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Long-Term Safety Analysis of the BBV152 Coronavirus Vaccine in Adolescentsand Adults: Findings from a 1-Year Prospective Study in North India
Article in Drug Safety · May 2024
DOI: 10.1007/s40264-024-01432-6

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https://doi.org/10.1007/s40264-024-01432-6

ORIGINAL RESEARCH ARTICLE

Long‑Term Safety Analysis of the BBV152 Coronavirus Vaccine
in Adolescents and Adults: Findings from a 1‑Year Prospective Studyin North India
Upinder Kaur1 · Aakanksha Jaiswal2 · Ayushi Jaiswal3 · Kunal Singh3 · Aditi Pandey3 · Mayank Chauhan4 ·Mahek Rai3 · Sangeeta Kansal5 · Kishor Patwardhan4 · Vaibhav Jaisawal6 · Sankha Shubhra Chakrabarti7
Accepted: 10 April 2024
© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2024

Abstract
Background and Objective Evidence on the long-term safety of COVID-19 vaccines is scarce. Here, in continuation of
our previously published results on short-term safety, we provide data on the long-term safety of the BBV152 vaccine inadolescents and adults.
Methods This was a prospective observational study conducted from January 2022 to August 2023. Adolescents and adults
receiving the BBV152 vaccine were interviewed telephonically about long-term adverse events of special interest (AESIs)
after 1 year of vaccination. Risk factors of AESIs and AESIs persistent for at least 1 month were identified.
Results Out of 1024 individuals enrolled, 635 adolescents and 291 adults could be contacted during the 1-year follow-up.
Viral upper respiratory tract infections were reported by 304 (47.9%) adolescents and 124 (42.6%) adults in this period.
New-onset skin and subcutaneous disorders (10.5%), general disorders (10.2%), and nervous system disorders (4.7%) werethe common AESIs in adolescents. General disorders (8.9%), musculoskeletal disorders (5.8%), and nervous system disorders (5.5%) were the common AESIs in adults. Menstrual abnormalities were noticed in 4.6% of female participants. Ocularabnormalities and hypothyroidism were observed in 2.7% and 0.6% of participants, respectively. Among serious AESIs (1%),
stroke and Guillain–Barre syndrome were identified in 0.3% and 0.1% of participants, respectively. Among adolescents,
female individuals, those with a history of allergy and post-vaccination typhoid were respectively at 1.6, 2.8, and 2.8 times
higher risk of AESIs. The majority of the AESIs persisted at the 1-year follow-up. Female individuals, adolescents withpre-vaccination COVID-19, those with co-morbidities, and those with post-vaccination typhoid had respectively 1.6, 2, 2.7,
and 3.2 times higher odds of persistent AESIs. Adults with co-morbidities had more than 2 times higher odds of AESIs andpersistent AESIs.
Conclusions The patterns of AESIs developing after BBV152 differed from those reported with other COVID-19 vaccines aswell as between adolescents and adults. With the majority of AESIs persisting for a significant period, extended surveillanceof COVID-19-vaccinated individuals is warranted to understand the course and outcomes of late-onset AESIs. Serious AESIs
might not be uncommon and necessitate enhanced awareness and larger studies to understand the incidence of immunemediated phenomena post-COVID-19 vaccination. The relationship of AESIs with sex, co-morbidities, pre-vaccination
COVID-19, and non-COVID illnesses should be explored in future studies.

1 Introduction
To limit the impact of COVID-19, various vaccines basedon novel and pre-existing technologies were approved for amass rollout. The COVID-19 vaccination program worldwide was started in December 2020 and early January 2021.
The viral vector and mRNA-based COVID-19 vaccines werethe vaccines distributed on a large scale worldwide. Vaccines

Key Points
Serious adverse events may occur in 1% of BBV152
recipients.
Extended surveillance is warranted post-BBV152 vaccine.
Female adolescents and those with comorbidities are athigher risk of adverse events.

Extended author information available on the last page of the article
Vol.:(0123456789)

U. Kaur et al.

based on inactivated SARS-CoV-2 included SinoVac-CoronaVac (China), Sinopharm-BBIBP‐CorV (China), andBharat BioTech-BBV152 (India). BBV152 was the second
most distributed vaccine in India after the adenoviral-vectored AZD1222 (COVISHIELD). Considering the assumed
benefits of vaccinating all individuals, the approval of someof the COVID-19 vaccines was later extended to adolescentsand children. The mRNA-based vaccines were the first to get
the nod for administration in adolescents and children globally [1]. In India, the BBV152 was the only vaccine that was
initially granted permission for a mass rollout in adolescentsof 15–18 years [2]. The short-term safety of COVID-19 vaccines approved for adolescents was shown to be favorable
in controlled settings [3–5]. In this context, we provided thefirst short-term safety data of BBV152 in adolescents andthe comparative safety profile in adults [6]. Despite nearly 2
years having elapsed since the approval of COVID-19 vaccines in adolescents, long-term data on the safety of thesevaccines released in the public domain have been minimal.
Here, in an extension of our previously published study, we
provide data on the long-term safety of the BBV152 vaccine
in adolescents and adults.

2 Methodology
2.1 Study Design and SettingThis was a 1-year prospective observational study thatstarted in January 2022 in a tertiary university hospital in
North India. The study aimed to provide short-term andlong-term safety data of the BBV152 vaccine in adolescentsand adults. Participants were initially contacted by telephone
after 14 days of receiving the vaccine and the interim safety
analysis in the form of adverse events following immunization (AEFIs) was published by us in 2022 [6]. Here, we
provide the long-term safety data of BBV152 in the formof adverse events of special interest (AESIs) assessed at the
1-year follow-up in the same study group.

2.2 Study Participants
Adolescents aged 15–18 years and adults aged 19 years andabove receiving any dose of BBV152 vaccine constituted
the study population.

