COVID-19: CoronaVac jab is less effective against the Gamma variant

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The Chinese CoronaVac jab, a key tool in Brazil’s fight against COVID-19, is less effective against the Gamma variant first detected in the virus-ravaged South American country, a study said Friday.

Researchers found that antibodies generated by the vaccine work less well against the variant than a previous coronavirus strain, while Gamma may also be able to reinfect people who had previously had the virus.

Gamma’s capacity to evade these immune system responses even in immunized people suggest “the virus can potentially circulate in vaccinated individuals – even in areas with high vaccination rates,” the study authors said in a press release.

In the small study, researchers at the University of Campinas in Brazil exposed both Gamma and a previous strain of the virus to antibodies in blood plasma from 53 vaccinated people and 21 people who had been previously infected with the virus.

In the vaccinated group, 18 people had received just one dose of CoronaVac—one of the main vaccines in Brazil’s coronavirus response – while 20 had recently received a second jab and a further 15 had been vaccinated as part of the Sinovac clinical trial in August 2020.

They found that Gamma was able to escape the antibodies of almost all the participants who had received only one dose, as well as those vaccinated in 2020.

The antibodies from those more recently vaccinated were effective, but less so than against the previous virus strain.

The study, published in The Lancet Microbe, also found that antibodies produced by previous infections had to be nine times higher to prevent infection by Gamma than to prevent illness from the previous strain.

The authors said those results mean people who have already survived a case of COVID-19 could be reinfected.

But they said since clinical trials suggest the vaccine is effective in preventing severe illness and death, it could be that the immune response is more complex.

Every dose counts

CoronaVac was approved by the World Health Organization for emergency use in June.

At the time the WHO said it had a 51 percent efficacy against symptomatic disease and 100 percent against hospitalization.

But results from CoronaVac phase 3 trials in Turkey – that did not take variants into account – published Friday in The Lancet found two doses of the vaccine had an efficacy of 83.5 percent in protecting against symptomatic infections.

It also found the vaccine was 100 percent effective against hospitalization.

The study involved 6,559 participants who received the vaccine and 3,470 who were given a placebo.

All were adults aged between 18 and 59 and were given doses 14 days apart.

The authors said the limitations of the trial include that the participants were under 60 and low risk, calling for further research to test efficacy among older adults and under 18s, as well as against new variants.

“The world needs every possible dose of any safe and effective vaccine against SARS-CoV-2,” they said.

Both papers are to be presented at this year’s European Congress of Clinical Microbiology & Infectious Diseases.


Global overview

Data as of 20 June 2021

Global numbers of cases and deaths continued to decrease over the past week (14-20 June 2021) with over 2.5 million new weekly cases and over 64 000 deaths, a 6% and a 12% decrease respectively, compared to the previous week (Figure 1). While the number of cases reported globally now exceeds 177 million, last week saw the lowest weekly case incidence since February 2021.

This week, the Americas and Western Pacific Regions reported numbers of new weekly cases similar to the previous week, while the South-East Asia and the European Regions reported a decline in the number of new cases. The African Region recorded a marked increase in the number of weekly cases as compared to the previous week (Table 1).

Globally, mortality remains high with more than 9000 deaths reported each day over the past week, however, the number of new deaths reported in the past week decreased across all Regions except for the Eastern Mediterranean and the African Regions.

The highest numbers of new cases were reported from Brazil (505 344 new cases; 11% increase), India (441 976 new cases; 30% decrease), Colombia (193 907 new cases; 10% increase), Argentina (149 673 new cases; 16% decrease), and the Russian Federation (108 139 new cases; 31% increase).

Globally, variant Alpha has been reported in 170 countries, territories or areas (hereafter countries; seven new countries in the past week), Beta in 119 countries (four new countries), Gamma in 71 countries (three new countries) and Delta in 85 countries (six new countries).

Special Focus: Update on SARS-CoV-2 Variants of Interest and Variants of Concern

WHO, in collaboration with national authorities, institutions and researchers, routinely assesses if variants of SARS-CoV-2 alter transmission or disease characteristics, or impact vaccine, therapeutics, diagnostics or public health and social measures (PHSM) applied by national authorities to control disease spread.

