Effect of a Combination of Treatment of Reginmune Capsule and Immunofree Tablets in the Treatment of Mild to Moderate COVID-19 Patients
Effect of a Combination of Treatment of Reginmune Capsule and Immunofree Tablets in the Treatment of Mild to Moderate COVID-19 Patients
While novel drug discovery and vaccine studies are time taking process, re-purposing old
 drugs against the COVID-2019 epidemic can help identify treatments, with known pre-clinical,
 pharmacokinetic, pharmacodynamic, and toxicity profiles, which can rapidly enter Phase 3 or 4
 or can be used directly in clinical settings. Immunofree has many of the herbs which have
 been evaluated by other trials published for Covid-19 treatment.

 The Immunofree tablet of the test product is an Ayurvedic proprietary medicine and is a
 combination of polyherbal mixture. The components of this formulation are known for their
 anti-viral and immunomodulatory effects. Also, Reginmune, owing to its immunomodulatory
 effect might help in easing the symptoms and decrease the viral load.
The symptoms of COVID-19 are mainly for respiratory disorders and similar to severe acute
 respiratory symptoms. The common signs of infection observed in COVID-19 patients include
 respiratory symptoms, sneezing, fever, cough, shortness of breath and other breathing
 difficulties. In case of severely infected patients, infection can cause pneumonia, severe
 acute respiratory syndrome (SARS), kidney failure and even death in many cases. There are
 many people who had high viral load but do not develop COVID-19 symptoms like coughing or
 sneezing. Such asymptomatic people serve as hidden carriers of virus and may further
 contribute in enhanced transmission of virus to other people. In absence of any emergency
 medicine or complete therapy for COVID-19; the prevention of spread of SARS-CoV2 virus and
 regulation of infection is the prime step in controlling this epidemic disease, in which the
 test products can be of immense value.

 The test product, Capsule Reginmune is a combination of some phytochemicals, amino acids,
 vitamins and minerals and a bio-polymer in cellular matrix. The components and their
 pharmacological activities are as follow:

 Echinacea is one of the more popular herbal supplements suggested for boosting immunity. Some
 respiratory and antiviral research has also been done on Echinacea. Echinacea is not
 mentioned by the Indian and Chinese Governments however in their guidelines for boosting
 immunity.

 Cats Claw (Uncaria Tomentosa)has shown potent anti-viral and immunomodulatory activity in a
 recent study. The results demonstrated an in vitro inhibitory activity by both extract and
 alkaloidal fraction, reducing DENV-Ag+ cell rates in treated monocytes. A multiple microbead
 immunoassay was applied for cytokine determination (TNF-alpha, IFN-alpha, IL-6 and IL-10) in
 infected monocyte culture supernatants. The alkaloidal fraction induced a strong
 immunomodulation: TNF-alpha and IFN-alpha levels were significantly decreased and there was a
 tendency towards IL-10 modulation. The researchers conclude that the alkaloidal fraction was
 the most effective in reducing monocyte infection rates and cytokine levels. The antiviral
 and immunomodulating in vitro effects from U. tomentosa pentacyclic oxindole alkaloids
 displayed novel properties regarding therapeutic procedures in Dengue Fever and might be
 further investigated as a promising candidate for clinical application.

 Vitamin C: Well accepted to increase immunity and an effective antiviral. However, not many
 people realize the vast difference in food derived vitamin C and ascorbic acid which is a
 dead synthesized molecule used to clean pools. Therefore, it is strongly recommended that one
 should only take food derived Vitamin C.

 Zinc: There is some evidence suggesting Zinc can shorten duration of the common cold and one
 study done in 2010 showing that Zinc had an effect on the older versions of Corona virus. An
 abundance of evidence has accumulated over the past 50 years to demonstrate the antiviral
 activity of zinc against a variety of viruses, and via numerous mechanisms. Clinical trial
 data support the value of zinc in reducing the duration and severity of symptoms of the
 common cold when administered within 24 hours of the onset of common cold symptoms. However,
 one must be careful as not all zinc is equally bioavailable and more than 150 mg of Zinc can
 lead to toxicity.

 Copper: A study suggested that copper deficiency may lead to reduction in the number of T
 cell lymphocytes and impaired host defense against infectious organisms.

 L- Lysine: Studies shows L-Lysine supplements may help to boost immunity against certain
 viral infections.

 Aloe Vera: Numerous studies for influenza and herpes has shown that Aloe polysaccharides
 (APS) extracted from Aloe vera leaves have evident effects on the therapy of virus infection.

 Lglutamine: Glutamine is the most abundant and versatile amino acid in the body. Glutamine is
 currently part of clinical nutritional supplementation protocols and/or recommended for
 immune suppressed individuals.

 L Arginine: Studies have shown that arginine suppressed the growth of HSV-1, concentration
 dependently and it can boost the activity of T-cells.

 L Isoleucine : It has shown to be effective against rotavirus infection. Magnesium Gluconate:
 It has shown some immunomodulatory effects which was measured by Natural Killer cells
 activities and phagocytosis.

 Sodium Hyaluronate: Hyaluronic acid (HA), one of the main components of extra-cellular matrix
 and most notably of the fundamental substance of conjunctive tissues, is not an inert
 structure. Conversely, it displays important biological properties and plays a significant
 role in crucial physiological processes especially when cellular plasticity is involved such
 as inflammation, immune reactions, angiogenesis and would healing. It is also strongly
 involved in neoplastic cells migration and therefore in metastatic spreading of malignant
 tumors.

 The Immunofree tablet of the test product is an Ayurvedic proprietary medicine and is a
 combination of polyherbal mixture. The components of this formulation are known for their
 anti-viral and immunomodulatory effects.

