International Journal of Public Health Science (IJPHS)

Vol. 12, No. 1, March 2023, pp. 32~40

ISSN: 2252-8806, DOI: 10.11591/ijphs.v12i1.22470  32

Vaccination efficacy against post-COVID-19 symptoms in Delta

and Omicron waves: a prospective cohort in East Indonesia

Nur Upik En Masrika1, Aryandhito Widhi Nugroho2, Pramon Viwattanakulvanid3, Bumi Herman3,4
1
Department of Biomedical Science, Faculty of Medicine, Khairun University, Ternate, Indonesia
2
Department of Surgery, Faculty of Medicine, Khairun University, Ternate, Indonesia
3
College of Public Health Sciences, Chulalongkorn University, Bangkok, Thailand
4
Clinical Epidemiology, Research Development & Publication, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

Article Info ABSTRACT

Article history: The post COVID-19 symptoms affect the productivity and the quality of life
among survivors. It is imperative to identify the effect of virus variants and
Received Sep 6, 2022 the vaccination against post-COVID-19 symptoms. There were 242
Revised Nov 3, 2022 participants from the eastern part of Indonesia diagnosed with COVID-19
Accepted Nov 22, 2022 during July 2021-July to 2022 were recruited online. The participants
underwent data collection and semi-clinical follow-up for post-COVID-19
symptoms within 30 days after the first symptoms or from the diagnosis day
Keywords: using a validated clinical questionnaire and physician confirmation. Fatigue
was the most reported post-COVID-19 symptom (27.7%), followed by
Delta strain chronic cough (21.5%) and headache (15.3%). Adjusted by confounding
Indonesia factors in hierarchical logistic regression, the differences in post-COVID-19
Omicron strain symptoms were insignificant across different variants. Regarding vaccine
Post-COVID-19 symptoms efficacy against three post-COVID-19 symptoms, people with two-dose
Vaccination efficacy vaccination significantly reported lower post-COVID-19 chronic cough
(adjusted Odds Ratio 0.244 95% CI OR 0.071-0.838), but the protection
against fatigue and the chronic headache was insignificant. There is an
indication that vaccine efficacy may be waning along with the emerging new
variants.
This is an open access article under the CC BY-SA license.

Corresponding Author:
Bumi Herman
College of Public Health Science Chulalongkorn University
Institute Building 3, 11th Floor, Chulalongkorn University Pathum wan, Bangkok, Thailand
Email: bumiherman@med.unhas.ac.id; bumi.h@chula.ac.th

1. INTRODUCTION
The Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrom
Coronavirus 2 (SARS-COV2), has become a global threat and affects multiple aspects. The manifestation of
COVID-19 is not only limited to the respiratory system but also other system organs, including the nervous
system and immune-related manifestation [1]. COVID-19 affects more than 596 million people globally, with
6.5 million fatalities. In South East Asia. Indonesia ranks second after Vietnam, with reported cases of 6.3
million and 157,478 cumulative mortality. Despite a huge target population, the vaccination level for COVID-
19 is acceptable, with 74% coverage for the first and 62% for the second. Furthermore, Indonesia has already
initiated the first booster for the general population and the second booster [2].
Significant progress in controlling the pandemic has been achieved globally, including implementing
boosters, heterologous vaccination, and developing different antivirus. The remarkable change in vaccination
is contributed to the reduction of severe cases, particularly the booster vaccination with messenger RNA
technology [3]. However, conflicting result is seen in the efficacy of different antivirus, including Favipiravir

