Coronastream February 2022: The thief of certainty 

Posted on February 17, 2022   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

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Last month, Coronastream looked at the Omicron variant of concern. In the weeks since, Omicron has filled the news to saturation point. While there is still much to learn about the variant, it is already clear that Omicron’s arrival is disrupting our carefully drawn maps and plans. The road map now looks like a bomb site. In this part of the world, a toxic combination of Delta and Omicron filled up hospital beds and intensive care bays over in the East. Greedy for territorial expansion, both variants travelled West to probe interstate border defences. While public health intervention held Delta at bay, Omicron hopped across the state border and is now boldly spreading in the community where no SARS-CoV-2 has gone before.  But unlike the neat endings of self-contained science fiction movies, raw facts point to an untidy end to one of the last bastions of the COVID-naïve. The West Australian COVID bunker is crumbling. Its tightly controlled borders will not last indefinitely. The key to understanding this sudden change in the fortunes of war is the uncertainty engendered by SARS-CoV-2’s unpredictable evolution. Our early recognition of coronavirus capacity to evolve its way out of public health goal (SARS-CoV-2 centre of gravity) has been returned to sender by carrier pigeon [don’t shoot the messenger]. After another month dominated by Omicron news, Coronastream will look at pandemic uncertainty and its consequences. 

CONGRUENCE: Diagnosis, treatment and care 

Omicron sub-lineage BA.2 may have "substantial growth advantage," UKHSA reports. 

This commentary notes one of the offspring of the original Omicron variant, BA.2, has rapidly come to dominate SARS-CoV-2 in several countries. This pattern of rapid spread suggests that BA.2 has a transmission advantage, however it is not yet clear whether that translates to a concurrent loss of virulence.  

Searching for diagnostic certainty, governing risk: Patients' ambivalent experiences of medical testing. 

This interesting paper explores the patient’s experience of using medical tests to establish medical certainty, and provides a helpful perspective on the ambiguities of the methods medicine uses to achieve its key decision point: a diagnosis. The authors explore the unintended consequence of a barrage of tests that promise diagnostic certainty, yet produce further uncertainty or raise new questions. They conclude that the development of tests that produce increasingly finer delineation between healthy and diseased populations will multiply uncertainty and heighten anxiety. This paper provides a useful narrative that explains the widespread confusion generated by the monumental proliferation of COVID tests. 

CONSISTENCY: Risk assessment 

Reduced risk of hospitalisation among reported COVID-19 cases infected with the SARS-CoV-2 Omicron BA.1 variant compared with the Delta variant, Norway, December 2021 to January 2022. 

This report from Norway compares the effect of Omicron sub-lineage BA.1 and the preceding Delta variant on hospital admission, and reveals reduced risk of admission. During the period under review, Delta infections fell and Omicron BA.1 became the dominant virus. 0.2% of Omicron and 1.1% of cases of Delta infection required hospital admission, with a median time to positive test of 1 and 4 days, respectively. In an estimate of proportionate risk, Omicron had a 73% overall reduction in risk of hospital admission. There were 9 COVID-19-related deaths from Omicron and 80 from Delta infections. The authors conclude that the lower risk of severe disease in infection by Omicron lineage variants does not necessarily lead to a reduced burden on hospitals. 

Early warning of a COVID-19 surge on a university campus based on wastewater surveillance for SARS-CoV-2 at residence halls. 

It is good to see surveillance methods research happening in the Centers for Disease Control’s back yard. This work from Emory University applied wastewater testing to a hospital, a quarantine centre and university halls of residence. The study showed that Moore swabs were not sensitive enough to reliably detect one or two cases in a residence building. There was too much uncertainty to use Ct values to estimate the number of affected COVID-19 cases. However, early detection of SARS-CoV-2 in wastewater samples from student residences after return from the spring break preceded a surge of COVID-19 cases on campus. This is further evidence that favours the use of wastewater testing to provide early warning of institutional outbreaks. 


Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts tropism and fusogenicity. 

Over the last two years, the ACE2 receptor and TMPRSS have been recognised as key contributors to cellular entry by SARS-CoV-2. In this paper, a multicentre group report on their comparison of Omicron variant BA.1 and the Delta variant. They found that Omicron spike protein has a higher affinity for the ACE2 receptor. While viral replication was similar in nasal epithelial cells, lower Omicron replication was observed in respiratory and gastrointestinal settings. Their experimental design shows that Omicron depends more heavily on an endocytic pathway. Less efficient S1/2 cleavage in Omicron and an inability to use TMPRSS2 reduced syncytium formation, and altered cellular tropism. The paper is currently in accelerated preview, reflecting the level of interest in what the Omicron lineage reveals about mechanisms of SARS-CoV-2 pathogenesis. 

Structural modelling of Omicron spike protein and its complex with human ACE-2 receptor: Molecular basis for high transmissibility of the virus. 

This report presents a structural analysis of the Omicron spike glycoprotein and shows the distribution of 30 mutations over the trimeric protein. Receptor Binding Domain complexing with the ACE-2 receptor has multiple mutations affecting the interface. These result in ionic interactions, hydrogen bonds and Van der Waals interactions. These findings add a molecular narrative to the above report by Meng and colleagues. 

COUNTERMEASURES: Treatment and other interventions 

The strategy behind Japan's response to COVID-19 from 2020-2021 and future challenges posed by the uncertainty of the Omicron variant in 2022. 

Japan weathered five successive COVID-19 surges. The evolution of their public health measures is summarised in Fig. 1. The authors are uncertain about the effects of the Omicron variant’s arrival in a sixth COVID-19 wave. They infer that the lower severity of Omicron infection presents less individual risk, while its higher transmissibility brings a higher collective risk. Their assessment is that forced co-existence with COVID-19 will require continued vaccination campaigns and individual behavioural changes. 

Mind the "worry fatigue" amid Omicron scares. 

This short article puts into words something many of us have probably noticed already: that Omicron has a potent effect on population-wide COVID anxiety, which may be followed by worry fatigue, perhaps even worry burnout. The authors highlight the responsibility mass media has for the news they communicate and its potential effect on health and welfare. The infodemic referenced in previous Coronastream coverage is a recurrent theme in pandemic management, and one we still haven’t got a grip on. 

Does the public know when a scientific controversy is over? Public perceptions of hydroxychloroquine in France between April 2020 and June 2021. 

Following on from the theme of worry fatigue in the previously cited paper, Schultz and colleagues report a study on public perception of hydroxychloroquine use in the context of COVID-19. They found a strong correlation between politically radical views (both left and right) and the efficacy of hydroxychloroquine, whereas high levels of trust in government correlated with a belief in hydroxychloroquine inefficacy. The authors conclude that as media coverage of scientific controversy increases during uncertain times, circulation of therapeutic promise may have persisting effects on attitudes towards science and medicine. 


Testing for COVID-19: 
  • WHO guidance on antigen detection in the diagnosis of SARS-CoV-2 infection 

Dealing with uncertainty: 
COVID-19 risk analysis: