Received: 1 May 2021 Revised: 26 July 2021 Accepted: 26 July 2021
DOI: 10.1002/JPER.21-0272
ORIGINAL ARTICLE
A case-control study on the association between
periodontitis and coronavirus disease (COVID-19)
Pradeep S. Anand1 Pranavi Jadhav1 Kavitha P. Kamath2
Salavadi Revanth Kumar1 Sandapola Vijayalaxmi1
1Department of Dentistry, ESIC Medical
College, Sanathnagar, Hyderabad,
Telangana, India
2 Saveetha Dental College and Hospitals,
Saveetha Institute of Medical and
Technical Sciences University, Chennai,
Tamil Nadu, India
3Department of Dentistry, Oral Health
Institute, Hamad Medical Corporation,
Doha, Qatar
4College of Dental Medicine, Qatar
University, Doha, Qatar
Correspondence
Pradeep S. Anand, Department of Den-
tistry, ESIC Medical College, Sanathnagar,
Hyderabad, Telangana State, India.
Email: deepusanand@yahoo.co.in
Sukumaran Anil, Chair, Hospital Research
Committe, Department of Dentistry, Oral
Health Institute, Hamad Medical Corpora-
tion, Doha P.O. Box 3050, Qatar.
Email: drsanil@gmail.com
584 © 2021 American Academy of Periodontology
Sukumaran Anil3,4
Abstract
Background: Coronavirus disease (COVID-19) and periodontitis share common
characteristics, such as an exaggerated inflammatory response. As periodontal
diseases were shown to be associated with respiratory diseases, such as pneumo-
nia, it is quite possible that a relationship may exist between periodontitis and
COVID-19. Hence, the aim of the present study was to determine whether peri-
odontitis and poor oral hygiene are associated with COVID-19.
Methods: A case-control study was conducted. Patients who had positive real-
time reverse transcription polymerase chain reaction results for severe acute res-
piratory syndrome coronavirus 2 (SARS-CoV-2) infection were included in the
case group (n = 79), and patients with negative results were included in the con-
trol group (n = 71). The periodontal examination involved recording the plaque
scores, calculus scores, tooth mobility, gingival bleeding, probing depth, reces-
sion, and clinical attachment level (CAL).
Results: Logistic regression analysis showed significant associations of mean
plaque scores ≥ 1 (odds ratio (OR), 7.01; 95% confidence interval (CI), 1.83 to
26.94), gingivitis (OR, 17.65; 95% CI, 5.95 to 52.37), mean CAL ≥ 2 mm (OR, 8.46;
95% CI, 3.47 to 20.63), and severe periodontitis (OR, 11.75; 95% CI, 3.89 to 35.49)
with COVID-19; these findings were more prevalent in the case group.
Conclusion: Based on the above mentioned observations, it can be concluded
that there is an association between periodontitis severity and COVID-19. Gin-
gival bleeding and dental plaque accumulation are also more frequent among
COVID-19 patients. Hence, it is essential to maintain periodontal health and good
oral hygiene as an important measure for COVID-19 prevention and manage-
ment.
KEYWORDS
clinical attachment level, coronavirus, COVID-19, oral health, oral hygiene, periodontitis,
SARS-CoV-2
wileyonlinelibrary.com/journal/jper J Periodontol. 2022;93:584–590.
ANAND et al.