Journal homepage: http://ijphs.iaescore.com

Int J Public Health Sci ISSN: 2252-8806  33

and Remdesvir [4]. Furthermore, emerging new variants, including Omicron and its subvariants, lead to a new
health burden. Omicron is known for its ability to escape immunity, including the vaccinated people, and higher
infectivity. Thus, putting all people at risk of getting infected [5].
Since the probability of people getting an infection remains high, the most critical question is whether
the current intervention (vaccination and new medication) is still effective in reducing the severity and whether
the people may experience residual symptoms, known as post-COVID-19 symptoms. For example, a study
demonstrates persistent symptoms that could last for seven months [6]. Moreover, these post-COVID-19
symptoms affect the quality of life, particularly in particular demographic characteristics and those with severe
disease [7].
However, there is limited study on how the different variants affect the occurrence of residual
symptoms. For example, a longitudinal study in Indonesia addressed persistent symptoms, including fatigue,
chronic cough, and chronic headache within 90 days [8], and the impact of vaccination against specific
symptoms, such as olfactory dysfunction [9]. However, these studies did not cover the current period where
the Omicron is the most prevalent strain. A systematic review elaborating the effect of vaccination against
post-COVID-19 symptoms in three different countries (United Kingdom, United States, and India) shows a
conflicting result. Seven studies demonstrated an improvement in long-COVID-19 symptoms when a person
received one dose vaccine, although four studies disclosed no change or worsening in long-COVID-19
symptoms after vaccination [10]. Furthermore, most of the studies were retrospective cohort, cross-sectional,
and case-control design which exhibit lower evidence.
Assessing the effect of new variants and the vaccination impact on the post-COVID-19 symptoms is
imperative. As the level of vaccination is higher compared to the period covered by the previous study, the
researchers considered involving participants from the eastern part of Indonesia to cover more unvaccinated
people who received the first dose as the level of vaccination in this area is low [11]. Therefore, this study was
intended to identify the effect of new variants and vaccination effort against the post COVID-19 symptoms,
specifically in eastern part of Indonesia where number of people with vulnerable condition (unvaccinated and
partially vaccinated) remains higher.

2. RESEARCH METHOD
2.1. Study design and timeline
This study used a nested cohort of the latest Indonesian post-COVID-19 survey data from July 2021-
July 2022, which encompassed the period of Delta and Omicron variants. Furthermore, this research focused
on a subset of data from the eastern part of Indonesia as this area is less superior in health infrastructure,
particularly procurement of booster shots. Hence this study could address the impact of recent virus strains on
post-COVID-19 symptoms in the areas that have not achieved herd immunity.

2.2. Participants and data collection

An online questionnaire with informed consent was disseminated to participants, and the recruitment
of participants was based on the snowball technique, referred to by family or colleagues. Assessment of
outcomes was conducted on day 30 after onset (or diagnosis day for those who remained asymptomatic). This
study did not limit the age. However, online recruitment and the snowball technique might not be feasible to
reach younger participants, reducing the generalizability of the findings in the younger population. As for the
elderly and those with limited ability to fill in the questionnaire, the survey allows participants to be
accompanied by other family members or colleagues when filling in the questionnaire.
Participants were deemed eligible if diagnosed with either a real-time polymerase chain reaction (RT-
PCR) test or an antigen test using the nasopharyngeal, nasal, throat swab, or pooled sample of these samples
[12]. However, the current regulation of testing does not allow a person to perform self-test antigens for
diagnosis, unlike in other countries such as Thailand. Furthermore, the antigen test available in Indonesia
should possess a sensitivity of more than 80% and 97% specificity [13]. Participants were excluded for the
following reason: people who received prolonged treatment of more than 30 days, those who did not provide
the outcome assessment results on day 30, and those with reinfection. However, no specific exclusion was
made for people with chronic diseases or other comorbidities.

2.3. Variables
The nested cohort was composed of demographic information, anthropometric measurements,
diagnosis methods, vaccination status (including a number of doses and type of vaccine), presence of
comorbidities (chronic disease), and health behaviour (including smoking, alcohol drinking, and physical
activity), symptoms during COVID-19 (yes or no), treatment (in this case, the prescription of antivirus), and
the status of treatment (home isolation, hospitalization, or both). This clinical information was based on daily
observations or medical resumes of hospitalized patients.

