Effectiveness of Kabasura Kudineer tablets in the management of asymptomatic and mild cases of COVID-19: A pilot double-blinded, randomized controlled trial

Abstract

Introduction

COVID-19 was declared a pandemic in 2020. It has had a devastating effect on human life and the global economy. To date, there is no proven therapy for COVID-19, even though rigorous research is ongoing to test multiple compounds across all systems of medicine. A need was felt to systematically explore the Indian system of medicine to assess its efficacy against COVID-19. The objective of the present study was to examine the effect of Kabasura Kudineer as a standalone therapy on the following: time required to achieve symptom relief & resolution, virological clearance, and levels of IL6, CRP and IgG, and compare it to the standard therapy available for treatment of COVID-19.

Methodology

A double-blinded randomized controlled trial was conducted in 110 participants. 55 participants were enrolled in the Kabasura Kudineer arm and 55 in the control (standard therapy + Kabasura Kudineer placebo) arm. Study participants were randomly allocated into the two study arms. They were assessed for symptoms at baseline, and on Day 5 and Day 10. RT PCR, CRP, IL6 and IgG levels were measured at baseline, Day 5 and Day 10. On day 28, participants were interviewed telephonically for symptom assessment alone.

Statistical analysis

A per-protocol approach was used. Significant difference between two groups was assessed at baseline, day 5 and day 10 using the Chi-square and Mann Whitney test.

Result

A total of 110 patients participated in study. Four patients in the Kabasura Kudineer arm and 9 in the Standard therapy arm were lost to follow-up. Baseline characteristics for both the groups were matched at baseline. 83.9% and 93.9% patients were relieved of all symptoms by the 10th day in Kabasura and standard therapy groups respectively. Decrease in CRP level was more pronounced in the Kabasura group compared to standard therapy viz. 3 mg/l and 1.26 mg/l. No significant difference was found in IgG level and IL6 levels in both the study groups. However, it was noticed that among the unvaccinated group, the surge in IgG levels was much higher in Kabasura Kudineer group than the standard therapy group.

Conclusion

Kabasura Kudineer as a standalone therapy was as effective and safe as the standard therapy among patients with asymptomatic to mild COVID-19.

1. Introduction

COVID-19 is caused by a novel coronavirus called SARS-CoV-2. The program for monitoring emerging diseases notified the world about pneumonia of unknown cause in Wuhan, China on 31st Dec 2019 [1] Over the next two months, WHO declared COVID-19 a pandemic [2]. Till July 2021, more than four million deaths were reported worldwide due to COVID, of which approximately 400,000 deaths were reported in India [3]. Actual deaths may be a hundred times more than the reported figure [4]. Researchers are working at a phenomenal speed to find possible ways to treat and prevent COVID-19, from investigating the possibility of repurposing existing drugs to searching for novel therapies against the virus. Current approaches to COVID-19 therapies generally fall into two categories: antivirals that prevent the virus from multiplying, or 2) immune modulators, which help the immune system fight the virus or stop it from overreacting dangerously. Some potential therapies act via a different pathway or multiple mechanisms [5].

Most COVID-19 cases demonstrate a mild clinical course, whereas other patients may rapidly progress to severe disease within 7–14 days [6]. Older age and comorbidities are the most significant risk factors associated with worse outcomes [7]. To date, there is no specific therapy against COVID-19, and the failure of many repurposed drugs adds to this difficulty [8,9]. Trials are being conducted across the world, not only exploring modern medicine but also traditional systems of medicine. The use of Chinese herbs in COVID-19 as per the proposed systematic review has also been stated [10]. There is a need to systematically explore the benefits of Indian traditional systems of medicine for broader acceptance across the globe. Siddha medicine is one ancient Indian system of medicine, more popularly practised in Tamil Nadu. According to Siddha system of medicine, the symptoms and signs of COVID-19 are identified as the aggravation of Iyam and which are later associated with other Uyir thathukkal Vali and Azhal and expressed as Thontham (Mukkutram) leads to Sanni [11]. Kabasura Kudineer [KSK), a Siddha formulation, had been used in respiratory disorders [12]. Classical KSK from Siddha literature comprises 15 herbs enriched with Phyto-components such as Cardiofoliolide, Cucurbitacin B, Apigenin and Pyrethrin that bind to the SARS COV-2 virus and block the viral replication [13]. [Table 1) Research done on Zinziber Officinale (ginger) demonstrated its antibacterial, antioxidant activity [14] and antiviral properties [15]. Tinospora cardifolia demonstrated hepato-protective and immunomodulatory properties in CCI₄-intoxicated mature albino rats [16]. Lin et al. identified chebulagic acid (CHLA) and punicalagin (PUG), hydrolyzable tannins isolated from Terminalia chebula Retz., (T. chebula) was effective in abrogating infection by human cytomegalovirus (HCMV), hepatitis C virus (HCV), dengue virus (DENV), measles virus (MV), and respiratory syncytial virus (RSV) [17].

