Posts Tagged ‘mask effectiveness’
Covid-19: remdesivir, masks, vaccine trials, arrhythmias
So to Dr Seheult’s coronavirus update 77, where he looks again at the antiviral drug remdesivir. A preliminary report from the New England Journal of Medicine describes results from trials comparing remdesivir with placebo in covid-19 patients at various levels of treatment, i.e, those receiving oxygen, those not receiving oxygen, those receiving high-flow oxygen or ‘noninvasive mechanical ventilation’, and those receiving full mechanical ventilation or ECMO (extracorporeal membrane oxygenation), and the finding was that remdesivir only made a statistically significant difference in the oxygen-receiving patients, which is more or less an intermediate phase. This may be due to the larger sample size that fell into this category. There were apparently small benefits in the non-oxygen category, but nothing in the more serious patient categories. The report’s conclusion:
These preliminary findings support the use of remdesivir for patients who are hospitalised with Covid-19 and require supplemental oxygen therapy. However, given high mortality despite the use of remdesivir, it is clear that treatment with an antiviral drug alone is not likely to be sufficient.
So remdesivir appears to be just one of many agents and therapeutics in the armamentarium of health authorities dealing with this pandemic, which over the past few months appear to have been utilised to reduce mortality and improve recovery times since the early phase of the outbreak in the USA, to judge from figures comparing, say, New York with Texas and Florida.
The update also discusses heat-treating the interior of police vehicles as a disinfectant, using a computer program. Basically a system has been devised to heat-treat unoccupied vehicles for 15 minutes to 133 degrees fahrenheit, long enough and hot enough to kill 99% of known pathogens, including SARS-CoV2, and it’s already being rolled out for police SUVs. Interesting, and obviously adaptive to other circumstances. The rest of the update discusses promising approaches as of the end of May, including convalescent plasma therapy, which I hope to look at later.
Update 78 starts with face masks. We here in South Australia have only suffered 459 cases in total, with 457 recovered and only 4 deaths. The majority of cases by far occurred in the early stages (March-April), and much has opened up since then, and the wearing of masks has always been optional here. However, the virus has had a resurgence in Australia’s more populated eastern states, so we’re on alert, and there’s been a partial closing down again. Still, most people I notice aren’t wearing masks. In the USA there seems to have been some prevarication from authorities like the CDC on mask-wearing, but with a further understanding, especially of asymptomatic and pre-symptomatic cases, they came out more strongly in favour of cloth masks ‘in public settings where other physical distancing measures are difficult to maintain (e.g. grocery stores and pharmacies), especially in areas of significant community-based transmission’. The WHO’s guidelines aren’t so strict possibly because they’re dealing with a broader base in which effective face masks are less readily available and need to be prioritised.
Also related to masking is a New England Journal of Medicine article on aerosols and droplets generated by speech, which have been implicated in Covid-19 transmission. A simple experiment was conducted using laser light scattering to illuminate droplets from a speaker without a mask, and then with one, and the difference was quite dramatic. Update 78 shows the video, and it’s worth a thousand words.
This update also highlights a website which I intend to explore further, especially as I seem to be spending a lot of time in the world of disease, pathogens and the fight against them. It’s called Regulatory Focus, and there’s a further link to its covid-19 therapeutics tracker, which tracks all the research and studies, of antivirals, monoclonal antibodies and any other medications that might relate in any way to the pandemic, and another link takes us to the covid-19 vaccine tracker. It provides information on phase trials, the vaccine type, the institutions and sponsors involved, etc.
In update 79, Dr Seheult picks out a few of the vaccine trials that seem to show most promise and are most likely to be available by 2021. First is the Moderna mRNA-1273 candidate, which will inject mRNA to produce proteins that generate an immune response. Now the standard clinical trial process for testing a vaccine involves three phases. Phase 1 tests primarily for safety, phase 2 largely looks at appropriate dosage, and phase 3 is the final, large human population trial. These phases have been fast-tracked more than ever before, as is well known, sometimes without the usual animal testing, which would generally raise ethical issues, but that doesn’t seem to be happening for covid-19 trials. The University of Oxford candidate is ‘a chimpanzee adenovirus vaccine vector called AZD1222’. It injects an epitope for an antigen into the patient. An epitope is a region of an antigen that antibodies detect and bind to. Other candidates come from the Merck company, Johnson & Johnson and Pfizer.
Update 80 deals with a very controversial issue, which is possible research industry malpractice, in the form of massaged results relating to a relatively small company, Surgisphere. Interestingly, it involves an overstatement of deaths here in Australia, among other inconsistencies, which have led to retractions of papers on hydroxychloroquine and chloroquine in prestigious journals such as the Lancet and NEJM. It seems that the papers may have exaggerated negative effects from the use of these anti-malaria medications, with or without the addition of a macrolide (a class of antibiotics), which has just added to the controversy surrounding them. There’s also a question about the use of the anti-parasite drug ivermectin, and some common heart medications, due to these now-retracted results.
Interestingly, update 81, posted back on June 9, highlights Australia as still succeeding in keeping numbers down as we head into winter. That’s not the case today (August 11). It goes on to introduce another website, Covid-trials.org, comprising data on ‘over 1400 trials’ (now over 1900) worldwide relating to covid-19, including ‘alternative therapy’ and ‘traditional Chinese medicine’. Hmmm. And of course all the more promising treatments. This and the previously mentioned vaccine and therapeutics trackers provide a wealth of ongoing detail about the who, the how, the what, the how much, etc.
The update also describes a trial of hydroxychloroquine ‘as post-exposure prophylaxis’ published in NEJM. 821 people known to be exposed to the virus were treated with either hydroxychloroquine or a placebo, and then tested for the virus. The result was a non-statistically significant prophylactic effect. There were minor gastrointestinal side-effects in the hydroxychloroquine group, but no cardiac arrhythmias, often associated with the drug. Dr Seheult explains something about these arrhythmias, which is interesting enough for me to dwell on.
When we look at an electrocardiogram (ECG) we find something like the drawing here, with a P-wave, and a T-wave at the end. Some medications can cause a prolonged QTc (the c stands for ‘corrected’), and in combination with others, this can result in cardiac arrhythmias, which generally have two types, as shown in the illustration at the top of this post – an over-fast beat (tachycardia) or a too-slow one (bradycardia).
So, although the positive effects of hydroxychloroquine in this study were minor, there may have been a greater benefit from adding zinc to the treatment, as Seheult suggests, because the drug acts as a zinc ionophore. An ionophore is a fat-soluble transporter material which can carry non-fat-soluble minerals like zinc through the fatty cellular membrane. Zinc inhibits the RNA-dependent RNA polymerase of the coronavirus, but it seems that as of mid-June no full-blown studies had been done to show a benefit, or otherwise, from the combination.
References
Coronavirus Pandemic Update 77: Remdesivir Update; COVID-19 in Mexico
Coronavirus Pandemic Update 78: Mask Controversy; Vaccine Update for COVID-19
Coronavirus Pandemic Update 79: COVID-19 Vaccines to Keep an Eye On – mRNA, Antigen, Others
Coronavirus Pandemic Update 80: COVID-19 Retractions & Data (Hydroxychloroquine, ACE Inhibitors)
Coronavirus Pandemic Update 81: New Data on Hydroxychloroquine Side Effects & Prevention of COVID-19
https://www.nejm.org/doi/full/10.1056/NEJMoa2007764
https://jamanetwork.com/journals/jama/article-abstract/2766943
https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker
https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-therapeutics-tracker