SINGAPORE - A number of Covid-19 vaccine candidates are undergoing late-stage trials and if successful, may be used to inoculate millions from as early as next month. Singapore has been in talks with pharmaceutical companies working on some of them, to secure doses for people here, said Health Minister Gan Kim Yong.
They include Pfizer, the United States company which announced that the vaccine it is developing with German company BioNTech has proven 90 per cent effective in clinical trials.
Given the strong demand for Covid-19 vaccines worldwide, Singapore is unlikely to get enough for every person here in the initial months, or even in the first year, especially since many require two doses per person.
A committee has been formed to prioritise the people who should be given the vaccines as they become available.
Senior Health Correspondent Salma Khalik speaks to experts to understand who should be given priority, how much protection these vaccines will likely give, and if life can revert to pre-Covid-19 days after the vaccines are rolled out.
Q: Should Singapore go with the first vaccines available or wait for one that might be more effective or safer?
Professor Ooi Eng Eong of Duke-NUS Medical School, who is the principal investigator for one of the 48 Covid-19 vaccine candidates currently in human trials around the world, said the decision will depend on how high the risk of infection is.
If the risk is high, it makes sense to take whatever is available.
But he added that waiting a few months will not change much of the information available. "Early results would all be showing short-term protection against Covid-19. There would not be sufficient data to know which would offer the best long-term protection against Covid-19," he explained.
Professor Dale Fisher, a senior infectious diseases consultant at the National University Hospital (NUH), said taking whatever vaccine is available is important to "prevent spread, prevent disease and hospitals getting overwhelmed, and to prevent deaths".
However, if these are not priorities, then countries can afford to wait to see if there are "yet unidentified adverse reactions" and how long the vaccine is effective for.
He added that it is still unclear how the vaccines will affect the elderly, those who are immune suppressed or suffer from severe illness.
Associate Professor Hsu Li Yang, an infectious diseases expert at the NUS Saw Swee Hock School of Public Health, said that before vaccines become commercially available, the results of their licensing trials will already be public so "it will be reasonably clear how effective and safe they are compared with one another".
He added: "If the first vaccine is effective and safe, and the others in the pipeline are similar, then there is little benefit to holding out other than waiting to see if there is a significant price difference."
Q: Is a person protected immediately after getting vaccinated? Does protection kick in after the first dose of a two-dose vaccine?
Many of the vaccines require two doses, given about a month apart. Prof Ooi said most clinical trials of Covid-19 vaccines start to measure efficacy two weeks after the full dose has been given.
Prof Fisher said for vaccines that manufacturers say require two doses, it will take two doses to provide effective protection.
He said Pfizer measured efficacy 28 days after the second vaccine dose. He added that if the second dose is not taken close to the 21 to 28 days stipulated, "then the first dose will be wasted".
Prof Hsu said while the first dose will give some protection, "missing out the second dose for a long period of time may negate the booster effect" which is important to achieve the full protection of the vaccine.
Q: Is there any advantage in a population getting a range of vaccines, rather than just using one for the whole country?
Given the huge demand for vaccines, countries may not have much choice about which and how many vaccines they can get.
Prof Ooi said the decision about which vaccines to use should be based on the safety and efficacy data from their phase three clinical trials. However, it might not make sense to compare across trials as their designs may be so different as to make this possible.
Prof Fisher said there is no advantage in using several types of vaccines unless they respond differently in different groups.
For example, some vaccines might be more effective for older or sick people, others might have more adverse reactions for them but work well in healthy people.
The main advantage of using different Covid-19 vaccines, said Prof Hsu, "is that there will be multiple supply lines so we can obtain a greater number of vaccine doses for the population".
Q: How many different types of vaccines will likely be available by next year?
Prof Fisher, who chairs the World Health Organisation's Global Outbreak Alert and Response Network, said there are more than 200 vaccine candidates, of which 48 are in human trials. There are already 11 in the final phase three clinical trials and some of these should become available.
But he added: "This doesn't mean all vaccines will be acceptable. Indeed many won't be adequately effective or safe."
Prof Hsu said he expects at least four to five vaccines by next year, with some becoming available within months of each other.
Q: How long will the protection from the vaccines last? Will it be like the influenza vaccine, which needs to be taken annually?
