With India recording massive spikes in COVID-19 cases, the focus has largely shifted towards fast-tracking trials and the approval process for locally made vaccines to curb the upsurge in coronavirus infections that has led to a public health disaster in the country. 

Amidst the second devastating wave of COVID-19, the emergency use authorization of Virafin/ZyCOV-D by the Drug Controller General of India (DGCI) is no less than a blessing for medical service providers struggling to battle against the novel coronavirus. The anti-viral drug produced by Ahmedabad-based pharmaceutical giant, Zydus Cadila has been approved for emergency use to treat moderate coronavirus infections in adults. Virafin is a DNA-plasmid product that involves the coronavirus’s genetic code (DNA or RNA), which stimulates the immune response in the recipient. A single dose of Virafin injection can significantly reduce symptoms of the disease as well as the viral load. The clinical trials have confirmed the safety, tolerability, and efficacy of Virafin, which supports fast recovery when subcutaneously injected in the early stages of infection. The emergency nod comes at a much-needed time for patients, providing them access to critical therapies to combat SARS-CoV-2. 

‘Virafin’ is a pegylated interferon alpha-2b(PegIFN) that signals proteins to strengthen the body’s defense mechanism against deadly pathogens. Thus, the medicine works as the immunological agent to combat infections in the body along with controlling respiratory distress and failure. Reducing the respiratory tension caused due to low oxygen levels, Virafin manages the disease effectively and reduces the need for supplemental oxygen. The Virafin drug is already being employed for the treatment for the treatment of Hepatitis C, another viral condition even before it was tested against the novel coronavirus.

Usually, when the viral load is between moderate to high, the oxygen demand becomes rapid. Stressing upon the efficacy of Virafin, Zydus Cadila outlines that the administration of medicine lowers the viral load in patients, which ultimately reduces their dependency on medical oxygen. In the clinical trials, it was found that most of the patients (91.15%) suffering from moderate symptoms of COVID-19 reported absolute zero viral load and showed RT-PCR negative within seven days of Virafin administration.

While the country continues to face an acute shortage of medical oxygen, the emergency use authorization of the drug would help the patients with early effects of coronavirus to avoid hospitalization. This would help to reduce stress on the overly burdened hospital staff, finding it hard to provide beds and adequate facilities to severely infected coronavirus patients. In a way, the Virafin drug is the ultimate solution to overcome the grave shortage of medical supplies, especially supplemental oxygen, and hospital beds across India.

Immunization via Zydus Cadila’s Virafin vaccine will prove to be instrumental in reducing the severity of the coronavirus disease and decrease the mortality rates attributing to SARS-Cov-2 in the country. So far, several anti-viral drugs available for the treatment of COVID-19 such as Remdesivir and Fabiflu have shown positive improvements, but these drugs cannot be absolutely relied upon due to lack of clinical data available for demonstrating their efficacy against the virus. Also, the unprecedented spike in cases has resulted in a huge demand-supply mismatch of Remdesivir injections, which has created an urgency to develop new substitutes to manage the disease. Also, Remdesivir is a six-dose therapy that requires to be administered in hospital settings whereas Virafin shows great efficacy in just a single-dose administration, which can be given to patients recovering at home. Virafin has great potential, and it will be able to offer support to the frontline workers in their battle against COVID-19 as it is multiple-fold potent than any other antiviral medications currently available for coronavirus treatment.

Just like other antiviral drugs, Virafin induces some side effects, which are somewhat similar to influenza symptoms. Besides, the medicine can alter blood composition in patients or cause neuropsychiatric disturbances, therefore it is crucial to be taken only after consulting a physician and under supervised conditions. The medicine cannot be availed over the counter without prescription due to its restricted use.

Zydus Cadila sources ingredients for the drug domestically and has a secure supply chain, unlike other drugmakers who are reliant on the USA for raw materials. However, Virafin is a three-dose vaccine, which could pose administration and logistical challenges. The company has not yet disclosed the price of the vaccine however, it will be positioned competitively against Remdesivir and other counterparts.

Although the drug will be available at local pharmacies in the near future, currently the company is planning to provide the vaccine to hospitals first. Round 50,000 vaccine doses are anticipated to be rolled out in May and by June-end, the capacity would be added to provide almost 10 lakh doses a month. Since there are not many manufacturers in the world that are equipped to produce a biological drug of this nature, contracting manufacturers is not an option. However, if the demand for the drug is high, Zydus Cadila can outsource through technology transfer, which can take the number of doses to 50 lakhs a month.

Other COVID-19 Vaccines in India

COVAXIN VACCINE

Bharat Biotech’s Covaxin is based on the inactivated whole SARS-CoV-2 virion, which is safe to be injected into the body. When administered, the vaccine prompts the immune system to make antibodies against the pathogen by stimulating the immune cells and ceases the reproductive ability of the virus. The vaccine requires to be injected in two dosages four weeks (28 days) apart and need to be stored at 2^oC to 8^oC. The administration of Covaxin has been approved for those 12 years and above. Covaxin demonstrated overall clinical efficiency of 81% against severe COVID-19 disease in phase3- trials.

