Annalisa Chiusolo shows how controversial drug hydroxychloroquine could make people immune to virus * Top Israeli researcher: ‘theory lacks backing’
COVID-19 damages the hemoglobin, impairing the ability of red blood cells to transport oxygen throughout the body, compromising the lungs and resulting in Acute Respiratory Distress Syndrome (ARDS), Italian pharmacology scholar Annalisa Chiusolo explained to The Jerusalem Post.
If her thesis is correct, it would resolve many outstanding questions about the novel coronavirus, such as the greater vulnerability of men – specifically male diabetics – to become seriously ill from the virus, as well as the lower rate at which pregnant women and children contract COVID-19.
Moreover, understanding this mechanism could lead the way to a quicker discovery of the most effective drugs to treat the virus.
Chiusolo is a graduate of the Faculty of Pharmacy of the University of Perugia, Italy, and works as a pharmacist in the European country. Her theory has been published by some of the country’s leading newspapers, including the Italian dailies Il Tempo and Il Giornale.
She told the Post that SARS-CoV-2, the formal name for the novel coronavirus, needs porphyrins for its survival – and probably for its replication – so it attacks hemoglobin, the protein that carries oxygen in the blood, which translates to less oxygen available for the body. The consequence of less oxygen is the accumulation of carbon dioxide.
“The lung cells become the site of the cytokine cascade, an enormous immune response, which is responsible for the acute lung inflammation that characterizes COVID-19 pneumonia,” she said. “The value of hemoglobin in the blood can be an important parameter to assess the SARS-CoV-2 infection: In men the normal value of hemoglobin (Hb) is higher than in women. This would explain the higher incidence of COVID-19 pneumonia in men compared to women, and the lower incidence and better prognosis in children and pregnant women, where Hb values are lower due to an increased need of iron, which makes less available this ‘nutrition’ for the virus.”
PNEUMONIA CAUSED by the coronavirus is also more prominent in elderly patients or middle-aged patients with diabetes, which Chiusolo said is linked to increased glycated hemoglobin.
As a pharmacist, Chiusolo next evaluated the use of hydroxychloroquine to treat SARS-CoV-2, which in some cases has been found to reduce hospitalizations from the virus. Hydroxychloroquine is currently in use for the treatment of autoimmune diseases worldwide, such as lupus and rheumatoid arthritis, and has been used for years to treat malaria.
She said that in addition to the drug’s antiviral and immunomodulatory effect, it binds to the ferriprotoporphyrin of the ecgonine methyl ester (EME), blocking the key enzyme of malaria. “So, I thought this same mechanism could be used against SARS-CoV-2… Indeed, a study by a Chinese university shows that SARS-CoV-2 binds to the beta chain of hemoglobin, inhibiting EME metabolism.”
Ferriprotoporphyrin is the group responsible for the oxygen binding of hemoglobin.
In Italy, top scientists are beginning to comment on Chiusolo’s theory. Dr. Giuseppe Ippolito, scientific director of the Lazzaro Spallanzani National Institute for Infectious Diseases in Rome, called her hypothesis, “suggestive, but it is necessary to deepen and research.”
Dr. Giovanni Martinelli, scientific director at the Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRCCS), validated that “much of the effects of oxygen starvation in COVID patients may be due to the displacement of Hbs protoporphyrin.”
BUT DOCTOR Amiram Goldblum, head of the Molecular Modeling and Drug Design Institute for Drug Research and the Fraunhofer Project Center for Drug Discovery and Delivery at the Hebrew University of Jerusalem, said that among the nearly 8,500 papers filed on the novel coronavirus in the last three months not one mentions porphyrin or protoporphyrin.
“As far as I am aware of the reduction of oxygen pressure in severe cases of the SARS-CoV-2 attack, it is due to blocking lung cells in a somewhat similar manner as emphysema – transforming the cells to be more rigid, fibrous entities,” he told the Post after reviewing Chiusolo’s study.
He said that the first FDA approved drug, Remdesivir by Gilead Pharmaceutical, is indicated only for those cases in which oxygen pressure was reduced to a more dangerous level.
“If the virus ‘eats up’ the porphyrin of hemoglobin, the first effect should be anemia, which affects oxygen intake but also affects substantial weakness and is easily measured,” Goldblum said. “I have not heard of any problems with lower hemoglobin in COVID-19 patients.”
And how about the use of hydroxychloroquine?
Chiusolo said that hydroxychloroquine could act as a prophylactic, preventing or limiting the symptoms of the disease while waiting for the formulation of the vaccine that specifically stimulates the antibody response of the body. She said it could make the patient immune to COVID-19 and/or limit its side effects.
The drug has been under investigation worldwide, including in the United States, after President Donald Trump last month called it a “game-changer” in the fight against coronavirus.
The Italian Medicines Agency (AIFA), the national authority responsible for drug regulation in Italy, has an approved trial of hydroxychloroquine on 2,500 patients, which will start in early July and focus on the use of hydroxychloroquine in prophylaxis, Chiusolo said. The study, for which preliminary data would be ready within 16 weeks, will look at whether the preventive intake of the drug decreases the probability of contracting COVID-19 when one comes directly into contact with a positive patient.
THE ROLE of hydroxychloroquine in the prevention and fight against coronavirus was also the subject of a study published in The International Journal of Antimicrobial Agents, which describes how a healthcare worker infected with the novel coronavirus traveled freely within a hospital before being diagnosed with the virus.
“It was not possible to quarantine everyone who had come into contact with the healthcare worker,” Chiusolo said. So, they treated 211 healthcare professionals and patients with hydroxychloroquine. After 10 days, nobody tested positive for the coronavirus.
Furthermore, Chiusolo told the Post, the Italian Society of Rheumatology interviewed 1,200 rheumatologists throughout Italy to collect statistics on contagions. Out of an audience of 65,000 chronic lupus and rheumatoid arthritis patients who systematically take hydroxychloroquine, only 20 patients tested positive for the virus.
“Nobody died, nobody is in intensive care, according to the data collected so far,” Chiusolo said.
However, she admitted that the drug is known to have some severe side-effects, especially for patients with prexisting health conditions such as heart disease. The drug was recently linked with increased risk of cardiac arrhythmia in COVID-19 patients by a research team at Beth Israel Deaconess Medical Center (BIDMC) in Boston.
“The accumulating evidence is that there is limited data to suggest efficacy and there’s growing evidence that suggests toxicity,” Dr. Howard Gold, infectious disease doctor at BIDMC, said of the drug hydroxychloroquine in an interview published by the Boston Herald.
The BIDMC study evaluated 90 adults infected with the novel virus, each of whom received at least one day’s treatment of hydroxychloroquine, which can stay in the body for up to three weeks, according to Gold.
“Scientists are very open to revolutionary ideas,” Goldblum said, but he noted that “science is built in steps… They must have some backing. In my opinion, currently there are none.”