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The researcher defined the severity of the disease according to World Health Organization guidance
based on the presence of pneumonia, including oxygen saturation of less than 94%, rapid breathing, or
abnormal imaging results [14]. As the genomic sequencing was not feasible, the researcher implemented an
approach to presume the possible strain of infection. The study period covered two dominant strains, where
from July to December 2021 was the period of Delta, and the initial case of the Omicron variant in December
2021 marked the beginning of the Omicron wave [15]. This study created the binary variable to represent the
assumed variant.

2.4. Outcomes
The researcher focused on three long COVID-19 symptoms, fatigue, chronic cough, and headache.
All outcomes were assessed using a clinical questionnaire since no specific algorithm or protocol exists to
measure the post-COVID-19 symptoms. Hence, the team applied a measurement using validated clinical
questionnaires.
This study implemented a measurement outcome using other clinical questionnaires with good
specificity and sensitivity. A fatigue severity scale (FSS) questionnaire is a 7-Likert scale with nine questions
to distinguish chronic fatigue symptoms that occur as the impact of the disease. Each question has a minimum
score of one and a maximum of seven. A cohort in Swiss revealed that a healthy individual had a mean score
of 3.00±1.08, which indicates that a mean score above three was defined as fatigue [16]. As for cough and
headache, the researchers applied the visual analog scale (VAS), where the minimum score is one and the
highest is ten. A score below three indicates mild or no significant disturbing headache [17], whereas in cough,
a VAS lower than 40 mm indicates a lower possibility of chronic cough [18]. Through the provided platform
enlisted in the questionnaire, participants with any reported post-COVID-19 symptoms underwent
confirmation by a physician.

2.5. Sample size

The estimation of sample size was derived from the one sample proportion formula. The researcher
selected chronic cough as the primary outcome due to the nature of the SARS-COV2 infection. The initial
study demonstrated that the Indonesian population's incidence of chronic cough within 30 days after
COVID-19 was 17.3% [8]. With a 95% confidence level, a 5% margin of error, and 10% of non-responsive
participants, the estimated sample size was 242.

2.6. Potential bias

The researchers addressed recall bias in certain variables, such as the days of symptoms. For the ease
of data collection and analysis, the presence of any symptoms was presented as a binary response. As for
vaccination information, the individual data could be retrieved from the PeduliLindungi account.

2.7. Quantification of variables

The researchers preserved continuous data as numbers, including age and body mass index. However,
some adjustments were made to specific variables. For example, following the protocol from the survey,
antivirus prescription time was described based on the time of diagnosis as <24 hours, 24-72 hours, >72 hours,
and not receiving any medication.
There is an assumption that vaccination will not be effective until 14 days [19]. Hence, by estimating
the date of vaccination and the day of infection, the researchers discretized the status of vaccination into three
levels: i) infected and unvaccinated, ii) infected after receiving one dose or after receiving a second dose less
than 14 days (level 1), and iii) infected more than 14 days after the second dose (level 2).

2.8. Statistical analysis

Descriptive statistics elaborated on the characteristic of the participants in the nested cohort, including
the prevalence of the selected post-COVID-19 symptoms. Bivariate and subgroup analyses were performed to
identify the crude association between the independent factors and post-COVID-19 symptoms. This study
estimated the effect of variants and vaccination on post-COVID-19 symptoms using hierarchical logistic
regression. The selection of other adjustment factors was based on the crude association of the factors.
Moreover, several independent factors may exhibit multicollinearity, which should be omitted from the final
model.

2.9. Ethical approval

Following the full board review of the study protocol, a research permit from the Research Ethics
Review Committee for Research Involving Human Research Participants of Hasanuddin University was
obtained (UH21110687) This study ensured that participants agreed to partake and were aware of future follow-

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up. The consent was granted electronically, and all the data was de-identified to maintain confidentiality.
Should further information (or immediate care) be required, the participants were allowed to contact the
research team for treatment referral.