2.3 Safety Analysis and Outcome Measures
All participants were interviewed telephonically about theoccurrence of AESIs. The format used for collecting information on AESIs was guided by the list of AESIs provided
by the CEPI-SPEAC-Brighton Collaboration, atypicaladverse events published in PubMed/MEDLINE, and ourown experience on COVID-19 vaccine-related atypicaladverse events reported in our center [7, 8]. Telephonic interviews were conducted by five different observers, including
graduate students (pre-final and final year MBBS students)
and post-graduate trainees (MD residents). A 3-hour training was given to each by the lead investigators (corresponding authors) and the initial few telephonic interviews wereconducted under the supervision of the lead investigators.
All symptoms were labeled using the low-level terms andsystem organ class (SOC) as per the M­ edDRA® terminology[9]. The severity of AESIs was rated using the US Food andDrug Administration-AEFI Severity Assessment Scale [10].
AESIs were labeled as ‘serious’ depending upon the World
Health Organization Scale of Seriousness of AEFIs [11].
Depending upon improvement, outcomes of AESIs wererated as ‘improved’ if no symptoms were present at the timeof follow-up or the participant was off therapy required initially for the management of AESIs and ‘partially improved’
if symptoms were persisting at the 1-year follow-up or were
controlled only on medication. Additionally, we enquired
about “persistent AESIs” pre-defined as “any symptoms persisting for a minimum period of 4 weeks at the time of one
year follow up” [7].
The final list of AESIs selected for the present study isprovided in Table 1 of the Electronic Supplementary Material (ESM). Briefly, we enquired about the occurrence of
infections such as upper respiratory tract infections, laboratory-confirmed COVID-19, and dengue, among others.
Among AESIs, detailed information was sought on newonset rheumatologic disorders, cardiac disorders such asheart failure, myocardial infarction or myocarditis, metabolic disorders such as diabetes mellitus, endocrinal disorders such as thyroid abnormalities, nervous system disorders
such as headaches, attention deficits, stroke and weakness inlimbs, hematologic disorders such as anemia and thrombocytopenia, skin disorders such as alopecia, reproductive disorders such as menstrual disturbances and flares of underlying diseases such as diabetes, hypertension, and arthropathy.
The causality assessment of ‘serious’ AESIs was performed
using the 2005 World Health Organization Scale of Assessment of AEFIs [12].

2.4 Sample Size
The sample size estimation of our 1-year follow-up study
was based on primary outcomes of rates of AEFIs following
the BBV152 vaccine. Details are provided in the publishedinterim analysis [6].

BBV152 Long-Term Safety Data

2.5 Statistical Analysis
Dichotomous data were analyzed as frequencies and percentages and depending upon the normality, mean or medianvalues were chosen for quantitative variables. The chi-square
test was separately applied to assess the association of independent variables such as demographic factors, co-morbidities, and pre-vaccination COVID-19 and post-vaccination
non-COVID-19 illnesses with the two dependent variables,
namely “AESIs” and “persistent AESIs”. The variables
with a p-value <0.05 in the bivariate analysis and those presumed to be clinically significant were incorporated in the
final logistic regression model to determine the risk factors.
Separate logistic regression analyses were performed for thetwo dependent variables, “AESIs” and “persistent AESIs”,
and for adolescents and adults separately. Hence, altogether
four different regression analyses were performed. SPSS version 16 (SPSS Inc., Chicago, IL, USA) was used to performthe statistical tests.

3 Results
A total of 1024 participants (698 adolescents and 326 adults)
receiving BBV152 were enrolled in the study in January
2022. The initial short-term AEFIs noticed within 14 daysof receiving the vaccine have already been published [6].
Data on long-term safety at the 1-year follow-up could be
procured for 635 adolescents and 291 adults. Information
about the total number of vaccine doses was not known for
58 adolescents and 66 adults. Thus, the association between
the number of doses and AESIs could be analyzed for 577
adolescents and 225 adults. Four deaths were reported in
adults. There were 635 adolescents and 287 adults subsequently assessed for persistent AESIs at 1 year. The detailsof the participants recruited and analyzed are depicted inFig. 1. Details of infections and AESIs reported in adolescents and adults are described subsequently.

3.1 Infections
3.1.1 Infections in Adolescents
A total of 304 adolescents (47.9%) reported viral upper respiratory tract infections (URTIs) and all except one weremoderate in severity. The majority of these infections werereported after June 2022. Among these 304, recurrent viral
URTIs (defined as three or more episodes in a year) werecited by 26. As laboratory tests for COVID-19 were notbeing opted for by patients during this period, no case ofviral URTI could be labeled as COVID-19. Laboratoryconfirmed and symptomatic dengue occurred in 22 (3.5%).

Eight cases (36.4%) of dengue were ‘severe’ or ‘serious’cases and three among them required hospitalization. Laboratory-confirmed typhoid was the third most common infection reported in 17 (2.7%) and was ‘severe’ in four cases.
Details are provided in Table 2 of the ESM.
3.1.2 Infections in Adults
Among 291 adults, viral URTIs were reported by 124(42.6%) and the majority were moderate in severity. Similar
to adolescents, laboratory tests for COVID-19 were not conducted in the cases of URTIs. Laboratory-confirmed typhoidand symptomatic dengue were observed in seven and six
cases, respectively. Severity wise, one case of viral URTI
was ‘severe’ and one case each of typhoid and dengue was‘serious’. Details are provided in Table 2 of the ESM.

3.2 AESIs in Adolescents
Among 635 adolescents, AESIs were recorded in 214(33.7%). Skin and subcutaneous disorders, such as alopecia(n = 67, 10.5%), general disorders (n = 65, 10.2%) such as
undiagnosed fever and weakness, and nervous system disorders (n = 30, 4.7%) such as headache and attention difficulty
were the three most common SOCs affected by AESIs inadolescents. Other common disorders included eye disorders(n = 23, 3.6%) such as refractive error and musculoskeletal
disorders (n = 18, 2.8%). Around 5.7% (n = 36) of adolescents reported a flare of underlying disease. Cutaneous disturbances in the form of increased hair fall, eye disturbancessuch as an increase in refractive error, and nervous system
disturbances such as an aggravation of headache were thecommon flares. Details are provided in Table 2 of the ESM.
3.2.1 Persistent AESIs in Adolescents
Among 214 adolescents with AESIs, 142 (66.3%) had persistent AESIs. Alopecia (n = 47), refractive errors (n =26), headache (n = 20), menstrual abnormalities (n = 17),and increased symptoms of allergy (n = 16) were the fivecommon persistent AESIs. With regard to SOCs, all casesof psychiatric disorders, 91.3% of eye disorders, 88.2% ofreproductive disorders, 83.3% each of musculoskeletal andimmune system disorders, 80% of nervous system disorders, and 64.2% of skin disorders were persisting till thelast follow-up with an approximate time of persistence of 5.5
months, 3.5 months, 10.5 months. 11.5 months, 6.5 months,
9.5 months, and 8.5 months, respectively. Details of SOCs of
persistent AESIs and the approximate times of persistence
are mentioned in Tables 3 and 4 of the ESM, and depicted
in Fig. 2.

