Coronastream January 2022: The virus formerly known as

Posted on January 26, 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 theJournal of Medical Microbiology

Just when we thought it was safe to ease off the restrictions in time for the festive holiday (or a little later if you live in Western Australia), that malicious SARS-CoV-2 pulled another stunt and forced a re-think on just about everything to do with COVID control. Now, when we were supposed to be "learning to live with" a more quiescent virus in peaceful co-existence, another Greek letter has muscled its way into every COVID case definition and public health instruction under the sun. In a matter of weeks. The speed at which this happened has been breathtaking. A doubling time of slightly more than two days has been reported from countries that are now seeing a new surge in daily cases. An early summary, relying heavily on experience from South Africa, suggested higher transmission, vaccine escape and lower virulence. Though the more optimistic commentators suggested this could be the pandemic circuit-breaker, epidemiologists cautiously point to a lag of several weeks between the first case reports and a surge in hospital admissions or COVID deaths. The WHO supports higher transmission and lower acuity of infection. There are some important caveats; rapid escalation of cases will still overload stressed health services even if cases are generally milder, long-term sequelae including long COVID may be different, and variations in the protective effect of current COVID vaccines may disrupt the global vaccination programme.  The precise origins of the Omicron VOC have yet to be worked out, but the disruption caused by its emergence highlight the urgent need to improve genomic surveillance in low-income countries, accelerate the global vaccine rollout, and hold the line on non-pharmaceutical interventions and controls. As we look at a fourth successive COVID year, we need to stretch infection science capability to bring this pandemic to an end. Of one thing we can be sure; there are plenty more letters in the Greek alphabet.

Congruence: clinical features

Covid-19: Runny nose, headache, and fatigue are the commonest symptoms of omicron, early data show.

This commentary on the commonest clinical features of COVID-19 captures the arrival of the Omicron variant and highlights the evolving nature of SARS-CoV-2 disease. The author re-emphasises that COVID-19 should be considered in all patients with cold-like symptoms. The commonest presenting features found in recent UK survey work are

  • runny nose
  • headache
  • fatigue (both mild and severe)
  • sneezing
  • sore throat
Covid-19: Omicron is causing more infections but fewer hospital admissions than delta, South African data show.

Early impressions that there has been a trade off between transmissibility and virulence in the Omicron variant are supported by early data from South Africa, which was first to report Omicron in late November. Noting that there is a lag between detection, early symptoms and the onset of more severe disease, this article notes that more than 90% cases in South Africa were already the Omicron variant, and with statistical correction for prior vaccination, had 29% lower hospital admission with lower requirement for critical care. These figures support increased transmission and infectivity, but reduced disease severity.

Consistency: Omicron surges

Epidemiological characterisation of the first 785 SARS-CoV-2 Omicron variant cases in Denmark, December 2021.

By 9 December, Denmark had detected 785 cases of Omicron variant infection, most of which had already been fully vaccinated and were acquired in Denmark. One in five had no identifiable link, indicating likely community transmission. Of these cases, only nine had required hospital admission and none had died.

SARS-CoV-2 B.1.1.529 (Omicron) Variant - United States, December 1-8, 2021.

The USA detected their first case of Omicron infection on 1 December, and by 8 December had 43 cases in 22 states. Of these, only one had required hospitalisation by that date and there had been no deaths at that point. Further MMWR reports from the CDC COVID-19 Response Team will make interesting reading, since they will give an indication of how quickly the Omicron variant can spread in a developed country during winter, and provide a clearer view of the attributable morbidity and mortality.

Cumulative dissonance: Origins, trajectory and unique properties

Where did 'weird' Omicron come from?

This article explores theories on origins of the Omicron variant. The separate evolutionary branch to the variant is a distinct outlier, for which there are several contending theories including prolonged undetected existence in an under-investigated locality, development in an individual with chronic immune deficiency, or transition through an intermediate non-human host.

Omicron SARS-CoV-2 variant: Unique features and their impact on pre-existing antibodies.

Kannan and colleagues look at the evolutionary origins of the Omicron variant's reduced susceptibility to neutralisation by antibodies. They note similarities to the Gamma (P.1) variant, since when 46 high prevalence mutations have been acquired by Omicron, of which half are localised in the spike glycoprotein and the remainder in the other major structural proteins of SARS-CoV-2. Their structural analysis shows that several of the spike protein mutations affect the major antibody binding site and thus affect antibody affinity.

The Electrostatic Potential of the Omicron Variant Spike is Higher than in Delta and Delta-plus Variants: A Hint to Higher Transmissibility?

Given the importance of the SARS-CoV-2 spike protein to cellular adherence and entry, the Omicron variant's spike protein mutations may modulate interaction with the receptor-binding domain and affinity with the ACE2 receptor. Pascarella and colleagues investigated these effects and found an unusually high electrostatic potential due to the variant's mutations. They suggest that this high charge may explain increased Omicron's enhanced infectivity. 

Curtailment: Vaccine efficacy

The impact of the Omicron variant challenges the argument that the pandemic can be brought to an end by vaccination alone. Now, more than before, we need to recognise the consequences of global inequities in vaccine rollout, ambivalence towards mass vaccination and a failure to coordinate messaging so that vaccination is not seen as an alternative to inconvenient population health controls.

Covid-19: Omicron and the need for boosters.
Elisabeth Mahase explores the arguments for and against booster doses of the commonly used vaccines, noting that the Omicron variant appears to reduce vaccine efficacy against infection. She highlights the difference between protection against SARS-CoV-2 infection and a need for hospital admission due to more severe disease.  While the UK has chosen an accelerated booster approach, in recognition of rapidly dwindling antibody levels after a two-dose vaccine course, Mahase points out that a large proportion of the world's population has yet to receive any dose of COVID vaccine. If Omicron did emerge out of the developing world, the argument for coordinated global vaccine rollout is all the more persuasive.
Third BMT162b2 vaccination neutralization of SARS-CoV-2 Omicron infection.

In this letter, Nemet and colleagues report a small cohort study on the neutralising effect of sera on SARS-CoV-2 variants from people who had received either two or three doses of the Pfizer-BioNTech vaccine. They found a greater effect after three vaccine doses than after two, and lower neutralisation with Omicron than Delta even after three doses. This study underlines the importance of a third vaccine dose at a time of Omicron circulation, but does not address the duration of vaccine protection.