Yoga, Meditation, Breathing Exercises, and Inflammatory Biomarkers with Possible Implications in COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Introduction:
COVID-19, a multisystem disease, has implications for various immunity and infection biomarkers. Yoga (Y), meditation (M), and pranayama (P), and their combinations have shown positive changes on those biomarkers among other than COVID-19 patients and healthy people. So, we aimed to document the evidence of possible implication in a systematic way.

Materials and methods:
We screened 84 full texts, published in the last ten years, from three databases, from which only 44 met the eligibility criteria, and then extracted the data related to demographic characteristics, intervention, results, and strengths and limitations in two MS-Excel grids, and then presented them in tables and figures. Furthermore, we carried out meta-analysis including subgroup and sensitivity analysis using a random effects model of 11 RCTs and reported the mean difference, heterogeneity, and p value with 95% CI and presented them with forest and funnel plots and the tables.

Results:
Twenty-five biomarkers of 4023 participants (range, 15-413) from 13 countries, healthy and clinical, from both sexes above 18 years, and from mainly clinical settings, were reported. YMP intervention, in solitary or in different possible combinations with varied durations among clinical and pregnant (range, 960-4800 minutes) and healthy (960-8400 minutes, excluding two studies of 20 minutes only) participants, was reported. It was revealed that 25 biomarkers, nine among the apparently healthy, 14 among the patients, and two among the pregnant, changed favourably (p < 0.05). Furthermore, either in meta- or subgroup-analysis, mean differences of IL-6 (-1.44 pg/ml) (95% CI) (-2.33, -0.55), (p = 0.002, I 2 = 82%), Cortisol (-40.75 pg/ml) (95% CI) (-64.13, -17.38), (p = 0.0006, I 2 = 87%), and TNF-α (-3.40 pg/ml) (95% CI) (-4.83, -1.98), (p < 0.0001, I 2 = 79%) showed statistically significant changes. Nonetheless, considerable heterogeneity and publication bias were observed among the studies.

Conclusion:
Although more than two dozens of biomarkers in individual studies showed favourable changes, only IL-6, Cortisol, and TNF-α produced significant combined results, even then with much less certainty. Further meta-analysis of biomarkers of COVID-19 patients is highly recommended. Registration: CRD42021283894.

Full text

Review Article
Yoga, Meditation, Breathing Exercises, and Inflammatory
Biomarkers with Possible Implications in COVID-19: A Systematic
Review and Meta-Analysis of Randomized Controlled Trials
Komal Shah ,
1
Chiranjivi Adhikari ,
2
Shubham Sharma ,
1
Somen Saha ,
1
,
3
and Deepak Saxena
1
,
3
1
Indian Institute of Public Health Gandhinagar (IIPHG), Gandhinagar 382042, India
2
Pokhara University, School of Health and Allied Sciences, Pokhara 30, Kaski 33700, Nepal
3
Datta Meghe Institute of Medical Sciences (DMIMS), Wardha 442107, Maharashtra, India
Correspondence should be addressed to Chiranjivi Adhikari; chiranadhikari@gmail.com
Received 19 July 2022; Accepted 1 September 2022; Published 7 October 2022
Academic Editor: Gabino Garrido
Copyright ©2022 Komal Shah et al. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Introduction.COVID-19, a multisystem disease, has implications for various immunity and infection biomarkers. Yoga (Y),
meditation (M), and pranayama (P), and their combinations have shown positive changes on those biomarkers among other than
COVID-19 patients and healthy people. So, we aimed to document the evidence of possible implication in a systematic way. Materials
and Methods. We screened 84 full texts, published in the last ten years, from three databases, from which only 44 met the eligibility
criteria, and then extracted the data related to demographic characteristics, intervention, results, and strengths and limitations in two
MS-Excel grids, and then presented them in tables and figures. Furthermore, we carried out meta-analysis including subgroup and
sensitivity analysis using a random effects model of 11 RCTs and reported the mean difference, heterogeneity, and pvalue with 95%
CI and presented them with forest and funnel plots and the tables. Results. Twenty-five biomarkers of 4023 participants (range,
15–413) from 13 countries, healthy and clinical, from both sexes above 18 years, and from mainly clinical settings, were reported.
YMP intervention, in solitary or in different possible combinations with varied durations among clinical and pregnant (range,
960–4800 minutes) and healthy (960–8400 minutes, excluding two studies of 20 minutes only) participants, was reported. It was
revealed that 25 biomarkers, nine among the apparently healthy, 14 among the patients, and two among the pregnant, changed
favourably (p<0.05). Furthermore, either in meta- or subgroup-analysis, mean differences of IL-6 (−1.44 pg/ml) (95% CI) (−2.33,
−0.55), (p�0.002,I
2
= 82%), Cortisol (−40.75 pg/ml) (95% CI) (−64.13, −17.38), (p�0.0006,I
2
= 87%), and TNF-α(−3.40 pg/ml)
(95% CI) (−4.83, −1.98), (p<0.0001,I
2
= 79%) showed statistically significant changes. Nonetheless, considerable heterogeneity and
publication bias were observed among the studies. Conclusion. Although more than two dozens of biomarkers in individual studies
showed favourable changes, only IL-6, Cortisol, and TNF-αproduced significant combined results, even then with much less
certainty. Further meta-analysis of biomarkers of COVID-19 patients is highly recommended. Registration: CRD42021283894.
1. Introduction
Yoga, meditation, and pranayama, or yogic breathing, have
been practised worldwide since antiquity. Research, both
here and elsewhere, has shown that practises like guided
asanas, specific pranayama, and meditation can improve the
body’s immune system responses. To develop a holistic
framework for individuals’ health, the interrelationships
between mind and body have been extensively studied in
recent times [1–5]. With the advent of the pandemic, re-
searchers and clinicians are in search of practises and
therapeutics that can reduce the impact of COVID-19 on
human health. In this line, recent reviews of complementary
and alternative medicine (CAM) and traditional Chinese
medicine (TCM) for COVID-19 have provided preliminary
evidence of effectiveness [6, 7]. In addition, a recent review
also underscored that the effects of natural compounds from
Nigella sativa are promising [8]. It has been stated that as
Hindawi
Evidence-Based Complementary and Alternative Medicine
Volume 2022, Article ID 3523432, 28 pages
https://doi.org/10.1155/2022/3523432

a result of COVID-19 disease, leukocytes, neutrophils, cy-
tokine levels [IL-2R, IL-6, IL-8, and IL-10], and infection
biomarkers like CRP, PCT, and ferritin are significantly
increased [9, 10]. Multiple studies have shown that yoga,
meditation, and pranayama interventions are efficacious in
regulating an array of biomarkers, including cytokines [4, 5].
Further research in this area is ongoing since the disease
is still uncertain in many aspects, especially regarding its
long-term complications [10] and the outbreak of possible
new mutants due to natural selection [11]. During the cy-
tokine storm that occurs in COVID-19 syndrome, proin-
flammatory cytokines are released uncontrollably. A positive
relationship between the severity of the viral infection and
the mortality rate was observed following an uncontrolled
and dysregulated secretion of inflammatory and proin-
flammatory cytokines [12]. Recent evidence also shows that
systemic vasculitis and cytokine-mediated coagulation dis-
orders act as the principal actors of multiorgan failure
among COVID-19 patients with severe complications [10].
Assessing the effect of different biomarkers in COVID-19
can help in the early diagnosis of the disease, confirming and
classifying the disease severity, identifying the high-risk
cohort, framing intensive care unit (ICU) admission crite-
ria, rationalising therapy, assessing response to therapies,
predicting outcomes, and framing criteria for discharge
from the ICU and/or the hospital [9]. So, it is the need of the
hour to assess and identify measures that can control the
dysregulated secretion of cytokines and other inflammatory
mediators with possible implications for COVID-19. Till
date, multiple studies have shown that yoga, meditation, and
pranayama interventions are efficacious in regulating an
array of biomarkers, including cytokines [4,5]. However,
these interventions and their outcomes presented over
different settings and durations have shown mixed results.
Considering the inconclusive evidence present, the het-
erogeneity in outcomes, and the duration of interventions
given in the previous studies, we sought to systematically
review the evidence of the effects of yoga, meditation, and
pranayama interventions on COVID-19 related in-
flammatory biomarkers by including only randomized
controlled trials (RCTs).
2. Materials and Methods
We conducted this review according to the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) guidelines.
2.1. Study Selection Criteria. A systematic literature search
was carried out after registering the review protocol in the
international prospective register of systematic reviews
(PROSPERO Regd. No. CRD42021283894). Peer-reviewed
RCTs published during the last 10 years (2010–2021) were
included. We sought to identify studies that used any version
of yoga, meditation, and/or pranayama, intervened as sol-
itary or in combination, among healthy and clinically ill
individuals in adults (≥18 years), including pregnant
women, to assess the effectiveness of biomarkers related to or
influenced by COVID-19. We were also guided by our
earlier scoping review on yoga, immunity, and COVID-19
for study selection [13]. e search was conducted mainly in
three databases: e Cochrane Library, PubMed, and Google
Scholar. Additionally, we also carried out a citation search.
Keywords and MeSH terms were informed by previous
literature searches. Six sets of search terms were used in-
cluding terms related to (i) yoga, (ii) meditation, (iii) pra-
nayama, (iv) intervention, (v) biomarker, and (vi) controlled
trial (S1_ Search Strategy with Keywords and MeSH).
2.2. Data Extraction and Analysis. Based on our previous
scoping review of yoga, immunity, and COVID-19 [13], we
developed and then extracted data using two standardized
MS-Excel grids. e data extraction form were initially
piloted (n= 2 studies) and then refined and finalised by all
reviewers. e data were extracted by two reviewers (CA and
ShS), and the third reviewer (KS) assessed when there was
a discrepancy. Pre-post effectiveness of YMP on biomarkers
was found using mean difference, difference in differences of
means (∆1-∆2), and effect sizes (Cohen’s d). However, we
only reported pvalues along with the direction of effec-
tiveness in interpreting the tests. e basic characteristics
and detailed findings of the included studies are given in
Tables 1 and 2, respectively.
For data synthesis, we developed an Excel grid for the
main outcomes (biomarkers). e evidence was synthesised
into a narrative form. A descriptive analysis of the char-
acteristics of study populations was carried out using range
values and proportions.
For meta-analysis, we calculated the mean difference
when at least three studies consistently reported the pri-
mary biomarkers. We produced forest plots, funnel plots,
and risk of bias (ROB) assessment charts using the
Cochrane risk of bias tool, from RevMan 5.4.1. e effect
size of the meta-analysis was estimated through random
effects, considering the post-pre mean change in biomarker
concentration and standard deviation (SD). Studies that
reported standard mean error (SME) were converted to SD,
and for those not specifying SME or SD, either of the two
was considered. Following the Cochrane guideline, we
calculated the pooled SD from the given parameters, in-
cluding an additional value of the correlation coefficient,
assuming 0.8. Regarding three-armed studies, we pooled
the mean and SD from the two experimental groups for the
outcome measure.
Subgroup analysis was performed post hoc by stratifying
the studies based on intervention type such as yoga, med-
itation, pranayama, or yoga only, or meditation only, and
intervention duration in weeks and minutes. For this, we
divided IL-6 into six subgroups, cortisol into two, and TNF-
a into three.
3. Results
3.1. Search Result. An initial search yielded 174 articles.
After removing the duplicates and excluding the articles
assessing the title and abstract, 87 articles were retrieved for
2Evidence-Based Complementary and Alternative Medicine

Table 1: Characteristics of included studies.
SN
Author,
(1st)
year,
and country
Intervention
type
Title
of the
article
Study
type
Participants (per-protocol)
Experimental
intervention
Control
intervention
Population
characteristics
(disease/healthy/
and clinical)
Population
characteristics
(age
and sex)
Biomarkers
Experimental
group
Control
group
1Zgierska et al., 2016,
USA [49] M
Mindfulness meditation and
cognitive behavioral therapy
intervention reduces pain
severity and sensitivity in
opioid-treated chronic low
back pain: Pilot findings from
a randomized controlled trial
26-week
parallel-arm pilot
randomized
controlled trial
(open-label)
21 (21) 14 (14)
Meditation and
cognitive-behavior
therapy and usual care
Usual care
alone
Chronic low back pain
(CLBP) with reported
having daily CLBP
(lum-bosacral area pain
or “sciatica” leg pain)
and treated with
minimum of 30 mg/day
of morphine-equivalent
dose (MED)
Minimum of 21 years
old, on average
51.8 ±9.7 years old,
80% white women.
CRP, IL-1ß, TNF-α, IL-6, and
IFN-ץ
2Bower et al., 2015,
USA [14] M
Mindfulness meditation for
younger breast cancer
survivors: a randomized
controlled trial
6-week single centre
two-arm RCT
(open-label)
37(30) 28 [22] Mindful awareness
practices
Wait-list
control
Diagnosed with stage 0 –
III breast cancer at or
before age 50 and
completed local and/or
adjuvant cancer therapy
(except hormonal
therapy) at least
3 months prior
Age mean (range)
Maps: 46.1 (28.4–60);
Control: 47.7
(31.1–59.6)
CRP, IL-6, sTNFRII
3Meyer et al., 2019,
USA [15] M
Differential reduction of
IP-10 and C-reactive protein
via aerobic exercise or
mindfulness-based
stress-reduction training in
a large randomized controlled
trial
8-week three armed
(two intervention
and a control),
matched controlled
arm (single-blinded)
Aerobic
exercise, 137
(126); MBSR
medication,
138 (127)
138 (132) Two arms; aerobic
exercise and MBSR
Wait-list
observational
control
Generally healthy and
reported to be inactive
Age, all, 50 ±12,
meditation; 49 ±11,
exercise 49 ±11;
control 51 ±12; male
all, 92, meditation 32,
exercise 27, control,
33
IL-6, CRP and
interferon-gamma-inducible
protein-10 (IP-10)
4Dada et al., 2018,
India [53] MP
Mindfulness meditation
reduces intraocular pressure,
lowers stress biomarkers, and
modulates gene expression in
glaucoma: a randomized
controlled trial.
21days prospective,
single blinded,
randomized
controlled trial
(single-blinded)
45 (40) 45 (42)
Mindfulness-based
stress reduction and
meditation group
Wait-list
control
Outpatient with primary
open angle glaucoma
(POAG)
Intervention: 20
females, mean age
57.88 ±8.17 years
control: 20 females,
age 56.63 ±7.12
Cortisol, IL-6, TNF-a at baseline
and post intervention
5Hayney et al., 2014,
USA [16] M
Age and psychological
influences on immune
responses to trivalent
inactivated influenza vaccine
in the meditation or exercise
for preventing acute
respiratory infection
(MEPARI) trial
8 weeks
3-experimental arm
randomized control
trial (single-blinded)
Meditation 51
(51), exercise
47 (47)
51 (51) (i) MBSR
(ii) Exercise Control group Healthy individuals were
recruited
MBSR : male 9, mean
age 60.0 (6.5) years;
control: male 10,
mean age 58.8 (6.8)
years; exercise: male
8, mean age 59.0 (6.6)
years
IGA, IL 10, interferoncat
baseline and 3 week
6Barrett et al.,2012,
USA [17] M
Meditation or exercise for
preventing acute respiratory
infection: a randomized
controlled trial
8-week randomized
3 parallel group trial
(open-label)
Meditation: 51
(51)
Exercise: 51
(47)
52 (51)
(i) Mindfullness
meditation
(ii) Moderate-intensity
exercise
Observational
control
Community-based
50 years or older
82% female, 94%
white, mean age
59.3 ±6.6 years
Interleukin-8 levels within
3 days of symptoms
7Gagrani et al., 2018,
India [18] M
Meditation enhances brain
oxygenation, upregulates
BDNF, and improves quality
of life in patients with primary
open angle glaucoma:
a randomized controlled trial
6 weeks prospective
randomized control
trial (open-label)
30 (30) 30 (30)
Meditation with
standard medical
treatment
Standard
medical
treatment
POAG (primary open
angle glaucoma) patients
21 females and 39
males, mean age of
57.28 ±9.37 years
Serum cortisol and serum IL-2
& IL-6 at baseline and post
intervention
8Lipschitz et al.,
2013, USA [19] M
Reduction in salivary
α-amylase levels following
a mind-body intervention in
cancer survivors—an
exploratory study
8-week 3
experimental arm
RCT (open-label)
Mbb, 19; Mm,
20 18
One of two
experimental
mind-body
interventions, namely,
mind-body bridging
(MBB) or mindfulness
meditation (MM)
Sleep hygiene
education
(SHE)
Cancer survivors with
any sleep disorder/
problem visiting health
facility
All, age 18–75, M14,
F43; SHE, 52 ±11,
M4, F14; MBB,
55 ±10, M6, F13;
MM, 51 ±9, M4, F16
Salivary cortisol at baseline and
4th week with two parameters
(waking, and daily output
Evidence-Based Complementary and Alternative Medicine 3

Table 1: Continued.
SN
Author,
(1st)
year,
and country
Intervention
type
Title
of the
article
Study
type
Participants (per-protocol)
Experimental
intervention
Control
intervention
Population
characteristics
(disease/healthy/
and clinical)
Population
characteristics
(age
and sex)
Biomarkers
Experimental
group
Control
group
9Rao et al., 2017,
India [20] M
Effect of yoga on sleep quality
and neuroendocrine immune
response in metastatic breast
cancer patients
3-month RCT
(single-blinded) 45 (25) 46 (21)
Integrated yoga-based
stress reduction
program
Education and
supportive
therapy sessions
Stage IV breast cancer
within 6 months–2 years
after diagnosis
Yoga group: average
age 48.9 (9.1) years
control: 50.2 (9.2)
Cortisol for 3 consecutive days
(at 0600 h, 0900h, and 2100 h)
10 Creswell et al., 2016,
USA [50] M
Alterations in resting state
functional connectivity link
mindfulness meditation with
reduced interleukin-6:
a Randomized controlled trial
4 weeks randomized
control trial
(single-blinded)
18 (17) 17 (17)
Health enhancement
through mindfulness
(HEM)
Health
enhancement
through
relaxation
(HER)
Right-handed
unemployed job-seeking
community adults
Hem : mean age
37.94 (10.96), 7
female and 11 male
Her : mean age 41.00
(9.55), 8 female and 9
male
IL-6
11
Andres-Rodriguez
et al., 2019, Spain
[52]
M
Immune-inflammatory
pathways and clinical changes
in fibromyalgia patients
treated with
mindfulness-based stress
reduction (MBSR) :
a randomized, controlled
clinical trial
8 weeks randomized,
controlled clinical
trial (single-blinded)
with 12 months
follow-up
15 (14) 16 (14) MBSR +TAU Treatment as
usual (TAU)
Female patients with
fibromyalgia (FM)
diagnosis according to
ACR 1990
Age, control, 52 ±8,
intervention, 55 ±8;
all female
IL-6, hsCRP, IL-10 and hsCRP,
and their different ratios
12 Buijze et al., 2019,
Netherlands [21] MP
An add-on training program
involving breathing exercises,
cold exposure, and meditation
attenuates inflammation and
disease activity in axial
spondyloarthritis – a proof of
concept trial
8-week open-label,
randomized,
one-way crossover
clinical
proof-of-concept
trial (open-label)
Early
intervention;
13 (13), late
intervention,
11 (11)
11 (11)
Add-on training of
breathing, cold
exposure, and
meditation
No intervention
at initial
intervention
Patients with a clinical
diagnosis of axial
spondyloarthritis
(axSpA) and fulfilled the
ASDAS classification
criteria and had active
diseases defined as
ASDAS>2.1 and
a high-sensitive CRP
(hsCRP) ≥5 mg/L
M�15, F �8;
age �35 ±7
HsCRP at 0, 4, 8, 24, 28 and
32 weeks
13 Mandal et al., 2021,
India [22] YP
Effect of structured yoga
program on stress and
professional quality of life
among nursing staff in
a tertiary care hospital of
Delhi—a small scale Phase-II
trial
12-week open-label,
phase-II RCT
(open-label)
58 (19) 52 (32) Yoga intervention Wait-list
control
Healthy staff nurses
working in a tertiary care
hospital
Intervention, mean
age, 35 ±8, M, 8, F,
50; control, mean
age, 33 ±7, M, 22, F,
30, F,
Serum cortisol and hsCRP were
assessed at baseline and
12 weeks
14 Viswanathan et al.,
2020, India [23] YP
Effect of yoga intervention on
biochemical, oxidative stress
markers, inflammatory
markers, and sleep quality
among subjects with type 2
diabetes in south India: results
from the SATYAM project
3-month
nonregistered
randomized
experimental study
(open-label)
150 (150) 150 (150) Yoga intervention Simple physical
exercises Type 2 diabetes
(i) Control: M-103,
F-47, age 52.8 ±7.0
(ii) intervention:
M-93, F-57, age
50.8 ±8.3
TNF-α, IL-6, TBARS, EC-SOD
and hsCRP were assessed at
baseline and 3 months
15 Shete et al., 2017,
India [24] YP
Effects of yoga training on
inflammatory cytokines and
C-reactive protein in
employees of small-scale
industries
3-month RCT
(open-label) 24 (19) 24 (18) Yoga Wait-list
control Healthy male adults Average age 41.5
(5.2) years
IL-6, TNF-α, hsCRP at baseline
and post intervention
16 Ganesan et al.,
2020, India [25] YMP
Effects of yoga therapy on
disease activity, inflammatory
markers, and heart rate
variability in patients with
rheumatoid arthritis
12-week
randomized control
trial (open-label)
83 (68) 83 (75)
Yoga therapy with
standard medical
treatment
Standard
medical
treatment
RA (rheumatoid
arthritis)
YG (yoga group): 63
female participants
(92.64%), mean age
of 41.33 years CG
(control group): 68
female participants
(90.66%), mean age
of 42.59 years
IL-1 α, IL-6, TNF-a, cortisol at
baseline and after 12 week
4Evidence-Based Complementary and Alternative Medicine

Table 1: Continued.
SN
Author,
(1st)
year,
and country
Intervention
type
Title
of the
article
Study
type
Participants (per-protocol)
Experimental
intervention
Control
intervention
Population
characteristics
(disease/healthy/
and clinical)
Population
characteristics
(age
and sex)
Biomarkers
Experimental
group
Control
group
17 Chen et al., 2016,
China [26] YMP
Effects of 8-week hatha yoga
training on metabolic and
inflammatory markers in
healthy and female Chinese
subjects: a randomized
clinical trial
8-week randomized
controlled trial
(open-label)
15 (15) 15 (15) Hatha yoga
intervention No intervention Healthy female
participants
Age, 18–25 years, all
females
MCP-1, TNF-α, IL-6, IL-8, and
IL-1β
18 Kiecolt-glaser et al.,
2014, USA [27] YP
Yoga’s impact on
inflammation, mood, and
fatigue in breast cancer
survivors: a randomized
controlled trial
12-week
randomized control
trial (single-blinded)
100 (96) 100 (90) Yoga Waitlist control Stage 0 to IIIa breast
cancer survivors
Yoga: mean age 51.8
(9.8) years Control:
mean age 51.3 (8.7)
years
IL-6, TNF- α, and IL-1beta
19 Kaminsky et al.,
2017, USA [28] P
Effects of yoga breathing
(pranayama) on exercise
tolerance in patients with
chronic obstructive
pulmonary disease:
a randomized, controlled trial
12-week
randomized control
trial
(double-blinded)
21 (21) 22([22) Pranayam plus
education Education
Physician diagnosed
COPD (chronic
obstructive pulmonary
disease) patients with
18 years age or older
Pranayam: female %
(67%), mean age 68
(7) Control: female%
(55%), mean age 68
(9)
IL-6, CRP, 6MWD, FEV1, IC,
rv/tlc, DLCO, va/tlc, Ti/Ttot
20 Bower et al., 2014,
USA [29] Y
Yoga reduces inflammatory
signaling in fatigued breast
cancer survivors:
a randomized controlled trial
12-week
randomized
intervention
(open-label)
16 (14), 13
(3 months
follow-up))
15 (15) Iyengar yoga
Health
education
control
Breast cancer survivors
of stage 0 - II with mean
diagnosis of
3.6 ±3.7 years ago
Average age of
54 ±5.4 years
sTNF Receptor-II, IL-1 RA, IL-6
and CRP, salivary cortisol
21 Twal et al., 2016,
USA [3] P
Yogic breathing when
compared to attention control
reduces the levels of
proinflammatory biomarkers
in saliva: a Pilot randomized
controlled trial
20-min pilot
randomized
controlled trial
(open-label)
10 (10) 10 (10) Yogic breathing (YB) Attention
control (AC)
Normal apparently
healthy
5 males and 5 females
in both groups. Age
ranged from 27 to
33 years
IL-1RA, IL-6, IL-10, IL-17,
IP-10, MIP-1b, TNF-α, (IL)-1β,
IL-8, MCP-1 assessed on 0, 5,
10, 15 and 20 minutes after
intervention
22 Hopkins et al., 2016,
USA [30] YP
Heated hatha yoga to target
cortisol reactivity to stress and
affective eating in women at
risk for obesity-related
illnesses: a randomized
controlled trial
8 weeks randomized
control trial
(single-blinded)
27 (27) 25 (24) Bikram yoga Wait-list
control
Community females age
25 to 45 years of age
Females with mean
age 33.5 (6.4) years
Cortisol at baseline and post
intervention
23 Banasik et al., 2011,
USA [31] YP
Effect of iyengar yoga practice
on fatigue and diurnal salivary
cortisol concentration in
breast cancer survivors
8-week randomized
controlled trail
(open-label)
9 (7) 9 (7) Iyengar yoga
Wait-list
control, no
intervention
Stage II–IV breast cancer
survivors
All womens were
caucasian; control
group age: 62.4 ±7.3
yoga group age:
63.33 ±6.9
Salivary cortisol at baseline and
8 weeks
24 Marques et al.,
2017, Portugal [54] YP
Influence of chair-based yoga
on salivary antimicrobial
proteins, functional fitness,
perceived stress and
well-being in older women:
a Randomized pilot
controlled trial
28 weeks RCT
(open-label) 15 (15) 10 (10) Chair based yoga
(CBY) Control group
Older women living in
two different health and
social caregiver centres
(HSC)
EG �average age
83.73 (6.86) years
GC �average age
82.73 (8.46) years
IgA and cortisol were assessed at
baseline and 28 week
25 Torkamani et al.,
2018, Iran [51] M
Effects of single-session group
mantra-meditation on
salivary immunoglobulin and
affective state:
a psychoneuroimmunolgy
viewpoint
20 minutes RCT
(single-blinded) 15 15 Meditation Control Healthy women Mean age 44 ±3 years
s-IgA at baseline, after lecture,
post-meditation and one hour
later
Evidence-Based Complementary and Alternative Medicine 5