U. Kaur et al.

Fig. 1  STROBE flow diagram of the study. AESIs adverse events of special interest

3.2.2 Risk Factors of AESIs and Persistent AESIs
in Adolescents
A bivariate analysis showed a statistically significant association of AESIs in adolescents with sex (p = 0.006), historyof allergy (p < 0.001), and the presence of any co-morbidity
especially asthma (p = 0.007). Though not statistically significant, a marginal association of AESIs was also observedwith post-vaccination typhoid (p = 0.09) (Table 1a). As
typhoid can influence the occurrence of clinical symptoms
such as musculoskeletal and subcutaneous disorders, it wasincorporated in the logistic regression model along withvariables sharing a statistically significant association (p <0.05) with AESIs in the bivariate analysis. After adjustingfor confounders, female individuals were observed to have a
1.57 times higher odds of AESIs compared with male individuals (p = 0.009), and a history of allergy to any stimulus
was associated with a 2.81 times higher odds of AESIs (p= 0.004) (Table 1b). A nearly similar odds (adjusted odds
ratio 2.76) of AESIs was observed with post-vaccination
typhoid (p = 0.042).
For persistent AESIs, a statistically significant association was noted with sex (p = 0.016) and the presence of aco-morbidity such as asthma (p = 0.007). With marginal
statistical significance, persistent AESIs were also morecommon in adolescents with a history of allergy, a prevaccination history of COVID-19, and post-vaccination
typhoid (p = 0.07 for each) (Table 2a). All these factors
were included in the regression analysis, which showed
a 1.61 times higher risk of persistent AESIs in female
individuals (p = 0.018) and a 2.71 times higher risk inadolescents with co-morbidities (p = 0.011). Pre-vaccination COVID-19 increased the odds of persistent AESIs
by around 2 times (p = 0.047) and a close to 3.2 times
higher risk of persistent AESIs was observed with postvaccination typhoid (p = 0.023) (Table 2b). No associationof persistent AESIs was observed with a history of allergy.

3.3 AESIs in Adults
Among 291 adults, AESIs were recorded in 83 (28.5%).
General disorders were the most common SOC affected by
AESIs (n = 26, 8.9%). This was followed by musculoskeletal disorders (n = 17, 5.8%) and nervous system disorders(n = 16, 5.5%). Other common disorders were gastrointestinal disturbances and skin and subcutaneous disorders,each seen in ten (3.4%) cases. A flare of underlying disease
was reported by ten adults (3.4%). Details are provided inTable 2 of the ESM.

BBV152 Long-Term Safety Data
Fig. 2  System organ classes(SOCs) affected by adverse
events of special interest(AESIs) and their persistence inBBV152 vaccinated adolescentsand adults. (Out of 635 adolescents and 291 adults for AESIs;
out of 635 adolescents and 287
adults for persistent AESIs)[eye disorders (ED), generaldisorders (GD), gastrointestinal
disorders (GITD), musculoskeletal and connective tissue
disorders (MCTD), nervous system disorders (NSD), skin andsubcutaneous tissue disorders(SSCD)]

3.3.1 Persistent AESIs in Adults
Among 83 adults with AESIs, 54 (65.1%) had persistent
AESIs. Joint pain (n = 12), weakness (n = 8), alopecia (n= 8), headache (n = 6), and dyspepsia (n = 4) were thecommon five AESIs that were persistent in adults at the
1-year follow-up. Regarding SOCs, 80% of gastrointestinal disorders, 75% of cardiac disorders, 68.7% of nervous
system disorders, and 60% each of skin and reproductive
disorders persisted at the 1-year follow-up with an approximate time of persistence of 5.25 months, 9.5 months, 9months, 12 months, and 10.3 months, respectively. Details
are described in Tables 3 and 4 of the ESM, and Fig. 2.
3.3.2 Risk Factors of AESIs and Persistent AESIs in Adults
With statistical significance, AESIs were more common
in adults aged 45 years and above (p = 0.035), those withco-morbidities such as hypertension (p = 0.009), and thosereceiving three doses of BBV152 (p = 0.001) (Table 3a).
Upon adjusting for confounders, the regression analysis
showed a 2.23 times higher risk of AESIs in adults with comorbidities (p = 0.04). Individuals receiving three doses andthose receiving a single dose of BBV152 were respectively
at 4.03 times and 2.16 times higher risk of AESIs comparedwith those receiving two doses. The difference was not significant between individuals receiving one and three dosesof BBV152 (Table 3b).
For persistent AESIs, the unadjusted analysis showed amarginally significant association with age (p = 0.056) anda significant association with the presence of co-morbidities(p = 0.004) (Table 4a). In the regression analysis, the effectof age was nullified and only the presence of co-morbidities
remained a significant determinant, increasing the odds

of persistent AESIs by 2.26 times (p = 0.025) (Table 4b).
Among co-morbidities, the risk of persistent AESIs was
attributed to hypertension. This was confirmed in a separate
regression analysis based on age groups and hypertension
as independent variables (results not shown).

3.4 Serious AESIs in Adolescents and Adults
A total of 11 (1.2%) participants (ten adults and one adolescent) developed serious AESIs. A case of hematemesis(upper gastrointestinal bleed) was reported in a 15-yearold female individual. Stroke events were reported inthree adults and one adult in his 20s was hospitalized for
Guillain–Barré syndrome (GBS). Using the World HealthOrganization Scale of Causality Assessment, the latter was
attributed a ‘probable’ association with the vaccine. Detailsof all serious AESIs are given in Table 5 of the ESM. Fourdeaths were reported in adults. A history of COVID-19
before receiving the vaccine was present in two of these.
Three deaths occurred in female individuals with stroke as
the main contributor in two. One among these had a historyof diabetes and hypertension and was in her late 60s and theother in her late 50s had a history of diabetes. The causeof death in the third woman could not be identified but the
woman in her early 70s had diabetes and hypertension andhad a history of multiple episodes of unconsciousness after
receiving the vaccine whose etiology could not be identified. The fourth mortality was recorded in a diabetic maleindividual in his 40s with a history of post-COVID-19 rhinocerebral mucormycosis before receiving the vaccine. The
concerned participant succumbed to the illness around 2.5
months after receiving the vaccine. Three of these fatalities
shared a ‘possible’ association with the vaccine while thefourth was ‘unclassifiable’.