3. RESULTS
The study involved 242 participants from the eastern part of Indonesia, where the vast majority of
them were from Sulawesi (70.2%), Maluku (20.6%), and Papua (9.2%). This cohort's mean age +SD was
32.73+10.65 years, dominated by females (53.3%). One hundred seventy people (70.2%) were infected during
the Delta wave, whereas 72 (29.8%) were contracted in the Omicron wave. Most were mild cases (90.1%),
followed by moderate (9.1%) and severe cases (0.8%). Average days of treatment +SD were significantly
shorter in those infected during Omicron than in Delta (11.94+3.5 versus 14.92+2.99 days, p<0.001). The most
reported symptom during infection was fever (93%), cough (86%), and headache (86%).
By calculating the day of infection and the last day of receiving the last dose of vaccine, there were
141 (58.3%) participants who were unvaccinated and contracted COVID-19. Furthermore, 19.5% of
participants only received one dose of vaccine or received their second dose but were diagnosed less than 14
days after receiving the second dose. Moreover, those infected more than 14 days after their second dose (fully
vaccinated) accounted for 22.2% of the cohort. Regarding the type of vaccine, among 101 people who received
the first dose, Sinovac was on the top list (85.1%), followed by AstraZeneca (7.9%), Sinopharm (3%), Pfizer
(3%), and Moderna (1%). A similar pattern was also seen in 56 fully vaccinated participants, although the
recipient of Sinopharm was the least (1.8%). This study also records two heterologous vaccinations (Sinovac
+ Astrazeneca and Sinovac + Moderna).
Within 30 days after diagnosis or the first day of the onset, a total of 111 (45.9%) participants reported
at least one persistent symptom. Fatigue was reported in 27.7% of participants, followed by chronic cough
(21.1%) and chronic headache (15.3%). Table 1 (see in Appendix) describes the characteristic of participants
according to the presence of any persistent symptoms within 30 days.
From Table 1 (see in Appendix), demographic and comorbid factors, including health behaviour
(smoking, alcohol drinking, exercise), and chronic disease, were not significantly associated with the presence
of any post-COVID-19 symptoms within 30 days, except for age, where people who developed residual
symptoms were significantly older than those who did not. A shorter duration of treatment was found in those
who did not report any residual symptoms. The severity of the disease is also linked to reported symptoms.
The researchers also noticed the significant association between variant and vaccination status and reported
symptoms. Table 2 depicts the association between variant, vaccination status, and each symptom during the
illness.

Table 2. Association between variants, vaccination status, and symptoms

Variant (Delta as reference) Vaccination status (Unvaccinated as reference) with 95% CI crude odds ratio
Variables
Crude odds ratio p-value First Second
Fever 0.580 0.285 0.562 (0.157-2.011) 0.418 (0.134 -1.306)
Myalgia 0.235 <0.001 0.200 (0.081-0.494) 0.241 (0.098-0.590)
Cough 0.359 0.005 0.219 (0.093-0.518) 0.535 (0.206-1.391)
Shortness of breath 0.376 0.001 0.221 (0.107-0.458) 0.306 (0.151-0.621)
Headache 0.201 <0.001 0.132 (0.053-0.327) 0.341 (0.127-0.912)
Sore throat 13.270 <0.001 0.308 (0.136-0.696) 0.058 (0.025-0.131)
Loss of smell 0.237 <0.001 0.199 (0.083-0.048) 0.220 (0.093-0.518)
Runny nose 0.364 0.001 0.480 (0.231-0.998) 0.588 (0.288-1.204)
Notes: Association of variants and symptoms estimated with chi-square, as crude odds ratio of vaccination was estimated with simple
logistic regression. The first and second refer to the vaccination level mentioned in the methodology.

Participants reported any symptoms during their COVID-19 episode as a binary response (yes or no),
regardless of the duration of the symptoms. According to Table 2, other than fever, people infected during
Omicron were less likely to report the symptoms aforementioned during treatment (p<0.05). Interestingly, sore
throat was more frequent during the Omicron period (<0.001). Full vaccination was crucial in preventing
myalgia, shortness of breath, headache, sore throat, and loss of smell (95% confidence interval crude odds ratio
shows value lower than 1) during the COVID-19 episode.
Table 3 shows no significant association between the variant and the occurrence of post-COVID-19
fatigue, but not with chronic cough and chronic headache. A similar pattern is also shown in severity and age.
However, there was a significant association between vaccination status on the day of diagnosis and all three
post-COVID-19 symptoms and the duration of treatment.

