Outbreak of Coronavirus Disease 2019 (Covid-19) in India and Consideration of Preventive Aspects by Ayurveda

Srivastava Niraj*1, Saxena Varsha2, Gehlot Sangeeta3, Singh B M4 1Department of Kaumarbhritya, Bal-Roga, Sardar Patel Institute of Ayurvedic Medical Sciences & Research, Lucknow, India 2Department of Shalya-tantra, Main campus, Uttarakhand Ayurveda University (UAU). Dehradun, India 3Department of Kriya Sharir, Faculty of Ayurveda, IMS, BHU, Varanasi, India 4Department of Kaumarbhritya/Balroga, Faculty of Ayurveda, IMS, BHU. Varanasi, India


INTRODUCTION
Coronaviruses (CoVs) have a single stranded RNA genome with a helical symmetry which is covered by an enveloped structure. Size of Coronaviruses ranges between 26.2 and 31.7 kilobases (kb) which is the largest size for RNA viruses. The name of Corona for virus is derived from Latin corona word which means "crown", due to its crown like spikes presentation over the surface of virus under microscope (Dogra et al., 2020). Coronaviruses belong to the Coronaviridae family and have three dissimilar genera: alpha, beta and gamma in which alpha-and beta Coronaviruses (CoVs) are widely spread in humans and bats, which cause mild respiratory infections. However, two beta Coronaviruses causing SARS-CoV emerged in China in 2002 and MERS-CoV emerged in Arabia (UAE) in 2012 were responsible for prevalent epidemics (WHO, 2020b). In December 2019 Novel Coronavirus 19 erupted in the Wuhan City, Hubei province in China country (East Asia). Origin of this virus is still controversial but as said by Chinese media the Huanan Seafood Wholesale Market of Wuhan city is source which is famous for consumption of seafood and unusual creatures like bats, snakes etc. The medical system of China recognized this new Coronavirus as Severe acute respiratory syndrome (SARS)-CoV-2 by the International Committee on Taxonomy of Viruses (ICTV) (Gorbalenya et al., 2020).The World Health Organization declared this disease as pandemic on 11th March 2020. Now coronavirus disease  has spread to many countries and Territories around the world. Worldwide total conirmed cases are 6,700,000 and have 394,875 fatalities as on 5 th June, 2020. As per the Ministry of Health and Family Welfare's latest data released on Saturday 5 th June, total number of cases in India has risen up to 2, 36, 657 including 115,942 active cases, 114,072 cured/discharged/migrated, 6,642 fatalities and single day jump is 9887 which is highest till date (MOHFW, 2020c) .In present scenario, there is no any speci ic vaccine to prevent or antiviral drug for the treatment of Covid-19 associated pathologies.
According to WHO approximately 4 billion people (80%) of the world, currently depend on herbal medicine for some aspect of primary health care. For any circumstances prevention from diseases is better than cure, so modulation of immune responses by different measures may be useful in reducing disease aggravation and mortality rate (Chaturvedi et al., 2020).
In Ayurveda, Rasayana drugs are known for their immunomodulation and rejuvenation properties, which are considered to play important role in Covid-19 management. Several experimental and clinical studies have demonstrated immunomodulatory effects of Rasayana drugs such as Ashwagandha (Withania somnifera), Guduchi (Tinospora cordifoloia), and Amalaki (Emblica of icinale) and many other drugs of Ayurveda (Ziauddin et al., 1996).

Aim and Objective
The main aim of this review article is to describe in detail about coronavirus disease  in India and preventive measures by Ayurveda along with their possible mechanism.

Structure of Corona Viruses
The RNA genome of Coronavirus is packed in the nucleocapsid protein and further covered with envelops. Main important structural proteins of Coronavirus are spike (S) protein (trimeric), membrane protein (M), envelop protein (E), and nucleocapsid protein (N). The RNA genome of Coronavirus has seven genes that are arranged in speci ic sequence ( Figure 1) (Guo et al., 2008)

