High vaccine uptake can control pandemic even with lifting social distancing

That vaccines can protect against Covid-19, in its severe forms, is well established from clinical trials.  Questions remained as to whether (i) when applied to the wider population, these benefits would hold, (ii) vaccines could reduce transmission and asymptomatic infection and (iii) in the ‘real world’ these benefits would be achieved after allowing a return to ‘normal life’.  Data published this weekend in the Lancet from Israel suggests that, at least for the Pfizer vaccine,  the concerns raised by these questions can be discounted

What did we know before this study?

• In clinical trials two doses of the vaccines achieved a reduction in the risk of contracting severe Covid-19 by over 90% in the 1-2 month period after vaccination
• There were more modest reductions in the risk of asymptomatic infections, suggesting that the vaccines may be less successful at stopping transmission

What did we want to know?

• Whether the reduction in severe infections was sustained for longer periods – it was always considered this was likely, but the clinical trials were too short to address this
• Whether if enough people were vaccinated, the cumulative effect would be to reduce transmission within a community – leading to eventually a greater reduction in asymptomatic cases 
• Whether premature lifting of social measures, despite high vaccination rates, would increase transmission and ensure the persistence of a ‘pool’ of infected cases within the community

How the Israeli experience can address these unknowns

• As has been well publicised, Israel has been the leader internationally in the speed of vaccinating its adult population.
• Only the Pfizer vaccine has been used in Israel and at the recommended 3 week interval
• There had been a steady roll out of the vaccine programme since the beginning of December

• By 3 April, 60% of all adults had had two doses, including 90% of those over 65  
• Israeli public health officials, as part of the ‘deal’ for Pfizer to provide Israel with enough vaccine to cover the country rapidly, agreed to collect data on all the cases of Covid-19 that arose since the start of the vaccine programme
• The epidemiologists in Israel have therefore been able to compare the risks of developing Covid-19 infection between people who had, and had not, been vaccinated

How did the Israelis do their analysis?

(You can skip this part if you want and go to the results below!)

• The analysis was quite complex but let me explain what they did
• The population data were obtained from the 2020 census and thus all adults were included in the analysis
• Data were gathered on all cases recorded in Israel from 24 January until 3 April 2021
• Cases of Covid-19 were identified both from the widely and freely available laboratory testing in that country as well as those who were admitted to hospitals
• It was thus possible to analyse separately the benefits of vaccination on reducing the risk of :
  • Cases with no symptoms (just from testing)
  • Cases with  symptoms but who had not gone to hospital
  • Cases in hospital
  • Cases classified as severe (life threatening)
• People who had only had one dose of the vaccine, and those whose second dose was less than one week before the end of the surveillance period, were excluded
• The research thus compared the reduction in the risk of infection between 
  • people who had been vaccinated, at least 7 days after their second dose 
  • people either (i) who remained unvaccinated or (ii) in those who were vaccinated – in the period before their second dose (+7 days)
  • To explain (ii) above consider the diagram below

• Suppose an individual had completed the course of vaccine on 19^th February, so by 26^th February they would be considered fully vaccinated 
• If they had developed Covid-19 in the 30 days up to26^th February (the orange period) this case would be counted as having occurred in a non-vaccinated person
• If they had developed Covid-19 in the 36 days after 26^th February up to April 3^rd (the blue period) this case would be counted as having occurred in a vaccinated person
• This person therefore contributed 30 unvaccinated and 36 vaccinated days to the overall analysis
• The rates of infection could then be compared between the total of ‘unvaccinated days’ and ‘vaccinated days’ in the whole population 

What did they find?

• The headline result was that the rate of infection in vaccinated people (expressed as cases per 100,000 vaccinated days) was much lower than in people who had not been vaccinated
• This was as true for very severe cases as for those which had been detected by testing but had not had symptoms

• The data can also be expressed as the reduction in risk following vaccination: ie how much less in percentage terms were the rates of infection between days after compared to before vaccine (or in those who had had not had any dose)
• This is what they found:

• There was an over 90% reduction in all cases, whatever their severity

How do these figures relate to the relaxation of lockdown measures?

• The helpful diagram below shows on the same chart the path of relaxation of lockdown measures and the rate of cases as reported by the laboratory

• Israel was going through a serious second wave at the end of the year when the vaccine programme began
• This was then accompanied by a stringent lockdown as well as the rapid rolling out of the vaccine programme
• There was a progressive reopening of Israeli society during February, but despite that  the number of cases has continued to fall
• Given the reduction shown above in the number of cases in the days following  vaccination, it is reasonable to conclude that:
  • Re-opening society clearly did not reduce the impact of the vaccine programme on the number of cases
  • The reduction in the numbers of all cases (ie including asymptomatic cases) suggests that transmission has also fallen again despite relaxation of lockdown and hence widespread vaccination is also leading to an interruption of transmission hastening the end of the pandemic.

Any cautions?

• The predominant variant in Israel in this period has been the UK variant, so if another variant took hold the results may not be as positive
• The data only refer to the Pfizer vaccine and for example other vaccines such as AstraZeneca may not achieve the same results
• As mentioned above it is still early days and we only have 5 months of data; waning immunity following vaccination is still a possibility  
• Israel is a very mixed society with a large number of ultra-Orthodox who have been at particular risk of infection
  • Indeed there were differences in vaccine rates between ultra-Orthodox and other population groups with only 40% of the former being vaccinated compared to 80% of the remaining Jewish population  

• It remains therefore to be seen if sub-groups such as the ultra-orthodox will continue to harbour the infection 

Conclusions

• I believe these data do add importantly to our view about the potential of a successful vaccine programme being capable of ending this pandemic whilst allowing a return to normal life within a reasonable period of time
• Whether this can be replicated in other countries  remains to be tested in time

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