Virus World

The BA.2.75* sublineage of SARS-CoV-2 B.1.1.529 (omicron) variant escapes neutralizing antibodies. We estimated effectiveness of prior infection in preventing reinfection with BA.2.75* using a test-negative, case-control study design. Effectiveness of prior pre-omicron infection against BA.2.75* reinfection, irrespective of symptoms, was 6.0% (95% CI: 1.5-10.4%). Effectiveness of prior BA.1/BA.2 infection was 49.9% (95% CI: 47.6-52.1%) and of prior BA.4/BA.5 infection was 80.6% (95% CI: 71.2-87.0). Effectiveness of prior pre-omicron infection followed by BA.1/BA.2 infection against BA.2.75* reinfection was 56.4% (95% CI: 50.5-61.6). Effectiveness of prior pre-omicron infection followed by BA.4/BA.5 infection was 91.6% (95% CI: 65.1-98.0).

Analyses stratified by time since prior infection indicated waning of protection since prior infection. Analyses stratified by vaccination status indicated that protection from prior infection is higher among those vaccinated, particularly among those who combined index-virus-type vaccination with a prior omicron infection. A combination of pre-omicron and omicron immunity is most protective against BA.2.75* reinfection. Viral immune evasion may have accelerated recently to overcome high immunity in the global population, thereby also accelerating waning of natural immunity.

Preprint available in medRxiv (Oct. 30, 2022):

https://doi.org/10.1101/2022.10.29.22281606 

Two doses of COVID vaccine cut the risk of infection and mild illness from the rising BA.2 subvariant, although protection wanes quickly.  The Omicron subvariant BA.2 is replacing its sister version, BA.1, as the dominant form of SARS-CoV-2 in many countries, which has led scientists to wonder whether the COVID-19 pandemic is about to throw these regions into disarray yet again. But a study1 published on 13 March shows that mRNA vaccines offer a similar degree of protection against the two strains — although protection against SARS-CoV-2 infection and symptomatic disease wanes within months of a third dose.

The study, published on the preprint server medRxiv, has not yet been peer reviewed. Researchers have known for months that the BA.1 subvariant evades much of the protection that mRNA vaccines offer against mild-to-moderate disease. Scientists quickly realized that BA.2 spreads more rapidly than BA.1, but it wasn’t immediately clear whether the newcomer would also prove to be more adept at evading vaccines.  “BA.2 could be even worse than BA.1 — this was the fear,” says Laith Abu-Raddad, an infectious-diseases epidemiologist at Weill Cornell Medicine–Qatar in Doha and a co-author of the study.

Abu-Raddad and his colleagues performed a massive observational study using vaccination records and SARS-CoV-2 test results from Qatar’s health-care system. They found that Qatari residents who received two doses of either the Pfizer–BioNTech or Moderna mRNA-based vaccine enjoyed several months of substantial protection against symptomatic disease caused by either BA.1 or BA.2. But protection waned to around 10% after only 4–6 months, meaning that the vaccines prevented only 10% of the cases that would have occurred if all of the individuals had been unvaccinated. Protection against BA.2 did not seem to wane any faster than protection against BA.1, and a booster shot brought the protection against symptomatic infection by either subvariant back to 30–60%. Surveillance data collected in the United Kingdom reveal a similar trend: vaccine effectiveness against symptomatic COVID-19 is less than 20% for both subvariants 25 weeks or more after a second dose, but rises to roughly 70% 2–4 weeks after a third dose. The researchers also analysed the degree of protection that mRNA vaccines offer against severe disease, but to do so they had to pool the data on BA.1 and BA.2 cases — a measure that was necessary because Qatar’s population is strongly skewed towards young people, making severe COVID-19 cases rare. Only after pooling did the researchers have enough cases to achieve meaningful results. This analysis showed that protection against severe disease remained at 68% or higher for at least 7 months, even in people who had only received two vaccine doses, and shot up to over 80% after a booster dose. Abu-Raddad says that because 70-80% of the pooled cases were BA.2, he suspects that vaccines still offer a high level of protection against severe disease in the face of surging BA.2 levels. 

Promising results

In an e-mail to Nature, virologist Andrew Pekosz at Johns Hopkins University in Baltimore, Maryland, wrote that, overall, the work is “a very sound study. Qatar has been at the lead when it comes to reporting data on COVID-19 vaccine effectiveness in a very rapid manner.” Abu-Raddad says the results give him hope because vaccines prevent many of the worst COVID-19 cases, even in response to BA.2. “The vaccines are actually working remarkably well, given the challenges of evolution,” he said. Pekosz agrees, adding in his e-mail that the results emphasize the importance of booster doses. “Focusing on the primary vaccination schedule isn’t enough any more. There have to be plans to effectively get populations vaccinated through a booster,” he wrote. But going forwards, Abu-Raddad thinks researchers should move away from designing vaccines against single variants and instead focus on pan-coronavirus vaccines. “This would be a more fundamental solution for the future,” he says.

Research cited available inn medRxiv (March 13, 2022):

https://doi.org/10.1101/2022.03.13.22272308 

Data from Qatar provide strongest evidence yet that COVID-19 vaccines can stop strains thought to pose a threat to immunization efforts.  Qatar’s second wave of COVID-19 was a double whammy. In January, after months of relatively few cases and deaths, the Gulf nation saw a surge driven by the fast-spreading B.1.1.7 variant, which was first identified in the United Kingdom. Weeks later, the B.1.351 strain, which is linked to reinfections and dampened vaccine effectiveness, took hold. Amid this storm, researchers in Qatar have found some of the strongest evidence yet that current vaccines can quell variants such as B.1.351. Clinical trials in South Africa — where B.1.351 was first identified — had suggested that vaccines would take a hit against such variants. But this study offers a fuller picture of what countries battling such variants can expect.  People in Qatar who received two doses of the Pfizer–BioNTech vaccine were 75% less likely to develop a case of COVID-19 caused by B.1.351 than were unvaccinated people, and had near-total protection from severe disease caused by that strain. The findings — published on 5 May in The New England Journal of Medicine1 — suggest that current RNA vaccines are a potent weapon against the most worrisome immune-evading variants. Pfizer, based in New York City, and BioNTech, in Mainz, Germany, are developing an updated RNA vaccine targeting B.1.351, as is Moderna, based in Cambridge, Massachusetts. Early results from Moderna’s efforts suggest that a booster shot of the updated vaccine triggers a strong response against B.1.351. “I think this variant is probably the worst of all the variants we know,” says Laith Jamal Abu-Raddad, an infectious-disease epidemiologist at Weill Cornell Medicine—Qatar in Doha, who led the Qatari study. “We have the tools, despite these variants, to control at least the severe forms of infection — and this should work quite well on transmission.”

Weaker protection

Researchers in South Africa identified B.1.351 in late 2020, and it’s now the predominant strain there. Laboratory studies show that the variant harbours mutations that blunt the effects of virus-blocking antibodies, and trials suggest that some COVID-19 vaccines are significantly less effective against the strain than against others. Early lab research suggested that RNA vaccines, including the Pfizer–BioNTech jab, would be weakened by B.1.351, but probably not fully compromised. In April, the companies announced that a small trial in South Africa had found the vaccine to be fully effective against B.1.351, but the study of 800 people recorded a total of just 6 infections caused by B.1.351 in the placebo group, so efficacy might have been much lower.  Abu-Raddad’s team analysed tens of thousands of COVID-19 cases that occurred between the start of Qatar’s vaccination campaign in late December and the end of March. Genome sequencing showed that B.1.1.7 and B.1.351 were the predominant coronavirus lineages during this period and, from mid-February, each accounted for about half of the country’s cases.  The researchers compared SARS-CoV-2 infection rates in vaccinated people with those in unvaccinated controls. People who received two vaccine doses were about 90% less likely to develop an infection caused by B.1.1.7, echoing findings from Israel, the United Kingdom and elsewhere. The researchers identified around 1,500 ‘breakthrough’ infections caused by the B.1.351 variant in vaccinated individuals, but only 179 of these occurred more than 2 weeks after the second dose. There were hardly any severe cases of COVID-19 caused by either B.1.1.7 or B.1.351 among fully vaccinated individuals. “Even though there were breakthrough infections, they didn’t lead to hospitalization and death, except very, very rarely,” says Abu-Raddad. Two people died of COVID-19 caused by B.1.351 after receiving their second vaccine dose, but it is very likely that they were infected before the protective effects of the booster shot began. “If, a year ago, I told somebody we would have 75% effectiveness against the worst variants we had, they would consider this extremely good news,” Abu-Raddad adds.

Promising data

Shabir Madhi, a vaccinologist at the University of the Witwatersrand in Johannesburg, South Africa, says the Qatari results are promising. The comparatively high levels of virus-blocking antibodies triggered by two doses of an RNA vaccine probably explain why it confers better protection against B.1.351 than do other vaccines, such as the one developed by the University of Oxford, UK, and pharmaceutical company AstraZeneca in Cambridge, UK. But Madhi expects that other vaccines will also prevent severe disease caused by that variant. In another 5 May New England Journal of Medicine study2, his team reported that the jab produced by biotechnology company Novavax in Gaithersburg, Maryland, lowered the risk of getting COVID-19 by 60% in participants without HIV in a South African trial involving more than 6,000 people. As-yet unpublished data show that the vaccine was highly effective against severe cases of COVID-19 caused by B.1.351, with no cases in vaccinated individuals and five in the placebo arm.  If vaccine efficacy is lower against B.1.351, even highly successful immunization programmes in countries affected by the variant might not reduce cases to the same extent as in countries dealing with less troublesome strains, says Madhi. “Nevertheless, by protecting high-risk individuals, we could still return to a relatively normal lifestyle, even with ongoing circulation.” Qatar, where more than one-third of the population has received at least one dose of the vaccine, might provide an early glimpse at how the worst coronavirus variants can be controlled. Abu-Raddad says there is evidence that the Pfizer–BioNTech vaccine might also be highly effective at blocking transmission of B.1.351. And after cases of the variant peaked in mid-April, he says, “things have been going extremely well, the numbers are going down very, very rapidly”.