169 (34.5)
4 (50)

0.49

0.56

0.09

0.85

<0.001

0.60

0.007

0.011

0.14

0.32

No (reference)

Yes

Post-vaccination typhoid

No (reference)

Yes

AllergyNo (reference)

Yes

Comorbiditiesa

Male (reference)

2.76 (1.04–7.34)

2.81 (1.40–5.65)

1.87 (0.87–4.03)

1.57 (1.12–2.21)

aOR (CI)

0.042

0.004

0.11

0.009

P-value

Out of N = 635, total number of vaccine doses not known for n = 58

Bold values denote statistical significanceb

Major co-morbidities in adolescents were asthma and hypothyroidism. Considering a small number of individual co-morbidities such as asthma and to prevent multicollinearity in the analysis,‘co-morbidities’ and not ‘asthma’ were included in the regression model. In a separate regression model including ‘sex,’ ‘asthma,’ ‘typhoid,’ and ‘allergy’ as risk factors, similar trends and statistical significance were observed for ‘sex,’ ‘typhoid,’ and ‘allergy’. High risk was observed with ‘asthma’ but with varying CIs and marginal statistical significance (results not shown)a

AESIs adverse events of special interest, aOR adjusted odds ratio, CI confidence interval

490

8

2

3

24 (30.4)

115 (34.7)

331

79

99 (32.6)

205 (33.2)

304

1

Number of ­dosesb

No

Yes

Viral upper respiratory tract infection

618

No

9 (52.9)207 (33.8)

613

17

7 (31.8)191 (32)

22

Yes

Post-vaccination typhoid

No

Yes

Post-vaccination dengue

597

No

23 (60.5)

212 (33.6)

631

38

2 (50)

208 (33.1)628

4

6 (85.7)

197 (32.6)

7

Yes

AllergyNo

Yes

Hypothyroidism

No

Yes

Asthmaa604

No

17 (54.8)

197 (33)597

31

17 (44.7)

14 (27.5)51

38

200 (34.2)

84 (28.2)

584

Yes

Comorbiditiesa

No

Yes

Pre-vaccination COVID-19

≥ 25

< 25

Body mass index (kg/m2)

298

Male

FemaleSex

130 (38.6)

0.006

337

FemaleSex

Tentative risk factors

P-value

AESIs, n (%)

Tentative risk factors

N

N = 635 (1b)N = 635 (1a)Table 1  Unadjusted (1a) and adjusted (1b) analysis of risk factors of AESIs in BBV152 vaccinated adolescents

U. Kaur et al.

BBV152 Long-Term Safety Data
Table 2  Unadjusted (2a) and adjusted (2b) analysis of risk factors of persistent AESIs in BBV152 vaccinated adolescents (N = 635)
Tentative risk factors (2a)SexFemaleMale
BMI (kg/m2)
< 25
≥ 25
Pre-vaccination COVID-19
Yes
No
Comorbiditiesa
Yes
No
Asthmaa
Yes
No
Hypothyroidism
Yes
No
Allergy
Yes
No
Post-vaccination dengue
Yes
No
Post-vaccination typhoid
Yes
No
Post-vaccination viral upper respiratory
tract infection
Yes
No
Number of doses of vaccine (N = 577b)
1
2
3

N

Persistent
AESIs, n (%)

P-value

Tentative risk factors (2b)aOR (CI)

P-value337298

88 (26.1%)
54 (18.1%)

0.016

Sex
FemaleMale (reference)

1.61 (1.09–2.37)

0.018

584
51

133 (22.8)
9 (17.6)

0.39

38
597

13 (34.2)
129 (21.6)

0.07

2.06 (1.01–4.19)

0.047

31
604

14 (45.2)
128 (21.2)

0.002

2.71 (1.25–5.86)

0.011

7
628

5 (71.4)
137 (21.8)

0.007

4
631

2 (50)
140 (22.2)

0.22

38
597

13 (34.2)
129 (21.6)

0.07

AllergyYes
No (reference)

1.47 (0.69–3.11)

0.31

22
613

4 (18.2)
138 (22.5)

0.79

17
618

7 (41.2)
135 (21.8)

0.07

Post-vaccination typhoid
Yes
No (reference)

3.19 (1.17–8.67)

0.023

304
331

69 (22.7)
73 (22.1)

0.85

79
490
8

18 (22.8)110 (22.4)
2 (25)

0.98

Pre-vaccination COVID-19
Yes
No (reference)
Comorbiditiesa
Yes
No (reference)

AESIs adverse events of special interest, aOR adjusted odds ratio, CI confidence intervalaMajor co-morbidities in adolescents were asthma and hypothyroidism. Considering a small number of individual co-morbidities such as asthma
and to prevent multicollinearity in the analysis, ‘co-morbidities’ and not ‘asthma’ were included in the regression model. In a separate regression
model including ‘sex,’ ‘asthma,’ ‘typhoid,’ ‘pre-vaccination COVID-19,’ and ‘allergy’ as risk factors, similar trends and statistical significancewere observed for all risk factors (results not shown)b

Total number of vaccine doses not known for n = 58

Bold values denote statistical significance or marginal statistical significance3.5 Symptoms with Reduced Frequency
and Severity
Though not included in the study format, some study participants self-reported the health benefits they observed after
receiving the BBV152 vaccine. Around 6.3% (n = 40) of

adolescents and 5.5% (n = 16) of adults mentioned a reduced
frequency or severity of health issues that they had had
before vaccination. Among these, reduced frequency and/or severity of URTIs was the most common health benefit
observed, being reported by 37 adolescents and 13 adults.

