At least eleven (11) COVID-19 vaccine candidates are in phase-3 of clinical trials. Multiple companies have announced encouraging results through preliminary analysis. Pfizer & BioNTech have already applied to US FDA for emergency use authorization (EUA). Other companies are expected to follow suit. Even if the vaccine candidates are approved, distribution & other challenzes exist.
Globally, as on 24 November 2020, over 58.7 million confirmed cases of COVID-19 have been reported. Over 1.38 million people have lost their lives to this virus across the globe. Recently, many parts of Europe have gone into a second lockdown following the resurgence of COVID-19 infections that is sweeping the continent while countries like India are bracing themselves for a possible second wave of infections.
Amidst all this, the ongoing COVID-19 vaccine trials are yielding encouraging results, raising hopes that a vaccine would soon be available and that too within one year since the infection was declared a public health emergency of international concern in January 2020.
11 Vaccine candidates are in the last stage of clinical trials
According to the World Health Organization’s (WHO) latest draft landscape of COVID-19 candidate vaccines as of 12 November 2020, there are 212 candidate vaccines of which 48 are in clinical evaluation stage and the remaining 164 are in pre-clinical evaluation stage. Among those in clinical evaluation stage, 11 are in phase-3 of clinical trials including the vaccines being developed by Sinovac, University of Oxford & AstraZeneca, Pfizer & BioNTech, Moderna, Johnson & Johnson, CanSino Biologics, Wuhan Institute of Biological Products & Sinopharm, Novavax, Gamaleya Research Institute, Bharat Biotech, and Beijing Institute of Biological Products & Sinopharm. There are three other vaccine candidates in phase-2 of clinical trials, 13 in phase-1/2, and 21 in phase-1.
Vaccines developed in India that are in the clinical trial stage are Covaxin developed by Bharat Biotech with ICMR in Phase-3 of trials, and Covishield developed by Serum Institute of India and ZyCov-D of Zydus Cadila that are currently in the phase-2 of trials.
Russia and China have approved vaccines
Russian President Vladimir Putin announced in August 2020 that the Russian government had approved the world’s first COVID-19 vaccine, named Sputnik V. The Russian Healthcare Ministry also tweeted that they had given a regulatory approval for the vaccine developed by Gamaleya Research Institute. Likewise, in June 2020, the Chinese military is reported to have given approval to the vaccine being developed by the Chinese company CanSino Biologics for a year as a specially needed drug.
The US Food and Drug Administration (FDA) has not yet approved or authorized any vaccine for COVID-19. Pfizer & BioNTech submitted their request for Emergency Use Authorization of their COVID-19 vaccine to the FDA. Emergency Use Authorization is issued when the FDA decides to administer the use of a drug, treatment, or vaccine amidst a pandemic or declared emergency. The Vaccines and Related Biological Products Advisory Committee (VRBPAC) of the FDA will be meeting on 10 December 2020 to discuss the request put forth by Pfizer & BioNTech.
Vaccine efficacy and effectiveness are different
Vaccine candidates in the last stage of trials have announced preliminary results of their efficacy. Efficacy of a vaccine is different from effectiveness. Researchers give vaccines to some people and a placebo to others (substances that resemble drugs but is made of inactive substance) and see how many get sick. For example, Pfizer had enrolled 43,661 volunteers for phase-3 of vaccine trial. Out of them, 170 got infected with COVID-19. Of the 170, a total of 162 of them were those who received a placebo shot. The remaining eight were those who had received the vaccine. Pfizer has announced that primary analysis demonstrates 95% efficacy.
What is given as 95% efficacy is the relative difference between the fraction of unvaccinated volunteers (those who received placebo shot) who got infected and the fraction of vaccinated volunteers who got infected. Thus, the efficacy of vaccine indicates the percentage reduction in disease occurrence among those vaccinated or in other words, the percentage decrease in the number of cases that would have been recorded if the vaccine were not introduced. The effectiveness of a vaccine on the other hand, measures the ability of the vaccine to prevent the disease in the real world, that is, among the general population. The WHO has suggested that the COVID-19 vaccine must have at least 50% efficacy on population basis.
What is the efficacy of the vaccines in advance stages of trials?
Pfizer’s initial results from the trial revealed that the vaccine was more than 90% effective in preventing COVID-19 in participants as per the interim analysis. Primary efficacy analysis showed that the vaccine had an efficacy rate of 95%. Further, the efficacy was consistent across age, gender, race, and ethnicity with an observed efficacy over 94% in adults over 65 years of age, according to Pfizer’s press release.
The vaccine developed by Moderna, as per the first interim review of data, had a efficacy of 94.5%. In the trials by Moderna, there were 95 symptomatic COVID-19 volunteers of which 90 were from the placebo group. Moderna is also intended to submit a request for Emergency Use Authorization in the US.
AstraZeneca announced that one of its dosing regimen was seen to be 90% effective when the volunteers received half a dose of the vaccine initially and a full dose after a month. Another dosing regimen showed 62% efficacy when volunteers received two full doses of the vaccine. Together, an average efficacy of 70% is seen. Serum Institute of India has partnered with Oxford University to produce this vaccine. The vaccine, Covishield, is low-cost, and logistically manageable, as tweeted by the institute’s CEO.
Russia’s Sputnik V which has already been approved by the Russian government has recorded an interim efficacy of 91.4% according to a press release. A total of 18,794 volunteers had received two doses and 39 had tested positive. The vaccine’s clinical trials are being conducted in India by Dr. Reddy’s Laboratories.
Who will distribute the vaccine first, when ready?
WHO has devised a COVID-19 vaccine allocation plan- Covax, under which fair allocations in two phases covering 20% of population and for expanding coverage will be done so as to ensure that all countries get an equitable access to the vaccine. The USA, which is among the worst hit by coronavirus, released a vaccine distribution strategy, Operation Warp Speed, under which several US Federal Government departments such as Health and Human Services (HSS), Agriculture, Energy, etc. and private sector will collaborate. In India, the Prime Minister recently reviewed preparedness of COVID-19 vaccine delivery, distribution, and administration. National and international institutions and regulators have been directed to collaborate. The Prime Minister also chaired a high-level meeting with all the Chief Ministers to review the status & preparedness of COVID-19 response. As per the official press release, the modalities of COVID-19 vaccine delivery, distribution and administration were also discussed during the meeting. However, the detailed distribution strategy has not yet been made public.
Multitude of challenges persist for vaccination
Majority of these trial results are announced through press releases leaving scientific concerns such as safety and effectiveness among older people unaddressed. Peer-reviewed publication is hence important and must not be side-lined while streamlining the approval process. On the other hand, information on how long the vaccine will protect is yet to be known. Even the side effects on a long-term basis are uncertain and can only be assumed based on the studies.
Even if the vaccines are approved through emergency authorization, carrying out immunization programs will also be a herculean task. Results of a survey, published in The Lancet showed that 14.2% of the respondents completely or somewhat disagreed with the statement that they would accept a COVID-19 vaccine if generally available and 17.9% completely or somewhat disagreed with the statement that they would accept a COVID-19 vaccine if their employer recommended it. Social media is flooded with a lot of misinformation pertaining to COVID-19 vaccines. In addition to this, the distribution infrastructure also poses a challenge.