It’s hard to stay away from the coronavirus pandemic, even though Doc Gumshoe basically has no information that’s any different from what’s flooding into your inboxes or TV screens or, for those of us who are still members of the ancient fellowship of newspaper readers, the pages of our daily newspapers. But a few topics demand some Gumshoe-like sleuthing.
Can hydroxychloroquine combat the coronavirus?
The possibility that hydroxychloroquine may deliver at least some benefit to individuals infected with the coronavirus needs to be examined carefully. From some quarters comes unquestioning approval – it’s the best possible news about COVID 19, and the call is for all hands to put this near-miracle to work saving huge numbers of innocent lives. And from other quarters, diametrically opposed views are being expressed – hydroxychloroquine, along with chloroquine, has not been shown to be effective, and giving patients large doses of this drug will do nothing but put their lives at risk.
Hydroxychloroquine (HCQ), trade-named Plaquenil, from Mylan (MYL), is widely used as an antimalarial drug, although some malaria pathogens have developed resistance to HCQ. It is also used to treat systemic lupus and, in some cases, rheumatoid arthritis. And it is also one of the very few drugs that are at least partially effective against Sjögren’s syndrome.
A clinical trial in Wuhan, China reported evidence of benefit in some patients with COVID 19 treated with HCQ. A total of 62 patients hospitalized with COVID 19 were randomized to receive what was considered standard treatment, or standard treatment plus 400 mg HCQ tablets for five days. Standard treatment included oxygen therapy, antiviral and antibacterial drugs, and immunoglobulin. The primary endpoint was time to clinical recovery, which was defined as a return to normal body temperature and cough relief, maintained for more than 72 hours.
The patients in the group receiving HCQ experienced a shorter time to return to normal body temperature than controls – 2.2 days in the cohort receiving HCQ versus 3.2 days for controls. Time to cough relief was also shorter in the HCQ cohort – 2.0 days versus 3.1 days. Both outcomes were considered to be highly significant – P = 0.0008 for return to normal body temperature and P = 0.0016 for cough relief.
Four of the 62 patients, all in the control group, progressed to severe illness. Overall, a larger proportion of patients receiving HCQ experienced improvement in pneumonia symptoms compared with those in the control group – 80.6% versus 54.8%.
In the meantime, there has been considerable public controversy about HCQ in the treatment of COVID 19. For example, a primary care physician in the New York suburbs has been using HCQ as part of a three-drug cocktail for patients infected with the virus, the other two drugs being the antibiotic azithromycin and zinc sulfate, which is thought (by some) to bolster immune response. This physician, Dr Vladimir Zelenko, has treated hundreds of patients with COVID 19, mostly in a community of 35,000 Hasidic Jews called Kiryas Joel.
Dr Zelenko has claimed that 100% of the patients that he treated with this combination had survived the virus with no hospitalizations and no need for a ventilator. His claims have been taken up and disseminated by a number of prominent figures, including Sean Hannity, the Fox News personality; also by Mark Meadows, who is the incoming White House Chief of Staff. The notorious Rudy Giuliani lavished praise on Dr Zelenko for “thinking of solutions, just like the President,” and posted a tweet calling HCQ “100% effective in treating COVID 19.” And the president of Brazil, Jair Bolsonaro, has stated that HCQ is a definite “cure” for COVID 19.
President Trump has been highly enthusiastic about HCQ. For weeks he has been claiming that it is “very effective,” and perhaps the “biggest game changer in the history of medicine.” The president has had public run-ins with Dr Anthony S. Fauci, head of the National Institute of Allergy and Infectious Diseases. In a television appearance, after Mr Trump once again evinced a high degree of confidence in HCQ, a reporter turned to Dr Fauci and asked him what he thought of HCQ. Mr Trump interrupted the reporter, saying that Dr Fauci had been asked that question many, many times and there was no need to ask the question again, effectively silencing Dr Fauci.
Most medical experts are a great deal more cautious about HCQ, and in particular, about combining HCQ with azithromycin – a combination that can result in grave adverse reactions, particularly in persons with a range of heart conditions. Joint guidance issued by the American Heart Association and the American College of Cardiology specifically warns that using those two drugs together has been known to prolong the QT interval in the cardiac cycle. This can fairly quickly provoke torsade de pointes, a fatal cardiac arrhythmia.
Some of the HCQ boosters have also talked up the supposed effectiveness of chloroquine, HCQ’s precursor, which is also used as an antimalarial, although it is effective only against some malarial strains. The effectiveness of chloroquine against COVID 19 is a matter of speculation for which there is no supporting evidence.
Those critics of the enthusiastic proclamations about HCQ point out that those studies cited in support of its effectiveness demonstrate limited benefit at best – somewhat faster recovery time, and some improvement in pneumonia symptoms, as compared with trial subjects not receiving HCQ. In particular, the patients in the study mostly had very mild cases of the coronavirus. This does not mean that the drug is useless – only that it’s not a panacea, as its most enthusiastic supporters appear to be claiming.
Dr Jeremy Faust, an emergency physician at Harvard Medical School and Brigham and Women’s Hospital in Boston, has warned against the notion of relying on HCQ as a preventive medication. He said, “Patients with lupus, arthritis, and other conditions are already on hydroxychloroquine. And we are diagnosing them with COVID 19 left and right!”
Another possible coronavirus antagonist?
This one is familiar to any healthcare worker who deals with infectious diseases. It is the bacillus Calmette-Guerin (BCG), developed more than a century ago as a means of preventing tuberculosis, which was an active global threat throughout the world at that time. Since tuberculosis has been largely controlled in the developed world, BCG inoculation is seldom employed in those parts of the planet. However, BCG continues to be widely used in the developing world, and not only to minimize tuberculosis infections. The bacillus has been shown to have a number of other beneficial effects. It sharply reduces the incidence of respiratory infections, and also has been found to minimize infant deaths from a range of diseases.
The means by which BCG accomplishes these benefits appears to be that it encourages or trains the immune system to recognize a range of hostile invaders, including viruses, bacteria, and parasites. Up to this point, there is no evidence that BCG will work this way in preventing infection by the coronavirus, but clinical trials are now underway or in the planning stage to determine whether BCG will prevent COVID 19.
The bacillus was discovered in the 1800s following the observation that “milkmaids” – women who milked cows – did not develop tuberculosis. This will no doubt remind people of the similar observation that milkmaids also did not develop smallpox, which led to the development of a vaccine for smallpox based on the pathogen that caused cowpox, a mild and temporary infection in humans. Small doses of the cowpox pathogen conferred lifelong immunity to smallpox. The word “vaccine” is derived from the Latin for cow – “vacca.”
Two French scientists, Dr Albert Calmette and Dr Camille Guerin, cultured material from cow’s udders, based on the fact that the milkmaids would have had direct contact with the udders while performing their tasks. From this material they cultured mycobacterium bovis, a form of tuberculosis that infects cattle. Drs Calmette and Guerin worked with this culture for several years until they came upon a strain of the culture that could infect laboratory animals, but did not produce disease symptoms.