U. Kaur et al.
Table 3  Unadjusted (3a) and adjusted (3b) analysis of risk factors of AESIs in BBV152 vaccinated adults
N = 291 (3a)Tentative risk factors

N = 225 (3b)N

AESI, n (%)

19–44

230

59 (25.7)

≥ 45

61

24 (39.3)

Age (years)

Sex
Female14440 (27.8)

147

43 (29.3)

< 25

233

68 (29.2)

aOR (CI)

P-value0.035

Age (years)

1.01 (0.49–2.10)

0.98

2.23 (1.04–4.75)

0.04

3 dose group
2 dose group (reference)

4.03 (1.51–10.77)

0.005

≥ 45
19–44 (reference)

≥ 25

58

15 (25.9)Yes25

10 (40)No266

73 (27.4)

0.62

Pre-vaccination COVID-19

Comorbidityb

Tentative risk ­Factorsa

0.78

Male

Body mass index (kg/m2)

P-value

0.18

Yes

60

25 (41.7)

No

231

58 (25.1)

Hypothyroidism

0.011

Comorbidityb
Yes
No (reference)

1.0

Yes

6

2 (33.3)

No285

81 (28.4)Yes18

7 (38.9)

No

273

76 (27.8)

Yes18

10 (55.6)

No273

73 (26.7)Yes24

5 (20.8)

No

267

78 (29.2)Yes

6

1 (16.7)

No285

82 (28.8)Yes7

3 (42.9)

No

284

80 (28.2)

Diabetes mellitus

0.31

Hypertension

Allergy

0.009

0.38

Post-vaccination dengue

0.68

Post-vaccination typhoid

0.41

Post-vaccination viral upper respiratory tract infection

0.053

Yes

124

28 (22.6)

No

167

55 (32.9)

140

17 (42.5)2164

42 (25.6)

1 dose group
2 dose group (reference)

2.16 (1.04–4.48)

0.039

3

21

13 (61.9)

1 dose group
3 dose (reference)

0.53 (0.17–1.65)

0.27

Number of d­ osesc (N = 225)

0.001

Number of doses

AESIs adverse events of special interest, aOR adjusted odds ratio, CI confidence intervalab

In N = 225 adults, the bivariate analysis showed ‘comorbidity’ and ‘number of doses’ to share a significant association with AESIs

Only ‘comorbidity’ and not ‘hypertension’ was included in regression model because of small sample size of individual comorbidity as well as
to prevent multicollinearity in analysis. In a separate regression done including ‘age,’ ‘number of doses,’ and ‘hypertension’ as independent variables, similar trends and statistical significance was observed with ‘number of doses’ and ‘age’. Hypertension did not emerge as an independentrisk factor of AESIs (results not shown)c

Out of N =291, total number of vaccine doses not known for 66 adults

Bold values denote statistical significanceBBV152 Long-Term Safety Data
Table 4  Unadjusted (4a) and adjusted (4b) analysis of risk factors of persistent AESIs in BBV152 vaccinated adults (N = 287, after removing 4
adults who died)
Tentative risk factors (4a)Age (years)
≥ 45
19–44
Sex
FemaleMale
Body mass index (kg/m2)
< 25
≥ 25
Pre-vaccination COVID-19
Yes
No
Comorbiditiesa
Yes
No
Hypothyroidism
Yes
No
Diabetes mellitus
Yes
No
Hypertensiona
Yes
No
Allergy
Yes
No
Post-vaccination dengue
Yes
No
Post-vaccination typhoid
Yes
No
Post-vaccination viral upper
respiratory tract infection
Yes
No
Number of d­ osesb (n = 221)
1
2
3

N

Persistent AESIs,n (%)

P-value

Tentative risk factors (4b)aOR (CI)

P-value

0.056

Age (years)≥ 45
19–44 (reference)

1.43 (0.69–2.98)

0.33

Comorbiditiesa
Yes
No (reference)

2.26 (1.11–4.62)

0.025

58
229

16 (27.6)
38 (16.6)

141
146

29 (20.6)
25 (17.1)

0.45

229
58

47 (20.5)
7 (12.1)

0.14

23
264

6 (26.1)
48 (18.2)

0.40

56
231

18 (32.1)
36 (15.6)

0.004

6
281

2 (33.3%)
52 (18.5%)

0.31

14
273

4 (28.6)
50 (18.3)

0.31

15
272

7 (46.7)
47 (17.3)

0.011

23
264

3 (13)
51 (19.3)

0.59

6
281

1 (16.7)
53 (18.9)

1.0

7
280

2 (28.6)
52 (18.6)

0.62

124
163

22 (17.7)
32 (19.6)

0.68

39
162
20

12 (30.8)
29 (17.9)
6 (30)

0.13

AESIs adverse events of special interest, aOR adjusted odds ratio, CI confidence intervalaOnly ‘co-morbidities’ and not ‘hypertension’ were included in the regression model because of the small sample size of individual co-morbidity
as well as to prevent multicollinearity in the analysis. In a separate regression done with ‘hypertension’ and ‘age’ as independent variables, similar trends and statistical significance were observed (results not shown)b

Total number of vaccine doses not known for 66 adults

Bold values denote statistical significance or marginal statistical significanceU. Kaur et al.

Details of the symptoms in which improvement was noticed
after BBV152 are mentioned in Table 6 of the ESM.

4 Discussion
In the absence of long-term safety data of COVID-19 vaccines, the main aim of the present study was to highlight thesafety issues in recipients of the BBV152 vaccine, particularly among adolescents, at the 1-year follow-up. Nearly 50%
of study participants complained of infections during thefollow-up period, predominated by viral URTIs. Close to one
third of the individuals developed AESIs. New-onset skinand subcutaneous disorders, general disorders, and nervous
system disorders were the three most common disorders
observed in adolescents after receiving the vaccine. Morethan 10% of adolescents complained of skin conditions,mainly in the form of alopecia and a similar percentage
had general disorders such as weakness. While the majority of general disorders had recovered, skin disorders were
present in the majority during the final follow-up with a
median time of persistence of 8.5 months. General disorders
and musculoskeletal disorders were the common long-term
AESIs in adults. General disorders had recovered in morethan 50% but symptoms of musculoskeletal disorders werepersisting in the majority for almost 6 months at the final
follow-up. Close to 5% of adolescents and adults complainedof nervous system disorders such as headaches, which werepersisting in the majority for around 9 months at the final
follow-up. Among other atypical and persistent AESIs, eyedisorders such as new-onset refractive error were reported
in 3.6% of adolescents and 5% of adolescent female individuals complained of new-onset menstrual abnormalities.
Hypothyroidism was reported by around 0.6% of adolescentsand adults, each.
The patterns and incidence of AESIs differ with respect tothe type of vaccine and study population. In a predominantly
adult-based population receiving the ChAdOx1-nCov-19
vaccine, nearly 14% developed AESIs contrary to the onethird rates of AESIs observed in the present study. Musculoskeletal disorders, general disorders, and cardiovasculardisorders were the common AESIs in that study, but theincidence reported was low, being 3.7%, 2.1%, and 1.4%,
respectively. Reproductive system disturbances and ocular
disturbances were less common and were documented in
0.7% (2% of female individuals) and 0.26% of participants,
respectively [7]. Three out of five mortalities reported with
ChAdOx1-nCoV-19 happened because of cardiac causes incontrast with the neurological events such as stroke reported
in the present study. Another 18-month long study commented upon the late AESIs after the protein subunit-based