Systems have been established to detect signals of potential Variants of Concern (VOCs) or Variants of Interest (VOIs) and assess these based on the risk posed to global public health. As these risks evolve, WHO updates the list of global VOIs and VOCs (Table 2) to support setting priorities for surveillance and research, and ultimately guide response strategies. National authorities may choose to designate other variants of local interest/concern, and are encouraged to investigate and report on the impact of these variants.

Here we provide updates on globally characterized VOCs and VOIs, as well as the updated countries/territories/areas reporting the detection of VOCs. No new VOCs or VOIs have been added to or removed from the list last week.

Phenotypic characteristics

Available evidence on phenotypic impacts of VOCs and vaccine performance against VOCs are summarised in Table 3, as well as in previous editions of the WEU.

Since the last detailed update on 8 June, new evidence has been published on the phenotypic characteristics of the Delta variant. A study from Singapore showed that infection with Delta variant was associated with higher odds of oxygen requirement, intensive care unit (ICU) admission, or death [adjusted odds ratio (aOR) 4·90, 95% CI 1.43-30.78].

Additionally, the aOR for pneumonia was 1.88 times higher (95% CI 0·95-3·76) for those infected with Delta compared to infection with non-VOC SARS-CoV-2 lineages. Additionally, the Delta variant was associated with significantly lower PCR cycle threshold (Ct) values – the lower the Ct level the greater the amount of viral RNA in a sample. Findings from this study also showed that there was a longer duration of sustained low Ct values (≤30) in Delta (median duration of 18 days) compared to non-VOC lineages of SARS-CoV-2 (13 days).87

A study in Japan estimating the relative instantaneous reproductive number (a measure of transmission at a specific point in time) showed that the Delta variant was associated with greater transmissibility when compared to the Alpha variant. When compared with the variants circulating in Japan before December 2020, the relative instantaneous reproduction number for Alpha was estimated to be at 1.56 and for Delta

1.78. Overall, this study showed Delta was associated with 1.23 times higher transmissibility than Alpha.88 This is consistent with the summary of Rt of Alpha, Beta, Gamma and Delta variants published by WHO in previous issues of the Weekly Epidemiological Update on COVID-19 and in Eurosurveillance this past week89.

Findings from a recently published retrospective cohort analysis involving nearly 840 000 participants with laboratory confirmed SARS-CoV-2 in England between 23 November 2020 and 31 January 2021 suggested that the Alpha variant, as compared to non-VOC SARS CoV-2 lineages, was associated with an increased risk of hospitalization between one and fourteen days after the first positive SARS-CoV-2 test (adjusted hazard ratio of hospital admission 1.52, 95% CI 1.47 – 1.57).

When looking at these results by age, they showed a higher risk of hospitalization among those aged ≥30 years as compared to younger participants.90 Another study comparing the secondary attack rates in households among Alpha index cases versus non-VOC index cases in Ontario, Canada found that the secondary attack rate for Alpha index cases was 1.31 times (31%) higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49).

When these analyses were further grouped into Alpha and non-Alpha index cases, there was evidence to suggest increased transmission among both asymptomatic (RR=1.91, 95% CI 0.96-3.80) and pre-symptomatic (RR=3.41, 95%CI 1.13-10.26) index cases.1

A study conducted to examine diagnostic accuracy of three SARS-CoV-2 antigen detecting rapid tests (Ag- RDT) in Germany between 20 January to 15 April 2021 showed comparable sensitivities in the performance of Ag-RDTs for Alpha, Beta and wild-type variants, irrespective of the infecting variant.91 This finding is consistent with a previously published evaluation by Public Health England which found no major changes in the diagnostic accuracy of six widely available Ag-RDTs for Alpha, despite a limited number of amino acid changes from the original viral sequence in the target antigen for most commercially available Ag-RDTs.22

A recent study using a transmission model based on clinical and epidemiological data from almost 1000 individuals from South Africa and Switzerland, estimated that the Alpha variant was associated with either

a 37% (95% compatibility interval, CI: 25–63%) increase in transmissibility or a 51% (95% CI: 32-80%) increase of the infectious duration or a combination of the two mechanisms. It was also estimated that the Beta variant was associated with a 23% (95% CI: 10-37%) increase in transmissibility or a 38% (95% CI: 15-78%) increase of the infectious duration.

