Coronastream: Who's got the crayons?

Posted on October 28, 2021   by 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

There has been a lot of talk by our leaders about road maps; their simplified illustration of the route out of the tightly controlled pandemic condition. The bright colours and cartoons summarise the local version of a staged retreat from peak public health restrictions. Now, almost every state here has a road map. The final destination may not yet be in sight, but there is a definite sense that it’s getting closer. When you’re in the one state that has yet to update its pandemic road map, you can be a little cynical about the calls from some in our community, who insist on a fixed date for an end to all remaining restrictions. After all, an arbitrary date or declared Freedom Day might go the way of all those other cancelled events SARS-CoV-2 has disrupted. A lot of health resources were diverted to the large Eastern states when they ran into serious problems after the July Bondi cluster fanned out. Now that those states are well along the bumpy ride out of COVID zero tolerance, the states without community transmission have been hustled into catch up mode, reluctant to relax until their vaccine uptake has caught up with the impressive coverage achieved in New South Wales and Victoria. There are specific challenges to rapid vaccine rollout in geographically dispersed populations, leaving aside the higher complacency that breeds, where SARS-CoV-2 does not. And here in the West, catch up is proving to be tough. Even if we don’t know what our own road map will look like, it would be good to know who has got the crayons.

CONGRUENCE: COVID in vaccinated health care workers before and after Delta variant arrival

Clinical and Genomic Characterization of SARS CoV-2 infections in mRNA Vaccinated Health Care Personnel in New York City

In this retrospective study of over 13,000 health care workers in New York, Robilotti and colleagues investigated the vaccination status and subsequent infection before and after the introduction of the delta variant of SARS-CoV-2. They stratified workers into fully, partially and unvaccinated cohorts. 12,379 received at least one dose of mRNA vaccine and 12,046 received both doses, mostly of BNT162b2. Of the vaccine recipients to develop COVID, all their infections were mild and did not require hospital admission. The 17 infections requiring admission and one death were in unvaccinated health care workers. Pre-delta variant, 134 infections followed the first vaccine dose, and 80 followed the second dose. Once Delta was in circulation, 5 occurred after the first dose and 179 after the second. Though there was little difference in clinical symptoms in vaccinated staff before and after Delta arrival, it did appear to reduce the proportion of asymptomatic detections.

During the transition from pandemic to endemic infection, there is further source of complexity due to the specific properties of emerging variants and the degree of vaccine coverage. This study helps us understand the interplay of those dynamics in a healthcare setting where unvaccinated persons continued to work. The complete absence of fatal and severe COVID in the vaccinated workforce is reassuring for occupational health.

CONSISTENCY: Modelling the pandemic over 12 months

One year of modeling and forecasting COVID-19 transmission to support policymakers in Connecticut.

As the local pandemic disease burden diminishes, public health authorities needed to decide how quickly to lift restrictions and measure the risk of recurrence. The uncertainty surrounding these decisions led to increasing reliance on mathematical modelling. Morozova and colleagues identified three questions that policymakers needed answers to:

  1. How soon can interventions like school closures and stay-at-home orders be lifted?
  2. How should public health interventions be implemented to minimizs the risk of a resurgence?
  3. What will be the effect of phased reopening plans on cases, hospitalisations, and deaths?

They developed a flexible, compartmentalised model of SARS-CoV-2 transmission and COVID progression, based on a susceptible-exposed-infectious-removed (SEIR) framework and applied it to 12 months of data from Connecticut, USA. They were able to estimate the effective reproduction number, cumulative infection incidence, infection hospitalisation and fatality ratios, and the case detection ratio. The model showed that standard SEIR transmission models function well in large populations with constant transmission and no major confounding events. However, influence on public health policy requires effective communication with policymakers who are familiar with near-real time reporting of disease statistics, but less so with the limitations of predictive modelling. This paper usefully documents the confidence limits of their estimated variables, and demonstrates the scope for more detailed geographic, age, vaccination status and time-dependent stratification.

CUMULATIVE DISSONANCE

Preliminary Evidence for IL-10-Induced ACE2 mRNA Expression in Lung-Derived and Endothelial Cells: Implications for SARS-CoV-2 ARDS Pathogenesis.

Angiotensin-converting enzyme 2 (ACE2) is expressed on pulmonary and other endothelial cells and provides a binding site for SARS-CoV-2 spike glycoprotein, leading to subsequent cellular infection. The anti-inflammatory cytokine, IL-10, can be raised in severe COVID. In this study, Albini and colleagues investigated the effect of IL-10 on ACE2 expression in a lung-derived cell line. Here they provide preliminary evidence of ACE2 mRNA increase in the cell line, plus enhanced ACE2 expression in endothelial cells by IL-10 treatment. Interestingly, they also observed that the antidiabetic agent metformin upregulated ACE2 in the lung cell line and endothelial cells. They note that upregulation of IL-10 may be clinically relevant to SARS and vasculitis in COVID through its effect on ACE2 levels.

COUNTERMEASURES

COVID-19 vaccine boosters: What do we know so far?

Now that many countries have had a large proportion of their population fully vaccinated for months and numerous studies appear to show variable degrees of waning immunity, there is a push to offer booster doses of one or other COVID vaccines. The discussion around booster doses has been usefully summarised by Kherabi and colleagues in this commentary. While clearly a work in progress, they introduce an increasingly divisive topic. Their headings are instructive: Why a booster dose? Data supporting a booster dose; and ethical issues of a booster dose and potential alternatives. The ‘why?’ question revolves around waning neutralising antibodies 5-6 months after a second vaccine dose, reduced vaccine efficacy of BNT162b2 (Pfizer-BioNTec), but sustained cell-mediated immunity at six months after vaccination. The real-world evidence for improved efficacy comes from an observational study of Israel’s booster programme used to counter the emerging Delta variant, in which a significant reduction of confirmed infections and severe COVID was seen during the short period of follow-up. In the USA and France, a third or booster dose of vaccine has been recommended for people over 65 years and in the 50–64 years age group with underlying medical conditions. However, the low rate of vaccination in low- and middle-income countries will contribute to continued transmission and emergence of new variants. Therefore, alternatives such as different vaccine dosing intervals and mixing vaccines represent an alternative. The use of COVID vaccine boosters is only really possible in wealthy countries and raises important issues for health ethics and policy.

Resources
  • WorkSafe Australia fact sheets and safety guidance for your workplace, including those who are working from home.
  • The Johns Hopkins Coronavirus Resource Center dashboard is worth a look if you haven’t been there for a while. If you use it regularly, you’ll know about the other displays they’ve developed to complement the global map and summary stats.