PastoCovac vaccine in Iran. Cutaneous disturbances (3.3%),
musculoskeletal disorders (1.1%), and neurological events(1.1%) were the common AESIs with PastoCovac given inheterogeneous regimens with the AstraZeneca or Sinopharmvaccine. The rates were further low with the standard regimen of the PastoCovac vaccine in which neurological, musculoskeletal, and metabolic disturbances were the common
events, each witnessed in 0.3% of individuals [13]. Apartfrom the type of vaccine and study population, the systemaffected and the incidence of AESIs are strongly influenced
by reporting rates and awareness regarding AESIs.
Among adolescents, the occurrence of AESIs and persistent AESIs was higher in female individuals, thosewith co-morbidities, those with a history of allergy to any
stimulus, and those developing typhoid after receiving thevaccine. Some association of persistent AESIs was also
observed with a pre-vaccination history of COVID-19. The
adjusted analysis showed female individuals to have a 1.6
times higher odds of AESIs. Adolescents with a history ofallergy and those developing typhoid after receiving the vaccine, each, were independently at a 2.8 times higher riskof AESIs. Considering the persistence of AESIs, female
individuals were at a 1.6 times higher risk, and adolescentswith co-morbidities were at a 2.7 times higher risk compared
respectively with male individuals and adolescents without
co-morbidities. The pre-vaccination history of COVID-19
and post-vaccination occurrence of typhoid increased theodds of persistent AESIs by 2 and 3.2 times, respectively. In
our previous work, the pre-vaccination history of COVID-19
was shown as an independent risk factor for long COVID-19,
AESIs, and persistent AESIs in recipients of the ChAdOx1nCoV-19 vaccine [7, 14]. Female individuals were also
the common victims of AESIs and persistent AESIs after
ChAdOx1-nCoV-19, similar to the findings of the present
study. These findings, which have been consistent acrossour several studies, emphasize the need for more stringent
vigilance in female recipients of COVID-19 vaccines andalso suggest revisiting the guidelines for vaccinating those
who have recovered from natural COVID-19.
The association of AESIs with post-vaccination typhoidneeds to be explored in future research. In the opinion of
consultants involved in the present study, many patients
showing seropositivity for typhoid during the second andthird wave of the pandemic were diagnosed eventuallywith COVID-19. The false cross-reactivity of Salmonella
typhi antibodies in patients of COVID-19 has also beenhighlighted in some studies [15]. Thus, the possibility ofobserved AESIs being determined actually by COVID-19
cannot be ruled out. Notwithstanding the above limitation,
AESIs were not associated with respiratory tract infectionsin adolescents or adults.

BBV152 Long-Term Safety Data

Interestingly, adults receiving three doses and thosereceiving one dose of BBV152 were respectively at four andtwo times higher risk of AESIs compared with adults receiving two doses of BBV152. A booster dose mechanisticallyenhances the production of anti-Spike antibodies above that
produced by the second dose. Significant cross-reactivity
has been shown between anti-SARS-CoV-2 antibodies anddiverse human antigens and this can explain the multi-system AESIs witnessed in the study participants [16]. Reasons
behind the high risk of AESIs in one dose group are elusive
but aberrant biochemical and immunological signatures havebeen observed in recipients of a SARS-CoV-2 inactivatedvaccine within the first few months of the first dose. Suchchanges include an increase in blood sugar, a decline in renal
function, an abnormal coagulation profile, increased nuclear
factor-κB signaling, decreased CD4+ regulatory T cells, andupregulation of inflammatory response signaling in monocytes [17].
In one of our previous works on COVID-19 vaccine effectiveness, a rather higher rate of COVID-19 was observedin one dose group compared with unvaccinated individuals, and transient immune suppression after the first dose
was cited as a possible reason in line with the post-vaccine
immunomodulation observed in the study by Liu et al. [14,17] However, whether the one-dose group is more vulnerable to AESIs also is worth exploring. The results concerning the boosters need corroboration from larger studies
owing to the limited number of adults receiving the third
dose of vaccine. Among adults, those with co-morbidities
such as hypertension were at more than 2 times higher riskof AESIs and persistent AESIs. It has often been emphasizedthat adults with comorbidities are more at risk of adverse
COVID-19 outcomes and hence should be prioritized for
vaccination. Our findings emphasize the need for balancing
these risks against those of higher AESIs in these groups.
Among serious AESIs, GBS occurred in one adult following the booster dose and shared a ‘probable’ association with the vaccine. The concerned adult however had ahistory of GBS 15 years previously and hence might havebeen more vulnerable to develop the syndrome after known
immunologic insults such as infection or vaccination. However, considering the global annual incidence of GBS (oneto two cases/100,000 people), the observed rate of one caseof GBS in 926 vaccinated individuals demands larger studies and increased awareness to comment on the incidence of
immune-mediated phenomena post-COVID-19 vaccination[18].
Four deaths (three female individuals, one male individual) were reported in adults. All of them had diabetes
while hypertension and a history of pre-vaccination COVID19 were present in three and two individuals, respectively. Stroke was the main contributor in two fatalities
and one fatality was due to post-COVID-19 rhinocerebral

mucormycosis, which supposedly disseminated after vaccination as reported by the caregivers. The fourth death
happened in a woman with multiple episodes of unconsciousness post-vaccination, the etiology of which remained
unidentified till death. In the absence of a definite causality
association, no conclusions can be drawn from these events.
Still, it is noteworthy that more deaths in our ChAdOx1
long-term safety study were reported due to cardiac events
whereas with BBV152, more stroke deaths were reported.

