COVID-19 with and without anosmia or

dysgeusia: A case-control study

The purpose of this study was to identify the clinical presentation and factors associated with 'new
loss/change of smell (anosmia) or taste (dysgeusia) at admission in patients positive by real time
polymerase chain reaction for SARS‐ CoV‐2 infection.
The ongoing pandemic of coronavirus (COVID‐19) caused with the aid of extreme acute
respiratory syndrome coronavirus 2 (SARS‐CoV‐2) continues to evolve and perplex the
clinicians across the globe. Although the exact pathophysiology of these symptoms has not been
identified, various animal models demonstrats high levels of angiotensin converting enzyme
proteins expression by nasal and olfactory guides the cells which are used by the SARS-CoV-2 to
infect the cells. Many of them believed that these symptoms are part of the neurological
manifestation of Covid-19 with evidence suggesting propogation of the virus through the
olfactory pathway.
Despite the recognition of anosmia and dysgeusia as an important clinical symptom and sign of
COVID-19, there is paucity of data describing various clinical features, co-morbidities and
clinical outcome associated with anosmia and dysgeusia in patients with COVID-19.
Cases-All the positively confirmed Covid-19 patients greater than 17 years of age with clinical
presentation of “new loss/ change of taste or smell” at admission during study period were
included in the study group.
Controls- Equal number of age and gender matched Covid-19 patients without clinical
presentation of “new loss/ change of taste or smell” at admission were included in the control or
comparison group.
Those were excluded with pre-existing history of anosmia and/or dysgeusia, nasal or oral illness,
neurodegenerative disorder, on chemotherapy or radiotherapy. Patients who were unable to give
history, transferred out, absconded were also excluded from the study.
A total of 261 COVID-19 patients were screened during the study period. A total of 55 patients
who were eligible were enrolled in the study group. An equal number of age and gender matched
patients who fulfilled the inclusion and exclusion criteria were enrolled in the control group.
The mean (SD) age was 36 (13) years and majority were men (n = 32, 58%) present in both the
groups. Comorbidities was present in 38 per cent (n = 21) of patients in the study group and 29
percent (n = 16) in the comparison group (p = .06). Hypertension and hypothyroidism were the
commonest co-morbidity in the study group (13% each) where as diabetes mellitus was among
the most commonest in the control group (7%). 25% of the study subjects (n = 14) and 18%
percent (n = 10) of the control group had history of smoking. Twenty two percent in the study
group (n = 12) and 11% in the comparison group (n = 06) consumed alcohol. There was no
difference in the baseline characteristics between the groups. History of contact with a COVID-19
patient was found in 29% (n = 16) and 31% (n = 17) in cases and control respectively.
The methodology use was that case records of patients with SARS-CoV-2 contamination admitted
to the COVID wards from May 1st to June 15th, 2020 had been retrieved. Information retrieved
included demographic features, along with age, gender, length of illness, signs, and signs and
symptoms at admission, laboratory parameters, treatment received, and discharge or demise from
health facility had been recorded.
 On assessment of the 55 patients with olfactory and gustatory symptoms, anosmia (96%, n = 53)
become more common than dysgeusia (75%, n = 41). Presence of each ansomia and dysgeusia
become identified in 71% of the patients (n = 31). Fever was found in 75% (n = 41) and 51% (n = 
28) in the “cases” and “controls,” respectively (p = .01). Rhinitis was found higher in controls (n 
= 20, 36%) as than cases (n = 09, 16%; p = .017).. The median (IQR) period of anosmia and
dysgeusia become 7 (4, 10) days and 7 (5, 2) days in the “cases” and “controls,” respectively.