Transmission
The virus that causes COVID-19 is mainly transmitted by droplet transmission contact transmission and aerosol transmission. Droplet transmission occurs when respiratory droplets (when the droplet particles are >5-10 µm in diameter) containing viruses produced from coughs or sneezes of infected person. Contact transmission occurs when a healthy person comes in contact with contaminated surface and then touches mouth, nose, or eyes by same hand. (Liu et al., 2020). SARS-CoV-2 is stable for up to 1 day on cardboard, 2-3 days on plastic and steel and up to three hours in aerosols. Therefore, it is potential to get infected by touching contaminated objects or through the air. It can also spread through sweat, stool, urine, and respiratory secretions. The incubation period for Covid-19 is from 2-14 days, with an average around 5.2 days. The incubation period for any disease is the time duration between infections and manifestation of symptoms. Infectivity index can be measured by using R0 (reproduction number or reproductive ratio) and in case of COVID-19 it is approximately from 2.7-4.2 (Li et al., 2020) .
Recent Studies show that COVID-19 in children is less common than adults because children have elevated angiotensin-converting enzyme 2 (ACE2) and lymphocyte count, suffer numerous viral infec-tions and recent BCG immunizations, which may boost their both innate and adaptive immunity (Wu and McGoogan, 2020). COVID-19 positive pregnant woman can transmit the virus to her fetus or neonate by vertical transmission is still unknown.

Clinical features
According to Indian Council of Medical Research (ICMR), New Delhi, 69% of the con irmed cases during testing in India were found to be asymptomatic. Common clinical features of COVID-19 can include fever (99%), dry cough (60%), myalgia (44%), fatigue (70%) and dyspnea but in advanced stages, infection can cause pneumonia, acute respiratory distress syndrome (ARDS), kidney failure and even death (Guan et al., 2020) .

Investigations
Early diagnosis of COVID-19 is essential for the isolation of con irmed cases to prevent further transmission in society. Some common lab investigations among COVID-19 patients are normal or decreased WBC count, decreased lymphocyte count (60%), elevated C reactive protein (CRP) due to in lammation, high lactate dehydrogenase and elevated Ddimer which is similar as seen in SARS-CoV and MERS-CoV infections. On chest imaging bilateral patchy shadows and ground-glass opacities (GGO) are seen (Mardani et al., 2020). A nasopharyngeal (NP) swab and/or an oropharyngeal (OP) swab are often recommended for screening or diagnosis of early infection COVID-19.Within 5 to 6 days of the onset of symptoms, patients with COVID-19 have demonstrated high viral loads in their upper and lower respiratory tracts. Nasopharyngeal (NP) swab has become the preferred swab as it is tolerated better by the patient, safe to operate. SARS-CoV-2 RNA was detected in only 32% of OP swabs, which was signi icantly lower than the level in nasal swabs (63%). At present con irmation of cases of COVID-19 is based on the unique sequences of viral RNA by nucleic acid ampli ication tests (NAAT) such as real-time reverse transcriptase polymerase chain reactions (RT-PCR) with con irmation by nucleic acid sequencing.

Trial Treatment
In present scenario, no speci ic virus target based drug or vaccine is available for COVID-19.The current therapy for Covid-19 involves only symptomatic treatment and supportive care along with prevention of complications. Now many drugs have been tried for treatment for COVID-19 that includes anti-malarial drug hydroxychloroquine (HCQ), convalescent plasma therapy, BCG vaccination and several antiviral drugs such as remdesivir, lopinavir etc. HCQ is considered as a remedy for COVID-19 treatment due to its immuno-modulatory, antiin lammatory, anti-viral effects and reducing viral replication rate. For the protection of high-risk individuals, ICMR, New Delhi, has recommended a protocol for prophylaxis use of HCQ for COVID-19 infection (MOHFW, 2020b). Convalescent plasma therapy is based on plasma of a patient who has recovered from COVID-19 contains speci ic antibodies which have ability to ight against SARS-CoV-2 infection. According to researches this is passive immunization and it can be used as preventive measure and for treatment in severe cases but chance of subsequent re-infection is more with therapy. It needs more extensive randomized controlled trials to assess the effectiveness of the therapy. In developing countries like India, BCG (Bacille Calmette-Guerin) vaccination is given to generally all the infants in the irst few days of life for prevention of severe forms of tuberculosis. This vaccine may have great connection to increased nonspeci ic immunity. When any infant immunized with BCG then live attenuated bacteria enter in the body, replicating and stimulating the non-speci ic effects on the immune system. When any other infection enters in body that is not even TB, they might respond more robustly manner. WHO has compared the incidence of COVID-19 cases in countries where the BCG vaccine is given in vaccination schedule and where it is not given and result is very amazing that less cases of COVID-19 are reported in countries where BCG vaccine has been given in neonatal/infantile age. Now many clinical trials are registered for the effects of BCG vaccination given to health care workers but in the absence of evidence, WHO did not recommend BCG vaccination for the prevention of COVID-19 (WHO, 2020a).

