Coronastream November 2021: Boosted

Posted on November 29, 2021   by Dr Tim Inglis

In this special blog series, medical microbiologists led by Dr Tim Inglis summarise some of the research that will be essential to inform COVID-19 countermeasures. Find out more about the project in Dr Inglis' Editorial 'Logic in the time of coronavirus', published in the Journal of Medical Microbiology. 

Our vaccination programme is running on a three-speed gearbox: fast, slow and idling. The latest COVID surge appears to be declining in Sydney and Melbourne where vaccine uptake has been high, but remote communities in Eastern Australia continue to see local transmission. In the West, vaccine uptake has been slower, reflecting the relatively COVID-free existence that has persisted through much of the recent pandemic period. Unfortunately, remote communities have some of the lowest double dose vaccination rates in the land, making them vulnerable to new incursions of SARS-CoV-2, for which health providers are now preparing. Whether or not decoupling of case numbers and severe disease translates across this wide brown land, stark differences in pandemic experience are emerging. These create uncertainty in health care workers and the wider population, as to how we're going to protect people during the next COVID surge. Many of our front-line workers completed their vaccine series over six months ago, so are due a non-mandatory booster dose. But when exactly should this be given, and to whom? Should it be at six months after dose two, as close to the next surge as possible, or somewhere in between? This blogger opted for the certainty of getting it done before the pre-Christmas rush, being happier with the assurance of renewed protection, than the risk of running it a bit too close to the expected surge. Third time round, the vaccine reaction was local and short-lived, leaving no excuse for time off work. Meanwhile, Singapore has run into another surge despite high levels of vaccine coverage. From a Singapore perspective, Australia is expected to enter a honeymoon period around the end of year holiday, followed by a similar surge in the first quarter of 2022. We have been warned – particularly the COVID naive states with no current community transmission. Sadly, there is a long history of reluctance to learn from others' experiences.

Congruence

Systematic review with meta-analysis of diagnostic test accuracy for COVID-19 by mass spectrometry 

In this review, Spick and colleagues provide us with an assessment of the comparative performance of a range of mass spectrometry methods use to exploit metabolic derangement in COVID-19. They noted an average sensitivity of 0.87, with better performances using viral proteomic analysis on nasopharyngeal swabs and metabolomic analyses of plasma and serum. They noted, that the inferior performance of other test matrices such as breath, sebum and saliva, were not yet mature enough for translation into clinical applications. This conclusion should serve as a caution against the premature adoption of emerging COVID diagnostic tests until they have undergone careful validation against widely adopted reference methods.

Consistency

Impact of Delta Variant and Vaccination on SARS-CoV-2 Secondary Attack Rate Among Household Close Contacts  

In this study of secondary SARS-CoV-2 attack rates in household contacts of primary COVID cases in Singapore, Ng and colleagues compare the impact of the Delta variant with earlier virus variants. They conclude, that the increased risk of Delta VOC acquisition was reduced by vaccination. Singapore has had a successful vaccination campaign using the Pfizer-BioNTec and Moderna vaccines. Their experience is being watched closely by neighbouring nations, so the findings of this study are instructive. In unvaccinated household contacts of index cases, the attack rate of the Delta variant was around twice that of other variants. This observation goes some way in explaining the difficulty of controlling community spread of the Delta variant. A further interesting finding was that older primary cases led to increased secondary infections, unlike other respiratory infections. Recognising that households are a setting where prevention is challenging, due to potential for prolonged exposure, Ng and colleagues estimate that mRNA vaccine retains a 55% efficacy against the Delta variant. Additional public health measures will therefore be needed to prevent community transmission, in addition to high vaccine coverage. 

Cumulative dissonance

Transmission, viral kinetics and clinical characteristics of the emergent SARS-CoV-2 Delta VOC in Guangzhou, China. 
The Delta variant of SARS-CoV-2 has quickly become the dominant form of the virus around the world. Insight into why and how it has achieved this notoriety is needed to develop improved countermeasures. Wang and colleagues studied seven transmission generations of the Delta VOC in Guangzhou between 21 May and 18 June, 2021, and compared with a wild-type infection cohort in 2020. They noted four generations of transmission in the first 10 days with a shorter incubation period, higher viral load and longer duration of viral shedding. Among the critically ill, there was a higher proportion of patients over 60 years old, and the Delta VOC had a higher risk of deterioration to critical illness than the wild type comparator.  
 
Community transmission and viral load kinetics of the SARS-CoV-2 elta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study. 

This prospective study from the UK investigated transmission and viral load kinetics in subjects with mild Delta VOC infection in the community. They found a 25% secondary attack rate of Delta variant infection for fully vaccinated individuals, compared with 38% in unvaccinated individuals. Fully vaccinated individuals had a faster decline of Delta VOC load decline than unvaccinated individuals with pre-alpha, alpha or Delta variants. Their conclusion, was that vaccination appears to reduce the risk of Delta VOC infection and accelerates viral clearance, though breakthrough infections in the vaccinated can still transmit efficiently including to fully vaccinated contacts. 

Countermeasures

Molnupiravir in COVID-19: a systematic review of literature. 

The prospect of an antiviral agent with demonstrable efficacy against SARS-CoV-2 has prompted a lot of comment in the lay media this month. While there is a lot about Molnupiravir, the peer-review literature has yet to catch up. Singh and colleagues have published a helpful reality check, that takes a look at the literature on this novel compound, including clinical trials, efficacy and safety data thus far. The studies they found document tolerable and safe use of a 1600mg daily dose without serious adverse effects over 5.5 days, a lower time to clearance associated with treatment and an interim report claiming a 50% reduction in hospital admission and death attributed to treatment in a placebo-controlled, double blind clinical trial. While noting the potential role for Molnupiravir in preventing progression of early SARS-CoV-2 infection to hospitalisation and death, they question its role in moderate and severe COVID. The data from these clinical trials is available for wider scrutiny in preprint form, but must wait for thorough peer review and corroboration in further trials before we have a clearer idea of where this interesting new antiviral agents fits into COVID clinical management pathways.  

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