It is too early to know. However, all the vaccine companies will be carrying out post-marketing surveillance which will be able to tell if booster vaccinations will be needed, and if so, when they should be given.
Prof Hsu said: "The duration of immunity after natural infection remains unknown at this point, and vaccines do not generally provide longer-lasting protection compared to natural infection."
Q: What does it mean when a vaccine is 90 per cent effective?
It means that among people taking part in a clinical trial, those who had received the vaccine were only one-tenth as likely to contact Covid-19, compared with those on placebo.
Associate Professor Alex Cook, vice dean of research at the NUS Saw Swee Hock School of Public Health said not enough is known about those who did get infected.
It may have been possible that they were infected before the vaccine took effect. All that tells us, he said, is that someone who has been vaccinated "probably" will not get Covid-19.
Prof Fisher explained that in the Pfizer trial, of the 22,000 people who received vaccine, only eight were infected. Of 22,000 who were given placebo 86 were infected.
"This is why we should watch this group of 44,000 people to see what happens to more people over time," he said.
Q: Once someone is vaccinated, would it serve as a passport to go about without a mask or social distancing?
Not in the early stages, said Prof Cook, but "when sufficient people are being vaccinated to reach herd immunity, then we could in principle make safe distancing optional".
Prof Hsu said people who have been vaccinated would not know if they form the 90 per cent who are protected or the 10 per cent who are not, unless they undergo testing to see if they have developed an immune response.
Prof Fisher said it would be difficult to personalise rules.
Q: What proportion of the population needs to be vaccinated for herd immunity to kick in?
That really depends on what the vaccine does, said Prof Ooi.
The primary goal now is for vaccines to protect against the disease, which means a person may get infected but not get sick. But this person might still pass the virus on to others.
It is only if the vaccine protects against infection that herd immunity can build up, since that would break the chain of transmission.
Prof Cook added that with a vaccine that is 90 per cent effective, about 60 per cent of the population needs to be vaccinated to confer herd immunity.
Prof Hsu added: "This doesn't mean that there will be no more Covid-19 cases. Just that outbreaks will be smaller and will naturally burn out each time they occur."
Q: Who should be given priority for the vaccines?
Singapore has set up a 14-member committee to look into this but some countries have already published their priority list.
In Britain, it will start with people aged 80 years and older, as well as health and social care workers. The next group are those 65 years and older, then younger high-risk individuals.
Family doctors will drive the immunisation exercise there, and will have to prioritise their other clinical activities to cope with the estimated 975 vaccinations per week needed at each location.
The European Union is prioritising people at risk and essential workers, as well as concentrating first on geographical locations with high incidence of infection.
Canada will be vaccinating the elderly, those with high-risk medical conditions, as well as people most likely to transmit the disease to the susceptible groups. These include healthcare workers and caregivers in long-term care facilities.
Also on Canada's priority list are people needed to maintain "essential services for the functioning of society" such as firefighters and grocery store staff.
Australia said priority groups include the elderly, aged-care and health workers, as well as other workers who are critical to the functioning of society.
Prof Cook said Singapore has a compact with healthcare workers.
"They put themselves in harm's way by working on the frontlines, and we owe them the protection to keep themselves well, as well as to avoid endangering their patients. This is a social debt we owe them regardless of their citizenship," he added.
He said given the stark differences in survival rates between older and younger people infected, the elderly should also be given high priority.
Prof Fisher said offering vaccines to healthcare workers and travellers can be justified. Given that there are about 100,000 people in healthcare, including the 58,000 doctors and nurses, there may be a need to risk stratify.
He added: "In Singapore our deaths have been in older people so I think we should focus there, or on nursing home workers."
Aside from those groups, Prof Fisher added: "Indeed our biggest threat remains migrant worker outbreaks and that as a strategy could well be justified."
Q: Should the Covid-19 vaccine be voluntary or compulsory?
It should be voluntary, said the experts, especially since there will not be enough for everyone at the beginning.
But Prof Cook added: "The exceptions are when you put others at acute risk by declining vaccination.
"For instance, a frontline healthcare worker who refuses the vaccine is potentially putting her or his patients at risk, and it's questionable whether that is ethically acceptable."