Precautions
Till date, no drug or vaccine is developed for prevention and treatment of COVID-19 so it will be better to take preventive steps. COVID-19 is mainly transmitted by respiratory droplets and physical contact so it is essential to practice precautionary measures to prevent transmission. Standard precautions consist of hand hygiene by alcohol-based hand rubs (ABHRs), Hand washing with soap and water at least for 20 seconds, Awareness should be done on importance of social distancing (maintain a distance of 1-1.5 meters), necessity of wearing medical masks (NIOSH-certi ied N95 or equivalent) and avoidance of touching eyes, mouth, or nose. (MOHFW, 2020a). Government of India has requested to endorse use of "Aarogya Setu mobile application" for information, risk alert and relevant advisories against COVID-19. On May5, 2020 Uttar Pradesh (UP) government 1. Yogasana, Pranayama (breathing techniques) and Meditation work as a holistic itness package. Yogasana improves mental strength, physical strength by down-regulation of the hypothalamic pituitary adrenal (HPA) axis and the sympathetic nervous system. Yoga improves immunity by drainage of lymph (a viscous luid rich in immune cells) which helps the lymphatic system to ight against infection. 2. Pranayama (breathing techniques) improves blood circulation and provides more Prana (oxygen) to the various parts of the body and also improves the power of respiratory muscles 3. Meditation increases production of serotonin that improves mood, immune system and energy level of the body. Meditation lowers the levels of blood lactate which reduces tendency of anxiety attacks (Gowda, 2017). c) Haldi (Turmeric), Jeera (Cumin), Dhaniya (Coriander) and Lahasun (Garlic) in cooking.

Curcumin is the main active component of Haldi (Curcuma longa)
and it is also responsible for its yellow color. Researchers have proved that Curcumin provides both innate and adaptive immunity by modulating immune cells. Curcumin provides immunomodulatory effects by neutrophils, macrophages, monocytes, natural killer cells (NK cells) etc. Curcumin also have antioxidant and anti-in lammatory effect  2. Jeera (Cuminum cyminum) is a good source of vitamin A, C, iron, potassium and minerals which boosts immune system and it is very rich in antioxidants, ights with free radicals and afterward lowers the risk of infections. 3. Lahasun (Allium sativum) is used for prevention and treatment of common cold. Lahasun (Allium sativum) is effective in reduction of blood pressure in hypertensive patients but it does not reduce lipoprotein level in blood which is a biomarker of atherosclerosis (Esmail and Al-Sna i, 2016) 4. Coriander (Coriandrum sativum) possesses anti-microbial, antioxidant, diuretic, anti-diabetic, anti-convulsant and anti-helminthic and anti-mutagenic activity.
has launched "Ayush Kavach app" which provides updates for measures to enhance immunity based on natural resources and Ayurveda.