Table 1: Continued.
SN
Author,
(1st)
year,
and country
Intervention
type
Title
of the
article
Study
type
Participants (per-protocol)
Experimental
intervention
Control
intervention
Population
characteristics
(disease/healthy/
and clinical)
Population
characteristics
(age
and sex)
Biomarkers
Experimental
group
Control
group
26 Gunjiganviet al.,
2021, India [55] YP
Yoga—an alternative form of
therapy in patients with blunt
chest trauma: a randomized
controlled trial
4-week RCT
(open-label) 46 (32) 43 (27)
Yogatherapy (YTP)
with standard chest
physiotherapy (CTP)
Chest
physiotherapy
(CTP)
Patients aged
18–65 years with isolated
blunt chest trauma and
who were managed
nonoperatively with or
without thoracostomy
tubes
Intervention: male
40, mean age 41.1
(12.40) years; control:
male 36, mean age
42.6 (11.59)
Serum levels of ILs TNF-a,
IFN-c; along with respiratory
indicators assessed
27 Pullen et al., 2010,
USA [32] YM
Benefits of yoga for african
american heart failure
patients
8-week RCT
(single-blinded) 21 (18) 19 (16) Hospital-based yoga
group
Control group
(CG, standard
medical care)
Systolic or diastolic heart
failure (HF) patients of
ischemic or nonischemic
etiology
Yoga: mean age 55.8
(±7.6); control: mean
age 52.5 (±12.7) years
IL-6, hsCRP, and EC-SOD
baseline to 8 weeks
28 Hecht et al., 2018,
USA [33] YM
A randomized, controlled
trial of mindfulness-based
stress reduction in HIV
infection
8-week single center,
randomized
controlled parallel
trial (single-blinded)
89 (76 at
3 month & 48
at 12 month)
88 (76 at
3 month
& 48 at 12
month)
MBSR Education
control
18 years of age or older
with HIV-1 infection
MBSR : median age
of 41 (22–63) years;
control: median age
of 39 (22–66) years
CD4+, hsCRP, IL-6 at baseline,
3 month and 12 month
29 Nijjar et al., 2019,
USA [34] YMP
Randomized trial of
mindfulness-based stress
reduction in cardiac patients
eligible for cardiac
rehabilitation
8-week pilot
randomized
controlled trial
(open-label)
31 (30) 16 (15)
Mindfulness-based
stress reduction
(MBSR)
Usual care
control
CR-eligible
(exercise-based cardiac
rehabilitation) cardiac
patients
Age, all, 61±11,
MBSR, 59 ±12,
control, 61 ±9;
hsCRP at baseline, 3 month, and
9 month
30 Huberty et al., 2019,
USA [35] YM
Online yoga in
myeloproliferative neoplasm
patients: results of
a randomized pilot trial to
inform future research
12-week pilot RCT
(single-blinded) 34 (27) 28 (21) Online yoga Wait-list
control
Myeloproliferative
neoplasm (MPN)
patients b) reported
engaging in ≥150 min/
week of physical activity
Yoga: female 25,
mean age 58.3 (9.3)
years; control: female
20, mean age 55.0
(11.4)
IL-6 and TNF-αwere assessed at
baseline and 12 week
31 Chen et al., 2017,
taiwan [56] YMP
Effects of prenatal yoga on
women’s stress and immune
function across pregnancy:
a randomized controlled trial
20-week prospective
RCT (open-label) 50 (48) 51 (46) Routine prenatal care
plus yoga intervention
Routine
prenatal care
Preganant women from
16 to 36 week’s of GA
Mean chronological
age 33.0 ±3.8 years
(range �24–43)
Salivary cortisol and IgA, and
CD4+T cell
32 SeyedAlinaghi et al.,
2012, Iran [36] YM
RCT of mindfulness-based
stress reduction delivered to
HIV + patients in Iran: effects
on CD4+ T lymphocyte count
and medical and
psychological symptoms
8-week randomized
control trial
(single-blinded)
120 (87) 125 (86)
Mindfulness-based
stress reduction
(MBSR)
Education and
support (ESC)
18+ years and
HIV + confirmed by
western blot.
Mean age was
35.1(SD�6.5) years
and 69% were male
33 Rajbhoj et al., 2015,
India [37] YMP
Effects of yoga module on
proinflammatory and
anti-inflammatory cytokines
in industrial workers of
lonavla: a randomized
controlled trial
12-week RCT
(open-label) 23 (19) 22 (18) Yoga Wait-list
control Industrial workers
Yoga group: mean
age 40.72 ±6.79 age;
control group: mean
age 40.18 ±6.31 age
IL-1β, IL-10 at baseline and post
intervention
34 Singh et al., 2011,
India [38] YMP Effects of yogic package on
rheumatoid arthritis
7 weeks days RCT
(open-label) 40 40 Yoga and usual
meditation
Usual medical
care Rheumatoid arthritis
Age, intervention,
mean 35.1 (±7.3),
control, mean 34.7
(±7.3) yrs
CRP at baseline and post
intervention
35 Nugent et al., 2019,
USA [39] YMP
Benefits of yoga on IL-6:
findings from a randomized
controlled trial of yoga for
depression
10-week RCT
(single-blinded) 48 (48) 39 (39) Hatha yoga
intervention (yoga)
Healthy living
workshop
(HLW)
Patients of major
depressive disorder with
age 18 years or older
Age, yoga, 46 ±13,
HLW, 45 ±14, total,
45 ±13; sex, yoga,
M4, F44, HLW, M10,
F29,
IL-6, CRP and TNF-α
6Evidence-Based Complementary and Alternative Medicine

Table 1: Continued.
SN
Author,
(1st)
year,
and country
Intervention
type
Title
of the
article
Study
type
Participants (per-protocol)
Experimental
intervention
Control
intervention
Population
characteristics
(disease/healthy/
and clinical)
Population
characteristics
(age
and sex)
Biomarkers
Experimental
group
Control
group
36 Gautam et al., 2019,
India [40] YMP
Impact of yoga-based
mind-body intervention on
systemic inflammatory
markers and co-morbid
depression in active
rheumatoid arthritis patients:
A randomized controlled trial
8-week randomized
control trial
(single-blinded)
36 (30) 36 (32)
Yoga-based
mind-body-based
intervention with
usual medical care
Usual medical
care
Outpatient of RA
(rheumatoid arthritis)
Age, yoga, mean
45.7(±1.6),
control,,control,
mean 42.1(±1.7) yrs
IL-17 A, IL-6, TNF-αat baseline
and 8 week
37 Sohl et al., 2016,
USA [41] YMP
A brief yoga intervention
implemented during
chemotherapy: a randomized
controlled pilot study
8 weeks RCT
(open-label) 8 (6) 7 (5) Yoga skill training
(YST)
Attention
control (AC)
Colorectal cancer stage
0-IV
Median age 61.0 (44.0
to 67.0) years, male 9
IL-6, IL-1RA, sTNF Ri, TNF-α,
CRP
38 Gautam et al., 2020,
India [42] YMP
Effects of an 8-week
yoga-based lifestyle
intervention on
psycho-neuro-immune axis,
disease activity, and perceived
quality of life in rheumatoid
arthritis patients:
a randomized controlled trial
8-week RCT
(single-blinded) 33 (31) 33 (31)
Yoga-based lifestyle
intervention (yoga
group)
Usual care
control
(non-yoga
group)
Patients of rheumatoid
arthritis
Age, yoga, mean, 45.1
(±8.7), F28 control,
mean 43.4 (±9.3) yrs,
F25
IL-6, IL-17A, TNF-αat baseline
and 8 week
39 Wolff et al., 2015,
Sweden [43] YMP
Yoga’s effect on inflammatory
biomarkers and metabolic
risk factors in a high risk
population – a controlled trial
in primary care
12-week three
armed (two
intervention and
a control), matched
controlled open
clinical trial
(open-label)
Group 1, 28
(21); group 2,
28 (20)
27 (22)
Yoga intervention
(group 1) and yoga
instruction (group 2)
for home practice
Standard care Adults diagnosed with
hypertension
Age Ex1, 66, F19,
Ex2, 64, F20, control,
61, F16, respectively
HsCRP and IL-6 were measured
at baseline and 12 weeks
40 Chanta et al., 2019,
ailand [44] Y
Effects of hatha yoga training
on rhinitis symptoms and
cytokines in allergic rhinitis
patients
8-week randomized
controlled trial
(single-blinded)
15 (14) 15 (13) Hatha yoga (YOG)
Normal
activities
(CON)
Allergic rhinitis patients
visiting university health
service center
Age, 18–45 yrs; sex,
CON, 14 (3 male, 11
female); YOG, 13 (3
male, 10 female)
IL-2 and IL-6 were assessed
from nasal secretions at baseline
and 8 week
41 Yadav et al., 2018,
India [45] YMP
Comparative efficacy of
a 12-week yoga-based lifestyle
intervention and dietary
intervention on adipokines,
inflammation, and oxidative
stress in adults with metabolic
syndrome: a randomized
controlled trial
12-week parallel,
two arm, RCT
(open-label)
130 (89) 130 (79)
Two interventions
were carried out.
Firstly, yoga-based
lifestyle intervention
(YBLI) and secondly,
dietary intervention
(DI)
Only dietary
intervention
(DI)
Younger apparently
healthy adults,
diagnosed with
metabolic syndrome
Aged 20–45 years,
both males and
females
TNF-α, IL-6, TBARS, SOD
assessed at baseline, 2 weeks and
12 weeks
42 Harkess et al., 2016,
austrailia [46] YMP
Preliminary indications of the
effect of a brief yoga
intervention on markers of
inflammation and DNA
methylation in chronically
stressed women
8 weeks randomized
control trial
(single-blinded)
11 (11) 15 (15) Yoga group Control group Women reporting
psychological distress
Mean age 41.12(4.28)
years IL6-1, IL6-2, hsCRP, TNF
43
Lim at al., 2015,
Republic of Korea
[47]
YMP
Regular yoga practice
improves antioxidant status,
immune function, and stress
hormone releases in young
healthy people: a randomized,
double-blind, controlled pilot
study
12-week
randomized double
blind control trial
(double-blinded)
12 (12) 13 (13) Yoga Control group Young healthy university
student
Control: median age
22 years, 8 women
yoga: median age 21
years, 6 women
Serum lipid peroxide level,
TNF-a, IFN--cand IL-12,
EC-SODs, and cortisol
44 Jorge et al., 2016,
Brazil [48] YMP
Hatha yoga practice decreases
menopause symptoms and
improves quality of life:
a randomized controlled trial
12-week 3
experimental arm
randomized control
trial (single-blinded)
Yoga 47 (40),
exercise 38 (29) 32 (19) (i) Yoga
(ii) Exercise Control
Healthy yoga-naive
women between 45 and
65 years
Yoga: mean age 54
(6) years; exercise:
mean age 56 (5)
years; control: mean
age 55 (4)
Salivary cortisol at baseline and
at 12 week intervention
Evidence-Based Complementary and Alternative Medicine 7