1 INTRODUCTION
Coronavirus disease (COVID-19) is a severe acute respira-
tory infection caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), which emerged in Wuhan,
Hubei, China, with subsequent global spread.1,2 Although
the disease results in mild symptoms in most cases, it pro-
gresses to severe pneumonia and multi-organ failure, lead-
ing to mortality, in some cases, depending on patient age
and the presence of comorbidities.3–5 Although risk fac-
tors, such as age, sex, and comorbidities, which increase
the risk of complications and mortality, have been high-
lighted, there is still a large proportion of patients with no
identified risk factors who suffer from severe COVID-19-
related adverse effects and complications.6
Periodontitis is a chronic, multifactorial, inflammatory
disease, associated with plaque biofilms and characterized
by the progressive destruction of the tooth-supporting
structures.7 Periodontitis increases the systemic inflam-
matory burden, as the inflamed periodontal tissues release
host-derived proinflammatory cytokines and tissue
destruction mediators into the circulatory system, which
can activate an acute-phase response in the liver and
can amplify systemic inflammation.8 The inflammatory
reaction in periodontitis results in increased levels of
inflammatory mediators, such as tumor necrosis factor-α,
interferon-γ, prostaglandin E2, interleukin (IL)-1β, IL-4,
IL-6, IL-10, ferritin, and C-reactive protein.9,10 Periodon-
topathic bacteria are involved in the pathogenesis of
respiratory diseases, such as pneumonia and chronic
obstructive pulmonary disease (COPD), as well as in that
of systemic diseases, including diabetes and cardiovas-
cular disease.11 Periodontopathic bacteria were detected
in the bronchoalveolar lavage fluid of patients with
COVID-19.12,13 There are similarities between the cytokine
storm in severe COVID-19 infections and the cytokine
expression profile in periodontitis, suggesting a possible
link between periodontitis and COVID-19 and its associ-
ated complications.14,15 The increased expression level of
angiotensin-converting enzyme 2 (ACE2) in the oral cav-
ity, promoted by periodontopathic bacteria, may increase
the SARS-CoV-2 infection rate.16 An elevated IL-6 level is
associated with excess inflammation, which contributes
to increased mortality in patients with COVID-19.17
Periodontal diseases can increase the inflammatory
response in patients, which might exacerbate the systemic
symptoms and clinical course of COVID-19. The poten-
tial association of periodontitis and COVID-19 severity can
be explained by the alteration in the expression of cellu-
lar receptors enhancing the virulence of SARS-CoV-2 and
by periodontal pockets acting as viral reservoirs.16,18 Very
few studies have been conducted to identify the associa-
tion between periodontitis and COVID-19. A study based
585
on radiographic assessment concluded that periodontitis
is significantly associated with higher risks of COVID-
19 complications and higher blood marker levels.19 Cur-
rently, no clinical data are available regarding the associ-
ation between COVID-19 and periodontitis. Therefore, the
present study was undertaken with the aim of determining
whether periodontitis and poor oral hygiene are associated
with COVID-19.
2 MATERIALS AND METHODS
The present study was conducted as a case-control study
at the Department of Dentistry, ESIC Medical College,
Hyderabad, India, during the period from August 2020
to February 2021. Patients visiting the dedicated COVID
Outpatient Department (OPD) of the institution who
had undergone real-time reverse transcription polymerase
chain reaction (rRT-PCR) for the diagnosis of COVID-19
were recruited for the study. The patient’s contact details
were collected from the Medical Records Section of the
Institution and were communicated through telephone by
the author PJ regarding their willingness for participation
in the study. Only the author PJ had knowledge regarding
the results of the reverse transcription polymerase chain
reaction (rRT-PCR) for COVID-19 diagnosis of the individ-
ual patients. Periodontal examination was performed by
the author PSA who was blind to the results of rRT-PCR
test. Subsequently, prior to data analysis, the patients for
whom complete set of data were available were categorized
as either case or control depending on the results of rRT-
PCR test by the author PJ. Patients who had positive rRT-
PCR results were included in the case group, and patients
with negative results were included in the control group.
Individuals aged 18 and above who had at least 20 teeth in
the oral cavity were included in the study.
Patients in the control group were scheduled for an oral
examination after the negative rRT-PCR, and patients who
were positive for the virus (case group) were scheduled
for an oral examination after the completion of treatment
when they were determined to be disease free through
a negative rRT-PCR. The following study variables were
recorded: age, sex, presence, or absence of symptoms on
visiting the COVID OPD, presence or absence of any sys-
temic diseases, tobacco consumption status (smoking and
smokeless; categorized as current user, former user, or
never user), and oral hygiene habits (types of oral hygiene
aids and frequency of daily oral hygiene practice). This was
followed by a complete periodontal examination during
which the dentition status was recorded, followed by the
recording of plaque scores, calculus scores, tooth mobil-
ity, gingival bleeding, probing depth (PD), recession (REC),
and clinical attachment level (CAL). All the permanent
586
teeth apart from the third molars were examined for the
purpose of the study.
As the dentition status, the numbers of present teeth,
carious teeth, and missing teeth were recorded. A tooth
was recorded as missing either if it was absent or if it was
indicated for extraction because of periodontal disease,
dental caries, or wasting diseases, such as abrasion and
attrition. A tooth was considered to be indicated for extrac-
tion because of periodontal disease either if it was non-
functional or if it exhibited considerable mobility. A tooth
was considered to be indicated for extraction because of
dental caries or tooth wear if it was deemed non-restorable.
Plaque and calculus scores were recorded in all the teeth
per the plaque index criteria of Silness and Loe20 and the
calculus component of the simplified oral hygiene index
of Greene and Vermillion,21 respectively. Gingival bleeding
was recorded as either present or absent22 in all the teeth,
and the percentage of bleeding sites was computed. Fur-
ther, PD, REC, and CAL were recorded at six sites per tooth
in all the teeth using a periodontal probe* . The mean val-
ues of PD, REC, and CAL, and mean percentage of inter-
proximal sites with various thresholds for periodontal dis-
ease (PD ≥ 4 mm, PD ≥ 5 mm, CAL ≥ 3 mm, CAL ≥ 4 mm,
CAL ≥ 6 mm) were compared between the two groups.
All the periodontal examinations were performed by a
single trained examiner (PSA) who was blind to the catego-
rization of the study participants. For calibration purposes,
examiner reliability was determined by re-examination of
a randomly selected quadrant among 10 patients who were
not part of the study. The patients involved in the calibra-
tion exercise were probed twice during the same visit, and
intra-class correlation coefficients were determined. The
intra-class correlation coefficients for PD and CAL were
0.92 and 0.90, respectively.
The study protocol was approved by the Human Ethics
Committee of the institution, and the study was conducted
in accordance with the Helsinki Declaration as revised
in 2013. Written informed consent in a language suitable
for the participants was obtained from all the prospective
study participants.
2.1 Statistical analysis
A sample size calculation with CAL as the reference vari-
able revealed that a sample size of 64 patients in each arm
would yield a power of 80% for a standardized difference
of 0.5 at a significance level of 0.05.23 All data were entered
onto a personal computer and were analyzed using soft-
ware for statistical analysis† . All categorical variables were
* UNC-15 probe, Hu-Friedy Manufacturing Co., Chicago, IL.
† SPSS software version 16, IBM Corporation, Armonk, NY.
ANAND et al.
analyzed using the chi-square test, and continuous vari-
ables were expressed as mean and standard deviation and
were analyzed using Student’s t-test. Mean percentages
of inter-proximal sites with various thresholds for peri-
odontal disease were computed and analyzed using Stu-
dent’s t-test after arcsine transformation. The proportions
of individuals with (a) a mean plaque score ≥ 1, (b) gin-
givitis (≥ 20% of sites with gingival bleeding), (c) mean
CAL ≥ 2 mm, and (d) severe periodontitis24 were com-
pared between the two groups using the chi-square test.
The associations of COVID-19 with poor oral hygiene, gin-
gival bleeding, and periodontal disease were determined
using a logistic regression model adjusted for variables that
were found to be significant in the univariate analysis.
3 RESULTS
Of a total of 196 patients who were provided with an expla-
nation regarding the purpose of the study, 167 agreed to par-
ticipate in the study. Nine patients were excluded as they
had fewer than 20 teeth, whereas eight participants opted
out because of discomfort during the periodontal examina-
tion. Among the 150 participants who had complete sets of
data, 79 were categorized as cases and 71 as controls. The
age, sex distribution, medical history, oral hygiene prac-
tices, and tobacco-related habits between the two groups
are presented in Table 1. Although the age of the partic-
ipants with COVID-19 was significantly higher than that
of the controls, the two groups did not differ significantly
in terms of sex distribution, medical history, and tobacco-
related habits. None of the study participants reported a
history of cardiovascular or renal diseases. A significantly
larger number of participants were in the habit of practic-
ing oral hygiene twice daily in the control group compared
to in the case group.
