Over the past few days, a debate has sparked on newspapers and over the internet: is a single dose of the COVID-19 vaccine effective against the infection? Is it better to follow the two-dose regimen as per human trials by the drug companies or is it better to delay the second dose in order to give the vaccine to a greater number of people?
Well, there are pros and cons in both strategies, not much data to support the single dose regimen, a wide range of opinion, and overall there is no right or wrong answer. It is not just a matter of medical science, but also of medical ethics.
First thing that needs to be said though is that if there was an unlimited supply of vaccine doses available right now and no issues in the supply chain, nobody would have started this discussion.
What are the experts saying about the single or 2-dose CoViD-19 vaccine debate?
Nobody is saying we should get a single dose of vaccine, but rather that we should delay the “booster” shot to 12 weeks after the first one instead of 2, 3 or 4 weeks as per human trials. The limited number of doses that each country has available for its population and the spiking number of cases, including a more infectious variant of the coronavirus, led to this dilemma and discussion. With regulatory agencies all of the world rushing to review the medical evidence and approve more and more of the currently studied vaccines (more than 40! ), we should expect an increase in the availability of CoViD-19 vaccine shots in the upcoming months. Fixing supply chain issues and an increased production should also help boost the number of vaccinations performed as we progress through the new year.
Another approach that is going to be discussed is splitting the current dosage (for the Moderna vaccine) in half to double the vaccinations [4,9][f], or to “mix and match” different vaccines depending on their approval and availability as the weeks go by.
What countries are considering a vaccination approach different from human trials?
The UK has already authorized delaying the second dose up to 12 weeks after the first one for both Pfizer and AstraZeneca vaccines. 
Denmark, Germany and Ireland are considering doing so as well.
Some experts voiced their opinion in the USA, but the FDA denied they will make any change without data supporting such choice. 
What is the current posology as per human trials and regulatory agency approval?
Moderna: 2 doses 4 weeks apart. About 95% efficacy rate.
Pfizer-BioNTech: 2 doses 3 weeks apart. About 95% efficacy rate 1 week after the second shot.
Oxford-AstraZeneca: 2 doses up to 12 weeks apart. 62% efficacy when 2 full doses administered and up to 90% efficacy when half dose primer and full dose booster administered.
Johnson & Johnson’s: 1 dose. Not approved, reviewing phase 3 trial data before seeking emergency approval (February 2021).
Bharat Biotech: 2 doses 4 weeks apart. Approved before phase 3 trial ending (India only, no published data on safety and efficacy).
Sinovac (China): 2 doses 2 weeks apart. Approved in some countries, data from phase 3 trials not published. 
Sputnik V (Russia): 2 doses 3 weeks apart. Approved in some countries, 91-95% efficacy.
Reasons for backing the single COVID-19 vaccine dose regimen
Saving more human lives is at the core of this debate. Greater vaccination coverage would decrease the deaths caused by this pandemic, even if not 100% effective. [2,20][k,l,m]
Herd immunity will not kick in until a high percentage of the population gets the vaccine and this approach would speed up reaching that objective. [l,m]
New strains of COVID, possibly more contagious, mean more stress on healthcare systems and more deaths more quickly. [l,m] New strains may also have reduced susceptibility to the currently developed vaccine. [n]
The first shot appears to provide already substantial benefit according to current data available. Sticking to the 2 shots schedule may be advised for high-risk categories, but there may be benefit in switching to single dose for everyone else. [l,m]
Since current (limited) data suggests immunity starting from 10-14 days after the first shot and even robust immunity in the case of the Moderna vaccine at 28 days after the first shot  it is unlikely that this immunity will suddenly drop by 8 or 12 weeks following a single dose vaccination. [l,m] Delaying the booster dose shouldn’t carry any risk (other than the increased risk of being infected by the coronavirus due to the lower efficacy of the single dose) nor have negative effects on the overall immunity after receiving the booster. [o] Delaying the doses may also actually improve efficacy. [17,i]
According to limited data a single dose of vaccine may be 52% effective (Pfizer), 73% effective (AstraZeneca ) and 90% effective (Moderna) although it is not known for how long. Regulatory agencies were willing to approve any vaccine proven safe with at least 50% effectiveness, so even if the single shot is a bit less effective as long as it stays above 50% efficacy should be fine. 
As some of the advocates of the delayed second dose say: “One dose could give a lot of protection … in the worst case, it will at least reduce the severity of the disease.” [8,e] and partial immunity is better than no immunity at all. [15,20][h,k] The purpose of this debate is to save many more lives. [17,h]
Reasons against the single COVID vaccine dose regimen
The main reasons against delaying the vaccine booster dose are that:
- There is no data to demonstrate that protection after a single dose is sustained after 21 days, it should be tested first in trials. [3,6,19][a,b,c,d,j]
- Partial immunity may cause the development of a new resistant strain
- It may cause further skepticism in the general public, who’s trust in this vaccine is not optimal.
- People may think they are protected when they are not and alter their behavior taking unnecessary risks. 
