Impact of COVID-19 on Pharma and Healthcare Industry

Our world is currently in the grip of the novel human SARS-CoV-2/COVID-19 virus pandemic. The term “novel” is used since this virus has not been encountered by humans previously. The virus which began its infectious spree in the Wuhan province of China has till now claimed approximately 0.2 plus million lives globally¹. The number of people infected by this virus around the globe stands at plus 3 million as of today and the number of countries and territories which are grappling with the infections is around 212¹. The ease and the sneaky manner by which the virus infects via human to human transmission have led to its expansion. Moreover this invisible intruder knows no preference with respect to race, ethnicity and social status of patients and is a common enemy. People with co-morbidities and those who are constantly exposed to the virus such as healthcare workers and aged family members seem to succumb to the virus. To prevent fatalities due to the viral infection and prevent the spread of the virus, numerous countries have declared a state of emergency by entering the lockdown mode. The lockdown has led to a disruption in the way people lead normal lives. The ugly side of the lockdown is that it has been abrupt, sparing no time for economies to come to terms with it. As a result there is a spike in unemployment, a sudden vacuum in the production and transport of essential commodities and a rise in the proportion of the population that is vulnerable in terms of finances and lack of essentials.

COVID-19 can infect the population through multiple ways, the primary route being via the nasal cavity though there are suggestions that it may also gain access through mouth or eyes. A person can get infected by 1) being in the vicinity of a COVID-19 patient who unwittingly spreads the virus by coughing and sneezing 2) being in close association with a COVID-19 patient 3) being in contact with contaminated surfaces and objects in which the virus remains viable and infective for several hours. Thus all advisories issued by health bodies around the world suggest quarantine for the infected person, wearing masks to avoid face touching, and constant hand washing or sanitizing. Depending on the inherent immune system of the patient, the severities of symptoms vary. In 80% of the cases, the symptoms are mild and patient recovers on his own while in some cases there is a need for intervention by healthcare experts in the hospital settings². The common symptoms are runny nose, throat ache, high fever, dry cough and shortness of breath. These usually get manifested within 14 days² of contracting the virus and have to be reported immediately, so that quarantine measures to prevent virus spread in the community can be applied.

In the past two months, COVID-19 has been extensively studied by doctors and scientists worldwide to find its Achilles heel. The virus gains access through the upper conducting airways of the respiratory system and symptoms remain mild if confined to these anatomical structures. It’s only when the virus travels down the respiratory tract to the alveolar region do things start getting nastier for the patient ³. The virus causes massive inflammation in these regions resulting in a “cytokine storm”⁴. These released pro-inflammatory cytokines are responsible for the necrosis of this sensitive tissue which is visible in chest radiography as bilateral patchy shadows or ground glass opacity⁵. The spiky virus gains entry to the cells through the interaction of its club-shaped spike protein with a receptor ACE2 (Angiotensin Converting Enzyme 2) on human cells ⁶. This interaction propels a host protein, transmembrane protease serine 2 (TMPRSS2) to cause the cleavage of the spike protein⁶ and enables the entry of the viral genome (a 30 kb plus- strand RNA)⁷ into the cells. The viral RNA then exploits the host’s translational machinery to produce its 29 proteins⁸ which play roles in replicating the viral RNA and producing new packaged virions. The release of new virions in the extracellular space promotes the sustenance of the infection as they infect new cells. New research into the infectivity of the virus has revealed its negative influence in the smooth functioning of other organs besides the lung viz., liver, kidney, intestines, brain, eyes and heart.

The healthcare industry which hitherto has been working silently pre-COVID-19 as world health guardians find itself suddenly under the spotlight. They are the key players in this pandemic and besides providing care to the infected patients; they have additionally been given the huge responsibility of finding a cure within a matter of a few months. The healthcare industry is thus at the forefront of this war against the virus. Many universities and pharmaceutical companies are repurposing old drugs with a hope that that one of them might be effective in curing patients infected with SARS-CoV-2. Repurposing drugs prevents the need for carrying out extensive toxicological studies since these have been already subject to such studies in the past before gaining FDA approval albeit for a different disease. This puts the drugs on the fast track for direct approval for treating patients infected with the virus. Some of the re-purposed drugs that are being investigated are given in Table No.1.

Table No. 1: Lead re-purposed drugs in the pipeline for treatment against SARS-CoV-2^9-10.

Besides these drugs which are at the frontline in therapy, adjunct therapies that could ameliorate the disease such as convalescent therapy, corticosteroid therapy, anti-cytokine therapy, immune- modulating therapy are also being investigated¹¹.

In the past decades, humankind has been able to eradicate many a virus by producing effective vaccines. An effective vaccine against COVID-19 would enable the world to disengage from strict social distancing norms and reduce the panic among its inhabitants. As many as 100 potential COVID-19 vaccines are now under development by biotech and research teams around the world and at least 5 of them are in Phase-I clinical trials. Though the results of these trials would be obtained by September 2020, some biotech companies have already begun mass production of these vaccines to prevent any kind of delay once FDA approval is obtained. One of the vaccines “ChAdOx1nCoV-19” developed by the University of Oxford¹² and currently in clinical trials is being mass-produced by Serum Institute of India¹³, Pune which plans to produce up to 60 million doses of the vaccine. Another Indian company Bharat Biotech, in collaboration with the University of Wisconsin-Madison and vaccine maker FluGen, is developing a nasal vaccine “CoroFlu”¹⁴. Another example of the development of a single dose intranasal vaccine against the virus is “AdCOVID” by Altimmune (USA) in collaboration with the University of Alabama at Birhingham12. To name a few more vaccine developments, Catelent Inc. (USA) has collaborated with Janssen Pharmaceutical Companies of Johnson & Johnson for the manufacture of its lead COVID-19 vaccine candidate and Entos Pharmaceuticals (Canada) is developing a DNA vaccine against COVID-19 called “Covigenix” based on its Fusogenix platform which formulates DNA in a proteo-lipid vehicle12. On a positive note, Israel’s Institute for Biological Research (IIBR) has claimed success in generating a monoclonal antibody that has the potential to neutralize SARS-CoV-2¹⁵.