Table 1.

Constituent of Kabasura Kudineer.

Sr No	Ingredient	Parts	Proportion (mg)
1	Zinziber Officinale	Rhizome	33.33
2	Piper longum	Fruit	33.33
3	Syzygium aromaticum	Bark, bud	33.33
4	Tragia involucrate	Root	33.33
5	Anacyclus Pyrethrum	Root	33.33
6	Hygrophilla auriculata	Root	33.33
7	Terminalia chebula	Fruit	33.33
8	Adathoda vasica	Leaf	33.33
9	Coleus ambonicus	Leaf	33.33
10	Saussurea lappa	Root	33.33
11	Tinospora cardifolia	Stem	33.33
12	Clerodendron serratum	Root	33.33
13	Andrographis paniculata	Whole plant	33.33
14	Cissampelos pareira	Root	33.33
15	Cyperus rotandus	Rhizome	33.33

A pharmacological review of the active ingredients of KSK highlights its activity against respiratory syndromes, as well as its antimicrobial, anti-inflammatory, antipyretic, immuno-stimulant and antiemetic properties [18,19]. Another study on the antiviral activity of KSK against SARS-COV-2 in Vero E6 cell lines demonstrated significant inhibition of SARS-COV-2 replication in the cells [20]. Sathiyarajeswaran P demonstrated 99% inhibition of SARS CoV inhibition 48 h post-infection in line with Remedesivir [21]. In vitro also demonstrate the immunomodulatory and thrombolytic potential of Kabasura Kudineer [22]. Another in-vitro study demonstrated 81.5% antiviral efficacy of the KSK at 0.5 mg/ml concentration in Vero E6 cell lines [23]. In-vivo evaluation of the drug in Syrian golden hamsters reported 65% viral load reduction in the hamster lungs among Kabasura Kudineer group [24]. In-silico computational screening studies have suggested KSK’s potential to inhibit spike protein in SARS-COV-2 [24,25]. Siddha medicine played a major in controlling the mortality rate of chikungunya and dengue in Tamil Nadu by administration of Nilavembu Kudineer in 2015 [26]. Siddha medicine has good potential to combat covid 19 and its variants. To date, Vitamin C, Zinc supplementation (CZ) is prescribed for asymptomatic covid 19 cases. The role of CZ is not yet clear. Therefore, we propose to investigate the role of KSK in the treatment of asymptomatic to mild COVID-19 infection as a standalone therapy.

Objectives

• To assess the effect of Kabasura Kudineer and compare it to standard treatment care protocol for asymptomatic and mild confirmed COVID-19 cases, specifically measuring the following: Time needed for symptomatic improvement and symptom relief for individual symptoms and those included in the Pandemic Respiratory Infection Emergency System Triage (PRIEST) score [27], variation in immunity markers (IL6, CRP, and IgG level and virological clearance by 10th day.

• To compare the change in IgG, IL6, and CRP levels from baseline to tenth day and RT-PCR status (on 5th and 10th day) in both arms stratified by vaccination status.

2. Materials and methods

2.1. Study design and trial site

The present study was a double-blind randomized controlled trial in two groups. The data was collected from May to June 2021. Adults with confirmed asymptomatic or mild cases of COVID-19 [28] reporting to the screening OPD (Out Patient Department) of AIIMS Rishikesh, Uttarakhand, India were invited to participate in the study and screened for eligibility.