Table 2: Details of included studies.
SN Author (1st), year,
country
Intervention
type Intervention details Key findings
(descriptive)
Strengths and
limitations
1Zgierska et al., 2016, USA
[49] M
(i) Included different meditations including
mini-meditation, loving kindness
meditation, and breathing meditations
relating to pain supported by psychologists,
(ii) In addition participants were encouraged
to practice formal mindfulness meditation
through the duration of the study
(i) Changes in Cohen’s d of CRP, IL-1ß,
TNF-α, IL-6, and IFN-ץranged from 0.05
to 0.53 and -0.16 to −0.51 (minimal to
medium)
(ii) Nonetheless all of these changes were
statistically insignificant (p>0.05)
(i) Statistically insignificant but from small
to moderate effects, indicate further study
(ii) e combined package of meditations
with breathing exercises may be explorative
2 Bower et al., 2015, USA [14] M
(i) Mindful awareness practices (MAPs) for
6 weeks including 2 hours group session
(ii) Consisting of experiential practice of
meditation and gentle movement exercises
(e.g., mindful walking)
(iii) Psychoeducation
(iv) Home practice of mindfulness technique
on daily basis beginning with 5 minutes per
day increasing to 20 minutes per day
(i) CRP level, IL-6, and sTNFRII, all
decreased in intervention groups but were
statistically nonsignificant
(i) wait-list control has not controlled for
nonspecific effects of the intervention
3 Meyer et al., 2019, USA [15] M
(i) MBSR (intervention group) consisted of
2.5-hr sessions once per week for 8 weeks
with an additional “half-day retreat.“, and
practice either formal or informal meditation
at home each day,
(ii) exercise (control group) consisted
a 2.5-hour session once per week for 8 weeks
(i) CRP changed with small
(ii) IP-10 changed minimally
(i) Randomizing participants (exercise and
meditation) may capture the comparative
immunity benefits
4 Dada et al., 2018, India [53] MP
(i) Daily group meeting for 60 minutes.
(ii) Participants introduced to slow and deep
breathing exercise from day 2 (till 21 days).
(iii) Every day, 15 minutes relaxation, and
45 minutes meditation was executed
(i) e cortisol level, IL-6, and TNF-α
decreased postintervention significantly.
(i) ere was no significant difference in the
biomarker in intervention and control group
and baseline.
5Hayney et al., 2014, USA
[16] M
(i) e MBSR included weekly 2.5-hour
group session and 45 minutes of daily at
home practice
(ii) e exercise included weekly 2.5-hour
group session and 45 minutes of daily at
home practice
(i) IgA decreased in the meditation group
(ii) Median interferon calso increased in
meditation group
(iii) Median Interleukin-10 production
showed a overall increase in meditation
group
(i) Statistical analysis between group and
within group change in biomarkers at
baseline and endline is not carried out
8Evidence-Based Complementary and Alternative Medicine

Table 2: Continued.
SN Author (1st), year,
country
Intervention
type Intervention details Key findings
(descriptive)
Strengths and
limitations
6 Barrett et al.,2012, USA [17] M
(i) Meditation group, was given, weekly twice
1⁄2-hour group sessions and 45 minutes of
daily at home practice, focusing on stress
manifestations which may lead to a healthier
mind-body response.
(ii) Exercise group was given, weekly twice
a 1⁄2-hour group session of didactic
instruction and moderately intensive exercise
using stationary bicycles, treadmills, and
other equipment, and 45 minutes of daily at
home practice of brisk walking or jogging
(i) IL-8 means of meditation and exercise
groups were 252 pg/ml and 36 pg/ml
higher than that of control group
(postintervention).
(i) Two cohort were selected at different time
point which might influence the results.
(ii) Sample size was marginal for statistical
significance
7Gagrani et al., 2018, India
[18] M
(i) Daily 45 minutes session was held in
which participants sit on the floor and close
their eyes to focus on breathing
(i) e mean serum cortisol level
decreased in the intervention (p�0.01)
(ii) e mean serum IL-6 level decreased
in (p<0.001)
(i) Sample size was probably non-normal
and insufficient (convenience sampling)
8Lipschitz et al., 2013, USA
[19] M
(i) Mindfulness-meditation (MM) included
the breath meditation, body-scan meditation,
walking meditation, and forgiveness
meditation
(ii) Sleep health education (SHE) included
ways to change daily activities and habits to
improve their sleep
(iii) Mind-body bridging (MBB) included
expanding awareness to face daily life
challenges by reducing stress and addressing
sleep issues.
(i) Waking cortisol decreased (ns)
(ii) MBB slightly outperformed (with
producing higher salivary cortisol
amount) compared to MM and SHE
intervention.
(i) Small sample size with a single day
collection and assessment
(ii) e difference of changes in the control
group and the two intervention groups is
very minimal, so providing very weak
evidence to conclude
9 Rao et al., 2017, India [20] M
(i) Integrated yoga-based stress reduction
program included 60-min two times/week
for 12 weeks and consisted of a set of asanas
(postures performed with awareness)
breathing exercises, pranayama, meditation,
and yogic relaxation techniques.
(ii) Participants were also asked to practise at
home and maintain a diary
(iii) Control intervention was given to
supportive counselling sessions, including
education and reinforcing social support
(i) Significant decrease in the cortisol level
in intervention group was observed only
at 0600 hr pre post-intervention (p<0.05)
(ii) e mean cortisol level decreased in
both the intervention and control groups
but insignificant
(i) Active control group
(ii) e sample for biomarkers were collected
at three time point
Evidence-Based Complementary and Alternative Medicine 9

Table 2: Continued.
SN Author (1st), year,
country
Intervention
type Intervention details Key findings
(descriptive)
Strengths and
limitations
10 Creswell et al., 2016, USA
[50] M
(i) Health enhancement through mindfulness
(HEM) included mindfulness-based stress
reduction consisting of mindfulness training
through body scan awareness exercise, sitting
and walking meditations, mindful eating,
mindful stretching, and discussion
(ii) Health enhancement through relaxation
(HER) included positive treatment
expectancies, group support, teacher
attention, physical activity, and mental
engagement.
(i) Mean raw IL-6 level decreased in the
HEM group from baseline to 4 month
follow-up,
(ii) mean raw IL-6 level increased in the
HER group from baseline to 4 month
follow-up
(i) Participants’retainment was good
(ii) Home practice was not followed and so,
not effective
11 Andres-Rodriguez et al.,
2019, Spain [52] M
(i) Mindfulness-based stress reduction
(MBSR) included 8 weekly sessions of around
2.5 h each for mindfulness exercises, with
home mindfulness practice (45 min/day) and
intensive mindfulness meditation retreat of
6 hours
(ii) Treatment as usual (TAU) included the
pharmacological and adjusted to the
fibromyalgia (FM) patients’ symptomatic
profile and counselling about aerobic exercise
(i) IL-10 decreased postintervention in
TAU and increased in MBSR group
(p�0.034) with high effect size
(ES � −0.72)
(ii) IL-6 increased postintervention in
both groups
(iii) HsCRP, decreased in both groups
(i) Low sample size under powers the study
12 Buijze et al., 2019,
Netherlands [21] MP
(i) 8-week add-on training program
consisted of breathing exercises for an
average of 30 breaths and strength exercises
(e.g., push-ups and yoga balance techniques),
gradual cold exposure with immersing
whole-body in ice-cold water (0–1°C) for
several minutes, and meditation with the eyes
closed for 15–20 minutes
(ii) During the first 4 weeks, participants had
group trainings twice weekly, the second
4 weeks once weekly.
(i) HsCRP progressively decreased and
increased in intervention and control
group in both endpoints, but remained
nonsignificant in both groups (p>0.05)
(i) Not powered to investigate efficacy
(ii) e adherence to the group sessions was
reported to be high
13 Mandal et al., 2021, India
[22] YP
(i) Consisted of asana, pranayama, and deep
relaxation technique
(ii) Included 5 minutes deep relaxation
technique practiced in supine position,
shavasana (corpse pose) to relax the
whole-body completely within a short
amount of time
(iii) Two sessions in a week each with
a duration of 50 minutes for 12 consecutive
weeks were conducted
(i) Although negative standardized mean
difference (SMD) values were obtained
for cortisol and hsCRP, both remained
nonsignificant (p�0.112,0.784),
respectively
(i) Both the per-protocol and intention to
treat analysis was conducted.
(ii) Association of stress with cortisol was
observed demanding further exploration
10 Evidence-Based Complementary and Alternative Medicine

Table 2: Continued.
SN Author (1st), year,
country
Intervention
type Intervention details Key findings
(descriptive)
Strengths and
limitations
14 Viswanathan et al., 2020,
India [23] YP
(i) Yoga included practice of asanas such as
thadasana, trikonasana, vajrasana, konasana,
patchimothasana, uttanapadasana,
sarvangasana, matchyasana, salabasana, and
pranayama including abdomen breathing,
nadisudhi, kabalbhati, sitali, and brahmari
relaxation technique, for a period of 50 min
for 5 days in a week for 3 months.
(ii) Exercise (control) group included simple
physical exercises for 50 min for 5 days in
a week for 3 months.
(i) TBARS, hsCRP reduced while SOD
increased in the control arm, whereas IL-6
and TNF-αdecreased in the intervention
group.
(i) Lack long-term follow- up. May be the
first study with a large sample size that
nonyoga group in a tertiary care centre for
diabetes.
(ii) High response rate (75%)
15 Shete et al., 2017, India [24] YP
(i) 1 h of yoga was carried out, with various
(>20) poses, including warm up, asanas, and
pranayama, per day, 6 days a week, divided
into three stages, namely, Adaptation stage,
advancement in yoga practice, and
continuation stage
(ii) Pranayama included anulom vilom,
bhramari, ujjayi, and kapalabhati
(i) Hs-CRP (p<.01), IL-6 (p<.001), and
TNF-a (p<.001) significantly reduced in
the YG after 12 weeks of yoga compared
to control
(i) e finding cannot be generalized due to
selection bias and small sample size
16 Ganesan et al., 2020, India
[25] YMP
(i) A total of 30 min; 3 times/week for
12-week yoga therapy was carried out in
a research centre with warming up yoga
exercises, followed by different (7) yogasanas
then followed by pranayama and then,
dhyana
(i) IL-6 and TNF- αdecreased in the
control group whereas IL- 1 α, cortisol,
IL-6 and TNF- αdecreased in the
intervention group, both significantly
(ii) In between group comparison all
biomarkers decreased but insignificantly.
(i) e biomarkers level where comparable at
baseline (p>0.05).
(ii) Observation was conducted only at
baseline and after 3 months.
(iii) Patients with low-to-severe disease
activity were included in the study.
17 Chen et al., 2016, China [26] YMP
(i) Hatha yoga sessions included twice per
week over the 8 wks consisting each session
of 60 minutes with breathing exercise,
loosening exercise, followed by different
poses. ese poses were followed by
relaxation/corpse pose and seated
meditation.
(i) TNF-αand IL-6 decreased significantly
between and within the group
(ii) IL-1βalso decreased in the yoga group
(p<0.05)
(i) Study is focused on metabolic syndrome
(MetS) among healthy females
(ii) Withholds a good retention rate
18 Kiecolt-glaser et al., 2014,
USA [27] YP
(i) Yoga group included two 90-minute
sessions per week with different poses in
different positions, for 24 sessions.
(ii) Each session was followed by different
four types of breathing practices
(i) All cytokines and TNF-αdecreased but
remained nonsignificant
(i) e attrition level was low
(ii) Between group interpretation was not
done
Evidence-Based Complementary and Alternative Medicine 11