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The researchers developed two hierarchical models for each symptom to assess the effect of variant
and vaccination while accommodating these significant confounders. The first model is the simple model
assessing the adjusted effect of variants and vaccination status. Meanwhile, the second is the integration of
potential confounders into the final model.

Table 3. Bivariate association of significant predictors with individual post COVID-19 symptoms
Variable Fatigue Chronic cough Chronic headache
Variant 0.062 0.013 0.05
Vaccination status during infected 0.007 <0.001 0.024
Severity* 0.543 0.026 0.074
Age 0.084 <0.001 0.043
Duration of Treatment <0.001 0.001 0.003
Notes: All categorical variables were tested with Chi-square, except * (Fisher Exact). The association of continuous predictors was
estimated with the non-parametric test, while significant at p-value <0.05.

The goodness-of-fit test shows better performance for the second model, except for the first model of
fatigue. Nevertheless, interpretation relies on the second model with adjusted factors. Despite insignificant,
people infected in the Omicron period were less likely to report post-COVID-19 fatigue (8.7%) and post-
COVID-19 chronic cough (17.1%) but not with chronic headaches, where people infected in the Omicron wave
were 1,097 times higher than in Delta. Full vaccination status did not provide significant protection for fatigue
and chronic headache, but not for chronic cough, with estimated protection of 75.6% (95% CI: 16.2%-92.9%).
Longer days of treatment were associated with chronic headache and fatigue but not with chronic cough.
Increasing age was also linear to the risk of developing a chronic cough. However, the inverse trend was seen
in the occurrence of chronic headaches.

4. DISCUSSION
4.1. Omicron infection was milder than Delta
This study revealed the COVID-19 and post-COVID-19 symptoms in Indonesia's different geographic
regions and COVID-19 waves, increasing the information's novelty. Aside from sore throat, prominent in the
Omicron period, all other symptoms were more prevalent in the Delta period, and the difference was significant
except fever. The United Kingdom's (UK) COVID-19 survey also showed similar findings [20]. Furthermore,
people infected during the Omicron period had a shorter treatment duration than Delta. Omicron shows a
shorter incubation time [21] and decreased lung infectivity in an in-vivo trial [22]. Hence, the researchers could
conclude that Omicron shows a milder impact than Delta.
The previous survey conducted during alpha, beta, and Delta waves showed a similar prevalence of
post-COVID-19 symptoms [8]. Fatigue remains the most reported post-COVID-19 symptom in this study and
is similar to the reported prevalence in a meta-analysis [23]. Another research pointed out that fatigue was
more prevalent in patients admitted to the intensive care unit [24]. In this study, the chronic cough was higher
than the chronic headache. The cough hypersensitivity state and neuroinflammatory condition of the vagal
sensory nerve stimulate cough in COVID-19 [25]. A study assessing the persistent cough in COVID-19 when
the original strain was dominant showed that 20.9% of hospitalized patients had a persistent cough after three
weeks [26]. The possible mechanisms of chronic headache in COVID-19 are a direct invasion of SARS-COV2
to the nerve and subsequent injury due to pro-inflammatory mediators and cytokines in the central nervous
system [27]. In a multicentric study where the wild-type variant was prevalent, 19% of patients experienced
headaches for up to three months [28]. This research showed a lower prevalence of three post-COVID-19
symptoms during the Omicron waves compared to the Delta period as shown in Table 1, indicating a milder
effect of Omicron than Delta in terms of the residual symptoms.

