry. Undergraduate medical students vaccinated with two doses of COVID-19 vaccine (Covaxin, Covishield) were included in the study. The study subjects were obtained using simple random sampling, including 79 from the 2018 batch, 37 from the 2019 batch, 50 from the 2020 batch, and 49 from the 2021 batch. The questionnaire collected details such as age, sex, height, weight, MBBS batch, details of COVID-19 vaccination (type of vaccine, time of first and second dose, time interval between the two doses), COVID-19 infection history, severity of illness [hospital admission, intensive care unit (ICU) admission, oxygen therapy], and risk factors for infection such as smoking, underweight, obesity, medications, and underlying diseases. The study was conducted after obtaining consent through a Google Form from the study participants. A structured questionnaire was circulated among them using Google Forms to collect details on study variables. The sample size for the present study was based on a study by Dash et al., with a prevalence of breakthrough infection of 83.2 and a 5% absolute precision, resulting in an estimated sample size of 215.3 The study was performed after obtaining ethical clearance from the institution (IEC: RC/2022/04).
The obtained results were exported to an MS Excel sheet, and statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) version 20.0. Data were summarized as frequency and percentage for qualitative variables, and mean and standard deviation for quantitative variables. Chi-squared tests were used to find associations between risk factors and the outcome variable. Associated risk factors were identified using multivariable logistic regression, with a p-value < 0.05 considered statistically significant.
RESULTS
Among 215 fully vaccinated medical students, 57 (26.5%) breakthrough cases were detected (Fig. 1). Of these 57 breakthrough infection cases, 21 were males (35.7%) and 36 were females (64.2%) aged between 18 and 24 years.
Fig. 1: Prevalence of COVID-19 breakthrough infections
Among 215 fully vaccinated students from four MBBS batches, the breakdown of breakthrough infections is as follows: 24 (30.3%) out of 79 in the 2018 batch, 9 (24.3%) out of 37 in the 2019 batch, 14 (28%) out of 50 in the 2020 batch, and 9 (18.3%) out of 49 in the 2021 batch had developed breakthrough infections.
On comparing the number of male students and female students who had developed breakthrough infections, there was a female predominance. Among the students who participated in the study, 110 students stayed in a hostel and 105 subjects stayed in their own house. Among the 110 subjects who stayed in the hostel, 29 (26.36%) developed breakthrough COVID-19 infection. Similarly, among the 105 subjects who stayed in their own house, 28 (26.7%) developed breakthrough infection.
Among students with breakthrough infections, 9 (16.07%) received Covaxin, while 48 (83.9%) received the Covishield vaccine. Specifically, among the 26 students who received Covaxin, 9 (34.6%) developed breakthrough COVID-19 infection. Similarly, among the 189 students who received the Covishield vaccine, 48 (25.39%) developed breakthrough infection (Fig. 2).
Fig. 2: Type of vaccine received in medical students with breakthrough COVID-19 infection
Among the students who developed breakthrough infections, 50 (89.23%) confirmed their infection using reverse transcription polymerase chain reaction (RT-PCR), while 6 (10.7%) used antigen tests for confirmation (Fig. 3).
The table indicates that a history of contact with a COVID-19 positive person was significantly associated with breakthrough infections (p-value = 0.0001). The percentage of breakthrough infections was higher among participants who had a history of contact with a COVID-19-positive person (41.2%) compared to those who did not have such a history (19.04%) (Tables 1 to 3).
