It is strange to think that the currently-accepted germ theory of disease is barely 150 years old. Largely credited to the French microbiologist Louis Pasteur and the German physician Robert Koch, the theory holds that infectious diseases are caused by specific microorganisms – contrary to Galen’s preceding miasma theory that diseases (such as the Black Death) were the result of noxious bad air arising from organic matter. As such, hand hygiene was poor and transmission rates were high. Then, in 1867, the British surgeon Sir Joseph Lister published his ground-breaking paper Antiseptic Principle of the Practice of Surgery. Lister’s views on the need for cleanliness in the operating theatre were revolutionary. He developed antiseptic surgical methods such as the use of carbolic acid to clean wounds and surgical instruments. Although initially criticised, even mocked, by the medical establishment, his methods were soon widely adopted and deaths from infection began to fall dramatically.  

Enter the modern day and we are in the midst of a germ-related crisis of our own. With Covid-19, we embrace hand hygiene and physical distancing but, while awaiting a vaccine, we remain conscious of the need for effective treatment. One world leader has regaled us with his views on the benefits of household bleach and hydroxychloroquine. The former suggestion was (hopefully) tongue-in-cheek, but the latter seemed a more sincere recommendation. So, does it work? Despite initial optimism, a recent analysis published in The Lancet by Mehra et al¹ cast doubt over the use of hydroxychloroquine for Covid-19. The authors reported on 14,888 patients who were treated with one of four treatments (chloroquine alone, chloroquine with a second-generation macrolide, hydroxychloroquine alone or hydroxychloroquine with a second-generation macrolide), and compared them with an 81,144-strong control group in relation to in-hospital mortality and the occurrence of de novo ventricular arrhythmias. Compared to controls, all four treatment groups were found to be independently associated with an increased risk of both adverse outcomes. But the ink was hardly dry on the page when, in dramatic fashion, the authors retracted the article over concerns about “the veracity of the data and the analyses”. 

Remdesivir is a greater reason for optimism. In the New England Journal of Medicine, Beigel et al published the preliminary findings of their double-blind, randomised, placebo-controlled trial of intravenous remdesivir in adults hospitalised with Covid-19 showing evidence of lower respiratory tract involvement.² Of 1,059 patients studied, 538 were treated with remdesivir 200mg (on day 1) followed by 100mg for nine days, while the remaining 521 comprised a control group who were given a placebo. According to the authors, those receiving the active drug had a median recovery time of 11 days, compared to 15 days in the control group. By day 14, the mortality rate was 7.1% among the remdesivir patients and 11.9% for their placebo counterparts. Serious adverse events were reported in a higher proportion of the control group (27%) than the treatment group (21.1%). The authors concluded that remdesivir is superior to placebo in shortening the time to recovery in adults hospitalised with Covid-19 with evidence of a lower respiratory tract infection. 

As we went to press, preliminary results were emerging from the RECOVERY trial in the UK (unpublished at that point), indicating that the steroid dexamethasone was showing beneficial effects on patients severely ill with Covid-19.³

Hope springs eternal. Stay safe.

References

1. Mehra MR, Desai SS, Ruschitzka F, Patel AN. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of Covid-19: a multinational registry analysis. Lancet 2020, May 22. doi.org/10.1016/S0140-6736(20)31180-6 (this article has been retracted)
2. Beigel JH, Tomaskek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC et al. Remdesivir for the treatment of Covid-19 – Preliminary Report. New Engl J Med 2020, May 28. doi:10.1056/NEJMoa2007764
3. www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---17-june-2020