A critical question for sceptics is whether there are any effective treatments for COVID-19 because if there are then the case for prolonging the lockdown is weakened. So far, the most promising candidates are Hydroxychloroquine, Remdesivir and, most unexpectedly, Ivermectin, a drug for treating head lice. Which of these potential treatments hold most promise? As background, a quick introduction to what a virus actually is, and how COVID-19 acts on the body. This wonderful article from Scientific American clearly explains how viruses are simply fragments of DNA. Not life as we know it, they cannot respire, cannot replicate without a host, but they can invade host cells, take over the nucleus and reprogram it to create clones of themselves, which then explode out of the used cell to continue the cycle of infection.
The virus is passed through the transmission of droplets exhaled, coughed or sneezed out by infected persons. Initially, the virus attacks exposed cells of the throat and eyes to invade and clone itself. Once established, the infected cells start to shed the cloned virus, and in the body’s attempts to expel it by coughing and sneezing, a cycle of infection is created as the host sheds virus cells into the surrounding environment, where they can survive in the air or on surfaces. Over the course of a few days the host’s immune system kicks in and creates sufficient antibodies to overwhelm the virus and stop it spreading within that host. By then, however, the virus has already moved on to its next victim(s).
From antibody tests recently carried out in the US, it appears that for the huge majority of those infected, that is as serious as it gets. Many people are asymptomatic or suffer such mild symptoms that they don’t bother to seek medical attention. However, COVID-19 can also lead to pneumonia, more often in the elderly and those with comorbidities, which itself causes further, more severe complications as the lungs fail to deliver sufficient oxygen around the body, causing Acute Respiratory Distress Syndrome (ARDS) and the eventual failure of major organs.
So when considering the effectivness of various treatments, we need to be clear about what those treatments are targeting. Of the pharmaceutical treatments, some are antivirals, aimed at inhibiting the ability of the virus to clone itself. Others are aimed at the secondary pneumonia and associated respiratory failure. A third group is aimed at the immune system, trying to prevent it over-reacting to the virus and triggering the onset of pneumonia. Ivermectin inhibits neurotransmission of parasites. Non-pharmaceutical interventions aimed at individual patients are focused on providing additional oxygen to the lungs. The active monitoring of blood oxygen saturation levels is being touted in this New York Times article as helping to predict the onset of severe pneumonia, even in patients who were asymptomatic for the virus.
Remdesivir was developed by Gilead Sciences, Inc. to fight the Ebola virus, but was never proven in clinical trials to be effective and is not licensed for use. It is designed to directly act as a virus inhibitor, overwhelming the virus’s own ability to replicate itself. There were six trials of its effect on COVID-19 patients in progress, but two in China have been terminated due to lack of available participants. The others are as yet inconclusive.
Lopinavir/retonivir (also marketed as Kaletra) is a combination of direct acting antivirals that also work by inhibiting the replication of the virus. It has been proven effective in HIV and used successfully for over 20 years, but so far has not been proven effective against COVID-19.
Hydroxychloroquine has also been put forward as a virus inhibitor, although acting to increase the overall pH level of the cell-level environment, inhibiting the ability of the virus to replicate. A note of caution: the March 20th ‘clinical trial’ conducted by Dr Didier Raoult, director of the Research Unit in Infectious and Tropical Emergent Diseases (URMITE) in Marseille, which seemed to show that hydroxychloroquine is an effective treatment, has been heavily criticised.
Interferons, which act indirectly on viruses by triggering autoimmune reactions in the body, are currently being tested for COVID-19. However, the disruption caused to the immune system could have catastrophic consequences, particularly for patients whose immune systems are already compromised or who are suffering with COVID-19 pneumonia.
Host-directed therapies, such as Naproxen (marketed as Aleve), whereby specific immunity pathways are modulated to relieve inflammation, are also suggested as being possible routes forward to relieve late-stage respiratory distress, and trials are underway. But at the moment no approvals for this use have been granted. Steriods also fall into this category.