| Breakthrough infection | Adjusted odds ratio (OR) [95% confidence interval (CI)] | p-value | ||||
|---|---|---|---|---|---|---|
| No (%) | Yes (%) | Total (%) | ||||
| Sex | Male | 68 (76.40) | 21 (23.60) | 89 (100) | 1.0 | |
| Female | 90 (71.43) | 36 (28.57) | 126 (100) | 1.29 (0.69–2.41) | 0.416 | |
| Total | 158 (73.49) | 57 (26.51) | 215 (100) | |||
| Body mass index (BMI) classification | Normal | 102 (80.95) | 12 (54.55) | 126 (100) | 1.0 | |
| Underweight | 10 (45.45) | 12 (54.55) | 22 (100) | 5.1 (1.97–13.18) | 0.001 | |
| Overweight | 36 (65.45) | 19 (34.55) | 55 (100) | 2.24 (1.10–4.57) | 0.026 | |
| Obesity | 10 (83.33) | 2 (16.67) | 12 (100) | 0.85 (0.17–4.13) | 0.840 | |
| Total | 158 (73.49) | 57 (26.51) | 215 (100) | |||
| Contact history | Yes | 40 (58.82) | 28 (41.18) | 68 (100) | 2.84 (1.51–5.35) | 0.001 |
| No | 118 (80.27) | 29 (19.73) | 147 (100) | 1.0 | ||
| Total | 158 (73.49) | 57 (26.51) | 215 (100) | |||
| Breakthrough infection | Adjusted OR (95% CI) | p-value | ||||
|---|---|---|---|---|---|---|
| No (%) | Yes (%) | Total (%) | ||||
| Sex | Male | 68 (76.40) | 21 (23.60) | 89 (100) | 1.0 | |
| Female | 90 (71.43) | 36 (28.57) | 126 (100) | 1.43 (0.73–2.78) | 0.288 | |
| Total | 158 (73.49) | 57 (26.51) | 215 (100) | |||
| BMI classification | Normal | 102 (80.95) | 12 (54.55) | 126 (100) | 1.0 | |
| Underweight | 10 (45.45) | 12 (54.55) | 22 (100) | 4.95 (1.85–13.23) | 0.001 | |
| Overweight | 36 (65.45) | 19 (34.55) | 55 (100) | 2.26 (1.08–4.72) | 0.030 | |
| Obesity | 10 (83.33) | 2 (16.67) | 12 (100) | 0.79 (0.15–4.01) | 0.779 | |
| Total | 158 (73.49) | 57 (26.51) | 215 (100) | |||
| Contact history | Yes | 40 (58.82) | 28 (41.18) | 68 (100) | 2.77 (1.43–5.36) | 0.002 |
| No | 118 (80.27) | 29 (19.73) | 147 (100) | 1.0 | ||
| Total | 158 (73.49) | 57 (26.51) | 215 (100) | |||
| History of contact | Breakthrough infection | p-value | ||
|---|---|---|---|---|
| No (%) | Yes (%) | Total (%) | ||
| No | 119 (80.95) | 28 (19.04) | 147 (100) | 0.0001 |
| Yes | 40 (58.80) | 28 (41.20) | 68 (100) | |
| Total | 159 (73.95) | 56 (26.04) | 215 (100) | |
Smoking habit was not significantly associated with breakthrough COVID-19 infections.
Fig. 3: Distribution of common clinical symptoms observed among students with COVID-19 breakthrough infection
Among the 215 students, 9 (16.07%) were asymptomatic. Among the students who were symptomatic, 49.1% had mild symptoms, 31.5% had moderate symptoms, and 3.5% had severe symptoms (Fig. 4).
Fig. 4: Distribution of severity of symptoms among students with breakthrough infection
Majority of students had their symptom resolved within 1 week (Fig. 5) and most of the students (92.8%) did not need hospitalization and were in home quarantine during breakthrough infection.
Fig. 5: Distribution of symptoms among students with breakthrough infection
None of the study subjects required ICU admission or administration of oxygen. No comorbidities were observed among students with breakthrough infections, and all subjects recovered completely.
DISCUSSION
Severe acute respiratory syndrome coronavirus 2 has created a great pandemic, which has taken the lives of many. Controlling the infection was a significant challenge, fought by the discovery of vaccines against this virus. However, the disease continued to spread, resulting in breakthrough infections. Postvaccination breakthrough infections have been reported from different parts of the world following the use of various COVID-19 vaccines. These breakthrough infections with SARS-CoV-2 in fully vaccinated individuals are of great concern. This study aims to identify the risk factors and clinical manifestations of breakthrough infections that occurred in fully vaccinated undergraduate medical students at a teaching hospital in Puducherry.
In the present study, among 215 undergraduate medical students who participated, 57 (26.5%) of them had developed COVID-19 breakthrough infection. There was a female predominance in the present study. Breakthrough infection cases occurred in 35.7% of males and 64.2% of females. Among the participants, 26.36% of students stayed in the hostel, and 25.7% of students stayed outside the hostel developed infection.
Among the infected persons, 16.07 and 83.9% were recipients of Covaxin and Covishield, respectively. This is similar to the study by Dash et al. from Eastern states of India, where they found 12.8 and 87.2% of breakthrough infections among Covaxin and Covishield users, respectively.3 This might be due to reduced immune protection generated by the Covaxin vaccine in its recipients. RT-PCR was the main modality used for confirmation of the disease.
