The Delta variant of the novel coronavirus is fighting back strongly. Prevention needs to learn from the real-world data of vaccines

Is it necessary to get a third booster shot? Who should get it? When is the best time to get it? Should social isolation policies be tightened or relaxed? ... Close observation and analysis of epidemiological data of the COVID-19 pandemic in other countries and regions will help us make appropriate epidemic prevention decisions.

Written by | Shi Jun

Although Israel leads the world in COVID-19 vaccination rates (more than 80% of adults have been vaccinated), the epidemic in Israel has shown signs of a resurgence in recent times, with a sharp increase in cases of the Delta variant of the coronavirus. According to a report from the Hebrew University of Jerusalem, 90% of new cases over the age of 15 were people who had completed vaccination. On July 23, Israeli media reported that the Pfizer vaccine was only 39% effective in preventing the spread of the Delta variant, but it could still prevent severe illness.

At the same time, the number of new crown cases in various parts of the United States has also increased. Similarly, a considerable number of confirmed cases are people who have completed vaccination, often referred to as breakthrough cases. As of July 17, Massachusetts has counted 5,166 breakthrough cases. Of these, 272 people were hospitalized and survived; 80 people died, including 23 who died without being hospitalized; and 57 died after being hospitalized. There are 4,344,836 fully vaccinated residents in Massachusetts, accounting for 63% of all residents.

Many doctors believe that the biggest reason for the recurrence of the epidemic is that the Delta variant is twice as contagious as the original strain.

Figure 1: News reports of an increase in the number of new infections in Massachusetts, USA[1]

Personally, I think there may be four reasons for this wave of repeated epidemics:

The variant strain is more contagious.

The effectiveness of the vaccine decreases over time.

The vaccines are less effective against the variants.

People who have been vaccinated are more likely to be careless and not pay attention to basic protection.

In addition to the Delta variant, what other variants are worth worrying about?

In early February of this year, I reviewed the variants of the coronavirus that had emerged at that time (see "A Review of the Variants of the Coronavirus: Mutations Will Continue, Where Will Humanity Go? | 117 Three People"). Since then, several new variants have emerged. On May 31, the World Health Organization adopted a new system to name the variants of the coronavirus.

Before the naming change, these variants, in addition to the letter + number names commonly used by the scientific community, were often referred to by the country where they were first discovered. For example, B.1.1.7, first discovered in the UK, is often called the "UK variant", while B.1.351 is called the "South African variant" and the newer B.1.617.2 is called the "Indian variant."

The new naming system uses Greek letters instead of the country names commonly used by the public, nor the "letter + number" model commonly used in the scientific community. This can avoid stigmatizing these countries. In addition, Greek letters are easier to pronounce and suitable for discussions among the general public, and can avoid the disadvantage of "letter + number" being difficult to remember. At the same time, scientists will continue to use the "letter + number" naming system.

It is not unnecessary to have a naming system to avoid stigmatization.

After the Delta variant was discovered in India and spread rapidly in many countries around the world, the Indian government asked social media platforms to delete content related to the "Indian variant." The WHO is worried that if the old naming method is used, countries may be reluctant to report new variants because they are worried that the new variants will be named after their own country.

The cruel truth is: as long as the number of new COVID-19 cases is not cleared to zero, new variants will appear.

When new variants emerge, scientists will work hard to understand their characteristics, such as:

Is it easier to spread?

Will it lead to more serious illness?

Can currently available virus testing methods detect it?

How do you respond to current COVID-19 drugs?

Also, have the vaccines currently approved for use weakened their ability to prevent diseases?

Studies have shown that so far, the coronavirus has several mutations in its spike protein that are particularly troublesome. Cases caused by coronavirus variants with these mutations may make specific monoclonal antibody therapies less effective. These mutations include:

L452R mutation. Found in several variants.

E484K mutation. Found in several variants.

K417N, E484K and N501Y mutation combination. Present in the Beta (B.1.351) variant.

The combination of K417T, E484K and N501Y mutations is present in the Gamma (P.1) variant.

The characteristics of several major new coronavirus variants can be summarized in the following table:

*The cited article has not been peer reviewed.