2.2. Inclusion criteria

• •18–55 years of age; male or female
• •Asymptomatic or mild confirmed cases of COVID-19 infection as per the GOI definition
• •Reported to OPD within three days of onset of symptoms if symptomatic and
• •Those willing to take AYUSH medicine

2.3. Exclusion criteria

• •Not willing to give consent or participate in the clinical trial
• •Patients with following comorbidities that are uncontrolled on regular medical treatment e.g.: hypertension, diabetes, thyroid disorders, heart diseases, liver or renal diseases, Patients on immunosuppressive therapy
• •Pregnant women or lactating mothers
• •Patients who had undergone major surgery in the last six months or hospitalized for more than three days for any condition.

2.4. Sample size

Being a pilot study, the sample size per treatment arm, as per the thumb rule, was 50 [29]. Accounting for some attrition during follow-up, 55 participants were enrolled in each study arm (Fig. 1).

Fig. 1.

CONSORT flow diagram.

2.5. Consent

Eligible participants were informed about the purpose of the clinical trial and written informed consent was obtained. Participants were made aware that they could withdraw anytime from the trial.

2.6. Randomization and data collection procedure

The study participants were allocated into two arms i.e. KSK arm and control arm (Standard therapy + KSK placebo), with the help of a computer-generated randomization code by an independent person (clerk)Codeswere handed to investigators (MK and MP) who prescribed the treatment. The participants, data collectors, and laboratory technician were blinded to study groups. Each participant was clinically examined and baseline laboratory investigations like CBC, CRP, IL6 and IgG were carried out. Trained data collector filled structured questionnaire that consisted of age, sex, vaccination status, comorbidity (if any), PRIEST score (Respiratory Rate, Oxygen saturation, heart rate, Blood pressure, Temperature, alertness, Inspired oxygen, Performance status), checklist of covid related symptoms, CRP, IL6, IgG and Hb levels at baseline. Follow-up forms on day 5 and day 10 consisted of a list of persistent or new symptoms on specific day, CRP, IL6 and IgG levels. Follow-up form on day 28 consisted of persistent or new symptoms on a specific day. Data collectors were not aware of the allocation of study groups.

2.7. Treatment groups

Participants allocated to KSK arm were given the Sri Sri Tattva Kabasura Kudineer tablet (KSK) and allopathy drug placebo. KSK tablet is a classical Siddha formulation that is licensed under Dept. of AYUSH, Karnataka, India (Table 1). The medicine and placebo (KSK and allopathy drugs) were purchased from Sri Sri Tattva, a Good Manufacturing Practice (GMP) certified company, to ensure quality. Placebo was made of 100% starch resembling exactly like an active drug. Allopathy active drugs, Generic – Paracetamol (650 mg), Levocetirizine 5 mg film-coated Tablets, Ascorbic Acid Tablets 100 mg (Vitamin-C Chewable Tablet 100 mg), Zinc Sulphate 20 mg was purchased from Amrit (Affordable Medicines and Reliable Implants for Treatment) pharmacy.

Each participant was given one bottle (either KSK tablet or placebo) and one brown-coloured opaque envelope (either allopathy drugs or placebo). This was done to blind both treating investigators as well as participants.

In KSK arm, participants were advised to take two tablets of bottle, thrice a day after food for 15 days. Along with this allopathy placebo in a brown envelope with three tablets resembling Vitamin C for 15 days, levocetirizine for 5 days and zinc tablet for 14 days.

The control group was provided, standard therapy paracetamol, levocetirizine, vitamin C, zinc tablets and KSK placebo.

Allopathic medicines were administered as per the Government of India standard protocol [28], i.e. Tab vitamin C oral twice a day for 15 days; Paracetamol 650 mg (if needed) not more than three tabs a day; Levocetirizine 10 mg od for five days; zinc tablet for 14 days. In addition, a KSK placebo was also administered as two tablets three times daily after food for 15 days.

Participants with comorbidity (if any) were advised to continue their routine antidiabetic, antihypertensive or thyroid medications.

2.8. Follow up

Participants were followed on Day 5 and Day 10 ± 2 in OPD irrespective of symptoms. Follow-up on the 28th day was done telephonically for any residual symptoms.

2.8.1. Laboratory investigations

Nasopharyngeal sample for RT-PCR was taken on Day 5 and Day 10. RT-PCR was done in an ICMR-accredited laboratory. A blood sample for CRP, IL6 and IgG was drawn on Day 10. IL6 estimation was done by Siemens, ADVIA Centaur XP assay measured in pg/ml, CRP by Diasys CRP U-hs measured in mg/l and IgG using iFlash-SARS-CoV-2 IgG assay measured in AU/ml.

PRIEST score was calculated on day 1 and day 5.

2.8.2. Advice to participants

Compliance with the treatment was assessed telephonically and were counselled for drug compliance. Those who were non-compliant on more than three occasions were noted as non-compliant and excluded from data analysis. Patients were also educated on COVID care, the importance of isolation, and monitoring the symptoms of their family members. Participants were advised to visit the hospital or call on the emergency contact number in case of aggravation of existing symptoms or development of new symptoms. They were treated as per standard emergency medicine protocol.

2.8.3. Deviation from protocol

Major deviation– Initially open-label single-blind study was planned, however to make the study more robust, Ayurveda and allopathy placebo were introduced in the planning of recruitment phase making it a double-blind study.

Minor deviation – Due to safety concerns, moderated COVID cases were not recruited. The DASS questionnaire on 28 days follow-up was not included, considering the feasibility. PCM 650 mg, not more than 3 tablets a day was used instead of PCM 500 mg  as it was convenient to take a lesser number of tablets.

2.9. Statistical analysis

Data was entered in MS Excel and exported to IBM SPSS version 25 (IBM corporation, Armonk, New York) for further analysis. Baseline characteristics of both groups were reported in terms of proportion/mean (SD). The difference between two study arms at baseline was assessed using chi-square and independent t-test. Analysis was conducted using the per-protocol approach. The differences between data variables at baseline and follow-up visits were assessed by chi-square (proportion) or Mann Whitney U test (continuous variable mentioned as Median). A a non-parametric test was used as the distribution of data was non-normal and less sample size. A p-value less than 0.05 was considered to be significant.

2.10. Ethical approval and trail registration

The present study was approved by IEC, AIIMS Rishikesh and registered with CTRI No CTRI/2021/04/032952.

3. Result

We screened 124 participants of which eligible 110 were recruited, with 55 in each study arm. Four in the Kabasura (KSK) group and six in the standard therapy group dropped out before the day 5 follow-up and were excluded from data analysis.

3.1. Demographic, clinical characteristics and vaccination status

Table 2 shows no significant difference in age, gender, vaccination status, comorbidity and Haemoglobin between study groups. The duration between the onset of symptoms, a positive COVID test and enrollment in KSK or standard therapy group was noted. 56.9% in the KSK group and 48.9% in the standard therapy group reported a history of full vaccination.

Tables 2.

Demographic and vaccination status of study participants.

	Kabasura (n = 51)	Standard care(n = 49)	P value
Age mean (SD)	30.6 (9.8)	34.14 (11.2)	0.09
Gender (m/f)	33/18	35/14	0.5
Full Vaccination n (%)	29 (56.9%)	24 (48.9%)	0.5
Comorbidity ∗
None n (%)	45 (88.2%)	39 (79.6%)	0.45
DM n (%)	4 (7.8%)	8 (16.3%)
Hypertension n (%)	2 (3.9%)	1 (2.6%)
Asthma n (%)	1 (1.96%)	1 (2.6%)
Thyroid n (%)	1 (1.96%)	2 (4.1%)
Hb in mg/dl mean (SD)	11.77 (1.98)	12.08 (1.8)	0.41
Day of enrolment- from day of onset of symptom -Median (range) ®	3 (1–3)	3 (1–3)	0.32
Day of enrolment- from day of positive report - Median (range)	2 (0–3)	3 (0–3)	0.26

∗ Multiple morbidity.

Dropouts excluding.

® excluding the asymptomatic.