 Kalmegh also known as Andrographis paniculata has been used in Ayurveda and other herbal
 traditions for boosting up the immune system. It is believed that the herb has potential
 antiviral and immunomodulatory properties owing to it containing andrographolide. The
 following studies are done on it which suggest potential benefit.

 Bhumyamalaki: It is also known as Phyllanthus niruri. It seems to exhibit anti-viral
 anti-inflammatory activity. The following studies for SARS suggest that this may be of
 benefit.

 Glycyrrhiza glabra is also known as licorice, mulethi, etc. It has been used in TCM, Ayurveda
 and other herbal traditions for lung health and stomach health. It is very alkalizing. It is
 believed that it has strong antiviral properties and hence this herb is in both Chinese and
 Indian recommendations. This herb contains glycyrrhizin which showed remarkable qualities in
 SARS research.

 Some reports suggest that strong extracts of this herb are central to the Chinese strategy in
 Wuhan. The following studies are done on it, which suggest potential benefit.

 Tulsi is also known as Ocimum sanctum has been used traditionally in India. It is considered
 a sacred herb in Ayurveda.Following studies are done on it which suggest potential benefit.

 Giloy is also known as Tinospora cordifolia has been used traditionally in Ayurveda as it
 helps in boosting gut immunity.

 Pushkarmool: It is also known as Inula racemosa and it may be an effective herb for flu
 symptoms. It also supports the normal functioning of the respiratory system.

 The drug Pushkarmool has been used in the indigenous system of medicine for a long time.
 Pushkarmool has been reported in the texts of Ayurveda as possessing Tikta, Katu and Ushna
 Virya and beneficial for the diseases of heart, throat. It is known to act as an expectorant.
 It is also used in Ayurveda as an expectorant and resolvent in indurations. Its
 pharmacological activities include cardioprotective activity, antiallergic activity,
 antimutagenic and antiapoptotic effects, anti-inflammatory & analgesic effect, adrenergic
 beta blocking activity.

 Alpinia galanga is also known as rasna, sugandhimool, etc. It has been used inTCM, Ayurveda
 and other herbal traditions for lung health and the potential to reduce the inflammatory
 process. It is believed that the herb has antiviral activity in human respiratory syncytial
 viruses. The following studies are done on it which suggest potential benefit.

 Draksha: It is also known as Vitis Vinifera. Studies suggeset that the herb possesses a broad
 spectrum of pharmacological and therapeutic effects such as antioxidative, anti-inflammatory,
 and antimicrobial activities.

 Haldi is also known as Turmeric, Curcuma longa, etc. Alkaloids derived from turmeric have
 shown potentially strong inhibitory effects on the neuraminidases from two influenza viral
 strains. The following studies are done on it which suggest potential benefit.

 Haritaki is also known as Terminalia chebula has been used in TCM, Ayurveda, and other herbal
 traditions for boosting immunity. The herb is also possibly useful for easing the symptoms
 associated with respiratory illnesses. The following studies are done on it which suggest
 potential benefit.

 Aloe Vera: Studies show that extracts of Aloe Vera may help to inhibit the activity of the
 virus and support the functioning of the lungs.

 Shilajit: It is also known as Asphaltum: It has been used traditionally by the Indian
 Ayurvedic and Siddha systems of traditional medicine to enhance the quality of life. Studies
 show that the minerals in Shilajit may also possesses immune boosting activities.

 Pippali: It is also known as Piper longum. It has been used traditionally in the Ayurvedic
 system for lung health. Studies suggest that it may help to improve lung function.

 Shaival: It is also known as Asthaxantin. Studies show that it may possess antimicrobial and
 anti-inflammatory properties.

 Damanaka - Also known as Artemisia, has potential anti-malarial properties.
Inclusion Criteria:

 -  Gender: Either male or non-pregnant, non-lactating female aged > 18-70

 -  Patients with RT-PCR confirmed diagnosis of COVID-19

 -  Patients with mild to moderate COVID-19 infection having either one of the following
 criteria: oPaO2/FiO2:200-300 OR Respiratory rate ? 24/min and SaO2/SpO2 > 90% on room
 air

 -  Subjects willing to give written informed consent

 -  Subjects able to take the drug orally and comply with the study protocol

 -  Women of child bearing potential must have a negative urine pregnancy test prior to
 study entry

 Exclusion Criteria:

 -  Patients with persistent vomiting

 -  Critically ill patients

 -  P/F ratio less than 200 (moderate-severe ARDS)

 -  Shock (Requiring Vasopressor to maintain a MAP more than 65 mm of hg or MAP below 65)

 -  Patients with known active hepatitis, tuberculosis and definite bacterial or fungal
 infections

 -  Patients with altered mental state

 -  Patients with multiple organ failure requiring ICU monitoring and treatment

 -  Patients with respiratory failure and requiring mechanical ventilation

 -  Patients with any concurrent medical condition or uncontrolled, clinically significant
 systemic disease (e.g. heart failure, hypertension, liver disease, diabetes, anemia
 etc.) that, in the opinion of investigator precludes the subject's participation in
 the study or interferes with the interpretation of the study results.

 -  Patients with history of serology tests positive for hepatitis B, hepatitis C, or
 human immunodeficiency virus.

 -  Patients who have received specific antiviral drugs ritonavir/lopinavir, or
 chloroquine, hydroxychloroquine, azithromycin, monoclonal antibodies within 1 week
 before admission

 -  Patient who have participated in another investigational study within 3 months prior
 to enrollment in this study

 -  Investigators, study personnel, sponsor's representatives and their first-degree
 relatives.

 -  Pregnant subjects