Table 2: Continued.
SN Author (1st), year,
country
Intervention
type Intervention details Key findings
(descriptive)
Strengths and
limitations
19 Kaminsky et al., 2017, USA
[28] P
(i) Pranayam plus education group practised
the dirgha three-part breath pranayam yoga
learning educational materials for one-hour
per session
(ii) Education (only) group learned of
education material for the whole 60 minutes
(i) in the intervention group CIP levels
decreased, whereas IL-6 increased (both
insignificantly)
(ii) e secondary biomarkers (FEV1, IC,
RV/TLC, DLCO) levels changed
(insignificantly) in the intervention group
(i) Instead of professional yoga instructors,
research coordinator provided training
(ii) Double blind controlled trial
20 Bower JE et al., 2014, USA
[29] M
(i) 12-week iyengar yoga included the yoga
focusing on postures, passive inversion
(upside-down postures), and passive
backbends (supported spinal extensions) for
90 minutes twice a week
(i) sTNF RII level decreased in the
intervention group (p�0.03 ) for both
group and time even after controlling the
confounders
(i) Inclusion of active control group
(ii) Small sample size
(iii) In some results, pvalues have not been
reported.
21 Twal et al., 2016, USA [3] P
(i) Yogic breathing (YB) group was given
a combination of 10 min of om chanting
(pranava pranayama) followed by 10 min of
thirumoolar pranayama (TMP), which
includes an inhalation (purakam),
breath-holding (kumbakam), and exhalation
(Resakam)
(ii) Attention control (AC) group performed
quiet reading for the same period in
independent one-on-one sessions
(i) MCP-1, IL-8, and IL-1βall, were found
decreased after the intervention of yogic
breathing, IL-8, and MCP-1 were also
with time.
(ii) ere was no significant difference in
the salivary levels of IL-1RA, IL-6, IL-10,
IL-17, IP-10, MIP-1b, and TNF-α
(i) First to demonstrate feasibility of the
salivary cytokines using multiplex assay.
(ii) Small sample size (YB �10; AC �10)
22 Hopkins et al., 2016, USA
[30] YP
(i) e yoga consisted of standardized series
of 26 hatha yoga postures, two breathing
exercises, and two savasanas (i.e., a resting/
relaxation posture) in a room heated to 104°F
(ii) e yoga sessions were at least two
90 minutes session per week for 8 weeks
(i) Mean cortisol level in both groups
decreased (more in yoga group)
postintervention.
(i) Two groups were heterogenous
(ii) Inferential analysis was not performed
23 Banasik et al., 2011, USA
[31] YP
(i) Iyengar yoga was taught which is more
physically demanding and has difficult poses.
(ii) Props were used to maintain proper
alignment and forms during the yoga.
(iii) e yoga session was of 90-min twice
weekly
(i) e mean salivary cortisol in morning
and 5 pm decreased in the intervention
group postyoga participation (p�0.018
and p�0.028, respectively)
(i) Saliva collection could have been biased.
(ii) Out of 18 participants only 14 completed
the study
24 Marques et al., 2017,
Portugal [54] YP
(i) ree 50-min session, 2-3 times/week
divided into three parts, namely, Joint
mobilization and exercises to promote
respiratory body awareness (10 min),
standing or sitting practice of �
asanas and
postures (30 min), and cool down and
relaxation (10 min)
(i) Insignificant increase in the salivary
cortisol level between the groups.
(ii) Increase in IgA level in the
intervention and decrease in the control
group both insignificantly
(i) e participants were polymedicated and
so, may differently influence the effects of the
intervention
12 Evidence-Based Complementary and Alternative Medicine

Table 2: Continued.
SN Author (1st), year,
country
Intervention
type Intervention details Key findings
(descriptive)
Strengths and
limitations
25 Torkamani et al., 2018, Iran
[51] M
(i) e participants of both the groups
attended the lecture (45 min) on
mantra-meditation.
(ii) Only the intervention group meditated
for 20 minutes
(i) Between group differences in the IgA
level was significant at postintervention
(p�0.0001) and an hour after
intervention (p�0.0001).
(i) Small sample size.
(ii) Participants were earlier enrolled in yoga
classes
26 Gunjiganvi et al., 2021,
India [55] YP
(i) Yogatherapy (YTP) included a maximum
of 1 hour of pranayama, and then gradually
moved to asanas, as tolerated on daily basis
till discharge (3–4 days of admission) and
then continue for 4 weeks at home.
(ii) Standard chest physiotherapy (CTP)
included percussion, vibration, cough
stimulation techniques, and breathing
exercises and mobilization
(i) Mean differences of most of the
biomarkers on day 1, 2, and 3, and at week
4 remained nonsignificant except IL-4 in
day 1, IL-10 in day 3, TNF-αon day 2, and
IFN-ץon day 2.
(ii) e intervention was noneffective at
4 week for VT (p�0.056) and FVC/FEV1
(p�0.30), but was effective for FVC
(p�0.008), FEV1 (p�0.009), and PEF
(p�0.016)
(i) One of the few studies explaining
yogatherapy as an additional rehabilitation
strategy in injured patients.
(ii) Home practice for 4 weeks may be biased
27 Pullen et al., 2010, USA [32] YM
(i) One-hour yoga session consisting of
breathing exercises (pranayama), standing
and seated yoga postures, followed by
relaxation with meditation, was conducted
twice per week, in a quiet room, for a total of
16 supervised sessions during an 8- to 10-wk
period.
(ii) Standard medical care was provided to
control group (CG)
(i) e levels of hsCRP, IL-6 and EC-SOD
decreased significantly in the intervention
group compared to the control group.
(i) Long-term follow-up of the patients’
adherence to the yoga and walking would be
questionable.
(ii) Home-based yoga activity track report
was difficult to maintain
28 Hecht et al., 2018, USA [33] YM
(i) MBSR included eight weekly classes of 2.5
hour duration, focusing body scan
meditation, gentle yoga for body awareness
and sitting meditation.
(ii) At sixth week an 8-hour silent retreat was
conducted and assignments was provided for
home practice.
(iii) Educational/control group carried out
1.5 hours of group session each week for
8 weeks that covered a variety of educational
topics about managing HIV infection
(i) ere was a increase in CD4 T cells,
decrease in IL-6 levels, increase in hsCRP
level, but all were nonsignificant.
(i) Assessed long-term effects of meditation.
(ii) Difficult to monitoring the interventions
at home
29 Nijjar et al., 2019, USA [34] YMP
(i) MBSR consist of mindfulness meditation,
breathing practices, and gentle yoga.
(ii) Consists of eight 2.5-hour weekly sessions
and one 6.5-hour retreat
(i) HsCRP decreased consecutively at
both endpoints but remained
nonsignificant (p�0.093, adjusted
difference)
(ii) A small single center pilot study to assess
the feasibility.
(ii) To be cautiously generalizable
Evidence-Based Complementary and Alternative Medicine 13

Table 2: Continued.
SN Author (1st), year,
country
Intervention
type Intervention details Key findings
(descriptive)
Strengths and
limitations
30 Huberty et al., 2019, USA
[35] YM
(i) Online yoga (OLY) intervention included
a 60-min/week home-based, online-streamed
yoga (online platform for yoga fitness and
meditation practice) for 12 weeks,
progressively, mild- to moderate-intensity
yoga classes based on hatha and
vinyasa-style.
(ii) Also included the videos for warm-up
and cool down, reminders for breathing with
the movements/poses, and a closing
mindfulness activity and final relaxation
(i) ere was a large decrease in TNF-αin
OLY participants (−1.3 ±1.5 pg/ml;
ES � −0.87, large effect size).
(ii) Change in IL-6 (ES � −0.26) was small
(i) Findings had not a well-defined
comparator.
(ii) e follow-up of 4 weeks is relatively
shorter
31 Chen et al., 2017, taiwan
[56] YMP
(i) Six 70-min yoga sessions per week for 20
weeks, with 10–12 women in each session,
which included physical postures/stretching,
deep breathing, guided imagery, and deep
relaxation
(i) Salivary mean cortisol differences at
weeks -16, 20, 24, 28, 32, and 36 were
significantly decreased (all p′s<0.05).
(ii) Salivary mean IgA differences at weeks
-16, 20, 24, 28, 32, and 36
postinterventions in yoga groups were
significantly increased (all p′s<0.05)
(i) First study showing the change in salivary
cortisol and IgA in pregnant women.
(ii) e study was powered to measure the
change.
(iii) Good retention (85%)
32 SeyedAlinaghi et al., 2012,
Iran [36] YM
(i) MBSR had 14 sessions, 1 hourly spread
over 8 weeks (weekly two sessions).
(ii) It consisted of sitting meditation, gentle
mindful hatha yoga, a body scan meditation,
and in the final session, a 6-hour retreat.
(iii) Education and support (ESC, control
group) group was given educational
information and pamphlets about living
healthily with HIV/AIDS.
(i) ere was a significant increase in the
CD4 counts in MBSR group (p<0.001),
3-months (p<0.001), 6-month
(p<0.001), and 9 month (p<0.05), but
decreased at 12-month
(i) e CD4+ level at baseline was
significantly different in both the groups.
(ii) Repeated measures were taken
33 Rajbhoj et al., 2015, India
[37] YMP
(i) Each yoga session was conducted for
45 min, six days a week, for 12 weeks,
excluding weekly holidays and consisted of
19 different yoga poses, 5 minutes for each,
followed by three different breathing
exercises and finally, om chanting
(i) e decrease in mean IL-1βlevels was
significant in the yoga group (p<0.05).
(ii) ere was a significant increase in the
mean IL-10 in the yoga group (p<0.05)
(i) e sample size was small. Different types
of poses may be difficult to remember to
carry on
34 Singh et al., 2011, India [38] YMP
(i) One and a half hour per day for 7 weeks
(i.e. 40 days approximately) excluding
Sunday.
(ii) Composed of practices (cleansing
practices like gayatri mantra (5 min), kunjal
(twice/week), jal nethi (thrice/week), ananas
(50 min/week), and healthy yoga diet),
pranayamas (20 min), and meditation
(15 min)
(i) Decrease in the CRP in the YG after
7 weeks of yoga (p<0.01) (i) Results were promising, and also, reliable
14 Evidence-Based Complementary and Alternative Medicine

Table 2: Continued.
SN Author (1st), year,
country
Intervention
type Intervention details Key findings
(descriptive)
Strengths and
limitations
35 Nugent et al., 2019, USA
[39] YMP
(i) Hatha yoga (intervention group) was
carried out at least one group class per week
for 10 weeks, and included breathing
exercises (pranayama) and seated
meditation; warm-ups and half sun
salutations; standing postures (asanas);
seated postures; an inversion and a twist; and
shavasana (relaxation) (80 min).
(ii) HLW (healthy living workshop) included
at least one HLW class (60 minutes long) per
week for 10 weeks, addressing alcohol,
nicotine, and caffeine; being a smart patient;
brain diseases; cancer prevention; diabetes;
nutrition (3 classes); germs, colds, and the flu;
physical activity (2 classes); sleep; physical
pain, prevalence and causes of depression;
and protecting your heart
(i) IL-6 levels reduced significantly in the
intervention group compared to control.
(ii) TNF-a and CRP did not show evident
significant change
(i) Sensitivity analysis of the effect on IL-6
and parameter estimates of growth model
have been carried out
36 Gautam et al., 2019, India
[40] YMP
(i) Patanjali raj yoga (classical yoga) was
taught to the participants for 120 minutes/
per day/5 session/8 weeks.
(ii) Including a set of different asanas
(physical postures), pranayama (breathing
practices) and dhyana (meditation)
(i) Between groups the mean reduction in
the CRP level, IL- 17A, IL-6, and TNF-α
in the yoga group from baseline to 8-week
was significant (p<0.05)
(i) Active control group could have
explained the change in biomarker is due to
the intervention or otherwise
37 Sohl et al., 2016, USA [41] YMP
(i) Taught a set of yoga skills training (YST)
by 3 trainers, consisting awareness
meditation, movement, and breathing and
relaxation.
(ii) For home practise an audio recording of
YST was provided and asked to practice
a 15-minute session (4times/week)
(i) No significant change was observed in
the levels of IL-6, IL- 1 ra, TNF- α, and
CRP (p>0.05)
(i) Underpowered sample
38 Gautam S et al., 2020, India
[42] YMP
(i) Yoga-based lifestyle intervention (YBLI)
included Patanjali’s ashtanga yoga, asanas
(physical postures), pranayama (breathing
techniques), dhyana (meditation), and
savasana (relaxation techniques). 120 min per
session, 5 days for 8 weeks.
(ii) Usual care group (control) were
continued with usual medical care and
normal routine activity for 8 weeks
(i) Significant decline was noted in the
levels of pro-inflammatory cytokines
(IL-6, TNF- α, and IL- 17A) in yoga group
after 8 weeks
(i) Lacking active control group.
(ii) Small sample size and misbalanced male
to female ratio, may limit the power of the
effects.
(iii) Long duration of the intervention
Evidence-Based Complementary and Alternative Medicine 15

