Introduction
Since the 2019 global dissemination of severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2), scientific advancements have enabled researchers to develop different
types of vaccines and other forms of prevention and treatment against coronavirus
disease 2019 (COVID-19).[1] The oral cavity is related to the development of COVID-19 as it allows the virus
direct access into the body.[2]
[3]
[4] According to the literature, clinical evidence has demonstrated that antiviral oral
solutions can inactivate SARS-CoV-2 and reduce clinical symptoms and severity of COVID-19.[2]
[5]
[6]
[7]
[8] Based on previous in vitro studies employing antiviral phthalocyanine derivative
(APD) solutions,[6]
[9] this case series evaluated the action of an APD oral spray for viral load reduction
in COVID-19 hospitalized patients.
Material and Methods
This prospective, single center, and consecutive case series study was conducted at
a public hospital in Brazil, in accordance with the principles of the declaration
of Helsinki and the ethical standards of human experimentation, with the approval
of the human research ethics committee (CAAE 34070620.6.0000.5417). From November
1, 2020, to January 14, 2021, COVID-19 patients diagnosed by real-time reverse transcriptase-polymerase
chain reaction (PCR) and admitted to the hospital were invited to participate. To
be enrolled in the study, participants had to be 18 years or older and present with
SARS for more than a week prior to admission. Participants signed an informed consent
form after agreeing to the risks and objectives of the study. The exclusion criteria
included patients who had medical contraindications to oral spray, an inability to
gargle/spit, and a baseline negative salivary PCR for the presence of SARS-CoV-2.
Patients were instructed to use ∼ 1.5 mL of the APD solution (3 pumps for each area:
throat, tongue, right cheek, and left cheek), switch between gargling/rinsing for
30 seconds, and conduct this regimen 5 times per day: upon awakening, after breakfast,
after lunch, after dinner, and before bedtime. This adjunctive protocol was performed
for 1 week along with standard COVID-19 treatment. Saliva was collected to evaluate
the presence of SARS-CoV-2 (PCR) before initiation of the oral spray protocol (baseline),
and again after 2 and 4 days of use.
Results
A sample of 11 patients from 14 selected SARS-CoV-2-positive patients was enrolled
in this study. According to [Table 1], 10 patients (91%) were male, and the median age was 58 years (range: 38–77 years).
The median onset of symptoms was 5 days before admission, with a 5-day median length
of hospital stay. Four patients (36.4%) had no comorbidities, and 1 patient (9%) was
admitted to the intensive care unit and subsequently passed. All patients received
standard care for COVID-19, including antibiotic, antiinflammatory, anticoagulation,
and oxygen support therapy. Regarding salivary SARS-CoV-2 detection, 6 patients (54.5%)
tested positive, and 5 patients (45.5%) tested negative after 2 days. After 4 days
of APD oral spray use, 3 patients (27.3%) tested positive, and 8 (72.7%) tested negative.
No side effects of using an APD oral spray have been reported.
Table 1
Case series: patients data and clinical characteristics
|
Patient no.
|
Age
|
Sex
|
Outcome
|
ICU need
|
Symptoms onset
|
Hospitalization time
|
PCR baseline
|
PCR D2
|
PCR D4
|
Underlying diseases
|
|
1
|
38
|
M
|
discharge
|
no
|
5
|
4
|
positive
|
negative
|
discharge
|
obesity
|
|
2
|
58
|
M
|
discharge
|
no
|
5
|
3
|
positive
|
negative
|
discharge
|
no comorbities
|
|
3
|
61
|
M
|
discharge
|
no
|
5
|
3
|
positive
|
negative
|
discharge
|
no comorbities
|
|
4
|
42
|
M
|
discharge
|
no
|
6
|
3
|
positive
|
negative
|
discharge
|
obesity, arterial hypertension
|
|
5
|
60
|
M
|
discharge
|
no
|
6
|
8
|
positive
|
negative
|
negative
|
no comorbities
|
|
6
|
48
|
W
|
discharge
|
no
|
5
|
5
|
positive
|
positive
|
negative
|
obesity, arterial hypertension, asthma, anemia
|
|
7
|
67
|
M
|
discharge
|
no
|
5
|
26
|
positive
|
positive
|
negative
|
arterial hypertension, smoking, glaucoma
|
|
8
|
55
|
M
|
discharge
|
no
|
3
|
5
|
positive
|
positive
|
negative
|
coronary heart disease
|
|
9
|
50
|
M
|
discharge
|
no
|
3
|
5
|
positive
|
positive
|
positive
|
no comorbities
|
|
10
|
65
|
M
|
discharge
|
no
|
3
|
12
|
positive
|
positive
|
positive
|
arterial hypertension, coronary heart disease
|
|
11
|
77
|
M
|
death
|
yes
|
5
|
22
|
positive
|
positive
|
positive
|
serious coronary heart disease, arterial hypertension, chronic renal failure, diabetes,
former smoker, arterial hypertension, alcoholism
|
Abbreviations: ICU, intensive care unit; M, male; PCR, polymerase chain reaction;
W, woman.
Discussion
In the present case series, the use of an APD oral spray protocol reduced the salivary
SARS-CoV-2 viral load in COVID-19 hospitalized patients. According to the literature,[2]
[3]
[4] the oral environment is directly involved in the pathophysiology of COVID-19.
Severe acute respiratory syndrome coronavirus 2 can replicate in the oral mucosa and
be transmitted by saliva. Oral antiviral solutions can reduce the viral load in saliva
and decrease the spread of the virus. Our previous study[6] demonstrated clinical improvement and reduction in hospitalization time (4-day median
length of hospital stay) when an APD oral solution was used as an adjuvant in a gargle/rinse
mouthwash protocol in COVID-19 patients. In the present study, 91% of patients were
discharged from the hospital with a 5-day median length of hospital stay. Thus, we
hypothesized that the APD oral spray protocol plays a role in faster recovery without
any side effects.
Considering the limitations of the present case series, the lack of a comparative
placebo control and sample size may have influenced our interpretation of the results.
However, the use of APD showed that 45.5% and 72.7% of the samples were PCR-negative
for SARS-CoV2 after 2 and 4 days, respectively. Similar results were reported in a
chlorhexidine oropharyngeal rinse-treated group (62.1%) and a combined chlorhexidine
oropharyngeal rinse and posterior oropharyngeal spray-treated group (86%) after 4
days.[10]
Simple and low-cost measures, such as the use of antiviral substances in mouthwashes
and mouth sprays, may accelerate COVID-19 recovery, thus reducing the progression
of severe, life-threatening cases of the disease.
Conclusion
Considering the limitations of this case series, the results suggest that the use
of an APD oral spray may reduce the salivary SARS-Cov-2 viral load. Further randomized
controlled clinical trials with larger sample sizes using this protocol are necessary.
