It is going to be a year since COVID 19 emerged as a dreadful virus in Wuhan, and rapidly became a pandemic, though initially not taken seriously. Soon masks, physical distancing and hand hygiene became the frontline strategy for containing its spread. A number of drug therapies evolved over time. Chloroquine/hydroxychloroquine, azithromycin, Favipiravir, ivermectin, and lopinavir-ritonavir came on board but had a variety of adverse effects, including adverse effects on heart, liver, pancreas, and blood and very little demonstrable benefit. In short, these agents failed.
Remdesivir, only became an important drug in patients with COVID 19 not needing ventilation and also got approved by several international drug controller authorities. It showed shortening of the course of the illness in less critically ill patients in a placebo-controlled trial. However, the duration of therapy 5 or 10 days did not seem to make a difference.
The treatment improving survival then hinged around steroids and anti-coagulants, steroids based on the background of the RECOVERY trial, concluded that therapy with dexamethasone at a dose of 6 mg once daily for up to 10 days decreased 28-day mortality in patients with COVID-19 on respiratory support. Patients not requiring oxygen showed no benefit but had a possibility of harm with corticosteroid therapy.
Infection with this virus has a unique laboratory signature including platelet deficiency and increased coagulability and tendency to form clots in lung arteries leading to typical lung problems leading to deaths. This brought in anti-coagulants to prevent clot formation. Prophylactic anticoagulation based on enoxaparin or fondaparinux started being used in hospitalized patients needing oxygen. Their utility after discharge is not clear and is a part of ongoing trials. Associated bleeding has to be weighed as a risk.
Prevention using vaccine has been a subject of several scientific studies and seems to be the only real hope. All vaccines aim to expose the body to an antigen that won’t cause disease, but will provoke an immune response that can block or kill the virus if a person becomes infected.
The first vaccine to be launched for human use has been the “SPUTNIK” vaccine made by Gamaleya Centre, Russia. They have been working on adenoviral vector-based vaccines since the 1980s, and now lead the world in developing these types of vaccines. During the vaccine creation process, a gene with the code of a coronavirus S (spike) protein is inserted into an adenoviral vector. This inserted component is safe for the human body, but still helps the immune system to react and produce the antibodies that protect us from infection. The vaccine has criticism attached to it because of abbreviating the phases and not publishing the protocol. Recently they announced to the press that it has a 92% success based upon an interim analysis of 20 COVID-19 cases identified among trial participants. These numbers according to experts are too few. They have also approached Indian companies for joint collaborations for mass scale production of this vaccine. Dr Reddy’s Laboratories Ltd. plans to distribute the Russian vaccine in India after conducting final-stage human trials going to begin very soon.
Zydus Cadila of India is working with 2 COVID vaccines, one using DNA and the other using replicating viral vector. Both are in Phase III at present. They are partnering with Codagenix vaccine which is in pre-clinical trials and their Novavax candidate is only a few months behind the Astra-Zenica Oxford vaccine.
The other very talked about vaccine is the Oxford vaccine which had in their preliminary report of its Phase 1 and 2 published in July 2020, shown an acceptable safety profile, and homologous boosting increased antibody responses. The vaccine was the chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19). These results, together with the induction of both humoral and cellular immune responses, support a large-scale evaluation of this vaccine in an ongoing phase 3 program involving several thousand subjects assessing safety and efficacy. In another publication very recently, they have shown that it appears to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose. Further assessment of the efficacy of this vaccine is being done in all age groups and individuals with comorbidities. Serum Institute of India, Pune one of the largest manufacturers of vaccines has a collaboration with Astra Zenica for bulk manufacture and has already a stockpile of 50 million vaccines and once it is approved by British authorities and the Drug controller General of India, 3.2 billion vaccine doses will be made available at its Indian facility. The vaccine does not have very fastidious requirements for storing and transporting beyond what is available with us.
The latest, very gratifying news has been the announcement by Pfizer. USA and BioNTECH, Germany after conducting the final efficacy analysis in their ongoing Phase 3 study of the mRNA-based COVID-19 vaccine, BNT162b2 . It seems to have met all the study’s primary efficacy endpoints. Analysis of the data indicates a vaccine efficacy rate of 95% in participants without prior SARS-CoV-2 infection (first primary objective) and also in participants with and without prior SARS-CoV-2 infection (second primary objective. The first primary objective analysis report is based on Efficacy which was consistent across age, gender, race and ethnicity demographics. The observed efficacy in adults over 65 years of age was over 94%. No safety issues have been reported to the US FDA which is closely monitoring the program. The trial will continue to collect efficacy and safety data in participants for an additional two years. The down side of this vaccine is that it needs very stringent conditions for storing and transporting which also have been developed. The companies have developed specially designed, temperature-controlled thermal shippers utilizing dry ice to maintain temperature conditions of -70°C±10°C. They can be used be as temporary storage units for 15 days by refilling with dry ice. Each shipper contains a GPS-enabled thermal sensor to track the location and temperature of each vaccine shipment across their pre-set routes leveraging Pfizer’s broad distribution network. The results have been published in well accepted journals. The vaccine is already launched in Europe and USA earlier this month, in high-risk populations. Based on current projections, the companies expect to produce globally up to 50 million vaccine doses in 2020 and up to 1.3 billion doses by the end of 2021. Indian Government is unlikely to procure this vaccine given the estimated cost of around Rs 2700 per vaccine but Pfizer reducing the price is still a possibility.
Our hope is therefore on the OXFORD vaccine from Astra Zenica and their collaborations with our mass producer of the vaccine Serum Institute of India. This hopefully will be supplemented with the other vaccines coming up from companies like Zydus Cadila. The time frame of availability could be by first quarter of 2021.
With the total number of cases in India of COVID-19, mounting around 10.2 million on 29th November 2020, the country’s death toll has mounted to 1,48,000. Fortunately, the mortality in our part of the world has been around 1.4 %, which is much lower than what was reported in Europe and America. We need to break this cycle, earlier the better and mass vaccination is going to bring in the much talked about herd immunity. Let us hope that the new year 2021 is going to bring in normalcy and the lessons learnt in 2020 will remain with us. We need to respect nature and its ways.
Author is a Cardiologist, recipient of Padma Shiri and Dr B C Roy Award