Outlook

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the end of the year. Sanofi and GSK seem to investigate if a lower dose of their vaccine could generate a strong booster response in people previously vaccinated with other vaccines.

Sanofi and GSK initially aimed at a production of 1 billion doses in 2021 but an “unfortunate setback” – a laboratory error due to reagents of poor quality or purity? (Aeberhardt 2021) – led to an insufficient immune response in older adults in a previous Phase I/II trial (Sanofi 20201211). The setback delayed the development of the Sanofi/GSK vaccine by five to six months.

The immediate prospects of the COVID-19 pandemic are excellent, good or undetermined – depending on where you live.

Israel

The immediate prospects seem to be excellent for Israel (Balicier 2021). Soon, 60% of the total population will be fully vaccinated (Figure 2, green dots) which corresponds to more than 85% of the adult population as a third of the population is less than 16 years old. At the end of April, four months after the beginning of the vaccination campaign, the vast majority of adults had been vaccinated (see Table 14).

Table 14. Israel, percentage of adults having received the first vaccine dose (by age group, end of April 2021): +90 years 99.2% 80-89 95.8% 70-79 98.3% 60-69 89.9% 50-59 88.9% 40-49 84.3% 30-39 80.3% 20-29 76.2%

Despite an almost fully open economy since 7 March, the number of new daily cases has steadily declined ever since (Figure 2, red dashed line). From the peak in mid-January, the number of daily new cases has fallen by 98%, the

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number of new critically ill patients by 93%, and the number of daily deaths by 87% (Figure 3). Of interest, this effect was achieved with 60% of the population vaccinated (not 70%, 80% or 90%!). Israel was the theater of the pivotal Dagan study (Dagan 2021; see also Efficacy, page 224).

Figure 2. SARS-CoV-2 cases in Israel, 10 May 2021. Impact of mass vaccination on the pandemic. The rolling 7-day average of new SARS-CoV-2 cases is shown in red (left vertical axis), the rolling 7-day average of deaths as the solid black line (right vertical axis). The percentage of people that have received at least one vaccine dose is shown in dotted green. The percentage of people that have been fully vaccinated is shown in solid green. The evolution of daily new cases and deaths was influenced by lockdown measures, transmissibility of circulating viruses and the vaccination campaign.

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Figure 3. Israel, 25 April 2021. After a massive vaccination campaign, the number of daily new cases fell by 98% (blue), the number of new critically ill patients by 97% (orange), and the number of daily deaths by 99% (green). Source and copyright: Eran Segal, 25 April, https://bit.ly/3nneHgN.

During the first 112 days (December 2020 through April 2021), Israel’s vaccination campaign has been estimated to have averted at least 150,000 SARSCoV-2 infections, 17,000 severe and critical hospitalizations, and 5,000 deaths (91% of these averted among individuals ≥ 65 years of age) (Haas 2021b).

United States

For the US, the prospects are good. Although some states saw increasing numbers of daily new cases in what could have been the beginning of a fourth wave, the impressive US vaccination campaign was able to control the epidemic. In May, some Americans started discovering pre-COVID-19 freedom. The new recommendations published on 13 May by the CDC (CDC 20210513): • If you are fully vaccinated, you can resume activities that you did prior to the pandemic. In general, people are considered fully vaccinated: o 2 weeks after their second dose in a 2-dose series, such as the Pfizer or Moderna vaccines, or o 2 weeks after a single-dose vaccine, such as Johnson & Johnson’s Janssen vaccine • Fully vaccinated people can resume activities without wearing a mask or physically distancing, except where required by federal, state, local, tribal, or territorial laws, rules, and regulations, including local business and workplace guidance.

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• If you haven’t been vaccinated yet, find a vaccine. Find more details at https://www.cdc.gov/coronavirus/2019ncov/vaccines/fully-vaccinated.html. The last obstacle before achieving community-wide immunity and a return to some pre-COVID-19 life? Vaccine hesitancy!

France

On 19 May, the French government ordered the progressive easing of restriction measures and – unknowingly? – an informative experiment: will an aggressive vaccination campaign at a time of relatively low vaccination coverage (only 15% of the population was fully vaccinated and an additional 17% had received the first vaccine dose) be sufficient to end the national epidemic? Or will there be a fourth wave, particularly among young, non-vaccinated people? For comparison, Israel opened most of its economy after a two-month lockdown on 7 March, when 57.1% and 43.8% of the population had received one or two doses, respectively (Figure 4). Les jeux ne sont pas encore faits.

Figure 4. France in May 2021. “Daily new confirmed COVID-19 cases per million people”. Published online at OurWorldInData.org – accessed 24 May 2021.

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In check

Figure 3 (see above) provides a glimpse of a world where SARS-CoV-2 is being kept in check. Over the next months, we will address the following questions: • Are COVID vaccines effective in children from 6 months to 11 years of age? • Can vaccine doses from different manufacturers be used? (First dose with vaccine A, second dose with vaccine B?) Preliminary data suggest that the second dose of heterologous vaccine schedules (BioNTech/Pfizer + AstraZeneca; or AstraZeneca + BioNTech/Pfizer) might induce more frequent, generally mild adverse events (Shaw 2021). Data about the primary immunological outcome are expected in June. • Which percentage of vaccinated people will have symptomatic or asymptomatic SARS-CoV-2 infection within 6, 12, 18 or 24 months after vaccination?

• Do vaccines prevent long COVID in vaccinated people who develop symptomatic SARS-CoV-2 infection? • Are fully vaccinated people less likely to transmit SARS-CoV-2 to others if they get infected? • To what extent will the B.1.351 and P.1 variants escape vaccineinduced immunity? If yes, will ‘updated’ versions of existing vaccines, especially the mRNA vaccines, be available soon? o Will the efficacy of these second-generation mRNA booster vaccines be diminished by ‘antigenic sin’? Probably not. o Will these second-generation vaccines have acceptable side effects? Two pieces of good news are coming in from the variants front. The BioNTech vaccine has been shown to be effective against B.1.351 (first detected in South Africa). In Qatar, in a real-world test, the effectiveness against any B.1.351 infection was 75%, approximately 20 percentage points lower than the effectiveness reported in studies from Israel (Dagan 2021, Haas 2021); however, effectiveness against severe, critical, or fatal disease was well over 90% (AbuRaddad 2021). In vitro data had already suggested that the SARS-CoV-2 vaccines would retain activity against the B.1.351 (first detected in South Africa) and P.1 (Brazil) (Moyo-Gwete 2021, Liu Y 2021, Lustig 2021, Reynolds 2021). In a more distant future, we will appreciate how SARS-CoV-2 contributed to advances in medicine. One of the first achievements could be a pan-