Publication cited available in NEJM (May 5, 2021):

https://www.nejm.org/doi/10.1056/NEJMc2104974

See also The Lancet (May 5, 2021):

https://doi.org/10.1016/S0140-6736(21)00947-8 

This study estimates the effectiveness of previous infection with SARSCoV2 in preventing reinfection with Omicron BA.4/BA.5 subvariants using a test negative, case control study design. Cases (SARSCoV2 positive test results) and controls (SARSCoV2 negative test results) were matched according to sex, 10 year age group, nationality, comorbid condition count, calendar week of testing, method of testing, and reason for testing. Effectiveness was estimated using the S gene target failure (SGTF) infections between May 7, 2022 and July 4, 2022. SGTF status provides a proxy for BA.4/BA.5 infections, considering the negligible incidence of other SGTF variants during the study. Effectiveness was also estimated using all diagnosed infections between June 8, 2022 and July 4, 2022, when BA.4/BA.5 dominated incidence. Effectiveness of a previous pre-Omicron infection against symptomatic BA.4/BA.5 reinfection was 15.1% (95% CI: -47.1 to 50.9%), and against any BA.4/BA.5 reinfection irrespective of symptoms was 28.3% (95% CI: 11.4 to 41.9%).

Effectiveness of a previous Omicron infection against symptomatic BA.4/BA.5 reinfection was 76.1% (95% CI: 54.9 to 87.3%), and against any BA.4/BA.5 reinfection was 79.7% (95% CI: 74.3 to 83.9%). Results using all diagnosed infections when BA.4/BA.5 dominated incidence confirmed the same findings. Sensitivity analyses adjusting for vaccination status confirmed study results. Protection of a previous infection against BA.4/BA.5 reinfection was modest when the previous infection involved a preOmicron variant, but strong when the previous infection involved the Omicron BA.1 or BA.2 subvariants. Protection of a previous infection against BA.4/BA.5 was lower than that against BA.1/BA.2, consistent with BA.4/BA.5 greater capacity for immune system evasion than that of BA.1/BA.2.

Preprint available at medRxiv (July 12, 2022):

https://doi.org/10.1101/2022.07.11.22277448 

BACKGROUND: Qatar experienced a large SARS-CoV-2 Omicron (B.1.1.529) wave that started on December 19, 2021 and peaked in mid-January, 2022. We investigated effects of Omicron subvariant (BA.1 and BA.2), previous vaccination, and prior infection on infectiousness of Omicron infections, between December 23, 2021 and February 20, 2022.

METHODS: Univariable and multivariable regression analyses were conducted to estimate the association between the RT-qPCR cycle threshold (Ct) value of PCR tests (a proxy for SARS-CoV-2 infectiousness) and each of the Omicron subvariants, mRNA vaccination, prior infection, reason for RT-qPCR testing, calendar week of RT-qPCR testing (to account for phases of the rapidly evolving Omicron wave), and demographic factors.

RESULTS: Compared to BA.1, BA.2 was associated with 3.53 fewer cycles (95% CI: 3.46-3.60), signifying higher infectiousness. Ct value decreased with time since second and third vaccinations. Ct values were highest for those who received their boosters in the month preceding the RT-qPCR test - 0.86 cycles (95% CI: 0.72-1.00) higher than for unvaccinated persons. Ct value was 1.30 (95% CI: 1.20-1.39) cycles higher for those with a prior infection compared to those without prior infection, signifying lower infectiousness. Ct value declined gradually with age. Ct value was lowest for those who were tested because of symptoms and was highest for those who were tested for travel-related purposes. Ct value was lowest during the exponential-growth phase of the Omicron wave and was highest after the wave peaked and was declining.

CONCLUSIONS: The BA.2 subvariant appears substantially more infectious than the BA.1 subvariant. This may reflect higher viral load and/or longer duration of infection, thereby explaining the rapid expansion of this subvariant in Qatar.

Preprint available in medRxiv (March 4, 2022):

https://www.medrxiv.org/content/10.1101/2022.03.02.22271771v1.full.pdf