While conventional medicines are at the forefront in the treatment of critically ill patients, the rich Indian traditional methods of medicine (Ayurveda) may be effective as a prophylactic that could prevent the virus from gaining a stronghold on the patient, i.e., these may be effective in the initial stages of viral infection, when the virus is localized at the nasal or throat regions. Local prophylaxis includes consumption of warm medicated waters which contain spices such as dry ginger (Zingiber officinale), yashtimadhu (Glycyrrhiza glabra), and nut-grass (Cyperus rotundus), rhizomes; khus (Vetiveria zizanioides), Indian sarsaparilla (Hemisdesmus indicus) roots; coriander (Coriandrum sativum) and fennel (Cuminum cyminum) seeds; and cinnamon (Cinnamomum verum) and catechu (Acacia catechu) barks¹⁶. Other methods suggested are medicated mouthwashes/gargles containing turmeric (Curcuma longa) rhizome, yashtimadhu or liquorice (Glycyrrhiza glabra) stem, neem (Azadiracta indica) and catechu (Acacia arabica) barks and salt, which have been proven beneficial in xerostomia (dry mouth), post-operative sore throat, oral ulcers, gingivitis, and bacterial growth¹⁶. The purpose of incorporating these herbal ingredients could be to enhance mucosal immunity against the virus. Application of medicated oils made from butter oil (Ghee) and vegetable oils like sesame and coconut to nasal passages may prevent the virus from gaining access to the soft tissues underneath the oily layer¹⁵. Immuno-modulators may be administered to patients to prevent the cytokine storm which causes acute inflammation and multi-organ failure. Based on research data by AYUSH (Center of Excellence, Center for Complementary and Integrative Health Interdisciplinary School of Health Sciences, India), Withania somnifera (Ashwagandha), Tinospora cordifolia (Guduchi), Asparagus racemosus (Shatavari), Phyllanthus embelica (Amalaki), and Glycyrrhiza glabra (Yashtimadhu) are known to be immune-modulators¹⁶. Active research on the active components of these herbal medicines against COVID-19 is the need of the hour. Additionally, to counter the depression and fear that may follow due to the lockdown and viral infection, practices of Meditation & Yoga are suggested and actively promoted by the Indian government.

Besides discovering drugs and innovations in vaccine development, the healthcare industry is also trying to find simple, quick and inexpensive methods to detect the virus in patients. The conventional method of detecting the virus is Real-Time Polymerase Chain Reaction (RT-PCR) where-in the viral RNA is detected from nasal swabs of infected patients. The method requires skilled technicians, expensive equipment and takes 5-6 hours to obtain results. The ID NOW platform of Abbott Pharmaceuticals (USA) has come with molecular testing devices that could give results in a matter of 15 minutes¹⁷. Not to be left far behind in the production of detection kits, India’s Myolab scientist Minal Dakhane Bhonsale has come up with a testing kit called “PathoDetect” which gives results in 2.5 hours and at a lower cost¹⁸. Other tests based on different techniques of virus detection are also underway, for example, the CSIR Research Group in Lucknow, India, has developed an innovative paper-based test based on CRISPR/Cas interactions¹⁹ and is currently validating the results. Serological tests based on antigen-antibody based interactions are also under development in India and many parts of the world. These rapid diagnostic tests, if found sensitive can enable greater testing without the need for skilled personnel.

Though the healthcare and pharma industry has risen to the challenge posed by COVID-19, the continuing lockdown has brought about disruptions in normal trade and working of the industry. Virtual modes of communication that were hitherto not given much significance pre-COVID 19 have emerged as the saviors of humanity during this crisis. There will be a paradigm shift in the relations between the pharmaceutical marketing segment officers and doctors and between doctors and patients. Online consultations and online prescriptions will be the new norm and will gain acceptance and preference. General practitioners will need to register themselves in the digital world and for some period of time till an effective vaccine is developed against the virus, the doctors would only entertain virtual visitations unless there is an emergency situation wherein the patient has to get admitted to the ICU (Intensive Care Unit) or has to visit a pathology laboratory for tests.

In the Indian scenario, COVID-19 has also opened new opportunities for the Pharma industry in the manufacture of bulk drugs and APIs. There will be a consensus now among the government and the pharma industry stakeholders to start manufacturing KSMs (Key Starting Materials) and other APIs (Active Pharmaceutical Ingredients) in India in an effort to increase the country’s self-sufficiency and to reduce the dependence on imports from other countries. As of today pharmaceutical industry imports 600 molecules for formulation purposes²⁰. Most of the starting materials of antibiotics, vitamins and hormones are sourced from China. There would be an increase in the promotion of Indian SMEs (Small and Medium Enterprises) to produce bulk drugs many of which had to shut down due to the inflow of comparatively cheap raw materials from China ^21-22. India is recognized as the “Pharmacy of the World” and it’s time it gained recognition as a lead player in the manufacture of bulk drugs and API, a title which it has to regain in the coming years.

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