Results
Sixty-six adult patients with history of confirmed COVID-19 and
olfactory dysfunction persisted more than 90 days after SARS-CoV-2
negative testing were enrolled in this prospective study. The age of the
patients ranged from 18 to 55 years. There were 38 females and 28 males.
The complete characteristics of the patients were described in Table 1.
Fisher’s exact probability test was used to assess the sample size.
Non-significant difference in the frequency of smoking between the
sodium chloride group and the DTPA group (5/28 vs. 4/29; p =
1.00). Differences in the frequency of comorbidities were also assessed
and the results were not significant between the sodium chloride group
and the DTPA group, as shown in Table 1.
Intra-nasal administration of DTPA had the ability to form a
calcium-DTPA complex and decreased the concentrations of calcium cations
in the mucus of the participants. DTPA had the selective ability to
sequester calcium cations at an optimized pH of 8 and form stable
complex products. The schematic reaction pathway for the reaction of
DTPA with calcium cations was shown in Figure 2.
Olfactory performance was evaluated using the Sniffin’ Sticks test
before and after treatment with topical sodium chloride or DTPA. T, D, I
and TDI were measured in each participant before treatment and 1 month
later. Mean T, D, I and TDI values before and after topical sodium
chloride and DTPA treatment for patients were shown in Table 2. The TDI
values were compared with the reported reference values. The mean values
of the TDI scores were calculated and presented in Table 2. Regarding to
the olfactory assessed score of DTPA group, 27 patients (84.38%) showed
an improved olfactory function and 5 patients (15.63%) did not show
improvement. This may be due to topical nasal sprays generally have
quite variable compliance and delivery efficiency, especially to the
olfactory cleft, so one would expect some subjects with little to no
response even to a highly efficacious drug. The results showed that the
mean ± SD of the TDI value before and receiving sodium chloride was
10.87±1.24 and 10.93±1.09, respectively, Table 2. While, the mean ± SD
of the TDI value before and after receiving DTPA was 11.75±1.22 and
20.39±3.25, respectively, Table 2. The results indicated non-significant
improvement in patients receiving sodium chloride. On the other hand,
there was a significant improvement in patients receiving DTPA with
clinical change from functional anosmia to hyposmia.
The concentration of calcium cations was quantitatively determined in
the nasal mucus of all patients. A selective electrode made of carbon
paste was developed for the electrochemical determination of calcium
cations. First, the values of electromotive force were measured in a
calcium concentration range of 100 to 0.001 mM to obtain a calibration
diagram relating the values of electromotive force to the negative
logarithmic value of calcium cation concentration. The designed sensor
exhibited a near Nernstian slope of 28.25 mV/decade with a detection
limit of 0.0001 mM in a linear range of 100 to 0.001 mM calcium cation
concentration. The concentrations of calcium cations in nasal secretions
were successfully determined using the developed electrode. The mean ±
SD of calcium cation concentration (mM) before and after receiving
sodium chloride was 38.39±3.04 and 37.06±2.64, respectively, Table 2.
Also, the mean ± SD of calcium concentration (mM) before and after
receiving DTPA was 37.54±2.06 and 24.39±4.52, respectively, Table 2. The
results showed a significant decrease in calcium concentration in the
patients received DTPA.
Statistical analysis, paired t test, was used to compare the
means and standard deviations of the TDI values for the sodium chloride
or DTPA groups before and after treatment. Comparison of the results for
the DTPA group revealed a significant difference with a relevant
clinical improvement in olfactory performance, t (32) = 16.60,p < 0 .00001. Similarly, comparison of the results for
the sodium chloride group revealed non-significant difference without
clinical improvement in olfactory performance, t (32) = 0.42,p =0.338. Also, an unpaired t test was used to compare
mean TDI values after receiving DTPA with TDI values after receiving
sodium chloride. The significant difference was indicated, t (39)
= 15.76, p < 0 .00001.