We often hear that the Delta variant is more contagious, but how is the Delta variant different from the original novel coronavirus? A new study recently further analyzed this variant[23].

There are several possible reasons why a virus becomes more contagious:

More falls off from the host.

The infectious period is prolonged, giving the virus a longer time to break away from the host's body and infect others.

The infectivity increases, and it can better infect host cells and bind better to receptors on the cell surface.

The stability in the environment is increased, more resistant to humidity and heat, etc.

Researchers investigated the first local transmission of the Delta variant in mainland China, and all 167 cases collected were traced back to the same source. Epidemiological data analysis showed:

After being exposed to the virus, people infected with the Delta variant tested positive more quickly, suggesting that the Delta variant grows faster in the body;

People infected with the Delta variant had a viral load 1,000 times higher than those infected with the original 2020 strain when first tested.

This shows that compared with the initial strain, the incubation period of the Delta variant is shorter, and the infected person excretes (spreads) 1,000 times more virus than before, which greatly increases the chance of infection for close contacts. At the same time, the shortened incubation period also means that people infected with the Delta variant can become contagious faster and have more opportunities to infect others. In other words, the virus spreads more efficiently.

By tracing the virus's transmission path and conducting phylogenetic analysis, the study also found that among the 167 cases, the Delta variant was transmitted through direct contact and indirect transmission, the latter most likely through aerosols rather than pollutants. In other words, the main transmission route of the Delta variant is still direct contact and indirect transmission through aerosols, rather than the popular rumor that it is "easier to spread in the air."

Figure 2. The solid line indicates highly confident direct contact transmission, and the dotted line indicates possible indirect transmission[23]. (Click to see larger image)

Therefore, there are two main reasons for the increased transmission rate of the Delta variant: more virus and faster transmission speed. However, the transmission method has not changed.

The effectiveness of existing vaccines against the Delta variant is not exactly the same, and research conclusions in different countries are not exactly the same.

A recent study published in the New England Journal of Medicine, based on real-world data from the UK, confirmed the vaccine efficacy data published by Public Health England in May. The study found that in the UK, two doses of the Pfizer COVID-19 vaccine were 88% effective in preventing symptomatic cases caused by the Delta variant and 93.7% effective against the Alpha variant. Two doses of the Oxford-AstraZeneca vaccine were 67% effective against the Delta variant and 74.5% effective against the Alpha variant[24].

Preliminary data from a small-scale study in Israel suggest that the effectiveness of the Pfizer vaccine in preventing COVID-19 infection has declined in recent weeks. According to the Israeli Ministry of Health, between June 20 and July 17 (the exact number of cases has not yet been announced), the Delta variant dominated COVID-19 cases in Israel. After two doses, the Pfizer vaccine was 39% effective in reducing the risk of infection, 40% effective in reducing symptomatic cases, 88% effective in reducing hospitalizations, and 91% effective in reducing the risk of severe illness [25].

There are two points worth considering about the cases of Israel and the United Kingdom:

First, Israel started mass vaccination relatively early, and the protective effect of the vaccine may have begun to decline.

Second, in the UK, the interval between the two injections of the Pfizer vaccine is more than 8 weeks, while in Israel the traditional interval is 3 weeks.

The UK initially extended the interval between the two doses of the Pfizer COVID-19 vaccine to 12 weeks at the end of 2020. As vaccine coverage in the UK has increased, this interval has now been shortened to 8 weeks. A preprint article that has not been peer-reviewed examined the immune response of 503 UK National Health Service (NHS) workers after receiving the Pfizer COVID-19 vaccine[26]. These workers received two injections at different time intervals in late 2020 and early 2021, when the Alpha variant was spreading rapidly in the UK. One month after the second injection, the researchers measured the antibody levels in the blood of these 503 people.

The results of the study showed that:

Regardless of whether the interval between the two injections of the Pfizer vaccine is short or long, it generally produces a strong immune response.

A 3-week vaccination interval produced less neutralizing antibodies than a 10-week interval.

After the first shot, although the antibody level decreased, the level of T cells (cellular immunity) remained high.

The longer intervals resulted in fewer total T cells, but a higher proportion of a specific type, called helper T cells, which are key to supporting immune memory.

