Coronastream: risk of resurgence, face masks in transmission and the retraction of that hydroxychloroquine paper

Posted on June 10, 2020   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.


Department of controversy: COVID-19 treatment clinical trial

The controversy surrounding the Lancet hydroxychloroquine paper came hot on the heels of last week's gentle introduction to some of the controversies surrounding COVID-19. Now that the paper has been officially retracted, it is worth reflecting on some of the lessons that can be learned for those of us who are still in the thick of trying to make sense of the raw science. Leading tropical medicine specialists who understand the use of hydroxychloroquine were quick to comment on the possibilities, problems and processes in the search for effective COVID-19 treatment. Those words of wisdom remain pertinent despite the deficiencies of science journalists identified in the Lancet study.

Admirers of Karl Popper's philosophy of scientific practice will note the irony of withdrawing a paper that claimed to undermine hydroxychloroquine's efficacy as a COVID-19 treatment. If we want to be sure that the grounds for falsification of efficacy are themselves false, we need to see the data. It is regrettable how quickly people of all persuasions have been left to jump to conclusions without an opportunity to scrutinise the data. Remembering Popper's principle of falsifiability: "…falsification of a high-level scientific theory is never brought about by an isolated observation or set of observations."

At least this clears the way for continuation of other clinical trials, perhaps with more caution than accelerated peer review allows.

Congruence: how long do symptomatic COVID-19 patients remain infective?

Predicting infectious SARS-CoV-2 from diagnostic samples

A practical issue that has come to the fore recently, is how quickly people with confirmed COVID-19 cease to be an infection risk to others. There has been a series of recent studies suggesting that RT-PCR positivity can persist for long periods in some patients who seem to have recovered. A Canadian group have published their findings on the RT-PCR cycle threshold, duration of clinical symptoms and infectivity of cell culture. Using the SARS-CoV-2 E gene target, they found that there was no evidence of cell culture infection after a duration of symptoms of more than eight days, or a cycle threshold of more than 24. Though this is not the same as demonstrating a lack of secondary cases or other indicators of actual human infectivity, it provides a starting point for setting laboratory and symptom duration decision points in order to letting people out of quarantine.

Consistency: resurgent COVID-19

Risk for COVID-19 resurgence related to duration and effectiveness of physical distancing in Ontario, Canada

In this correspondence, Tuite and colleagues explored the effect of relaxing physical distancing on data from Ontario, Canada. They predict that relaxing distancing without compensating by increases in detection, isolation and contact tracing would lead to a resurgence of disease. Ominously, returning to normal levels of contact were predicted to result in exceeding intensive care capacity. Their modelling found that without distancing there would be 37.4 intensive care admissions per 100,000 people, while with distancing it would be two. It seems that where the worst of the pandemic is over, watchful caution is going to be necessary for some time to come.

Cumulative dissonance: laboratory markers for progression of COVID-19

Lactate dehydrogenase and susceptibility to deterioration of mild COVID-19 patients: a multicentre nested case-control study

In this observational study of 143 COVID-19 patients, Shi and colleagues used multivariate analysis to show that the correlates of progression to severe disease were advanced age and raised lactose dehydrogenase levels (LDH: 316.4 ± 86.4 vs. 222.4 ± 73.8). Raised LDH is an indicator of tissue damage. It has been reported as a predictor of mortality in acute respiratory distress syndrome, influenza A/ H1N1 and is a common finding in patients with MERS-CoV infection. This report of raised LDH in early COVID-19, raises the interesting possibility that subclinical tissue damage could be prospectively monitored.

Curtailment: the protective benefit of mask-wearing

Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis  

The wearing of facial protection has been the subject of discussion, argument and speculation since the early stages of the pandemic. The WHO-sponsored SURGE study group have now published a systematic review and meta-analysis of protective measures including the use of face masks. They identified 172 observational studies, 44 comparative studies and NO randomised controlled trials. With those caveats, Chu and colleagues found that virus transmission was lower when physical distancing was one meter or more. They concluded that use of face masks "could result in a large reduction in risk of infection", with stronger evidence for N95 masks than disposable surgical masks or similar. They also noted that eye protection was associated with reduced infection.

Given the lack of randomised controlled trial data for the individual components of this package of protective measures, the jury is clearly still out on masks. We look forward to convincing data one way or another, to inform usage in public settings.


Picture of the week: Resurgent epidemic curve, South Korea