3.2. Symptoms at the time of registration, day 5 and day 10

At the time of enrollment, both groups were comparable in the percentage of participants exhibiting the recorded symptoms, except shortness of breath, which was reported by more participants in the standard therapy group than the KSK group (30.6% and 11.7% respectively). At baseline, 76.5% of participants in the KSK group reported one or more symptoms compared to 89.8% in the standard therapy group, however, no significant difference was found between the two study groups (Table 3). In the KSK group, 23.5% (n = 12) were asymptomatic at baseline (Table 3); 43.1% (n = 23) reported no symptoms at day 5, and 83.3% (n = 43) were relieved of all symptoms on day 10 (Table 4). Among the standard therapy group, 10% (n = 5) were asymptomatic at the time of enrolment (Table 2) which increased to 36.7% (n = 18) on day 5 and 93.9% (n = 46) on day 10 (Table 4). On the 28th day follow up none of the participants had any residual symptoms.

Table 3.

Symptom at time of onset of COVID 19 among study participants.

Symptom	KSK (n = 51) n (%)	Standard care(n = 49) n (%)	P value
Any Symptom	39 (76.5%)	44 (89.8%)	0.177
Fever	30 (58.8%)	27 (55.1%)	0.7
Sore throat	35 (68.6%)	36 (73.4%)	0.59
Runny nose	25 (49%)	26 (53%)	0.68
Cough	22 (43.1%)	28 (57.1%)	0.16
Shortness of breath	6 (11.8%)	15 (30.6%)	0.02∗
Other
Myalgia	23 (43.09%)	14 (28.5%)	0.15
Headache	2 (3.9%)	0	Not calculated
Diarhoea	3 (5.8%)	1 (2.04%)	Not calculated
Weakness	5 (9.8%)	2 (8.1%)	Not calculated
No smell	4 (7.8%)	9 (18.4%)	0.14

∗ significant.

Table 4.

Symptoms on day 5 and 10 among study participants.

Symptom	KSK (n = 51)	Standard care(n = 49)	P value
Day 5
None	23 (45.1%)	18 (36.7%)	0.39
Cough	15 (29.4%)	12 (24.4%)	0.58
Myalgia	6 (11.7%)	10 (20.4%)	0.24
Sore throat	4 (7.8%)	5 (10.2%)	0.74
Fever	2 (3.9%)	4 (8.1%)	0.43
Weakness	5 (9.8%)	9 (18.3%)	0.22
Day 10
None	43 (84.3%)	46 (93.9%)	0.23
Weakness	5 (9.8%)	3 (6.1%)	0.71
Cough	1 (1.96%)	0	Not calculated
Fever	1 (1.96%)	0	Not calculated
Chest pain	1 (1.96%)	0	Not calculated

3.3. Lab investigation at the time of registration, day 5 and day 10

Among the KSK group, 15 (29.4%) participants were negative on day 5 compared to 14 (28.5%) in the standard therapy group. No difference was found in the proportion of RT-PCR negativity rate among both groups. There was no difference in CRP, IL6 and IgG1 levels at the baseline between the study groups. The median value of CRP on day 10 was higher in the standard therapy group (3.1) than in the KSK group (2.1). After ten days, the median value of IL6 was 3.1 and 2.2 in the KSK and standard therapy groups, respectively. The median value of IgG after ten days was 144.5 in the KSK group and 98 in the standard therapy group. The median value of Priest score was two at baseline in both study groups which remained the same on Day 5. (Table 5)

Table 5.

Laboratory investigation and Priest score at baseline, day 5 and day 10 among study participants.

Investigations/Priest score	KSK (n = 51)	Standard therapy (n = 49)	pvalue
RTPCR Negative day 5	15 (29.4%)	14 (28.5%)	0.92
RTPCR negative Day 10	26 (50.1%)	27 (55.1%)	0.68
CRP (mg/l) baseline Median (IQR)	4.9 (7.24)	7.65 (9.5)	0.14
CRP (mg/l) Day 10 Median (IQR)	2.1 (3)	3.1 (2.47)	0.047 ∗
IL6 (pg/ml) baseline Median (IQR)	12.1 (36.5)	7.1 (14.9)	0.069
IL6 (pg/ml) Day 10 Median (IQR)	3.1 (4.1)	2.2 (3)	0.605
IgG (AU/ml)baseline Median (IQR)	1.9 (17.54)	4.2 (25.5)	0.45
IgG (AU/ml) Day 10 Median (IQR)	144.5 (242.2)	98 (214.65)	0.21
Priest score (baseline) Median (IQR)	2 (2)	2 (3)	0.12
Priest score (Day 5) Median (IQR)	2 (3)	2 (1)	0.66

∗ significant.