4.2. Variant, symptoms, and residual effect

The bivariate analysis showed that all symptoms except fever were significantly different, showing
that Omicron shows a lower tendency to develop symptoms than Delta as presented in Table 2, except sore
throat. Fever remains a consistent symptom over different variants, despite a decreasing trend in reported fever.
A study identified that the odds ratios of fever in Delta and Omicron waves were similar [29]. Regarding post-
COVID-19 symptoms, people infected in the Delta waves were more likely to experience chronic cough and
chronic headache, but the probability of fatigue was similar between variants as shown in Table 3. There is a
limited peer-reviewed study concerning this issue. However, a pre-print of a study in Norway showed a
different finding that chronic cough is similar in two variants [30].

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Demographic factors did not play a significant role in post-COVID-19 symptoms. The risk of
developing post-COVID-19 symptoms within 30 days was similar in terms of occupation, health behaviour,
and the presence of chronic disease, although, in the final model as shown in Table 4, older age was associated
with post-COVID-19 chronic headache and chronic cough. However, a large-scale study of non-hospitalized
patients shows contrary findings where women, young people, smokers and patients with comorbidities were
prone to any post-COVID-19 symptoms [31]. There was no significant difference in all post-COVID-19
symptoms regarding the Favipiravir prescription. Favipiravir shows low clinical improvement, thus providing
insignificant protection for residual symptoms [4].

Table 4. The hierarchical model of post COVID-19 symptoms

Variable Model 1 Model 2
Odds 95% CI odds Odds 95% CI odds
B B
ratio ratio ratio ratio
Model for post-COVID-19 fatigue
Omicron variant (Delta Ref) -0.371 0.690 0.272-1.751 -0.091 0.913 0.352-2.368
Unvaccinated (ref)
The first dose, or <14 days after the second dose -0.269 0.764 0.27-2.164 0.025 1.025 0.352-2.984
Infected >14 days after the second dose -1.16 0.313 0.127-0.776 -0.709 0.492 0.192-1.261
Duration of Treatment (in days) 0.198 1.219 1.081-1.374
Hosmer Lemeshow p-value 0.829 0.085
Model for post-COVID-19 chronic cough
Omicron variant (Delta Ref) -0.025 0.975 0.332-2.862 -0.187 0.829 0.265-2.600
Unvaccinated (ref)
The first dose, or <14 days after the Second Dose -1.532 0.216 0.055-0.852 -0.79 0.454 0.106-1.935
Infected >14 days after the second Dose -1.694 0.184 0.059-0.573 -1.412 0.244 0.071-0.838
Duration of Treatment (in days) 0.05 1.051 0.922-1.199
Mild severity (Ref)
Moderate 0.919 2.507 0.889-7.072
Severe 1.29 3.633 0.174-75.844
Age in years 0.085 1.089 1.051-1.128
Hosmer Lemeshow p-value 0.757 0.967
Model for post-COVID-19 chronic headache
Omicron varian (Delta Ref) -0.224 0.799 0.248-2.578 0.092 1.097 0.329-3.658
Unvaccinated (ref)
The first dose, or <14 days after the Second Dose -1.161 0.313 0.068-1.442 -1.378 0.252 0.053-1.209
Infected >14 days after the second Dose -0.86 0.423 0.146-1.231 -0.602 0.548 0.178-1.685
Duration of Treatment (in days) 0.182 1.2 1.038-1.388
Age in years -0.06 0.942 0.904-0.981
Hosmer Lemeshow p-value 0.329 0.561