Table 2: Continued.
SN Author (1st), year,
country
Intervention
type Intervention details Key findings
(descriptive)
Strengths and
limitations
39 Wolff et al., 2015, Sweden
[43] YMP
(i) Group 1 met once a week for 60 min and
practiced kundalini yoga consisting of
various yoga (30 min) movements and
positions, breathing techniques, and
meditation.
(ii) Group 2 were given a doctor’s
appointment (20 min), received instructions
for two yoga exercises and did the left nostril
breathing, followed by spinal flex
(i) e mean change in IL-6 and hsCRP
levels in the intervention group were
insignificant.
(i) IL-10 was not detectable in a majority of
the patients.
(ii) e study was carried out in a primary
care settings.
(iii) e participants were group matched
rather than individually.
(iv) Track of yoga practise was assessed
through self-report
40 Chanta a et al., 2019,
ailand [44] Y
(i) Training for 60 minutes per session three
times a week for 8 weeks.
(ii) e hatha yoga consisted of 10 minutes of
warm-up, followed by seated mountain pose
(iii) Seated sun pose, boat pose.
(iv) Workout for approximately 40 min
(i) IL-2 increased postintervention
significantly in the yoga group (p<0.05)
but decreased in the control group,
indicating that chronic exercise could
delay immunosenescence.
(ii) IL-6 increased postintervention in
both the groups but remains insignificant
(p>0.05)
(i) Study is related to respiratory system,
which may be important for COVID-19.
(ii) Increase in IL-6 contradicts with other
yoga intervention
41 Yadav et al., 2018, India [45] YMP
(i) Active intervention was carried out for 2
hours a day for 14 days, consisting physical
postures, pranayama, interactive lecture, and
ending with meditative relaxation, and then
followed for next 10 weeks at home.
(ii) Dietician provided dietary intervention
(DI) for both the groups
(i) IL-6 and TBARS levels significantly
decreased in the intervention group at
two points of analysis.
(ii) TNF- αand SOD levels changed in
groups (both within and between), but
were insignificant.
(i) Both groups are homogenous.
(ii) Intention to treat analysis could not be
carried out.
(ii) Home-based interventions have been
suffered with noncompliance, which was
often difficult to assess
42 Harkess et al., 2016,
austrailia [46] YMP
(i) An hour class of total 16 classes were
offered twice weekly for 8 weeks.
(ii) Hatha yoga was taught
(i) A moderate correlation (rho �0 .608,
p<0.01 between TNF and IL-6 was
observed.
(ii) e friedman and mixed
between–within subjects ANOVA test
represented nonsignificant changes in
IL-6 or TNF and hsCRP levels,
respectively.
(iii) Studied in a nonclinical population
(i) e first study to explore DNA
methylation.
(ii) A pilot study with small sample size and
low power of the test
16 Evidence-Based Complementary and Alternative Medicine

Table 2: Continued.
SN Author (1st), year,
country
Intervention
type Intervention details Key findings
(descriptive)
Strengths and
limitations
43 Lim SA at al., 2015,
Republic of Korea [47] YMP
(i) 1 day a week for 90 minutes, over 12 weeks
(ii) yoga consists of
(i) Yoga body poses (asanas for 35 min).
(ii) Exercises involving awareness and
voluntary regulation of breath (pranayamas
for 30 min)
(iii) Meditational practices (for 25 min).
(iii) Participants attended at least 10 of the
total 12 weeks and at least three times at
home during the experiment period by
watching a 40-minute DVD
(i) e serum TBARS, and IL-12, TNF- α,
IFN- creduced significantly in the
intervention group and within group
comparison respectively.
(ii) e serum SOD levels decreased and
cortisol levels increased significantly only
in the control group.
(i) Many stress related biomarkers were
studied.
(ii) e sample size was small, and the
findings may not be generalized
44 Jorge et al., 2016, Brazil [48] YMP
(i) 75-min of supervised practices twice
a week, for 12 weeks.
(ii) Posture included the four typical
movement of the vertical column (flexion,
extension, lateral bending, and rotation),
abdominal fitness practices, and balance
exercises.
(i) e salivary cortisol level increased in
both the groups, but significant change
was observed only in the control group
(p<0.001).
(ii) e salivary cortisol level decreased in
exercise group
(i) At baseline the cortisol level were
different.
(ii) Uneven attrition was observed in three
groups
M�Meditation, P �Pranayama, Y �Yoga, MP �Meditation and pranayama both, YP �Yoga and pranayama both, YM �Yoga and meditation both, and YMP �Combination of yoga, meditation, and pranayama.
Evidence-Based Complementary and Alternative Medicine 17

full text. We removed 40 full-text articles that failed to meet
the inclusion criteria, as well as 3 articles that were un-
available in full text. Finally, 44 articles were selected for the
review (Figure 1).
3.2. Description of Included Studies. e study consisted of
randomized control trials ranging from less than one week
(including two studies which had an intervention of
20 minutes) to 28 weeks (including one study which had
12 months of intervention). e majority of the in-
terventions ranged from 5 to 16 weeks (n�35) [14–48],
either solo (Y or M or P) or in combinations (YM, YP, MP,
and YMP). ere were studies providing yoga (n�2) (Y)
[29, 44], pranayama (n�2) (P) [3, 28], meditation (M)
(n�11) [14–20, 49–52], meditation and pranayama (n�2)
(MP) [21, 53], yoga and meditation (n�4) (YM)
[32, 33, 35, 36], yoga and pranayama (n�8) (YP)
[22–24, 27, 30, 31, 54, 55], and yoga, meditation, and pra-
nayama (n�15) (YMP) [25, 26, 34, 37– 43,45–48, 56] as
interventions. Most of the studies had two groups (in-
tervention and control), while 6 studies were reported to
have 3-experimental arms. e studies were carried out in 13
countries, with the maximum number of studies coming
from the USA (n�19, 43%), followed by India (n�13, 30%),
Iran (n�2, 5%), and one each in China, ailand, Spain,
Netherlands, Sweden, Republic of Korea, Brazil, Australia,
Taiwan, and Portugal. e interventions given included
Iyengar, Patanjali Raj, Hatha yoga, and other forms of yoga,
mindfulness-based stress reduction (MBSR), and pranayama
(Tables 1 and 2).
3.3. Study Quality. Of the 44, twenty-three RCTs were open-
label, followed by 19 single-blinded and 2 double-blinded
trials. Among the 37 full RCTs, one was a crossover design.
e comparator arms included 23 controls or wait-list or
attention or observational controls, 11 usual or standard
care, and 10 were given placebo or active control. Placebo
interventions included health education (HE) with or
without supportive therapy, counselling, exercise, re-
habilitation, relaxation, healthy living workshop (HLW),
dietary intervention, physical exercise, sleep hygiene edu-
cation (SHE), and stress reduction. Risk of bias (ROB) of 11
studies included in meta-analyses, three were found to be
low, one medium, and seven with high risk (Table 3).
3.4. Participants. A total of 4023 participants were included
in 44 trials, ranging from 15 to 413 participants. Most
participants were patients, including those either from in-
patient or out-patient clinics or hospital settings. Only a few
studies (n= 4) were carried out in community and educa-
tional institutions. Almost all studies included both men and
women aged 18 years or above, whereas some trials were
exclusively conducted only on females (n= 13)
[14, 20, 26, 27, 29–31, 46, 48, 51, 52, 54, 56] (Tables 1 and 2).
3.5. Intervention. e trials encompass various forms of
asanas, deep relaxation, and other techniques of yoga,
meditation, and pranayama. e participants (intervention
group only) learned the poses and techniques in the presence
of an instructor, and then they were asked to practise the
learning at home or in their free time. In only one study,
participants learned through an online platform. Except for
two studies [16, 19], the daily duration of intervention was
less than an hour (n= 10) [3, 18, 21–23, 25, 37, 41, 53], one to
two hours (n= 25) [14, 20, 24, 26–32, 35, 38–40,
42–49, 52, 55] and more than two hours. e intervention
duration of the trial by Banasik and colleagues [31] was taken
from the authors’ previous study [57] (n= 7)
[15–17, 33, 34, 36, 50].
3.6. Outcomes
3.6.1. Yoga (Y). Two studies that included only yoga as an
intervention reported soluble tumour necrosis factor re-
ceptor II (sTNF RII) (a cell surface receptor for the
proinflammatory cytokine), C-reactive protein (CRP), in-
terleukin 1 receptor antagonist (IL-1RA) [29], interleukin 2
(IL-2) [44], cortisol [29], and Interleukin 6 (IL-6) [29, 44].
e duration of intervention ranged between 1440 and
2160 minutes.
3.6.2. Pranayama (P). Two studies [3, 28] used pranayama
as an intervention with a duration ranging from 20 to
720 minutes. e following biomarkers were studied: IL-6,
CRP, 6 minute walk distance (6MWD), diffusing capacity of
the lungs for carbon monoxide (DLCO), forced expiratory
volume in 1 sec (FEV1), inspiratory capacity (IC), residual
volume to total lung capacity ratio (RV/TLC), alveolar
volume to total lung capacity ratio (VA/TLC), and in-
spiratory time to total breathing cycle time ratio (Ti/Ttot)
[28]. A second study reported monocyte chemoattractant
protein 1 (MCP-1), interleukin 8 (IL-8), interleukin 1 beta
(IL-1β), IL-1RA, IL-6, interleukin 10 (IL-10), interleukin 17
(IL-17), interferoncinduced protein-10 (IP-10), macro-
phage inflammatory protein 1-beta (MIP-1b), and tumor
necrosis factor (TNF-α) [3].
3.6.3. Meditation (M). A total of 11 studies [14–20, 49–52]
had only meditation as the intervention. e duration of the
intervention ranged from 20 minutes to 12 months. e
following biomarkers were reported in the trial: CRP
[14, 15, 49], IL-1 beta, TNF-α[49], interferon gamma (IFN-
c) [16, 49], IL-8 [17], sTNFR II [14], cortisol [18–20], IL-6
[14, 15, 18, 49–52], immunoglobulin A (IgA) [16], IL-10
[16, 50–52], high-sensitive C-reactive protein (hsCRP)
[50–52], and IP-10 [15].
3.6.4. Meditation and Pranayama (MP). Two studies had
a combination of meditation and pranayama [21, 53],
ranging from a duration of 336 to 1200 minutes. IL-6, TNF-α
[53], and hsCRP [21] were studied in these trials.
3.6.5. Yoga and Meditation (YM). With four studies having
both yoga and meditation [32, 33, 35, 36] intervention,
18 Evidence-Based Complementary and Alternative Medicine