Potential side-effects: Injection site pain, headache, fever, body ache, abdominal pain, nausea, dizziness-giddiness, tremor, cold, cough, injection site swelling, sweating and fatigue.

COVISHEILD VACCINE

Manufactured by Serum Institute of India, Covishield is based on the viral vector platform. The vaccine has been made by modifying the chimpanzee adenovirus called ChAdOx1. When administered, the vaccine induces the immune system to produce more antibodies and directs it to attack any coronavirus infection. The vaccine requires to injected in two dosages between four and twelve weeks apart. Leaving a longer gap between the injection of the first and second doses increases the overall effectiveness of the jab. The vaccine needs be stored at temperatures between 2^oC to 8^oC. People above the age of 18 and above can get vaccinated with Covishield. The vaccine has an overall efficacy of 70% after administering half dose the first time and shows 90% efficacy after taking the full dose a month later.

Potential side-effects: Tenderness, pain, redness, itching, injection site swelling or bruising, chills, fever, headache, joint aches, redness, warmth.

PFIZER BIONTECH VACCINE

The Pfizer BionTech vaccine is a messenger RNA (mRNA) COVID-19 vaccine, including both enzymatically produced components from naturally occurring substances as well as synthetic produced components. The vaccine does not have any live virus and its active ingredients are potassium chloride, sodium chloride, dibasic sodium phosphate dihydrate, monobasic potassium, phosphate, sucrose, etc. Unlike traditional vaccines that utilizes dead or portions of actual virus to stimulate immune system response, Pfizer actually delivers a message to body’s cells via a lipid nanoparticle envelope to generate the spike protein, which in turn spurs defence mechanism to generate antibodies specific to SARS-COV-2-spike protein. Two dosages of the vaccine require to be administered three weeks apart. People above the age of 16 and above are ideal candidates for the Pfizer vaccine. The vaccine can be stored in the temperatures between 2^oC and 8^oC for up to 5 days.

Pfizer vaccine is 94% effective at preventing the COVID-19 virus with symptoms. Besides, the vaccine shows 90% efficacy in preventing people with chronic health conditions such as diabetes, obesity, among others, from developing the COVID-19 virus with symptoms.

Potential side-effects: Injection site pain or swelling, fatigue, muscle pain, chills, joint pain, fever, nausea, malaise, and lymphadenopathy (enlargement of the lymph nodes).

Being a DNA vaccine, Virafin is easy to redesign quickly against a mutating virus. The vaccine is delivered through the intradermal route, that makes its administration convenient and effective whereas other vaccines such as Covaxin, Covishield, and Pfizer are delivered through the intramuscular route.

Note: The vaccines typically take two weeks after vaccination to build immunity against the virus so a person could still catch coronavirus infection just after vaccination.

Challenges Ahead

Vaccine storage 

As India ramps up for the mega COVID-19 vaccination drive, the safe delivery of vaccines can become a huge roadblock. Being the world’s second-most populous country, India needs to have adequate cold storage units and cold chain facilities to maintain the potency of vaccines while it plans to inoculate 400-500 million doses by July 2021. Securing last mile connectivity is an immense challenge for India to implement as the vaccines need storage temperatures that cannot be realistically managed in a large-scale Indian campaign. However, the government is planning to rope in private cold chain operators for more cold storage spaces and transport load to facilitate the nationwide immunization program.

Vaccine Hesitancy

Vaccine hesitancy is not new in India. It is one of the major factors for the ten major health threats worldwide. According to World Health Organization, the main factors for vaccine hesitancy are lack of trust in healthcare services, safety and efficacy concerns, complacency, and inconvenience of getting the jab. But, leaving behind few pockets of infected people can remain a threat to the rest of the world therefore, to end up the vicious circle of contagious stains, everyone needs to come forward to get vaccinated. 

Vaccine Wastage

Vaccine wastage can occur during transportation both at service and delivery. Not following the cold chain operational guidelines, mishandling vaccines, administering vaccines without considering manufacturing dates, or accidents can also result in vaccine wastages. The only solution to minimize wastage is adequate granular planning at vaccination centers, compliance to operation guidelines, and proper training. 

Conclusion

Witnessing the horror brought down by the second wave of coronavirus, the vaccine manufacturing and administration is expected to increase multi-fold. It is inevitable to assume that India would not be hit by the third wave, which could be even more disastrous than the second wave that the country is currently experiencing. Immunizing 60% of the population, nearly 80 crore people is the only solution to curb the spread of coronavirus, for which 160 crore doses will be required. Increasing capacity of indigenous vaccines in place can address the huge-supply demand mismatch and expand the basket of vaccines for domestic use.

Source : TechSci Research