The authors concluded that Beta might be expected to outgrow Alpha in regions where the level of naturally acquired immunity against previously circulating variants exceeds 20% to 40%.92 The study also measured viral load in 950 individuals and found that infections with variant Alpha exhibited a higher viral load and longer viral shedding compared to non- VOCs.

Findings from another study showed that the receptor binding domain (RBD) of the Alpha and Beta variants bound ACE2 with 1.98- and 4.62 times greater affinity than non-VOCs, respectively. This enhanced affinity likely mediates increased infectivity by lowering the effective concentration of virions required for cell entry.93

In a rapid scoping review examining the impacts of VOCs on health systems, authors of a recently published study suggested that a combination of public health and social measures (e.g., masking, physical distancing, lockdowns, testing) should be implemented alongside a vaccine strategy to improve population and health system outcomes.94

VOC impacts on vaccines

Since the 8 June update, two studies have provided evidence of the effectiveness of Pfizer BioNTech- Comirnaty and AstraZeneca-Vaxzevria vaccines against the Delta variant. The first is a follow-up to a United Kingdom study published last month by Lopez Bernal et al., which reported on vaccine effectiveness (VE) of full courses of both Pfizer BioNTech-Comirnaty and AstraZeneca-Vaxzevria vaccines against symptomatic disease due to the Delta variant; VE against Delta, while slightly reduced, was maintained for both vaccines (88% for Pfizer BioNTech-Comirnaty and 67% for AstraZeneca-Vaxzevria).41

In the follow-up study, Stowe et al. report on the effectiveness of these vaccines against severe disease (hospitalization) due to Delta among persons ≥ 16 years in the United Kingdom. The authors combined odds ratios for symptomatic COVID-19 disease from a test-negative case-control analysis with hazard ratios for hospitalization among symptomatic cases to estimate overall VE against hospitalization. VE estimates against hospitalization due to Delta and Alpha variants ≥ 14 days post second dose was estimated to be 96% (95% CI: 86-89%) and 95% (95% CI: 78-99%) respectively, for Pfizer BioNTech-

Comirnaty and 92% (85% CI: 75-97%) and 86% (95% CI: 53-96%) respectively, for AstraZeneca-Vaxzevria. Single dose effectiveness against hospitalization ≥ 21 days after immunization remained high for Pfizer BioNTech-Comirnaty at 94% (95% CI: 46-99%) against Delta and 83% (95% CI: 62-93%) against Alpha.

Effectiveness of one dose of AstraZeneca-Vaxzevria against hospitalization was similar for Delta and Alpha variants, but reduced relative to two doses at 71% (95% CI: 51-83%) and 76% (95% CI: 61-85%), respectively.40

A second study from Scotland by Sheikh et al. applied a test negative case-control design to a large COVID- 19 surveillance platform and found that two doses of Pfizer BioNTech-Comirnaty were 83% (95% CI: 78-87) and 79% (95% CI: 75-82%) effective against symptomatic disease and infection due to Delta, respectively,

≥ 14 days after receipt of second dose in persons 15 years and older. These estimates were somewhat reduced compared to VE estimates against Alpha: 92% (95% CI: 88-94%) and 92% (90-93%) for symptomatic disease and infection, respectively. The study also showed reduced effectiveness of two doses of AstraZeneca-Vaxzevria against Delta compared to Alpha with VE estimates of 61% (95% CI: 51- 70%) and 60% (95% CI: 53-66%) against symptomatic disease and infection ≥ 14 days after second dose,

respectively, compared to corresponding estimates of 81% (95% CI: 72-87%) and 73% (95% CI: 66-78%) against Alpha. Single dose effectiveness against Delta was similar to that of Alpha with low VE for both vaccines and for both symptomatic disease and infection ≥28 days after immunization with VE estimates ranging from 18% to 39%. In a separate cohort analysis, single dose effectiveness against hospitalization