ranging over a duration of 720 to 1740 minutes, including
both learning and practising. Biomarkers included in the
study were hsCRP [32, 33], IL-6 [32, 33, 35], extracellular
superoxide dismutase (EC-SOD/SOD) [32], CD4+ [33, 36],
and TNF-α[35].
3.6.6. Yoga and Pranayama (YP). Eight studies were
spanned from 1 hour to 28 weeks of yoga and pranayama
intervention [22–24, 27, 30,31, 54, 55]. e following
markers were studied: IL-6 [23, 24, 27], hsCRP [22–24],
cortisol [22, 30, 31, 54], TNF-α[23, 24, 27, 55], TBARS and
EC-SOD/SOD [23], IL-1 beta [27], IL-8, IL-10, IL-2, IL-12,
IFN-c, IL-4, tidal volume (TV), forced vital capacity (FVC),
and FEV1 and peak expiratory force (PEF) [55].
3.6.7. Yoga, Meditation, and Pranayama (YMP). A total of
fifteen studies had a combination of three forms of in-
tervention [25, 26, 34, 37–43, 45–48, 56]. e following
biomarkers were found studied in the trial: IL-1βand IL-10
[37], IL-1β[26], CRP [38–41], IL-17A [40, 42], IL-6 levels
[25, 26, 39–41, 43, 45, 46], TNF-α[25, 26, 39, 41, 42, 45, 47],
cortisol [25, 47, 48, 56], TBARS, SOD [45, 47], IFN-c[47],
hsCRP [34, 43, 46], IgA [56], IL-1α[25], IL-8, and MCP-1
[26] (Tables 1 and 2).
3.6.8. Meta-Analysis. For meta-analysis, eleven studies
[14, 18, 19, 23, 25, 29, 39, 40, 42, 44, 52] only focused on three
biomarkers among the patients met the inclusion criteria, so
we calculated the mean differences. e mean differences of
IL-6, TNF-α, and cortisol were −0.58 pg/mL (95% CI (−1.37,
0.17)) [14, 23, 25, 29, 39, 40, 42, 44, 52], −2.62 pg/mL (95% CI
(−4.29, −0.96)) [23, 25, 39, 40, 42], and −26.71 ng/ml (95% CI
(−59.41, 5.99)) [18, 19, 25], respectively. Considerable
heterogeneity was observed between the studies (IL-6
(I
2
�95%, p<0.000001), TNF-α(I
2
�93%, p<0.000001),
and cortisol (I
2
�98%, p<0.00001) (Figure 2).
3.6.9. Subgroup Analysis. In subgroup analysis (Table 4),
yoga-pranayama-meditation (p�0.002), 6–12-week
(1000–2000 min) intervention (p�0.0006), and 8–12-
week (3000–4800 min) were found with an overall effect
significant in IL-6, cortisol, and TNF-α, respectively. In the
meditation subgroup of IL-6, a marginal overall effect
(p�0.05) with no heterogeneity (I
2
�0%) was observed.
3.6.10. Sensitivity Analysis. In a sensitivity analysis, we
found a significant overall effect (p�0.04) by removing
three studies of high risk of bias (C1.2) in IL-6. Similarly, in
TNF- α, by removing one moderate risk study (B1.3)
(p�0.003) and two high risk studies (C1.2) (p<.00001),
overall effects remained significant (Table 5).
3.6.11. Publication Bias. Publication bias was assessed using
funnel plots. e majority of the studies were found outside
of the 95% CI as visualised, signifying a high publication bias
[14, 23, 25, 29, 39, 40, 42, 44] (Figure 2).
4. Discussion
e review included 44 studies from 13 countries (including
the USA, followed by India, which conducted the maximum
RCTs), comprising 4023 people. e studies were conducted
in different populations (healthy, diseased, and pregnant)
ranging from 20 to 4800 minutes. Our main findings
demonstrate that yoga, meditation, and pranayama, either
alone or in combination, are effective in improving
Records identified from (174):
Google Scholar (n =41)
PubMed (n =70)
Cochrane (n =40)
Citation Searches* (n =23)
Records excluded from Abstract/Title
screening (Irrelevant outcome/Study
design (n =55)
Records screened (n =142)
Reports not retrieved (n=3)
Not accessible (n=2)
Only Abstract (n=1)
Reports assessed for
eligibility
(n =84)
Reports excluded (n=40)
Non-RCT (n=2)
Duplicate (n=1)
Aerobic exercise (n=1)
Qigong intervention (n=7)
Other biomarkers (n =27)
Not within the date range (n=2)
Studies included in:
Systematic review (n =44)
Meta-analysis (n=11)
Identification of studies via databases and other searches
Identication
Screening
Includ ed
Records removed before screening:
Duplicate records removed (n =32)
Records removed by EndNote
soware (n=2)
Records removed manually (n=30)
Reports sought for retrieval
(n =87)
*Some articles were included also from earlier (published) scoping review carried out by the team members
(i)
(i)
(i)
(i)
(ii)
(iii)
(iv)
(v)
(vi)
(ii)
(ii)
(i)
(ii)
(iii)
(ii)
(iii)
(iv)
Figure 1: PRISMA flow chart and screening of studies.
Evidence-Based Complementary and Alternative Medicine 19

Table 3: Cochrane risk of bias assessment.
Study
name
Random
sequence
generation
Allocation
concealment
Blinding
of participants
Blinding
of outcome
assessment
Incomplete
outcome
data
Selective
reporting
Other
bias
Overall
risk
of bias
Risk
of bias
rating
∗
Andres-rodriguez et al. 2019 Low Low Some concerns Low Low Low Some concerns Low A1.2
Bower et al. 2015 Low Low High High Some concerns Low High High C1.2
Bower et al. 2014 Low High High Some concerns High Low High High C1.3
Chanta et al. 2019 Low High High Low Some concerns Some concerns High High C1.3
Ganesan et al. 2020 Low Low High Some concerns Some concerns Low Some concerns Medium B1.3
Gautam et al. 2019 Low Low Some concerns Low Low Low Some concerns Low A1.2
Gautam et al. 2020 Low Low Some concerns Low Low Some concerns Low Low A1.2
Nugent NR et al. 2019 Low Low High High High Low High High C1.2
Vishwanathan et al. 2020 Low Low High High High Low High High C1.2
Gagrani et al. 2018 Low Low High High Low Low Some concerns High C1.1
Lipschitz et al. 2013 Low Low High High Low Low High High C1.1
Review author’s judgments about each risk of bias item across all the included studies. ∗Rating was based on the risk of bias. i.e. “low overall bias”—rated as “A,” “medium overall bias” —rated as “B,” and “high
overall bias”—rated as “C”. Subsets were further categorized (i.e. C1.0, C1.1.) according to the bias in the individual domain.
20 Evidence-Based Complementary and Alternative Medicine

Risk of Bias
ABCDEFG
Experimental Control
Study or Subgroup Mean SD Total Mean SD
Weight
(%)
Tot a l
Mean Difference Mean Difference
IV, Random, 95% CI IV, Random, 95% CI
Andres-Rodriguez et al (M), 2019 0.07 2.72 34 0.27 9 32 4.1
Bower et al (M), 2015 −0.05 0.53 39 0.16 0.39 32 16.4
Bower et al (Y), 2014 0.16 0.51 13 0.27 0.79 15 15.6
Chanta et al (Y), 2019 2.4 7.21 13 2 5.45 14 2.1
Ganesan et al (YMP), 2020 −54.49 41.24 68 −33.34 50.77 75 0.2
Gautam et al (YMP), 2019 −0.9 0.96 36 −0.01 0.85 36 15.8
Gautam et al (YMP), 2020 −1.1 1.02 33 −0.1 0.91 33 15.6
Nugent et al (YMP), 2019 −0.87 1.22 48 1.57 2.56 39 13.6
Vishwanathan et al (YP), 2020 −9.3 0.76 150 −10.2 0.76 150 16.5
Total (95% CI) 434 426 100.0
Heteroge neity: Tau2 = 0.90; Chi2 = 173.26, df = 8 (P < 0.00001); I2 = 95%
−20−10
Favours [experimental]
01020
Test for overall effect: Z = 1.51 (P = 0.13)
−0.20 [−3.45, 3.05]
−0.21 [−0.42, 0.00]
−0.11 [−0.60, 0.38]
0.40 [−4.45, 5.25]
−21.15 [−36.25, −6.05]
−0.89 [−1.31, −0.47]
−1.00 [−1.47, −0.53]
−2.44 [−3.31, −1.57]
0.90 [0.73, 1.07]
−0.58 [−1.34, 0.17]
Favours [control]
+ + ? ?
?
?
? ?
? ? ?
??
? ?
+− − −
−−−−
−
−
− − −
− − −
− −
−
−
+
+ +
+
+
+
+
+
+
+
+ + + +
+ + +
+
+
++
+
+
+ + +
+
+
(a)
Risk of Bias
ABCDEFG
Study or Subgroup Experi mental Contr ol
Mean SD MeanTot a l
Mean Difference Mean Difference
SD
Weight
(%)
Total IV, Random, 95% CI
Ganesan et al (YMP), 2020 −30.65 44.36 68 −20 48.82 75 1.1
Gautam et al (YMP), 2019 −2.98 2.26 36 1.05 4.05 36 22.6
Gautam et al (YMP), 2020 −3.3 2.33 33 1 4.14 33 22.0
Nugent et al (YMP), 2019 0.26 1.43 48 0.18 1.78 39 26.5
Vishwanathan et al (YP), 2020 −3.1 0.7 150 −0.7 0.7 150 27.7
Total (95% CI) 335 333 100.0
Heteroge neity: Tau2 = 2.60; Chi2 = 59.25, df = 4 (P < 0.00001); I2 = 93%
Test for overall effect: Z = 3.09 (P = 0.002)
−10.65 [−25.92, 4.62]
−4.03 [−5.55, −2.51]
−4.30 [−5.92, −2.68]
0.08 [−0.61, 0.77]
−2.40 [−2.56, −2.24]
−2.62 [−4.29, −0.96]
IV, Random, 95% CI
−20 −10
Favours [experimental]
01020
Favours [control]
? ? ?
??
? ?
−
− − −
− − −
−
−
+
+
+
+
+
+
+
+ + + +
+ + +
+
+
++
+
(b)
Risk of Bias
A B C D E F G
Study or Subgroup Expe rimental Control Mean Differe nce
Mean SD Total Mean SD
Weight
(%)
Total IV, Random, 95% CI
Mean Difference
IV, Random, 95% CI
Gagrani et al (M), 2018 −50 32.44 30 3 16.29 30 32.6
Ganesan et al (YMP), 2020 −44.05 41.43 68 −14.91 16.29 75 33.2
Lipschitz et al (M), 2013 −0.7523 5.2369 20 −1.36 1.97 18 34.3
Total (95% CI) 118 123 100.0
Heteroge neity: Tau2 = 805.76; Chi2 = 88.79, df = 2 (P < 0.00001); I2 = 98%
Test for overall effect: Z = 1.61 (P = 0.11)
−100 −50 0 50 100
Favours [experimental]
−53.00 [−65.99, −40.01]
−29.14 [−39.65, −18.63]
0.61 [−1.86, 3.08]
−26.71 [−59.32, 5.89]
Favours [control]
???
?− −
−
−
− −
+
+
+
+ + +
+
++
+
+
(c)
0
SE (MD)
2
4
6
8
10
−20 −10 0 10 20
MD
(d)
Figure 2: Continued.
Evidence-Based Complementary and Alternative Medicine 21

immunity in healthy and clinical populations (including
pregnant women) by regulating anti- and pro-inflammatory
biomarkers. Key findings (which were statistically signifi-
cant) are (i) among clinical participants, there was a decrease
in IL-6 [18, 23, 32, 40, 42, 53], IL-1β[31], IL 17/17A [40, 42],
IL- 1α[25], CRP [39, 41], hsCRP [32], TNF/TNF- α
[23, 25, 35, 40, 42, 46, 53, 55], sTNFR II [29], cortisol
[18, 25, 31, 53, 56], TBARS [23]; and an increase in CD4+
T cells (nonsignificant) [33, 36], IL-2 [44], FEV1, PEF, VT,
and FVC [55]; (ii) among healthy participants, an increase in
IL-10 [37], IFN-c, cortisol [47], and IgA [51]; and a decrease
in IL-6 [24, 45], CRP [15], TNF-α[24, 26], hsCRP [24], EC-
0
SE (MD)
2
4
6
8
10
−100 −50 0 50 100
MD
(e)
0
SE (MD)
2
4
6
8
10
−100 −50 0 50 100
MD
(f)
Figure 2: Forest plots including risk of bias (ROB) (a, b, and c) and funnel plots (d, e, and f ) of effects of yoga (Y), meditation (M) and/or
pranayama (P) on various biomarkers among patients; for ROB; A �Random sequence generation (selection bias); B �Allocation con-
cealment (selection bias); C �Blinding of participants and personnel (performance bias); D �Blinding of outcome assessment (detection
bias); E �Incomplete outcome data (attrition bias); F �Selective reporting (reporting bias); and G �Other bias.
Table 4: Subgroup analysis.
Parameters Subgroups No. of
trials
Mean difference
[95% CI]
Heterogeneity Overall Effect
Q I
2
(%) Z pValue
IL-6
Yoga-meditation-pranayama 4 −1.44 [−2.33, −0.55] 16.92 82 3.16 0.002
Meditation only 2 −0.21 [−0.42, 0.00] 0.00 0 1.92 0.05
Yoga only 2 −0.10 [−0.59, 0.38] 0.04 0 0.42 0.67
6–10 wk (<1000 min) 3 −1.08 [−2.94, 0.79] 2.12 92 1.13 0.26
8–12 wk (1000–2000 min) 2 −9.14 [−30.12, 11.84] 7.21 86 0.85 0.39
6–10 wk (>2000 min) 4 −0.26 [−1.35, 0.82] 107.66 97 0.48 0.63
Cortisol Meditation only 2 −25.80 [−78.33, 26.73] 63.15 98 0.96 0.34
6–12 wk (1000–2000 min) 2 −40.75 [−64.13, −17.38] 7.83 87 3.42 0.0006
TNF-α
Yoga-meditation-pranayama 4 −3.00 [−6.20, 0.20] 42.08 93 1.84 0.07
10–12 wk (≤1080 min) 2 −2.46 [−11.40, 6.48] 1.89 47 0.54 0.59
8–12 wk (3000–4800 min) 3 −3.40 [−4.83, −1.98] 9.53 79 4.68 <0.0001
Interstudy heterogeneity was tested by using the Cochran Qstatistic (Chi
2
) at a significance level of p<0.10 and quantified by the I
2
statistic.
Table 5: Sensitivity analysis.
Parameters Mean
difference [95% CI]
Heterogeneity Overall Effect
Q I
2
(%) Z p- Value
IL-6
Removing (3) A1.2 studies −0.42 [−1.34, 0.49] 115.80 96 0.91 0.36
Removing (1) B1.3 studies −0.53 −1.28, 0.21] 165.60 96 1.40 0.16
Removing (3) C1.2 studies −0.67 [−1.31, −0.04] 15.36 67 2.09 0.04
Removing (2) C1.3 studies −0.71 [−1.60, 0.17] 171.86 97 1.58 0.11
TNF-α
Removing (2) A1.2 studies −1.41 [−3.81, 1.00] 48.33 96 1.15 0.25
Removing (1) B1.3 studies −2.53 [−4.20, −0.86] 58.10 95 2.96 0.003
Removing (2) C1.2 studies −4.19 [−5.29, −3.09] 0.75 0 7.44 <0.00001
Cortisol Removing (1) B1.3 studies −25.80 [−78.33, 26.73] 63.15 98 0.96 0.34
Sensitivity analysis, showing progressive effects on pooled mean differences of removing data by trials’ risk of bias rating. Interstudy heterogeneity was tested
by using the Cochran Qstatistic (Chi
2
) at a significance level of p<0.10 and quantified by the I
2
statistic.
22 Evidence-Based Complementary and Alternative Medicine