Table 1 Clinical, laboratory features, treatment details, and outcomes

The mean (SD) of serum bilirubin was found 0.9 mg/dl (0.25) in study group and 0.6 mg/dl (0.2)
in thee comparison group (p < .0001). Serum creatinine level was found higher in the “cases” with
median (IQR) value of 0.9 mg/dl (0.8, 1.2) as compared to 0.8 mg/dl (0.6, 0.9) (p = .0001). A
statistically significant remarkable difference was also seen in the platelet count (p = .0009). The
median (IQR) platelet count was lower in the “cases” (1.5 lakh/mm 3 [1, 2.2]) as contrasting to
“controls” (1.94 lakh/mm3 [1.53, 2.56]).
Data were entered into Microsoft Excel 2013 and analyzed using Stata 1. Missing values of
clinical and laboratory variables were thought to be normal for the purpose of statistical analysis.
Continuous variables are presented as mean (SD), or median (interquartille range [IQR]) as
appropriate. Categorical variables are presented as absolute numbers (%). Continuous variables
were differntiated using either independent Student's t test or Wilcoxon rank-sum test (based on
the distribution of the data). Categorical data were compared using χ2 test or Fischer's exact test as
appropriate. For assessing the factors associated with anosmia or dysgeusia , univariate analysis
followed by multivariate analysis of key variables including age, gender, presence of underlying
co-morbidities, key clinical features and laboratory parameters was performed. In the multivariate
model by logistic regression, only those variables that were clinically relevant and did not result
in multicollinearity were included as the independent variables.
On comparing cases with controls, in univariate analysis, fever which was higher in cases,
rhinitis which was lower in cases, thrombocytopenia, high levels of creatinine and bilirubin was
all higher in cases were significantly associated with anosmia or dysgeusia.

Table 2 Univariate analysis of factorsassociated with anosmia or dysgeusia

On multivariate analysis of factors associated with anosmia or dysgeusia found rhinitis

(OR, 0.28; 95% CI, 0.09–0.83); p = .02) thrombocytopenia (OR, 0.99; 95% CI, 0.99–0.99; p 
= .01) and high levels of creatinine (OR, 7.6; 95% CI, 1.5–37.6; p = .01) to be factors which are
associated with anosmia or dysgeusia.

Table 3 Multivariate analysis of factors associated with anosmia or dysgeusia

 The reported prevalence of olfactory dysfunction in multiples of case series have been ranged
from 5.14% to as high as 98.33% whereas the reported prevalence of gustatory dysfunction had
ranged from 5.61% to 92.65%.
The study conducted highlights the presence of these two dysfunctionsin patients with COVID ‐19
in almost 21% of patients. Till now the studies have made attempts to study certain factors
correlated with olfactory dysfunctions, this study was probably the first attempt to identify various
demographic and clinical factors connected with olfactory and gustatory dysfunction.
Thrombocytopenia and high levels of serum creatinine levels were associated importantly with
presence of anosmia or dysgeusia and renal derangements have been associated with these
dysfunctions, its sudden onset in COVID‐19 patients is still unanswered. Another feature
identified in this study is significantly lower incidence of rhinitis in patients with anosmia or
dysgeusia. Rhinitis was also found to have significant link on multivariate analysis as well. While
anosmia or dysgeusia have been found to be higher in patients with rhinitis due to nasal
congestion and obstruction, while certain other studies have suggested affinity of certain viruses
for structures of the olfactory sensory epithelium as a causative mechanism.Its lower incidence in
COVID‐19 patients with rhinitis in this study also suggests towards a complex pathophysiology
which is yet to be elucidated.
The exact pathophysiology is not clear till now, with various hypothesis and animal models
suggesting transneural penetration througholfactory bulb. It has also been illustrated that ACE ‐2
receptor used by SARS‐CoV‐2 to bind and penetrate into the cell, is also expressed on the
epithelial cells of the oral cavity. Another feasible mechanism involves cellular receptor
neuropilin‐1, which is expressed in the respiratory and olfactory epithelium.It has been illustrated
to significantly potentiate SARS‐CoV‐2infectivity.
Although Prospective study with large sample size using validatedtools is required to identify the
true incidence and various factors associated with these clinical presentations.