Table 2 presents the dental and periodontal variables
between the two groups. Although there were no signifi-
cant differences between the two groups in terms of miss-
ing teeth, carious teeth, and calculus scores, the partici-
pants with COVID-19 had significantly higher mean values
of plaque scores, number of mobile teeth, gingival bleeding
scores, PD, REC, and CAL compared to the controls. The
mean percentages of inter-proximal sites with PD ≥ 4 mm,
PD ≥ 5 mm, CAL ≥ 3 mm, CAL ≥ 4 mm, and CAL ≥ 6 mm
were also significantly higher in the case group than in the
control group.
The proportions of individuals with a mean plaque score
≥ 1, gingivitis, mean CAL ≥ 2 mm, and severe periodonti-
tis were significantly larger in the case group than in the
control group (Table 3). The results of the logistic regres-
sion analysis are shown in Table 4. This analysis showed
significant associations of COVID-19 with mean plaque
ANAND et al. 587

TA B L E 1 Age, sex distribution, tobacco-related habits, and systemic diseases in the case and control groups
Case group Control group
Variable (n = 79) (n = 71) P
Age (mean ± SD) 43.34 ± 10.16 38.24 ± 10.72 0.003b
Sex (No./Percentage) Males 50 (63.3) 35 (49.3) 0.084a
Females 29 (36.7) 36 (50.7)
Smoking status (No./Percentage) Current smoker 6 (7.6) 7 (9.9) 0.484a
Former smoker 7 (8.9) 3 (4.2)
Never smoker 66 (83.5) 61 (85.9)
Smokeless tobacco use (No./Percentage) Current user 2 (2.5) 3 (4.2) 0.822a
Former user 7 (8.9) 7 (9.9)
Never user 70 (88.6) 61 (85.9)
Diabetes (No./Percentage) Yes 8 (10.1) 8 (11.3) 0.821a
No 71 (89.9) 63 (88.7)
Hypertension (No./Percentage) Yes 16 (20.3) 8 (11.3) 0.134a
No 63 (79.7) 63 (88.7)
Neoplasia (No./Percentage) Yes 2 (2.5) 0 0.177a
No 77 (97.5) 71
Oral hygiene practice (No./Percentage) Once daily 68 (86.1) 40 (56.3) < 0.001a
Twice daily 11 (13.9) 31 (43.7)
Abbreviation: SD, standard deviation.
a
Student’s t-test.
b
Chi-square test.

TA B L E 2 Periodontal status of the participants in the case and control groups

Variable (Mean ± SD) Case group (n = 79) Control group (n = 71) P*
Missing teeth 0.81 ± 1.14 0.69 ± 1.13 0.520
Carious teeth 1.76 ± 1.59 1.79 ± 1.60 0.911
Plaque scores 0.77 ± 0.50 0.29 ± 0.30 < 0.001
Calculus scores 1.26 ± 0.80 1.01 ± 5.07 0.643
Mobile teeth 2.95 ± 2.26 1.35 ± 1.81 < 0.001
Gingival bleeding 0.62 ± 0.24 0.29 ± 0.20 < 0.001
PD 2.09 ± 0.48 1.48 ± 0.36 < 0.001
REC 0.20 ± 0.25 0.05 ± 0.10 < 0.001
CAL 2.28 ± 0.56 1.51 ± 0.42 < 0.001
Proportion of interproximal sites with various thresholds of disease
PD ≥ 4 mm 13.20 ± 10.67 1.79 ± 4.07 < 0.001
PD ≥ 5 mm 5.89 ± 6.86 0.59 ± 1.72 < 0.001
CAL ≥ 3 mm 39.71 ± 21.85 11.26 ± 15.07 < 0.001
CAL ≥ 4 mm 16.48 ± 12.18 2.43 ± 5.21 < 0.001
CAL ≥ 6 mm 2.52 ± 33.18 0.27 ± 0.83 < 0.001
Abbreviations: CAL, clinical attachment level; PD, probing depth; REC, recession; SD, standard deviation.
*Student’s t-test.

scores ≥ 1 (odds ratio (OR), 7.01; 95% confidence interval 4 DISCUSSION

(CI), 1.83 to 26.94), gingivitis (OR, 17.65; 95% CI, 5.95 to
52.37), mean CAL ≥ 2 mm (OR, 8.46; 95% CI, 3.47 to 20.63),
and severe periodontitis (OR, 11.75; 95% CI, 3.89 to 35.49)
after adjusting for age and the frequency of oral hygiene
practices.
The findings of our study revealed that periodontitis is
significantly associated with COVID-19. Periodontitis is a
multifactorial disease leading to the destruction of the sup-
porting structures of the teeth, and its association with
588
TA B L E 3 Proportion of study participants with various thresholds of disease in the case and control groups
Variable (No./Percentage) Case group (n = 79)
Plaque score ≥ 1 19 (24.1)
Gingivitis 74 (93.7)
Mean CAL ≥ 2 mm 51 (64.6)
Severe periodontitis 39 (49.4)
Abbreviation: CAL, clinical attachment level.
*Chi-square test.
T A B L E 4 Logistic regression after adjusting for age and
frequency of oral hygiene practices
Variable OR P 95% CI
Plaque score ≥ 1 7.01 0.005 1.83-26.94
Gingivitis 17.65 < 0.001 5.95-52.37
Mean CAL ≥ 2 mm 8.46 < 0.001 3.47-20.63
Severe periodontitis 11.75 < 0.001 3.89-35.49
Abbreviations: CAL, clinical attachment level; CI, confidence interval; OR,
odds ratio.
systemic conditions has been widely studied.11,25 COVID-
19 has been shown to be more severe among patients
with comorbidities, such as diabetes, cardiovascular dis-
eases, and renal diseases.5 Oral dysbiosis resulting from
increased dental plaque in periodontitis may provide an
environment for the oral carriage of respiratory pathogens,
thereby causing COVID-19-related complications. In a sys-
tematic review, Scannapieco et al.25 concluded that there
was a significant association between poor oral hygiene
and nosocomial pneumonia. Periodontitis has been linked
with both COPD and pneumonia either by the direct aspi-
ration of oral pathogens into the lungs or by the alter-
ation of mucous surfaces in the respiratory tract, promot-
ing adhesion, and the invasion of pathogens.26–28 This may
also aid in explaining the association between periodontal
disease and COVID-19 observed in the present study.
Periodontopathic bacteria induce the release of proin-
flammatory cytokines in the lower respiratory tract, and
these cytokines may play a role in COVID-19.16 It has also
been suggested that periodontitis and periodontopathic
bacteria can increase oral colonization by SARS-CoV-2,
and thus, the oral cavity may serve as a reservoir for the
virus.16,29,30 The presence of viruses in periodontal lesions
has been previously demonstrated,31 and it has been shown
that periodontal pockets and dental plaque can harbor
pathogens, such as Helicobacter Pylori, and may thus serve
as reservoirs for infection.32,33 It has also been shown that
periodontitis,34 gingival bleeding,35 the presence of dental
plaque,36 and the presence of respiratory pathogens in the
oral cavity34,37 can increase the risk of the development of
pneumonia among hospitalized patients.38 In the present
ANAND et al.
Control group (n = 71) P*
3 (4.2) 0.001
36 (50.7) < 0.001
15 (21.1) < 0.001
7 (9.9) < 0.001
study also, dental plaque and gingival bleeding were found
to be associated with COVID-19.
Studies showing the association between periodontitis
and COVID-19 are limited. A study by Marouf et al.19
reported that patients with severe periodontitis are more
likely to develop complications associated with COVID-
19 than patients with milder forms of periodontitis. They
diagnosed periodontal disease from archived patient radio-
graphs. To the best of our knowledge, the present study
is the first to clinically compare the periodontal status of
individuals with COVID-19. A clinical periodontal exam-
ination requires a close interaction with the patient, and
therefore, the periodontal examination for all the partic-
ipants was scheduled after ensuring a negative rRT-PCR
result in order to minimize the risk of the transmission of
the virus to the investigators.
Smoking is considered a risk factor for both COVID-
19 39,40 and periodontitis.41,42 However, in the present
study, there was no significant difference between the
groups in terms of tobacco-related habits. This could also
be related to the small number of smokers. The pres-
ence of systemic diseases that were considered risk fac-
tors for COVID-19 or of periodontal disease was also not
significantly different between the groups. Gingival bleed-
ing and plaque scores were found to be significantly high
among the COVID-19 patients. An earlier study found a
higher risk of mortality in individuals with COVID-19 who
had bleeding gums and concluded that the mortality risk
was higher in patients with periodontal disease.43 Larvin
et al.43 concluded that it is essential to assess the oral
health status of patients with COVID-19 in order to prevent
adverse outcomes. The study group was recruited after the
recovery from COVID-19; the stress associated with the dis-
ease and its treatment might have had an effect on the oral
hygiene practice as well as on the periodontal condition
of these patients.44 Stress elevates salivary cortisol levels,
which in turn reduces immune responses and upregulates
various inflammatory markers, leading to gingival inflam-
mation and periodontal tissue destruction.45
This is a pioneer study that was undertaken to evaluate
all possible periodontal parameters and oral hygiene levels
by directly examining patients with COVID-19. There are
some limitations associated with this case-control study.
ANAND et al.
Because of the serious transmission risk, the patients could
not be examined during the course of the active phase
of the disease. Nevertheless, as periodontal destruction
is a slow process,46 it may be assumed that the partici-
pants in the case group were suffering from periodontitis
prior to developing the SARS-CoV-2 infection. As patients
were not examined during the course of the disease, only
patients who were willing to revisit the institution for
the purpose of the study were available for data collec-
tion. During this process, valuable data from patients with
severe forms of the infection may have been lost. However,
as this was an initial study, the data that were generated
may be used for directing future research with improved
methodology and with a larger sample size in order to bet-
ter understand the association between periodontitis and
SARS-CoV-2 infection.
5 CONCLUSION
Within the limitations of this case-control study, it can be
concluded that there is an association between periodonti-
tis and COVID-19. The increased prevalence and severity of
periodontitis and associated poor oral hygiene might con-
tribute to the aggravation of SARS-CoV-2 infection. Gin-
gival bleeding and dental plaque accumulation were also
found to be more frequent among the COVID-19 patients.
Hence, it is essential to maintain periodontal health and
good oral hygiene as an important measure for the preven-
tion and management of COVID-19 and its complications.
Further clinical trials assessing the periodontal status in
patients with COVID-19 are needed to more firmly estab-
lish the links between SARS-CoV-2 infection and peri-
odontal disease.
AC K N OW L E D G M E N T S
None
F U N D I N G I N F O R M AT I O N
None
E T H I C A L A P P R O VA L
The study was approved by the Institutional Ethics Com-
mittee of the ESIC Medical College & Hospital, Sanathna-
gar, Hyderabad, with the reference number F0188/05/2020.
CONFLICTS OF INTEREST
The authors declare no conflicts of interest.
AU T H O R CO N T R I B U T I O N S
Pradeep S. Anand, Kavitha P. Kamath, and Sukumaran
Anil contributed to the design of the study, interpreta-
tion of results, and drafting of the manuscript and revis-
589
ing it critically. Pradeep S. Anand did the clinical examina-
tion. Pradeep S. Anand, Pranavi Jadhav, Salavadi Revanth
Kumar, and Sandapola Vijayalaxmi contributed to data col-
lection. Pradeep S. Anand and Kavitha P. Kamath con-
tributed to data analysis. All authors have approved the
final manuscript for submission.
ORCID
Pradeep S. Anand https://orcid.org/0000-0002-0006-
2928
Sukumaran Anil https://orcid.org/0000-0002-6440-
8780
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How to cite this article: Anand PS, Jadhav P,
Kamath KP, Kumar SR, Vijayalaxmi S, Anil S. A
case-control study on the association between
periodontitis and coronavirus disease (COVID-19). J
Periodontol. 2022;93:584–590.
https://doi.org/10.1002/JPER.21-0272