Prevention of COVID-19 by Ayurveda
The body's immune system is most effective weapon in people to ight against COVID-19. Good nutrition, exercise and proper sleep are three important pillars which is extremely necessary for improving the immune system in human. Ayurveda propagates the contributions of nature in maintaining health and improving immunity. Ayurveda recommends local and systemic prophylaxis trial for respiratory diseases that may be useful in COVID-19 prevention. On the basis of Ayurvedic literature, scienti ic publications and recommendation by eminent Vaidyas ministry of AYUSH has advised the self-care guidelines on 31 March 2020 for protective health measures and boosting immunity especially for respiratory health. The advisory of AYUSH neither has claimed effective treatment for Corona virus nor any speci ic drug to combat for COVID 19. All the sugges- Chyawanprash is an Ayurvedic health tonic described in the Charaka Samhita. It is a polyherbal Avaleha which has 50 medicinal herbs and their extracts which is used to endorse health and prevent diseases.
2) Main ingredient of Chyawanprash is Aamalaki (Emblica of icinalis) which is rich source of vitamin C. Acharya Charak has described that Aamalaki is the best rejuvenating herbs (Pandey and Chaturvedi, 2005)  2) A decoction of the leaves of Tulsi (Ocimum sanctum Linn) is very effective for the treatment of respiratory disorders (bronchitis, asthma, in luenza, cough and cold) (Kumar et al., 2010a) 3) Researchers have proved that Black pepper (Piper nigrum) has immuno-modulatory, anti-in lammatory, anti-oxidant and anti-microbial activity. 4) Dalchini (Cinnamomum zeylanicum) has antioxidant, antimicrobial, anti-in lammatory, anti-cancer, and antidiabetic property. 5) Shunthi (Zingiber of icinale) has anti-in lammatory, antiplatelet aggregation, antimicrobial, anti-fungal and antirhinovirus activity. The main ingredient of fresh ginger is betasesquiphellandrene which is effective against Rhinovirus and many bacterial infections. 6) Munakka (Raisin) have cough suppressant activity so it is effective in management of dry cough and due to its soothing property Munakka (Raisin) reduces irritation in the throat. 7) Munakka (Raisin) ights against the free radicals and have antioxidants, anti-in lammatory and antimicrobial properties (Rekik et al., 2016). c) Golden milk once or twice a day. (Half tea spoon Haldi powder mixed in 150 ml hot milk) 1) Golden milk is very effective in boosting up of immunity because both milk and turmeric are powerful antioxidant, detoxi ication agent, anti-in lammatory and having immunomodulatory properties. 1) Pratimarsh Nasya is administration of oil through the nostrils in dose of 2 drops morning and evening. It can be given daily and even in all the seasons.
2) Drug of Nasya Karma (sesame oil / coconut oil or Ghee) may be absorbed by receptor cells of olfactory mucosa, sensory receptors of trigeminal nerve and cavernous sinus. It helps in removal of morbid Dosha and maintains equilibrium. b) Oil pulling therapy once or twice a day by 1 tsf sesame or coconut oil in mouth. (Do not drink, Swish in the mouth for 2 to 3 minutes and spit it followed by warm water rinse) 1) Oil pulling therapy is a potent detoxifying technique that is mentioned in the Charaka Samhita as a Kavala or Gandusha. Oil pulling therapy uri ies the entire system by oil gargling because tongue is connected to different organ such as kidneys, lungs, liver, heart etc.
2) The sesame plant (Sesamum indicum) contains several kinds of sesame lignans which has antifungal activity. Polyunsaturated fatty acids prSesent in sesame oil reduces free radical injury occurring in oral cavity (Anand et al., 2008)  1) Steam inhalation is very useful for respiratory system disorders. Mint oil is widely used essential oil and its main ingredients are menthol and iso-menthone. It helps in boosting the immune response and has anti-in lammatory, anti-microbial and analgesic property.
2) Chewing Ajwain seeds (Trachyspermum ammi) with lukewarm water is very effective for cough, cold and clearing nasal blockage by discharging the mucus easily (Rajan et al., 2011) . b) Lavanga (Clove) powder mixed with natural sugar / honey can be taken 2-3 times a day in case of cough or throat irritation 1) Researchers have established that honey has immunoglobulin, vitamins and iron in large quantity. Regular use of honey strengthens the white blood corpuscles to battle against bacterial and viral infections (Kumar et al., 2010b). 2) Clove showed antiviral activity against Herpes Simplex virus and other viruses due to eugenin constituent isolated from clove buds. Clove possesses antimicrobial, anti-oxidant, antifungal properties and is one of the Nature's premier antiseptic.
tions have been divided in four steps such as general measures (Table 1), Ayurvedic immunity promoting measures (Table 2), Ayurvedic procedures (Table 3) and prophylactic treatment during dry cough / sore throat ( Table 4) (Ministry of AYUSH, 2020) .

Future researches in Ayurveda concerns to COVID 19
Ayurveda has potential to save millions of lives from SARS-CoV-2 infection by enhancing host defence and immune homeostasis. In Ayurveda, Rasayana therapy is known for their immunomodulation and rejuvenation properties, which are important in prevention and treatment of Covid-19. The Min-istry of AYUSH has released its independent advisory to public for self -care measures, which has received a wholehearted response. The Ayurveda has received better government support after the establishment of the Ministry of AYUSH. For validation of Ayurvedic formulation, against Covid-19, the AYUSH Ministry and Council of Scienti ic and Industrial Research (CSIR) has started collaborative work on four Ayush formulations. These formulations are Ashwagandha, Yashtimadhu (Mulethi), Guduchi + Pippali and AYUSH-64. Competitive study is also plan between Hydroxychloroquine and Ashwagandha for high-risk population.

