Yesterday, November 11
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The Insider publishes the opinion of Tanya Melnik, assistant professor of medicine at the University of Minnesota, on what medications can help treat coronavirus and what to take as supportive care.
Here are the main points.
COVID-19 begins as an outpatient disease and, fortunately, for most patients, it passes at this stage, but severe cases are also enough.
From the very beginning of the viral epic, most of the effort was devoted to rescuing those who ended up in the hospital, and there was little study of patients in the early stages of the disease.
It is very difficult to understand who will carry the disease without any special complications, and who will be in intensive care on mechanical ventilation. Even in risk groups, there are quite enough people who have been imprisoned at home with minimal symptoms – to the delight of loved ones and the amazement of doctors.
However, much more shock is caused by patients without any risk factors, who nevertheless ended up in intensive care for several weeks and did not always get out of it successfully. It is not possible to figure out who is really worth treating and who is better to leave alone, because everything will be all right with them. Research in this direction is ongoing, but the results are still few, and there are currently no good risk calculators for clinical use.
In the United States, only two drugs are used as etiotropic treatment aimed at the cause of the disease – remdesivir, which was developed to treat Ebola and hepatitis C, and the plasma of COVID-19 patients with antibodies.
The effect of the antiparasitic drug ivermectin is being studied, but the role of this inexpensive and safe drug is not yet clear. There is also a pathogenetic treatment aimed at mitigating the course of the infection. At this stage, steroids, inhibitors of certain inflammatory factors, and anticoagulants are used.
The last type of treatment is supportive therapy, non-specific treatment – both pharmacological and general therapy.
Treatment
The early stages of infection with COVID-19 are similar to those of respiratory viral infections. It is at these stages that etiotropic therapy directed against the multiplication of the virus would be effective. The search for a cure for colds has been going on for a long time, but everything that should work in theory and even work at the cellular level for some reason refuses to produce any significant effect in clinical trials.
A couple of existing antiviral drugs used in the treatment of viral respiratory diseases, oseltamivir and ribavirin, target a very limited number of viruses. The effectiveness of the same oseltamivir leaves much to be desired even against influenza. And very few people remember the sad fate of pleconaril, which never reached widespread clinical use, although it gave hope.
What can now be considered for outpatient treatment of coronavirus infection?
Favipiravir
This drug began its journey as a remedy against the influenza virus, but has not proved itself very well, it has not been approved against seasonal flu. Therefore, in his native Japan, he was left for pandemic needs: favipiravir lay in the manufacturer’s bins and waited in the wings. Fujifilm has repeatedly tried to attach it to treat Ebola, West Nile, Zika and even rabies.
But favipiravir showed not very convincing results and again went to the regiment until the worst times. Such times, as you know, came in February 2020: in the Fujufilm laboratory, dust was routinely shaken off the drug and sent to China.
The results were quite encouraging: hospitalized patients cleared the virus faster, and chest images showed a positive trend. Given the extremely small number of patients in the experimental and control groups, the conclusion about the need for further testing was quite reasonable.
Several small studies since the first publication are still showing encouraging results, including that the virus clears faster in outpatients with favipiravir treatment. The results of large randomized clinical trials (RCTs) will have a long wait.
Whether favipiravir works in terms of reducing the risk of hospitalization and death is not known for certain.
Given that this drug is not approved for outpatient treatment of COVID-19 in any country in the world, it would be premature to recommend it for widespread use.
Further study of favipiravir is necessary, including at the outpatient stage, at least to determine the ratio of risk to benefit.
Hydroxychloroquine and chloroquine are quinine derivatives
Both of these antimalarial drugs have already been tried more than once in the fight against viral infections.
Their antiviral activity has been known for over 50 years. HIV, adenovirus, hepatitis C – hydroxychloroquine (or chloroquine) suppressed replication of the virus in a culture of cells in a test tube rather well, but did not cope with the same task as successfully in the body, be it a test animal or a patient. Both drugs proved effective against the SARS-CoV virus long before its more infectious cousin SARS-CoV-2 took over the world.
In this regard, quinine derivatives were tested first in cell culture, and then in humans. The first studies with positive results were published back in March.
The studies were carried out on several dozen patients and were not of high quality. Nevertheless, in a matter of days, hydroxychloroquine received worldwide recognition and widespread adoption, up to including it in national treatment protocols for coronavirus infection.
Large clinical trials have begun. And if in some retrospective studies a positive effect was observed, then none of the randomized clinical trials confirmed the effectiveness of hydroxychloroquine.
