What do we know about covid vaccines and preventing transmission?

BMJ 2022; 376 doi: https://doi.org/10.1136/bmj.o298  (Published 04 February 2022) Cite as:  BMJ 2022;376:o298

Authors: Chris Stokel-Walker,

Vaccines that work against SARS-CoV-2 have helped change the course of the pandemic by reducing illness and hospital admissions. But Chris Stokel-Walker asks what we know about their impact on preventing transmission.

The range of vaccines developed in record time by pharmaceutical companies and research laboratories have helped quell the worst effects of SARS-CoV-2. But much of the focus of research has been on effectiveness in preventing infection, illness, and hospital admission. What is less well measured is the impact of vaccination on preventing onward transmission.

What evidence do we have that covid-19 vaccines prevent transmission?

Most papers to date (notably, many are preprints and have yet to be peer reviewed) indicate vaccines are holding up against admission to hospital and mortality, says Linda Bauld, professor of public health at the University of Edinburgh, “but not so much against transmission.”

The first weekly covid-19 vaccine surveillance report for 20221 from the UK Health Security Agency (UKHSA) was more positive than Bauld’s assessment—but didn’t say outright that covid-19 vaccines prevent transmission. “Several studies have provided evidence that vaccines are effective at preventing infection,” it states, “Uninfected people cannot transmit; therefore, the vaccines are also effective at preventing transmission.”

A study2 of covid-19 transmission within English households using data gathered in early 2021 found that even a single dose of a covid-19 vaccine reduced the likelihood of household transmission by 40-50%. This was supported by a study of household transmission among Scottish healthcare workers conducted between December 2020 and March 2021.3 Both studies analysed the impact of vaccination on transmission of the α variant of SARS-CoV-2, which was dominant at the time.

A subsequent study,4 conducted later in the course of the pandemic when the delta variant was dominant, showed vaccines had a less pronounced effect on denting onward transmission, but were still effective.

How could vaccines help reduce transmission?

Vaccines aren’t preventing onward transmission by reducing the viral load—or amount of SARS-CoV-2—in your body. “Most studies show if you got an infection after vaccination, compared with someone who got an infection without a vaccine, you were pretty much shedding roughly the same amount of virus,” says Paul Hunter, professor in medicine at the University of East Anglia. One study,5 sponsored by the US Centers for Disease Control and Prevention (CDC), found “no difference in infectious virus titer between groups” who had been vaccinated and had not.

Instead, it’s the principle that the UKHSA identified above: if you don’t get infected in the first place thanks to a vaccine, you can’t spread it. Once you’re infected, you still can—although what we know about the window when you’re most likely to transmit the virus to others has improved.

Does the omicron variant make a difference?

Few studies have looked at the omicron variant, although a report published in January 2022 by the European Centre for Disease Prevention and Control cited a small Danish household study:6 “People who have completed the primary series of vaccination experienced secondary attack rates (SARs) of 32% in households with omicron and 19% in households with delta. For people who received a booster, omicron was associated with a SAR of 25%, while the corresponding estimate for delta was only 11%. There was an increased transmission for unvaccinated people, and a reduced transmission for booster vaccinated people, compared with fully vaccinated people,” summarised the report.7

Preliminary data from Japan’s National Institute of Infectious Diseases found that patients infected with omicron shed viral particles for longer compared with those infected with other variants. The amount of viral RNA in patients with omicron was highest three to six days after diagnosis or symptom onset. This appears to be two or three days later than other variants.8 Hunter said the new data “muddy the waters” on the matter.

Vaccine effectiveness against infection, hospital admission, and mortality have all taken a hit when pitted against the omicron variant, and it seems only logical that the impact against transmission would likewise drop.

“The main point of vaccines is not to do with preventing transmission,” says Anika Singanayagam, academic clinical lecturer in adult infectious disease at Imperial College London. “The main reasons for vaccines for covid-19 is to prevent illness and death.” Therefore, we shouldn’t be too disappointed that it’s still possible to pass on the virus while vaccinated, she says, “Damping down on transmission is not a particularly easy thing with omicron.”

What impact does that have on policymaking?

The fact that vaccines are good at preventing serious infection, but less good at preventing transmission makes policymaking difficult. The UK has changed its rules9 on the amount of time those who test positive for covid-19 must spend in self-isolation, first from 10 days to seven, then to five, provided they test negative on a lateral flow test. That decision follows the US, which cut the self-isolation period to five days in late December10 because “the majority of SARS-CoV-2 transmission occurs early in the course of illness.”

“They’re recognising that vaccines aren’t preventing transmission, and you’ve got too many people having to isolate,” says Bauld. “Policymakers have decided that the game’s up on transmission, but that you need a different approach.”

Decision makers have a difficult decision, says Singanayagam: they want to enable life to continue as normally as possible—which may mean vaccinated people getting infected with covid because of community or household transmission—while also carefully monitoring that vaccine effectiveness to lower the risk of hospital admission, severe illness, and death is not dented.

Could future vaccines be more effective against onward transmission?

Again, first generation covid vaccines were evaluated against reducing hospital admissions and death in the challenging first year of the pandemic. They wouldn’t have been expected to generate sterilising immunity and block transmission. But, says Singanayagam, now that we have a suite of vaccines using different approaches, there is some opportunity to think about future jabs for different situations.

“There are avenues to think about the development of vaccines that can have more of an effect on transmission,” she says. Those are usually vaccines delivered more locally, such as directly through the respiratory tract, which could tackle the source of major transmission, rather than the lungs, which is where the first generation of vaccines was targeted in order to prevent severe infection. “That’s probably the way things will move in the future.”

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References

  1. UK Health Security Agency. Covid-19 vaccine surveillance report: week 1. 6 January 2022. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1045329/Vaccine_surveillance_report_week_1_2022.pdf
  2. Dabrera G.Dunbar JK,Andrews NJ, Zaidi A, Hall JA, Harris RJ, Effect of vaccination on household transmission of SARS-CoV-2 in England. N Engl J Med2021;385:759-60.  doi:10.1056/NEJMc2107717  pmid:34161702CrossRefPubMedGoogle Scholar
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First case of postmortem study in a patient vaccinated against SARS-CoV-2

Author:TorstenHansenaUlfTitzeaNidhi Su AnnKulamadayil-HeidenreichbSabineGlombitzacJohannes, et. al.

Highlights

• We report on a patient with a single dose of vaccine against SARS-CoV-2.

• He developed relevant serum titer levels but died 4 weeks later.

• By postmortem molecular mapping, we found viral RNA in nearly all organs examined.

• However, we did not observe any characteristic morphological features of COVID-19.

Immunogenicity might be elicited, while sterile immunity was not established.

Abstract

A previously symptomless 86-year-old man received the first dose of the BNT162b2 mRNA COVID-19 vaccine. He died 4 weeks later from acute renal and respiratory failure. Although he did not present with any COVID-19-specific symptoms, he tested positive for SARS-CoV-2 before he died. Spike protein (S1) antigen-binding showed significant levels for immunoglobulin (Ig) G, while nucleocapsid IgG/IgM was not elicited. Acute bronchopneumonia and tubular failure were assigned as the cause of death at autopsy; however, we did not observe any characteristic morphological features of COVID-19. Postmortem molecular mapping by real-time polymerase chain reaction revealed relevant SARS-CoV-2 cycle threshold values in all organs examined (oropharynx, olfactory mucosa, trachea, lungs, heart, kidney and cerebrum) except for the liver and olfactory bulb. These results might suggest that the first vaccination induces immunogenicity but not sterile immunity.

Keywords

SARS-CoV-2VaccineAutopsyHistologyRT-PCR

We report on an 86-year-old male resident of a retirement home who received vaccine against SARS-CoV-2. Past medical history included systemic arterial hypertensionchronic venous insufficiencydementia and prostate carcinoma. On January 9, 2021, the man received lipid nanoparticle-formulated, nucleoside-modified RNA vaccine BNT162b2 in a 30 μg dose. On that day and in the following 2 weeks, he presented with no clinical symptoms (Table 1). On day 18, he was admitted to hospital for worsening diarrhea. Since he did not present with any clinical signs of COVID-19, isolation in a specific setting did not occur. Laboratory testing revealed hypochromic anemia and increased creatinine serum levels. Antigen test and polymerase chain reaction (PCR) for SARS-CoV-2 were negative.

For More Information: https://www.sciencedirect.com/science/article/pii/S1201971221003647

The animal origin of SARS-CoV-2

  1. Authors: Spyros Lytras1, Wei Xia2, Joseph Hughes1, Xiaowei Jiang3, David L. Robertson1
  2.  See all authors and affiliationsScience  27 Aug 2021:Vol. 373, Issue 6558, pp. 968-970
  3. DOI: 10.1126/science.abh0117

Although first detected in December 2019, COVID-19 was inferred to be present in Hubei province, China, for about a month before (1). Where did this new human disease come from? To understand the origin of the COVID-19 pandemic, it is necessary to go back to 2002. At that time a novel respiratory coronavirus appeared in Foshan, Guangdong province, China, and spread to 29 countries (2). Altogether ∼8000 people were infected with severe acute respiratory syndrome coronavirus (SARS-CoV) before public health measures controlled its spread in 2003. The zoonotic origin of SARS-CoV was subsequently linked to live animals available at markets. Further sporadic spill-over events of SARS-CoV from animals took place in Guangzhou, Guangdong, and some researchers working with cultured virus were infected in laboratory accidents (3), but ultimately SARS-CoV was removed from the human population. Trading of susceptible host animals is an important common theme in the emergence of SARS and COVID-19.