A simple crosstabulation pointed out crude protection of having at least one dose against the presence
of symptoms (except fever) compared to unvaccinated in the overall cohort. However, full vaccination did not
show consistent efficacy as full vaccination did not significantly prevent fever, cough, and runny nose as
presented in Table 2. Nevertheless, vaccination still benefits in preventing three post-COVID-19 symptoms as
shown in Table 3, although this is only a crude effect.
To accommodate the confounding effect, the researcher applied logistic regression to assess the
impact of SARS-COV2 variants and vaccination on the selected post-COVID-19 symptoms. In post-
COVID-19 fatigue, adjusted by the duration of treatment, people infected during the Omicron period were less
likely to develop fatigue, although it was not significant. Furthermore, insignificant protection was also seen in
those fully-vaccinated individuals infected more than 14 days after their second dose as presented in Table 4.
There was no significant difference in chronic headache between variants, adjusted by age and
duration of treatment. The same finding also occurred in the full vaccination status. Interestingly, adjusted by
age, treatment duration, and disease severity, full vaccination shows a 75.6% protection against chronic cough
as shown in Table 4. However, this study had an inconsistent effect of being partially vaccinated against post-
COVID-19 symptoms. A large community study recorded a higher reduction of post-COVID-19 after receiving
the first dose (12.8%) compared to the second dose (8.8%) [32].
The possible explanation for why people with full vaccination status have low protection against post-
COVID-19 symptoms is that the efficacy of vaccination decrease over time [33]. People may get infected after
certain months of full vaccination. This study did not calculate the days between the last dose and infection
and treated it as continuous data when considering the vaccination effect. Furthermore, access to booster
vaccination remains limited in this study area.
Another issue is that these inconsistent findings were probably due to methodology. Although there
was a limitation involving heterogeneous participants such as vaccination type (as Sinovac recipients dominate
this nested cohort), most of the participants were recruited during the Delta period, and there was lower
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recruitment for those who were unvaccinated. People may now be more reluctant to report themselves to the
health provider, thus reducing the recruitment of participants at the current time. Regarding data management,
a potential bias should be considered, such as the days of treatment. The World Health Organization defined a
protocol for isolation and treatment [34]. However, the current definition seems to be heterogenous across time,
such as released by antigen results or the 5+5 rules. Thus, the duration of treatment has potential measurement
bias. Currently, there are no COVID-19-specific measurements of the post-COVID-19 outcome. However, the
measurement tools used in this study are the tools that are currently being assessed by the post-COVID-19 core
outcome Set study, which reduces the measurement bias in outcome assessment [35]. Lastly, the researchers
also acknowledge that assuming the type of variants according to the date of infection is not equivalent to
genomic sequencing.

5. CONCLUSION
Despite the limited methodology, this study addressed a new finding that the Omicron shows milder
clinical manifestation than Delta variants, although there was no difference in post-COVID-19 symptoms within
30 days. However, the researchers also acknowledge that the efficacy of vaccination against post-COVID-19
symptoms was not consistent compared to the previous study, except for preventing chronic cough. Nevertheless,
it is still essential to increase the accessibility of vaccination, including boosters in low-resource settings such as
Eastern Indonesia, to reduce the non-health burden due to post-COVID-19 symptoms.

ACKNOWLEDGEMENTS
The researchers thank Khairun University, Hasanuddin University, and Chulalongkorn University for
the research collaboration. The funder of this sub-site study, Khairun University, has no role in the study design,
data collection, analysis, decision to publish, or manuscript preparation. This nested study is part of registered
study NCT05060562 on the US clinical trials website.

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BIOGRAPHIES OF AUTHORS

Bumi Herman is a Medical Doctor and researcher of clinical research and

public health at the College of Public Health Science Chulalongkorn University Bangkok,
Thailand, and visiting lecturer at the Faculty of Medicine Hasanuddin University Indonesia.
His expertise is in health data science, health policy, respiratory medicine and infectious
disease. He can be contacted at email: bumiherman@med.unhas.ac.id.

Nur Upik En Masrika is a general practitioner and a permanent lecturer at the

Department of Biomedical Science, Faculty of Medicine, Khairun University, Ternate,
Indonesia. Her research interest is in factors affecting organ function. In the last two years
studying about COVID-19. She can be contacted at email: nurupik@unkhair.ac.id.