5 Limitations
The study enrols individuals vaccinated with BBV152. To
understand the link of AESIs with COVID-19 vaccines, acontrol arm of unvaccinated individuals is needed to compare the rates of AESIs between the two groups. In theabsence of data on background rates of the observed AESIs,
no comments can be made on changes in the incidence ofthe observed events in the post-vaccination period. The
findings of our study are confined to BBV152 and should
not be extrapolated to viral vector or mRNA vaccines. The
study primarily involved adolescents and the sample size ofadults was relatively small. Larger adult-based studies areneeded to understand the long-term safety of BBV152 inadults. The study participants belonged to the northern belt
of India and ethnicity-related differences in vaccine tolerability should be explored. The sample size was decided
based on the primary outcome of AEFIs and not based on
AESIs as no study on the incidence of AESIs was available
when the present study was started. However, considering
the high observed rates of overall AESIs, the study seems
to be well powered for detecting AESIs. The observed rates
of serious AESIs such as stroke and GBS however will need
confirmation from vaccine-specific larger multicentric studies. The final follow-up being at 1 year, the study is subject
to recall bias at certain points. For example, the exact timeof onset of AESIs was not available but the approximate
time of persistence of AESIs was obtained. For the same
reason, the time of improvement of AESIs was not recorded.
To reduce contamination by recall bias and in line with theprotocol of our previous study on the long-term safety of
the ChAdOx1-nCoV-19 vaccine, the health issues confirmedby participants to be present for at least 1 month during
the final follow-up were considered “persistent AESIs” [7].
However, some of the AESIs not persisting during the final
follow-up but which lasted for a significant period at any
time since vaccination might have gone unreported. Further,as the reporting rates of COVID-19 went down in India after
May 2022 (end of the third wave), routine testing for SARSCoV-2 was not performed in individuals developing viral
URTIs, and it was voluntary on the part of those having any
symptoms. The possibility of COVID-19 cannot be excluded

U. Kaur et al.

in these individuals. Importantly, however, no association
was observed between AESIs and respiratory infections.
The relationship of AESIs with typhoid and pre-vaccination COVID-19 needs corroboration from larger studies
owing to the smaller representation of these subsets. The
specific laboratory test used for the diagnosis of typhoid was
not enquired. Furthermore, in the experience of the study
researchers (UK, SSC, KP, VJ, and SK), findings concernedwith seropositivity for typhoid should be interpreted cautiously as the test was commonly found to be co-positivein patients of COVID-19 during the second and third waveof the pandemic. The possibility of sera of patients with
COVID-19 showing cross-reactivity in the serological tests
designed for typhoid needs to be determined. For the same
reason, the high rates of AESIs observed in the study should
be interpreted cautiously as the likelihood of typhoid cases
actually being COVID-19 cannot be excluded. Although
all interviews were conducted by medical students andresidents, the possibility of inter-observer bias in collecting
AESIs cannot be eliminated. More than 5% of participants
self-reported reduced viral URTIs. The percentage might befalsely low as symptoms improving after vaccination were
not a part of the designed questionnaire used in the present
study.

6 Conclusions
Nearly one third of participants receiving the BBV152 vaccination reported AESIs. Female adolescents and thosewith a history of allergy are at a higher risk of AESIs after
the BBV152 vaccine. Vaccinated adolescents developing
typhoid after BBV152 might also be at a higher risk of
AESIs, but the finding of seropositivity for typhoid needs
to be viewed cautiously. Adolescent female individuals andthose with co-morbidities are at a higher risk of persistent
AESIs. Focussed monitoring for persistent AESIs is warranted for individuals with a pre-vaccination history of
COVID-19. Adults with co-morbidities, especially hypertension, are at a higher risk of AESIs and persistent AESIs
after BBV152 administration. The patterns of AESIs developing after BBV152 differ from those seen after ChAdOx1nCoV-19 as well as among different age groups. Vigilanceis advised in adolescents for alopecia, headache, and menstrual abnormalities and in adults for musculoskeletal andnervous system disorders. Serious AESIs including stroke
and GBS should be actively investigated to determine theiractual incidence post-vaccination and to identify the persons vulnerable to them. With the majority of the AESIs
persisting for a significant period, extended surveillance issuggested for COVID-19-vaccinated individuals to understand the course and outcomes of late-onset AESIs. The relationship of AESIs with sex, co-morbidities, pre-vaccination

COVID-19, and non-COVID illnesses should be exploredin future studies.
Supplementary Information The online version contains supplementary material available at https://d​ oi.o​ rg/1​ 0.1​ 007/s​ 40264-0​ 24-0​ 1432-6.
Acknowledgments Upinder Kaur and Sankha Shubhra Chakrabarti
thank the Institutions of Eminence Scheme in the Banaras Hindu University for research support. Sankha Shubhra Chakrabarti thanks the
Indian Council of Medical Research for research support.

Declarations
Funding No funding was received for the conduct of this study or the
preparation of this article.
Conflicts of Interest/Competing Interests Upinder Kaur, Aakanksha
Jaiswal, Ayushi Jaiswal, Kunal Singh, Aditi Pandey, Mayank Chauhan,
Mahek Rai, Sangeeta Kansal, Kishor Patwardhan, Vaibhav Jaisawal,
and Sankha Shubhra Chakrabarti have no conflicts of interest that are
directly relevant to the content of this article.
Ethics Approval The study was conducted after permission fromthe Institute Ethics Committee of the Institute of Medical Sciences,
Banaras Hindu University. No human experimentation was performed.
All procedures were performed as per the Declaration of Helsinki andits subsequent modifications (Ethical Approval number: Dean/2022/
EC/3210 and Dean/2021/EC/2526).
Consent to Participate Written informed consent/assent to participate
was obtained from each participant in the study.
Consent for Publication Written informed consent/assent for publication was obtained from all participants.
Availability of Data and Material All data produced in the present study
are available upon reasonable request to the corresponding authors, as
per institutional and national legal norms and procedures.
Code Availability Not applicable.
Authors’ Contributions Conceptualization: UK, SSC, SK, VJ, KP.
Methodology: UK, SSC, VJ. Formal analysis and investigation: UK,
VJ, AJ, AJ, KS, AP, MC, MR. Writing, original draft preparation:
UK, AJ AJ, KS, MR. Writing, review and editing: UK, SSC. Funding
acquisition: none. Resources: none. Supervision: UK, VJ. All authors
read and approved the final version.

References
1. World Health Organization. Interim statement on COVID-19 vaccination for children. 2022. Available from: https://​www.​who.​
int/​news/​item/​11-​08-​2022-​inter​im-​state​ment-​on-​covid-​19-​vacci​
nation-​for-​child​ren. Accessed 30 Apr 2022.
2. MOHFW. Guidelines for COVID-19 vaccination of children
between 15-18 years and precaution dose to HCWs, FLWs &60+ population with comorbidities. 2022. Available from: https://​www.​mohfw.g​ ov.​in/​pdf/​Guide​lines​forCO​VID19​Vacci​natio​nofCh​
ildre​nbetw​een15​to18y​earsa​ndPre​cauti​onDos​etoHC​WsFLW​s&​
60pop​ulati​onwit​hcomo​rbidi​ties.​pdf. Accessed 30 Apr 2024.
3. Frenck RW, Klein NP, Kitchin N, Gurtman A, Absalon J,
Lockhart S, et al. Safety, immunogenicity, and efficacy of theBBV152 Long-Term Safety Data

4.