Three years after the SARS epidemic began, investigations revealed that horseshoe bats (Rhinolophus) in China were harboring related coronaviruses (4). These collectively form the species SARS-related coronavirus (SARSr-CoV), which comprises the Sarbecovirus subgenus of the Betacoronavirus genus. It was inferred that a sarbecovirus circulating in horseshoe bats seeded the progenitor of SARS-CoV in an intermediate animal host, most probably civet cats (3). Although other possible intermediate hosts for SARS-CoV were identified, in particular raccoon dogs and badgers (for sale with civet cats in animal markets), it is a population of civet cats within markets that appear to have acted as the conduits of transmission to humans from the horseshoe bat reservoir of SARS-CoV, rather than civet cats being a long-term reservoir host species. Presumably a captive civet cat initially became infected by direct contact with bats—e.g., as a result of bats foraging in farms or markets—or was infected prior to capture. Following the SARS epidemic, further surveillance revealed the immediate threat posed by sarbecoviruses from horseshoe bats. Despite this clear warning, another member of the SARSr-CoV species, SARS-CoV-2, emerged in 2019 that spread with unprecedented efficiency among humans. There has been speculation that the Wuhan Institute of Virology (WIV) in Hubei was the source of the pandemic because no SARS-CoV-2 intermediate host has been identified to date and owing to the WIV’s geographic location.

SARS-CoV-2 first emerged in Wuhan city, which is >1500 km from the closest known naturally occurring sarbecovirus collected from horseshoe bats in Yunnan province, leading to an apparent puzzle: How did SARS-CoV-2 arrive in Wuhan? Since its emergence, sampling has revealed that coronaviruses genetically close to SARS-CoV-2 are circulating in horseshoe bats, which are dispersed widely from East to West China, and in Southeast Asia and Japan (5). The wide geographic ranges of the potential reservoir hosts—for example, intermediate (R. affinis) or least (R. pusillus) horseshoe bat species, which are known to be infected with sarbecoviruses—indicate that the singular focus on Yunnan is misplaced (5). Confirming this assertion, the evolutionarily closest bat sarbecoviruses are estimated to share a common ancestor with SARS-CoV-2 at least 40 years ago (5), showing that these Yunnan-collected viruses are highly divergent from the SARS-CoV-2 progenitor. The first of these viruses reported by WIV, RaTG13 (6), is certainly too divergent to be the SARS-CoV-2 progenitor, providing key genetic evidence that weakens the “lab-leak” notion. Additionally, three other sarbecoviruses collected in Yunnan independently of the WIV are now the closest bat coronaviruses to SARS-CoV-2 that have been identified: RmYN02, RpYN06, and PrC31 (see the figure).

For More Information: https://science.sciencemag.org/content/373/6558/968.full

The OC43 human coronavirus envelope protein is critical for infectious virus production and propagation in neuronal cells and is a determinant of neurovirulence and CNS pathology

Authors:Jenny K.Stodola1GuillaumeDubois1AlainLe CoupanecMarcDesforgesPierre J.Talbot

Highlights

Coronavirus structural envelope (E) protein specific motifs involved in protein-protein interaction or in homo-oligomeric ion channel formation are needed for optimal production of recombinant infectious virus.•

Fully functional E protein of HCoV-OC43 is crucial for viral propagation in the CNS and neurovirulence.•

Fully functional E protein of HCoV-OC43 is crucial for efficient viral propagation in the central nervous system and thereby for neurovirulence.

Abstract

The OC43 strain of human coronavirus (HCoV-OC43) is an ubiquitous respiratory tract pathogen possessing neurotropic capacities. Coronavirus structural envelope (E) protein possesses specific motifs involved in protein-protein interaction or in homo-oligomeric ion channel formation, which are known to play various roles including in virion morphology/assembly and in cell response to infection and/or virulence. Making use of recombinant viruses either devoid of the E protein or harboring mutations either in putative transmembrane domain or PDZ-binding motif, we demonstrated that a fully functional HCoV-OC43 E protein is first needed for optimal production of recombinant infectious viruses. Furthermore, HCoV-OC43 infection of human epithelial and neuronal cell lines, of mixed murine primary cultures from the central nervous system and of mouse central nervous system showed that the E protein is critical for efficient and optimal virus replication and propagation, and thereby for neurovirulence.

For More Information: https://www.sciencedirect.com/science/article/pii/S0042682217304361