Professor Susanna Dunachie, the lead researcher of the study, said that two shots of the Pfizer vaccine are better than one shot, but the interval between the two shots can be flexibly arranged according to the situation. For the current situation in the UK, she believes that an eight-week interval is the best time.

Although this kind of close observation and analysis of data is conducted in Israel, the United Kingdom and other countries and regions in the world, it has important implications for the public health policies of other countries. For example, whether and when a third booster shot is needed? Is it necessary to resume social isolation? And other questions can all be made by referring to the data of these countries and regions.

Existing COVID-19 vaccines are developed for strains that haven't had these mutations. Although studies have shown that existing COVID-19 vaccines are less effective against some variants, they still appear to prevent severe illness after infection. Further research is needed to determine the exact conclusions, and vaccine manufacturers are also developing new vaccines for these variants.

References

[1] https://www.nbcboston.com/news/local/more-than-5100-breakthrough-covid-cases-reported-in-mass-at-least-80-have-died/2435719/.

[2] Davies, NG, et al., Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science, 2021. 372(6538).

[3] https://depts.washington.edu/pandemicalliance/2021/01/25/nervtag-note-on-b-1-1-7-severity/.

[4] https://www.fda.gov/media/145802/download.

[5] Wang, P., et al., Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature, 2021. 593(7857): p. 130-135.

[6] Shen, X., et al., SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines. Cell Host & Microbe, 2021. 29(4): p. 529-539.e3.

[7] Edara, VV, et al., Infection and mRNA-1273 vaccine antibodies neutralize SARS-CoV-2 UK variant. 2021: p. 2021.02.02.21250799.

[8] Collier, DA, et al., Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies. Nature, 2021. 593(7857): p. 136-141.

[9] Wu, K., et al., mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants. 2021: p. 2021.01.25.427948.

[10] https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3779160.

[11] https://cmmid.github.io/topics/covid19/reports/sa-novel-variant/2021_01_11_Transmissibility_and_severity_of_501Y_V2_in_SA.pdf.

[12] https://www.fda.gov/media/145611/download.

[13] Madhi, SA, et al., Safety and efficacy of the ChAdOx1 nCoV-19 (AZD1222) Covid-19 vaccine against the B.1.351 variant in South Africa. 2021: p. 2021.02.10.21251247.

[14] https://ir.novavax.com/press-releases.

[15] https://www.jnj.com/johnson-johnson-covid-19-vaccine-authorized-by-us-fda-for-emergency-usefirst-single-shot-vaccine-in-fight-against-global-pandemic.

[16] Wang, P., et al., Increased Resistance of SARS-CoV-2 Variant P.1 to Antibody Neutralization. 2021: p. 2021.03.01.433466.

[17] Deng, X., et al., Transmission, infectivity, and antibody neutralization of an emerging SARS-CoV-2 variant in California carrying a L452R spike protein mutation. 2021: p. 2021.03.07.21252647.

[18] https://khub.net/documents/135939561/405676950/Increased+Household+Transmission+of+COVID-19+Cases+-+national+case+study.pdf/7f7764fb-ecb0-da31-77b3-b1a8ef7be9aa.

[19] Jangra, S., et al., SARS-CoV-2 spike E484K mutation reduces antibody neutralization. The Lancet Microbe, 2021. 2(7): p. e283-e284.

[20] Annavajhala, MK, et al., A Novel and Expanding SARS-CoV-2 Variant, B.1.526, Identified in New York. 2021: p. 2021.02.23.21252259.

[21] Greaney, AJ, et al., Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies. Cell Host & Microbe, 2021. 29(3): p. 463-476.e6.

[22] Garcia-Beltran, WF, et al., Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. Cell, 2021. 184(9): p. 2372-2383.e9.

[23] https://virological.org/t/viral-infection-and-transmission-in-a-large-well-traced-outbreak-caused-by-the-delta-sars-cov-2-variant/724.

[24] Lopez Bernal, J., et al., Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. 2021.

[25] https://www.cnbc.com/2021/07/23/delta-variant-pfizer-covid-vaccine-39percent-effective-in-israel-prevents-severe-illness.html.

[26] https://www.pitch-study.org/PITCH_Dosing_Interval_23072021.pdf.