Among the students with breakthrough infections, 50% had a history of contact with laboratory-confirmed COVID-19 cases in this study. This is similar to the study conducted among healthcare workers in Qatar, where they identified 59.7% of subjects with a history of contact with confirmed cases.10 This is probably because healthcare professionals have more contact with confirmed cases compared to undergraduate medical students. Among the study subjects, 21.4% were underweight, 41.07% were normal weight, 33.9% were overweight, and 3.57% were obese. None of the subjects had a smoking habit or any underlying comorbidities. However, in the study by Dash et al., 23.4% of cases had underlying comorbidities such as diabetes, hypertension, hypothyroidism, and asthma.3 The absence of comorbidities in the current study may be due to the subjects being students who are younger in age compared to the elderly working population.
In the current study, 15.8% of infected persons were asymptomatic. Fever was the predominant symptom in 69.64% of subjects. Other predominant symptoms were cough, body ache, loss of taste and smell, sore throat, headache, and running nose, in decreasing order of appearance. In the study done by Dash et al., 13.3% of cases had asymptomatic infection.3 The increase in the occurrence of asymptomatic infection among undergraduate students is probably due to their young age and better immunity compared to working adults. In other studies, common symptoms reported include fever, headache, loss of taste, myalgia, and features of upper respiratory tract infection, which is similar to the results of the current study.2,3
Majority of the subjects (51.8%) had their symptoms resolved within 1 week of occurrence. However, in 21.42 and 3.57% of subjects, it took 2 weeks and >2 weeks for symptoms to resolve, respectively. In a study among healthcare workers, they found 19% of subjects with symptoms persisting for >6 weeks.8 This decrease in the duration of symptoms is probably due to the young age-group and absence of underlying medical comorbidities among the medical students.
In this study, 7.1% of subjects were admitted to the hospital after contracting COVID-19 infection. In another study among healthcare workers, 9.9% of hospital admission cases were identified.3 Younger age may be a major factor leading to less hospitalization. None of the study subjects needed ICU admission or oxygen therapy.
Knowing about various aspects of breakthrough COVID-19 infection will help in providing booster doses and arranging more platforms to educate about self-precautions, which can help reduce the incidence of breakthrough infections.
To conclude, 56 study subjects (26%) had breakthrough infections, with a female predominance. Forty-seven of these cases (83.9%) received the Covishield vaccine, with the major risk factor being contact with confirmed infected cases. The majority of cases experienced symptoms such as fever, cough, body ache, loss of taste and smell, sore throat, and headache, which resolved within 1 week. None of the subjects with breakthrough infections had underlying comorbidities.
Thus, identifying the incidence, severity, and factors responsible for breakthrough infections with SARS-CoV-2 is important as it may inform the response choices by healthcare authorities. Asymptomatic cases of breakthrough infections may pose a threat to vulnerable populations.
This study had several limitations. The number of cases was relatively small. The study populations were younger age groups; therefore, we could not determine the protection from severe infections in vulnerable older populations and persons with comorbid conditions. Antibody titers were not detected to correlate with the severity of infections.
APPENDIX
Questionnaire
1. Age:
2. Sex:
3. Height:
4. Weight:
5. MBBS batch:
6. Address:
7. Where are you staying? Hostel/outside campus
8. Did you get vaccinated against SARSCoV2 infection? Yes/no
If yes,
What type of vaccine was it? Covaxin/Covishield/Sputnik
When was the first dose taken? Date/month/year
When was the second dose taken? Date/month/not taken
What was the time interval between the two doses of vaccine?
9. Do you have the habit of smoking? Yes/no
10. Are you on any long-term medication? Yes/no
If yes, please specify it…
11. Did you get infected with SARSCoV2? Yes/no
If yes, when did you get infected? Prevaccination/postvaccination/both
12. If you get infection postvaccination,
Did it occur after 14 days of second dose of vaccination? Yes/no
Is there any history of contact with confirmed cases at that time? Yes/no
How did you confirm the diagnosis? RT-PCR/antigen test/antibody test
What was your condition at that time? Asymptomatic/mild/moderate/severe
What was the symptom that you had? Cough/fever/breathing issues/bodyache/loss of taste and smell/sore throat/diarrhea/others (specify)
When did your symptoms disappear? Within 1 week/within 2 weeks/beyond 2 weeks
Did you get admitted to hospital? Yes/no
Have you been admitted in ICU because of this infection? Yes/no
Have you given oxygen therapy? Yes/no
Any other complication……
13. If you have any underlying medical condition please specify it……
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