SOD/SOD [32], TBARS [45, 47], MCP-1 [49], and IL-1β
[26, 37] was observed (iii) among the pregnant women, the
intervention was effective in increasing IgA and decreasing
cortisol levels [56] (Figure 3).
Many studies have reported that fluctuations in bio-
markers among COVID-19 patients play vital roles in im-
munity [58–67] (Table 6).
In a case report, a 55-year-old COVID-19 positive with
comorbidities had his COVID-19 symptoms alleviated as well
as his blood sugar level improved after treatment with ayur-
vedic medicine, yoga, dietary suggestions, lifestyle modifica-
tions, and allopathic medications [68]. Another ongoing study
can strengthen the importance of yoga intervention in im-
proving the health of COVID-19 patients [69].
Many studies have explored various immunity bio-
markers in COVID-19 patients. T cells, an important
component of lymphocytes responsible for robust immu-
nity, are reduced significantly during severe infections, in-
cluding COVID-19 [58, 59]. Cytokines (IL-6, IL-10, IL-8, IL-
2R, and so on) consist of various biomarkers produced by
both innate and adaptive immune cells [70], which play
a vital role in inflammation [71]. A fatal cytokine storm is
usually observed in COVID-19 patients who are critically ill
[72]. Cytokine storms lead to damaged tissues, resulting in
thrombotic tendency and multiple-organ failure [73], sug-
gesting cytokine control necessary. Both individual studies
and systematic reviews indicate the importance of IL-6,
reporting it to be an independent predictor of disease se-
verity and survival in COVID-19 patients [74–77]. CRP,
a prominent marker of systemic inflammation, was elevated
in the majority of COVID-19 patients with severe illness
compared with mild or nonsevere patients [78–80]. Cortisol
regulation acts as an adaptive immunity, but extreme cor-
tisol responses (relative adrenal insufficiency) are associated
with a higher mortality rate [81–83]. Cortisol levels were
high in COVID-19 positive patients compared to negative
[84] and nonfatal [85] COVID-19 patients.
Although meta-analyses showed an overall decrease in
stress biomarkers (IL-6, TNF-α, and cortisol), only TNF-α
was significant. However, subgroup analysis showed TNF-α
(8–12 wk, 3000–4800 minutes), IL-6 (yoga-meditation-
pranayama), and cortisol (6–12 wk, 1000–2000 minutes)
statistically significant reductions favouring intervention.
Our findings are in line with earlier conducted meta-
analyses in which both IL-6 and TNF-αwere reduced in
the intervention group following the yoga and meditation
[86, 87]. e change was significant in one study reporting
IL-6 [86], whereas there was an insignificant decrease in IL-6
and TNF-α[87], which could have been due to smaller
number of studies (n�2) included in the analysis. Recent
reviews on the effects of phytosterols and the effect of an
herb, Nigella sativa, have also been shown to reduce the
cytokine storm; however, these are beyond the scope of this
review and so, further suggested [8, 88].
In the scarcity of RCTs reporting the effectiveness and
efficacy of yoga, meditation, and pranayama in COVID-19
patients, our findings further add to the yoga-based in-
terventions and their effects on the inflammatory bio-
markers. rough our findings, it may be possible to
recommend treatment strategies to promote the health of
both mild to moderate and severe cases, including symp-
tomatic and asymptomatic COVID-19 patients.
Population
Total 4023 (range; 15-413)
Clinical, healthy and pregnant
Clinical (mainly) and educational settings
Both sexes above 18 yrs (31 studies)
Only female (13 studies)
Inter vent ion
YMP
(15)
YM/MP/YP
(14)
Y/P
(4)
Healthy
M
(11)
Many Cytokines,
TBARS, Cortisol
Decrease
CD4+ T Cell,
IL-2, IgA
Clinical/Pregnant
Increase
hsCRP, TNF-a,
TBARS, some
cytokines, EC-
SOD/SOD
Decrease
Cortisol,
Yoga related Biomarkers in Covid-19: A Systermatic Review
IFN-y,
CD4+, IL-10,
IgA
Increase
Duration (minutes)
Clinical/Pregnant
YMP (1080-4800)
M (1890)
YM/YP/MP/P/Y
(960-1440)
Healthy
YMP (960-3240)
M (1200-8400)
YM/YP/MP/P/Y
(20-2200)
RCTs
Intervention
Single or
combinations of YMP
Single to multiple
sessions
Institution and
home-based
intervention
Open label (23
studies)
Comparator
Health education
Counselling
Rehabilitation
Dietary intervention
Physical exercise
Sleep hygiene
education
Stress reduct ion
Strengths
Range of participants (healthy,
elderly, MetS, clinical, pregnant)
Probably effective
Applicable in low resource-settings
Safe and flexible in application
Limitations
Considerable heterogeneity (93-98%)
High publication bias
Diverse settings (13 countries)
Large range of intervention (20-8400 min.)
Less precise (meta-analysis findings)
Figure 3: Summary of findings.
Evidence-Based Complementary and Alternative Medicine 23

Table 6: Comparison of the selected biomarkers among COVID-19, other patients, and healthy participants.
Biomarkers
COVID-19 patients (nonRCTs after disease emergence) Intervention type and dose min (range)
Mild/moderate/noncritically ill
(compared
to control or
average)
Severe/critical/ICU/
dead
Ψ
Diseased Healthy
1.
Lymphocytes
†
↑
γ
(T cells) [58] ↓[58,
σ
59] ∗↑CD4+; YM (840–1200) [33,36] ___
2. IL-6 No change [58]
↓[63] ↑[
σ
58,
σ
63] ↓M(1890) [18], MP (1260) [53], YP (1200–3000) [23,32], YMP (4800)
[40,42] ↓YP [24], YMP (4800) [45]
3. IL-10 ↑[58] ↑[58,63] ___ ↑YMP (3240) [37]
4. CRP ↑[58]
↓[63]
↑[
σ
58,
σ
60,61,62,
σ
63,
δ
64] ↓YMP (3600–4800) [38,40] ↓M (1200) [15]
5. IL-1β↑[63] ↑[65] ↓YP (2160) [27] ↓YMP (960–3240) [26,37]
6. Cortisol ___ ↑[
δ
64] ↓MP (1260) [53], M(1890) [18], YP (1440) [31], YMP (1080–1400)
[25,56] ↑YMP (1080) [37]
7. TNF-α↓[63] ↑[
ϕ
66,
σ
67] ↓YMP (960–4800) [25,40,42,46], MP (1260) [53], YP (1800–3000)
[23,55], YM (980) [35]
↓YMP (960) [26], YP (2160)
[24]
∗Nonsignificant.
†
Lymphocytes (CD4+, CD8+, B cells, and natural killer cells).
γ
Moderately increase.
σ
Higher compared to that of mild/moderate cases.
δ
Compared to COVID-19 negative ICU patients.
ϕ
Compared to survived COVID-19 patients.
Ψ
e disease participants were diabetes, cancer, RA, HF, and so on, but not COVID-19 patients. ↑�Increase; ↓�decrease; -�no association or study not found.
24 Evidence-Based Complementary and Alternative Medicine

e Indian Public Health Standards (IPHS), in its re-
vised set of standards released in 2012, has integrated yoga
as one of the components to be prescribed for AYUSH
facilities [89]. Our findings strengthen the usefulness of
yoga and its fraternity, which is in tandem with the rec-
ommendation of IPHS to implement yoga in primary and
secondary health facilities. A minimum of an hour of in-
tervention following a higher duration of yoga followed by
pranayama and meditation in healthy and asymptomatic
COVID-19 patients can have a positive impact on their
health. As COVID-19 patients become more severe, pra-
nayama should be practised for longer periods, followed by
meditation and yoga, as various asanas in yoga might be
complicated to perform in such patients. Our findings
suggest that the intervention can have a long-term positive
effect even if practised at home, but beyond 8 weeks,
participants might feel unmotivated to continue. erefore,
post-8-week refresher training might be granted as food for
thought.
Despite this, the review has certain limitations. Because
the studies and participants were from various settings and
countries, significant heterogeneity was observed in the
meta-analyses, which may cast doubt on the summary
effects to some extent and should be approached with
caution. Moreover, due to the low number of studies in-
cluded in meta-analyses, it was unwise and so restricted to
carry out quantitative analysis such as Egger’s or Begg’s
tests for publication bias. In the systematic review, we
included seven pilot and feasibility RCTs, which may have
compromised the internal validity of the review. Fur-
thermore, only a single study was respiratory-related (acute
respiratory distress syndrome, ARDS) as a disease out-
come; it should be extrapolated in COVID-19 patients with
solicitude.
5. Conclusion
e systematic review of 44 studies revealed 25 immunity
biomarkers, among healthy, clinical, and pregnant women,
with possible implications for yoga-related interventions in
COVID-19. Total doses of yoga, meditation, or pranayama
ranged between 20 and 8400 minutes. However, a smaller
dose of YMP was found to make significant changes among
pregnant or clinical patients in comparison to healthier ones.
Clearly, the combined action of YMP may be effective in
lowering IL-6, cortisol, and TNF-αlevels in patients, spe-
cifically with 2625, 3900, and 1500-minute interventions,
respectively, spanned over 8–12 weeks. Also, the YMP
package is warranted for pilot RCT among COVID-19 mild
to moderate patients with standard care before reaching
a firm conclusion. Furthermore, meta-analyses of bio-
markers and phytosterols of COVID-19 patients are highly
recommended.
Data Availability
Data extracted from the studies, of systematic reviews and
meta-analysis, are provided by the corresponding author
upon request.
Additional Points
Highlights of the review. What we knew previously: Some
practices of complementary and alternative medicine
(CAM), traditional Chinese medicine (TCM), and herbal
medicine possibly have positive effects on COVID-19 pa-
tients. Biomarkers (around 25) are found to be favourably
changed by yoga, meditation, and pranayama (breathing
exercises) (YMP) among different clinical (other than
COVID-19) and healthy participants. Different biomarkers,
leading to cytokine storm, are affected in COVID-19. What
this review added on: YMP interventions can change the
levels of biomarkers favouring health status of healthy,
clinical, and the pregnant women with nine, fourteen, and
two biomarkers, respectively, altogether 25, which may have
possible implications in COVID-19. Clearly, combined
action of YMP with specific durations might be effective in
reducing IL-6, cortisol, and TNF-αamong the COVID-19
patients.
Disclosure
e funder had no role in designing the study, collecting,
analysing, interpreting the data, preparing the manuscript,
and deciding to publish.
Conflicts of Interest
e authors declare that they have no conflicts of interest.
Authors’ Contributions
Komal Shah, Chiranjivi Adhikari, and Shubham Sharma
contributed equally. All the authors reviewed and approved
the final manuscript for submission.
Acknowledgments
e authors duly acknowledge the Govt. of India, De-
partment of Science and Technology (GOI, DST) for fi-
nancial support. e authors are also thankful to the authors
and coauthors of the included studies. e authors also
acknowledge Dr. Varna VP, MPH student of IIPHG
2020–2022 batch, GJ, India, for her contribution. is work
was supported by the Government of India, Department of
Science and Technology (grant numbers DST/SATYAM/
COVID-19/2020/72).
Supplementary Materials
S1_Search Strategy with Keywords and MeSH. (Supple-
mentary Materials)
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