Ivermectin is used in parasitic infections, but had shown antiviral properties during the West Nile virus outbreak. Laboratory cell culture tests have shown it to be able to kill COVID-19 within 48 hours, but there are major concerns about its toxicity to humans.
Convalscent blood plasma is a biologic route also being pursued, which saw some successful use against SARS.
‘Chloroquine is a potent inhibitor of SARS coronavirus infection and spread‘, Martin Vincent et al, Virology Journal, August 22nd 2005
‘The Open-Air Treatment of PANDEMIC INFLUENZA’, Richard A. Hobday and John W. Cason, American Journal of Public Health, October 2009
‘Studies claim malaria drug Chloroquine effective against coronavirus‘ by James Delingpole, Brietbart, March 18th 2020
‘Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial‘, Didier Raoult et al, International Journal of Antimicrobial Agents, March 20th 2020
‘Man dies after taking chloroquine in an attempt to prevent coronavirus‘, NBC News, March 24th 2020
‘COVID-19: More hydroxychloroquine data from France, more questions‘ by Véronique Duqueroy, The Hospitalist, April 1st 2020
‘Frequently Asked Questions for COVID Management Support Document‘, Massachusetts General Hospital, April 1st 2020
‘EMA recommends Remdesivir for Treatment of COVID-19 Under Compassionate-Use Rules‘, by Cory Renauer, The Motley Fool, April 3rd 2020
‘Coronavirus hope as drug prescribed for head lice “completely stops the deadly infection replicating in cells within 48 hours”‘ by Vanessa Chalmers, Mailonline, April 4th 2020
‘LA doctor seeing success with hydroxychloroquine to treat COVID-19‘, Eyewitness News, ABC, April 7th 2020
‘BCG jabs mean you are six times less likely to get coronavirus, study finds‘ by Verity Bowman, The Telegraph, April 8th 2020
‘Israeli COVID-19 treatment shows 100% survival rate – preliminary data‘ by Maayan Jaffe-Hoffman, The Jerusalem Post, April 8th 2020
‘A promising COVID-19 treatment gets fast-tracked‘ by George Spencer, Johns Hopkins Magazine, April 8th 2020
‘Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-2019)‘, by Mark Alipio, SSRN, April 9th 2020
‘Doctor gambles on clot-busting drug to save virus patients‘ by Lauran Neergaard, AP News, April 11th 2020
‘Ebola drug shows promise in early coronavirus trials‘ by Tom Whipple, The Times, April 13th 2020
‘Is it dangerous to take ibuprofen?‘ by Dr Roger Henderson, Spectator USA, April 14th 2020
‘Coronavirus patients given US trial drug remdesivir “are off ventilators in a day”‘ by Rhys Blakely and Alex Ralph, The Times, April 18th 2020
‘Are viruses alive?‘ by Luis P. Villareal, Scientific American August 8th 2008
‘The infection that is silently killing coronavirus patients‘ by Dr Richard Levitan, New York Times, April 20th 2020
‘Largest analysis of hydroxychloroquine use finds no benefit for coronavirus, increased deaths‘ by Nathanial Weixel, The Hill, April 21st 2020
‘French researchers to test nicotine patches on coronavirus patients‘ by Kim Willsher, The Guardian, April 22nd 2020
‘Smoke fags, save lives‘ by Chrisophter Snowdon, Spiked, 23rd April 2020
‘Smokers “four times less likely” to contract Covid-19, prompting nicotine patch trials on patients‘ by Henry Samuel, The Telegraph, April 23rd 2020
‘Donald Trump suggests injecting people with ‘DISINFECTANT’ and hitting ‘the body with a very powerful light’ could kill coronavirus in bizarre White House briefing outburst‘, Geoff Earl, MailOnline, April 24th 2020
‘Remdesivir: Drug has “clear-cut” power to fight coronavirus‘ by James Gallagher, BBC News, April 29th 2020