5.
6.

7.

8.

9.
10.

11.

BNT162b2 Covid-19 vaccine in adolescents. New Engl J Med.
2021;385:239–50.
Xia S, Zhang Y, Wang Y, Wang H, Yang Y, Gao GF, et al. Safety
and immunogenicity of an inactivated COVID-19 vaccine,
BBIBP-CorV, in people younger than 18 years: a randomised,double-blind, controlled, phase 1/2 trial. Lancet Infect Dis.
2022;22:196–208.
Ali K, Berman G, Zhou H, Deng W, Faughnan V, Coronado-Voges
M, et al. Evaluation of mRNA-1273 SARS-CoV-2 vaccine in adolescents. N Engl J Med. 2021;385:2241–51.
Kaur U, Anju KL, Chauhan M, Joshi A, Das A, Kansal S, et al. A
prospective observational study on BBV152 coronavirus vaccine
use in adolescents and comparison with adults: interim results ofthe first real-world safety analysis. Drug Saf. 2022;45:1099–109.
Kaur U, Fatima Z, Maheshwari K, Sahni V, Dehade A, Anju
KL, et al. Long-term safety analysis of the ChAdOx1-nCoV-19
corona virus vaccine: results from a prospective observational
study in priority vaccinated groups in North India. Drug Saf.
2023;46:553–63.
Safety Platform for Emergency vACcines S. D2.3 Priority list ofadverse events of special interest: COVID-19. 2020. Available
from: https://m​ edia.t​ ghn.o​ rg/a​ rticl​ es/C
​ OVID-1​ 9_A​ ESIs_S​ PEAC_​
V1.1_​5Mar2​020.​pdf. Accessed 30 Apr 2024.
Medical dictionary for regulatory activities. MedDRA hierarchy.
Available from: https://​www.​meddra.​org/. Accessed 6 Apr 2024.
US DHHS, FDA. Guidance for industry: toxicity grading scale
for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials. Available from: https://​www.​fda.​gov/​
media/​73679/​downl​oad. 2007. Accessed 30 Apr 2024.
World Health Organization. Monitoring and responding to adverse
events following immunization (AEFIs). 2021. Available from:https://​www.​who.​int/​docs/​defau​lt-​source/​covid-​19-​vacci​nes-​
safety-​surve​illan​ce-​manual/​covid​19vac​cines_​manual_​aefi_​20210​
104.​pdf. Accessed 6 Apr 2024.

12. Puliyel J, Naik P. Revised World Health Organization (WHO)’s
causality assessment of adverse events following immunization:a critique. F1000Res. 2018;7:243.
13. Sadat Larijani M, Sorouri R, Eybpoosh S, Doroud D, Moradi
L, Ahmadinezhad M, et al. Assessment of long-term adverse
events regarding different COVID-19 vaccine regimens within
an 18-month follow-up study. Pathog Dis. 2023;81:ftad010.
14. Kaur U, Bala S, Joshi A, Reddy NTS, Japur C, Chauhan M, et al.
Persistent health issues, adverse events, and effectiveness of vaccines during the second wave of COVID-19: a cohort study froma tertiary hospital in North India. Vaccines (Basel). 2022;10:1153.
15. Singh M, Chakraborty A, Tyagi AK. False sero-positivity ofSalmonella typhi specific antibody in dengue and corona virus
infected patients: an observational study. J Pure Appl Microbiol.
2023;17:434–8.
16. Vojdani A, Vojdani E, Kharrazian D. Reaction of human monoclonal antibodies to SARS-CoV-2 proteins with tissue antigens: implications for autoimmune diseases. Front Immunol.
2021;11:617089.
17. Liu J, Wang J, Xu J, Xia H, Wang Y, Zhang C, et al. Comprehensive investigations revealed consistent pathophysiological alterations after vaccination with COVID-19 vaccines. Cell Discov.
2021;7:99.
18. Bragazzi NL, Kolahi A-A, Nejadghaderi SA, Lochner P, Brigo F,
Naldi A, et al. Global, regional, and national burden of GuillainBarré syndrome and its underlying causes from 1990 to 2019. J
Neuroinflammation. 2021;18:264.
Springer Nature or its licensor (e.g. a society or other partner) holds
exclusive rights to this article under a publishing agreement with theauthor(s) or other rightsholder(s); author self-archiving of the accepted
manuscript version of this article is solely governed by the terms ofsuch publishing agreement and applicable law.

Authors and Affiliations
Upinder Kaur1 · Aakanksha Jaiswal2 · Ayushi Jaiswal3 · Kunal Singh3 · Aditi Pandey3 · Mayank Chauhan4 ·Mahek Rai3 · Sangeeta Kansal5 · Kishor Patwardhan4 · Vaibhav Jaisawal6 · Sankha Shubhra Chakrabarti7* Upinder Kaur
drupinder.bhu@gmail.com* Vaibhav Jaisawal
drvaibhav29@gmail.com* Sankha Shubhra Chakrabarti
sankha.chakrabarti1@bhu.ac.in
1

Department of Pharmacology, Institute of Medical Sciences,
Banaras Hindu University, Varanasi, Uttar Pradesh 221005,
India

2

Department of Kaumarbhritya/Balroga(Ayurveda‑Paediatrics), Institute of Medical Sciences,
Banaras Hindu University, Varanasi, Uttar Pradesh, India

3

Institute of Medical Sciences, Banaras Hindu University,
Varanasi, Uttar Pradesh, India

View publication stats

4

Department of Kriya Sharir (Ayurveda‑Physiology), Instituteof Medical Sciences, Banaras Hindu University, Varanasi,
Uttar Pradesh, India

5

Department of Community Medicine, Institute of Medical
Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh,
India

6

Department of Kaumarbhritya/Balroga(Ayurveda‑Paediatrics), Institute of Medical Sciences,
Banaras Hindu University, Varanasi, Uttar Pradesh 221005,
India

7

Department of Geriatric Medicine, Institute of Medical
Sciences, Banaras Hindu University, Varanasi,
Uttar Pradesh 221005, India