≥28 days after immunization among SARS-CoV-2 positive individuals was estimated for Pfizer BioNTech- Comirnaty and AstraZeneca-Vaxzevria vaccines combined; VE was estimated to be 62% (95% CI: 42-76%) and 72% (95% CI: 57-82%) against Delta and Alpha, respectively, demonstrating lower protection against Delta compared to Alpha (though confidence intervals overlap, indicating no statistical significance).42

Together, these studies suggest moderately reduced VE at preventing symptomatic disease and infection due to the Delta variant as compared to Alpha. While the Scotland study suggests there could be reduced effectiveness of vaccines against hospitalization due to Delta as compared to Alpha, confidence levels overlap and VE for individual vaccines was not estimated.

No such reduction in VE was observed for hospitalization in the United Kingdom study for either Pfizer BioNTech-Comirnaty or AstraZeneca- Vaxzevria vaccines. The studies also provide further evidence of the importance of two doses of both Pfizer BioNTech-Comirnaty and AstraZeneca-Vaxzevria in preventing hospitalization, symptomatic disease and infection due to both Delta and Alpha variants.

A third study by Skowronski et al. evaluated the effectiveness of a single dose of Pfizer BioNTech- Comirnaty or Moderna-mRNA-1273 against infection with SARS-CoV-2 Alpha and Gamma variants among older adults in Canada using a test-negative case-control design; 85% of participants had received Pfizer BioNTech-Comirnaty and 15% had received Moderna-mRNA-1273 vaccine.

VE against Alpha and Gamma variants ≥21 days after the first dose were 67% (95% CI: 57-75%) and 61% (95% CI: 45-72%), respectively, compared to 72% (95% CI: 58-81) against non-VOC SARS-CoV-2 viruses.39 While the VE point estimate against Gamma was somewhat lower compared to Alpha and non-VOCs, all confidence intervals were overlapping, indicating no statistical significance.

Geographic distribution

As surveillance activities to detect SARS-CoV-2 variants are strengthened at local and national levels, including by strategic genomic sequencing and sharing of sequences and supporting meta-data, the number of countries/areas/territories (hereafter countries) reporting VOCs has continued to increase (Figure 4, Annex 1).

In the past two weeks, Alpha continued to be reported in new countries, including smaller island nations in the Americas and Southeast Asia Regions. Delta, now reported in 85 countries globally, continues to be reported in new countries across all WHO Regions, 11 of which were newly reported in the past two weeks. This distribution should be interpreted with due consideration of surveillance limitations, including differences in sequencing capacities and sampling strategies between countries.

WHO recommendations

Virus evolution continues to be expected, and the more SARS-CoV-2 circulates, the more opportunities it has to evolve. Reducing transmission through established and proven disease control methods such as those outlined in the COVID-19 Strategic Preparedness and Response Plan, as well as avoiding introductions into animal populations, are fundamental to and crucial aspects of the global strategy to reduce the occurrence of mutations that have negative public health implications. PHSM remain critical to curb the spread of SARS- CoV-2, including all variants that evolve.

Evidence from multiple countries with extensive transmission of VOCs has indicated that PHSM, including infection prevention and control (IPC) measures in health facilities, have been effective in reducing COVID- 19 case incidence, which has led to a reduction in hospitalizations and deaths among COVID-19 patients. National and local authorities are encouraged to continue strengthening existing PHSM, IPC and disease control activities.

Authorities are also encouraged to strengthen surveillance and sequencing capacities and apply a systematic approach to provide a representative indication of the extent of transmission of SARS- CoV-2 variants based on the local context, and to detect unusual events.

reference link: https://reliefweb.int/sites/reliefweb.int/files/resources/20210622_Weekly_Epi_Update_45.pdf


More information: The Lancet Microbe: Neutralisation of SARS-CoV-2 lineage P.1 by antibodies elicited through natural SARS-CoV-2 infection or vaccination with an inactivated SARS-CoV-2 vaccine: an immunological study, www.thelancet.com/journals/lan … (21)00129-4/fulltext

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