3.4. Effect on laboratory parameters in a different group based on vaccination status

Table 6 shows that the CRP level in KSK group decreased by 3 mg/l and 1.26 mg/l in fully vaccinated and unvaccinated groups, respectively, which was almost twice the decrease in standard therapy group. The decrease in IL6 was larger in the KSK group when compared to the standard therapy group (−7.9 vs −5.7 in completely vaccinated; −6.15 vs −3.8 in unvaccinated). The increase in IgG level in fully-vaccinated participants was similar in both study groups. Among the unvaccinated group, the increase in IgG levels was 140.2 in the KSK group and 46.2 in standard therapy group.

Table 6.

Effectiveness of KSK and standard therapy according to vaccination status.

Laboratory investigation	Complete vaccination		No vaccination
	Kabasura Median (IQR)/n (%)	Standard therapy Median (IQR)/n (%)	Kabasura Median (IQR)/n (%)	Standard therapy Median (IQR)/n (%)
CRP Baseline	5.5 (50.3)	8.8 (92.4)	3.2 (56.4)	5.7 (43.2)
CRP Day 10	2.4 (17.5)	3.4 (53.2)	1.6 (21.6)	2.9 (10.4)
Difference	−3.08 (42.1)	−6.1 (46.9)	−1.26 (36.1)	−3.1 (48.6)
IL6 Baseline	12.2 (156.4)	7.5 (125.8)	10.6 (78.3)	5 (161.5)
IL6 Day 10	3.4 (27.2)	2.8 (19.6)	2.15 (26)	1.7 (30.7)
Difference	−7.9 (146.8)	−5.7 (126.6)	−6.15 (77.3)	−3.8 (157.5)
IgG Baseline	1.59 (117.2)	8.75 (240.3)	2.85 (306.6)	1.4 (54.1)
IgG Day 10	143 (376)	58.6 (344.5)	182.9 (409)	158 (376.8)
Difference	159 (460)	106 (418)	140.2 (316.2)	46.2 (353)
RTPCR negative Day 5	9/29 (31%)	7/24 (29.2%)	6/22 (27.3%)	7/25 (28%)
RTPCR negative Day 10	15/29 (51.7%)	14/24 (58.3%)	11/22 (50%)	13/25 (52%)

3.5. Side effects and their management

Five Participants in the KSK group noticed side effects such as bloating, tachycardia, nausea and anxiety. After a thorough assessment, tachycardia was not related to KSK, and KSK was continued after one day. For gastric related problems, participants were counselled to take the drug with food and milk. No other adverse event was reported.

4. Discussion

Data showed comparable patient outcomes for the KSK and the standard therapy study group, with respect to time taken to resolve symptoms, time for RT PCR conversion to negative, CRP levels, IL6 levels, and increase in IgG level after 10th day of enrolment. This is the only clinical double-blinded, randomized study to the best of our knowledge that studies the effect of KSK as a standalone therapy in asymptomatic to mild cases of COVID-19 patients. In addition to symptom relief, which may be subjective, serum inflammatory markers (CRP, IL6), immunological markers (IgG) were also measured and RTPCR test was conducted twice within ten days of enrollment to compare the patient outcomes in the two study arms, thus gathering objective and subjective evidence of the effectiveness of therapy. With no preliminary study on the effect of Kabasura on COVID-19 patients, we were interested in understanding the effect of KSK on study participants, so we used a per-protocol approach.

KSK, in the recent past, is effective in the treatment of influenza [30], dengue and chikungunya infection [31]. In the present study, by Ddy 5, 45% of participants in the KSK group experienced symptom relief compared to 37% in the standard therapy group. This may be due to twice the number of participants in the standard therapy group experiencing shortness of breath on the day of enrollment. However, by day 10, more than 80% of participants reported symptom relief in both groups. All the cases were asymptomatic or mild, and PRIEST scores did not vary from baseline to fifth day of enrollment.