Ashwagandha (Withania somnifera)
Ashwangandha may be bene icial in providing antiviral immunity by increasing Interferon-gamma (IFN-gamma responses) and anti-in lammatory activities by decreasing the quantity of Interleukin -1, Interleukin -6 and Tumor necrosis factor which are the main factors related for COVID-19.Ashwangandha may be an effective agent in the management of COVID-19infection by modulation of host Th-1/Th-2 immunity  Guduchi (Tinospora cordifolia) The major phytocomponents reported in Guduchi are tinosporine, diterpenoid Cordifolioside-A etc.
Cordifolioside-A has reported to acquire immunomodulatory activity and enhances innate immunity against COVID-19 infections. Tinosporin, diterpenoid has very effective anti-viral property especially for the treatment of retroviruses and other viral diseases (Akhtar, 2010) .

Mulethi (Glycyrrhiza Glabra)
The major phytocomponents reported in Mulethi (Yashtimadhu) is glycyrrhizin which is very effective in inhibiting replication of the SARS-associated virus.

AYUSH 64
Ayush-64 is a patented anti-malarial medicine developed by the Central Council for Research in Ayurvedic Sciences (CCRAS). It is a combination of 4 Ayurvedic drugs Saptaparna stem bark (Alstonia scholaris), Katuki roots (Picrorhiza kurroa), Chirayata whole plant (Swertia Chirata) and Kuberaksha seed (Caesalpinia crista). National task force for COVID-19 constituted by ICMR recommends the use of Hydroxychloroquine (HCQ) for prophylaxis of SARS-CoV-2 infection for high risk population. Now plans to check the ef icacy of Ayush-64 medicine for the same.
In Ayurveda, Rasayana is mentioned which can be helpful to accomplish a prolonged happy and healthy life. In concern to SARSCoV-2 infection, Rasayan therapy may have bene its in many ways such as cutback in recovery time, reduction in duration of stay in hospital, enrichment in clinical cure rate and prevention from ailment. In the present scenario, India needs fast-track clinical trials on Ayurvedic Rasayan such as Ashwagandha (Withania somnifera), Pippali ((Piper longum), Shatavari (Asparagus racemosus ), Guduchi (Tinospora cordifolia), Yashtimadhu (Glycyrrhiza Glabra) and Aamalaki (Phyllanthus emblica ) for prophylaxis of SARSCoV-2 infection.

CONCLUSION
Coronavirus disease 2019 (COVID-19) is an infection caused by the novel coronavirus severe acute respiratory coronavirus 2 (SARS-CoV-2).The infection manifests as a mild lu to severe acute respiratory infection. The World Health Organization (WHO) declared COVID-19 as a global pandemic on March 11, 2020. The disease spreads by droplet infection from person to person. Currently, the laboratory diagnosis of SARS-CoV-2 is based on nucleic acid ampli ication tests (NAAT) like realtime reverse transcriptase (RT-PCR). At present no approved treatment or vaccine is available in all over the world for COVID-19.India has an opportunity for a worldwide leadership by developing evidencebased and scienti ically proved prophylactic strategies on the basis of Ayurveda to protect people from SARS-CoV-2 infection. On March 31, 2020, Ministry of AYUSH has released its independent advisory to public for self -care measures, divided in four steps such as General Measures, Ayurvedic Immunity Promoting Measures, Ayurvedic Procedures and prophylactic treatment during dry cough / sore throat. All recommendations of AYUSH ministry have literature and scienti ic publication support. It is very helpful for society and after this evidence-based and scienti ically proved suggestion; Government of India has planned to conduct clinical trials on three herbal drugs (Ashwagandha, Guduchi and Mulethi) and an Ayurvedic anti-malaria medicine AYUSH-64 for their preventive properties against Covid-19 infection. Rasayan therapy may have bene its like cutback in recovery time, reduction in duration of stay in hospital, enrichment in clinical cure rate and prevention from ailment. In the present scenario, fast-track clinical trials are the need of hour on Ayurvedic Rasayan such as Ashwagandha (Withania somnifera), Pippali ((Piper longum), Shatavari (Asparagus racemosus ), Guduchi (Tinospora cordifolia), Yashtimadhu (Glycyrrhiza Glabra) and Aamalaki (Phyllanthus emblica) for prophylaxis of SARSCoV-2 infection.

Source of support
The authors declare that they have no funding support for this study.