- Doubling the doses doesn’t fix the issues with distribution and administration of the doses, you need to be able to double that capacity as well. [10,g]
What do the regulatory agencies say?
On January 4th the US FDA released a statement about making changes in vaccine administration: while the changes are reasonable and should be evaluated in clinical trials, at this time, there is no evidence supporting such changes and for this reason they will not be supported by the FDA. 
The WHO as well feels the lack of evidence is reason enough to not support any changes.
The EU’s drug regulator (EMA) supports sticking to the schedule as per human trials and states that more data is needed before authorizing any change. 
The UK Joint Committee on Vaccinations and Immunisation (JCVI) recommends a 12-week delay between the primer shot and the booster shot. 
Meanwhile there is good news from a recent study that suggests that the presence of antibodies due to symptomatic or asymptomatic infection may substantially reduce the risk of SARS-CoV-2 reinfection for at least 6 months. 
Post Published on 6 Jan 2021
Covid-19 vaccination: What’s the evidence for extending the dosing interval?
The British Medical Journal, Jan 2021
a Dr. Tim Schacker, vice dean of research for the University of Minnesota Medical School.
b Dr. William Morice, President of Mayo Clinic Labs.
c Dr. Anthony S Fauci, director of the US National Institute of Allergy and Infectious Diseases.
d Pfizer and BioNTech.
e Dr. Stanley Plotkin, professor emeritus at the University of Pennsylvania.
f Dr. Moncef Slaoui, head of Operation Warp Speed, the US federal vaccine program.
g Dr. Saad B Omer, director of the Yale Institute for Global Health
h Dr. Michael Mina, asst. prof. at Harvard School of Public Health
i Dr. Andrew J Pollard, Director of the Oxford Vaccine Group
j World Health Organization
k Dr. Akiko Iwasaki, professor at Yale School of Medicine
l Dr. Ashish K Jha, dean of the Brown School of Public Health
m Dr. Robert M Wachter, chair of the department of medicine at UCSF
n Dr. Ali Nouri, president of the Federation of American Scientists
o British Society for Immunology
- 1 Questions hang over UK’s rollout of Oxford/AstraZeneca jab. Analysis: regulator surprises by approving 12-week gap between first and second shots of vaccine as well as Pfizer/BioNTech shot.
The Guardian, 30 Dec 2020
- 2 It’s time to consider delaying the second dose of coronavirus vaccine.
AK Jha, RM Wachter – The Washington Post, 03 Jan 2021
- 3 Experts Debate Wisdom of Delaying Second COVID-19 Vaccine Dose.
D McNamara – Medscape Medical News, 04 Jan 2021
- 4 US, UK Officials Seek to Stretch Vaccine Doses.
R Ellis – WebMD Health News, 04 Jan 2021
- 5 Draft landscape of COVID-19 candidate vaccines.
World Health Organization (WHO), 29 Dec 2020
- 6 FDA Statement on Following the Authorized Dosing Schedules for COVID-19 Vaccines.
U.S. Food & Drug Administration, 04 Jan 2021
- 7 Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers.
SF Lumley et al. – The New England Journal of Medicine, Dec 2020
- 8 Why you’re not fully protected from COVID-19 after a single vaccine dose.
M de Graaf, H brueck – businessinsider.com, 5 Jan 2021
- 9 U.S. May Cut Some Moderna Vaccine Doses in Half to Speed Rollout, Official Says.
B Pierson – Reuters, 5 Jan 2021
- 10 Covid-19: Virus Hammers California as Deaths and Hospitalizations Surge.
The New York Times, 6 Jan 2021
- 11 Covaxin: What was the rush to approve India’s homegrown vaccine?
BBC News, 5 Jan 2021
- 12 Brazil institute says CoronaVac efficacy above 50%, but delays full results.
Reuters, 24 Dec 2020
- 13 WHO Target Product Profiles for COVID-19 Vaccines.
World Health Organization, Apr 2020
- 14 Questions hang over UK’s rollout of Oxford/AstraZeneca jab.
The Guardian, 30 Dec 2020
- 15 Tweet by Michael Mina
- 16 Second interim analysis of clinical trial data showed a 91.4% efficacy for the sputnik v vaccine on day 28 after the first dose; vaccine efficacy is over 95% 42 days after the first dose.
Press Release – sputnikvaccine.com , 24 Nov 2020
- 17 U.K. Authorizes Covid-19 Vaccine From Oxford and AstraZeneca.
The New York Times, 30 Dec 2020
- 18 UK Healthcare Products Regulatory Agency, 29 Dec 2020
- 19 No data to support UK delay of vaccines’ second dose, says WHO.
The Guardian, 5 Jan 2021
- 20 Tweet by Akiko Iwasaki
- 21 Tweet by Ali Nouri
- 22 Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
LR Baden et al. – The New England Journal of Medicine, Dec 2020
- 23 Covid-19 vaccination: What’s the evidence for extending the dosing interval?
The British Medical Journal, Jan 2021
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