Vaccination efficacy against post-COVID-19 symptoms in Delta and Omicron… (Nur Upik En Masrika)
40  ISSN: 2252-8806

Pramon Viwattanakulvanid is an Assistant Professor at the College of Public

Health Science Chulalongkorn University Thailand. His research interest is health behaviors,
patient empowerment, health promotion, patient support group, traditional Chinese exercise
(Qigong), and health care access. His multi-skills in the areas of health care, health care
access and patient support group created research studies related to patient empowerment,
burdens to the caregivers, and knowledge gaps among medical professionals. He also plans
to expand my skills and knowledge to do more upcoming research studies in traditional
Chinese exercises to promote health in elderly and in patients with chronic illness.
Additionally, I would like to create more work related to Artificial intelligence (AI) and
public health together. He can be contacted at email: pramon.v@chula.ac.th.

Aryandhito Widhi Nugroho is a neurosurgeon and a public health researcher

graduated from the Department of Neurosurgery, University of Indonesia, Indonesia and
NCD Leading Postgraduate Program, Shiga University of Medical Science, Japan. Currently,
he is pioneering the neurosurgical service in the province of North Maluku, Indonesia, while
also teaching in the Faculty of Medicine, Khairun University, North Maluku, Indonesia. His
research interest is in spine and pediatric neurosurgery, non-communicable diseases, and
health care equity. He can be contacted at email: aryandhitowidhinugroho@gmail.com.

Appendix

Table 1. Characteristic of participants and reported persistent symptoms within 30 days

Reporting at least one persistent symptom within
p-
Variable Subset 30 days
value
No (%) Yes (%)
Age (year) Mean (standard deviation) 31.43+10.78 34.26+10.33 0.017
Body mass index (kg/m2) Mean (standard deviation) 22.89+3.99 23.45+5.16 0.751
Sex Female 69 (53.5) 60 (46.5) 0.830
Male 62 (54.9) 51 (45.1)
Occupation Medical personnel 45 (59.2) 31 (40.8) 0.283
Non-medical personnel 86 (51.8) 80 (48.2)
Education level Junior high school 2 (100) 0 (0) 0.222#
Senior high school 30 (54.5) 25 (45.5)
Diploma 33 (45.8) 39 (54.2)
Bachelor's degree and graduate level 66 (58.4) 47 (41.6)
Hypertension No/unknown 122 (54.2) 103 (45.8) 1.000#
Yes, controlled 5 (55.6) 4 (44.4)
Yes, uncontrolled 4 (50.0) 4 (50.0)
Diabetes No/unknown 125 (55.1) 102 (44.9) 0.201#
Yes, controlled 1 (16.7) 5 (83.3)
Yes, uncontrolled 5 (55.6) 4 (44.4)
Smoking status No 117 (52.5) 106 (47.5) 0.075
Yes 14 (73.7) 5 (26.3)
Alcohol consumption No 122 (52.8) 109 (47.2) 0.059
Yes 9 (81.8) 2 (18.2)
Moderate exercise/week >3 times per week 23 (69.7) 10 (30.3) 0.111
2-3 times per week 31 (56.3) 24 (43.7)
1 or less per week 77 (50.0) 77 (50.0)
Vaccination status during The first dose, or <14 days after the
32 (68.1) 15 (31.9) <0.001
infected second dose
Infected >14 days after the second
41 (75.9) 13 (24.1)
dose
Unvaccinated 58 (41.1) 83 (58.9)
Favipiravir administration <24 hours after diagnosis 18 (58.1) 13 (41.9) 0.292
24-72 hours after diagnosis 15 (53.5) 13 (46.5)
>72 hours after diagnosis 5 (31.2) 11 (68.8)
Not receiving any treatment 93 (55.7) 74 (44.3)
Severity Mild 125 (57.3) 93 (42.7) 0.006#
Moderate 6 (27.3) 16 (72.7)
Severe 0 (0) 2 (100)
Variant Delta 83 (48.8) 87 (51.2) 0.011
Omicron 48 (66.7) 24 (33.3)
Duration of treatment Mean (standard deviation) 12.94+3.61 15.32+2.69 <0.001
Notes: All categorical variables were tested with Chi-square, except # (Fisher Exact). The association of continuous predictors was
estimated with the non-parametric test, while significant at p-value <0.05.

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