By day 10, 50% of the participants turned negative on RT-PCR in both groups. In an earlier retrospective study, conducted by Meenakumari et al. to determine the impact of integrated treatment (Kabasura and Standard therapy), participants who tested RT PCR positive and were treated with KSK irrespective of the date of onset of symptoms or date of enrollment were assessed. The study reported that 74% of asymptomatic and 65% of mild symptomatic patients turned negative for COVID-19 in RT-PCR within 4–7 days [32]. In contrast, we included patients within 0–3 days of onset of their symptoms.

A significantly lower CRP level was noted on day 10 in the KSK group compared to the standard therapy group, although the two groups were comparable at baseline. IL6 and IgG levels were comparable in both groups on Day 10.

Saravan J et al. also demonstrated that Kabasura Kudineer has antibacterial, anti-inflammatory and antipyretic activity [12]. Apart from this, many studies have confirmed the immunomodulatory and antioxidant activity of phytochemical constituents of KSK [33,34]. Molecular docking studies confirm phytochemical constituents in Kabasura Kudineer have a strong binding affinity and interaction with SARs COV 2 spike protein [25,35].

It was remarkable to note that the increase in IgG level within the unvaccinated KSK group was 140 pg/ml compared to 46 pg/ml among the standard therapy unvaccinated group, however, this difference was not statistically significant, possibly due to the small sample size. A decrease in the CRP level was higher in the standard therapy group while a higher IL6 decrease was reported in KSK group, although neither differences were statistically significant. Decrease in CRP and IL6 was more pronounced in the fully vaccinated compared to the unvaccinated participants. The vaccinated and unvaccinated participants were comparable in age and comorbidities. Thus, we hypothesize that the larger drop in CRP and IL6 in the vaccinated participants could be due to the synergistic effect of vaccination and KSK which can be investigated further. We also hypothesize that the greater increase in the IgG levels in the unvaccinated group may be due to the immunomodulatory effect of KSK. Gastritis reported in both arms (two in KSK and one in stand therapy) may be due to the effect of Covid −19 itself or medications [36] This needs to be explored further in a larger randomized clinical trial. KSK was found to be safe with minor side effects.

4.1. Limitation of study

Due to ethical issues, only asymptomatic cases or mild cases were recruited. Ayurveda practitioner (R.R) was involved in patient care only on the emergence of side effects while no Siddha practitioner was involved. Fundamental concept of drug administration in Siddha system was not followed before drug administration, else the gastric-related side effects could have been avoided in KSK group.

5. Conclusion

Kabasura Kudineer is equally effective as the standard therapy in achieving symptom relief and resolution, decreasing inflammatory parameters such as CRP and IL6 and increasing immunological response (IgG) in asymptomatic and mild COVID-19 cases as a standalone therapy. Virological clearance was seen in approx. 50% of participants in both arms. There was more than two times increase in IgG level in KSK arm compared to standard therapy among unvaccinated participants. Also, twice a decrease in CRP level was noted in KSK arm compared to standard therapy irrespective of vaccination status. It can be administered safely as no adverse events are noted. We believe that being a single drug it provides ease of administration compared to the multiple drugs in the standard therapy regimen.

Source of funding

This project was funded by Ved Vignan Maha Vidya Peeth, on behalf of its research wing Sri Sri Institute of Advanced Research (VVMVP-SSIAR) There is no role of the sponsor(s) in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Author credit statement

MK - Conceptualization, Methodology, Investigation, Writing-Original draft, Fund acquisition, Project administration, Supervision.

MP - Methodology, Investigation, Writing-Original draft, Project administration.

BO and B – Investigation, Editing.

SS and YB– Project administration, statistical analysis.

PD - monitored participants closely for any side effect or adverse event and do causality assessment, submit report to institutional IEC, sponsorer and Pharmacovigilance committee.

VS –Supervision, Resources and Proof reading.

Declaration of competing interest

None.