The hypothesis regarding the mechanism of action of the drug varied from a direct antiviral effect (preventing the virus from entering the cell), immunosuppression (reducing the risk of a cytokine storm) to an auxiliary effect (zinc ionophore). A pivotal randomized clinical trial, planned by the US National Institutes of Health, was successfully canceled in early summer due to a lack of volunteers.
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So far, it is reliably known that at the time of hospitalization, hydroxychloroquine (or chloroquine) is ineffective.
Whether taking one of these drugs is effective in the early stages of infection is unknown. Two clinical trials showed no effect on prevention or early treatment of COVID, but both had too few participants.
Trials are ongoing, so there is hope that the quinine issue will eventually be resolved.
Antiplatelet and anticoagulants
A high risk of thrombosis was identified with COVID almost at the very beginning of the epidemic. Back in the spring, publications from Italy and the USA reported on arterial and venous thrombosis detected at autopsies, as well as strokes, heart attacks and thromboembolism in patients after hospitalization. The question of the need to use drugs that prevent blood clots arose very early.
In medical practice, antiplatelet agents are distinguished – drugs that prevent the activation and aggregation (“sticking”) of platelets, and anticoagulants – drugs that reduce the activity of blood clotting factors.
At the moment, much more is known about the use of anticoagulants in hospitalized patients with COVID-19, but there are still a lot of questions about the effectiveness and appropriateness of these drugs.
There are even more questions about the need and effectiveness of antiplatelet agents and anticoagulants at the outpatient stage. Unfortunately, no reliable data has been collected for the months of the pandemic. Aspirin was considered in a retrospective cohort study of hospitalized patients who took it within 7 days prior to hospitalization or received it in hospital.
Compared to the rest of the patients, the small aspirin cohort had fewer patients requiring invasive ventilation and ICU treatment.
Since most of them took aspirin before hospitalization for indications that have nothing to do with coronavirus, it can be safely concluded from the study that low-dose aspirin should be continued for those who are already taking it. At the moment, aspirin intake cannot be recommended for the treatment of COVID either on an outpatient basis or during hospitalization.
Supportive therapy
Vitamin D
The effect of vitamin D has also been studied in patients with viral infections, including acute respiratory diseases. A fairly large analysis of several RCTs showed a reduction in the risk of disease with vitamin D. The most pronounced protective effect was recorded in patients with vitamin D deficiency.
Regular intake (once a day or once a week) was more effective than single high doses. But at the same time, unfortunately, taking vitamin D did not reduce the risk of complications.
Zinc
Interest in this element and its role in infectious diseases has led to a number of randomized clinical trials “Zinc against ARVI”. Zinc has been tested for both prophylactic and therapeutic purposes, across a wide range of age groups.
A review of all the offsuit studies came out very timely this summer. Zinc reduced the risk of ARVI in healthy children under the age of 10, but did not help adults at all, and in any dose. The therapeutic use of zinc has been shown to shorten the time of illness and relieve symptoms.
While zinc was fighting SARS, and scientists were arguing about the role of trace elements in the treatment of infectious diseases, COVID-19 entered the arena. Noticing familiar respiratory symptoms, the researchers began to measure zinc levels in sick people and compare them to those in healthy people. At the same time, clinicians decided not to wait for results, but to immediately “chain” COVID with zinc, since it has at least some activity against viruses. To the delight of clinicians, the level of zinc in the plasma of patients was much lower than that of healthy people.
Cautious admonitions that plasma zinc levels do not reflect tissue levels, and that when inflammation is active, generally falls off quickly, did not help much.
The results of retrospective studies, during which zinc were given along with a whole set of other drugs, are a little encouraging: scientists have come to the conclusion that zinc can improve the condition of patients. In addition, several clinical trials with zinc against COVID-19 are planned or are already underway, so a sane answer for this element may well be received in the foreseeable future.
However, one should not expect big miracles from it – retrospective cohort studies are not always confirmed by randomized clinical trials. Therefore, at the moment, it is quite difficult to make specific recommendations on the use of zinc for the prevention and treatment of COVID.
Vitamin C
Vitamin C is a unique substance that has undergone clinical trials in the treatment of scurvy even before it became known about the existence of vitamins, and, in fact, about clinical trials. Since then, a lot has been learned about vitamin C and its function in the body, including its need for the normal functioning of the body’s immune system.
There is no data on the effectiveness of vitamin C against COVID-19 in outpatients. Low vitamin C levels have been observed in patients with severe coronavirus infection. But this does not mean that correcting vitamin C deficiency reduces the risk of complications.
Risk factors for complications of COVID-19 (diabetes, overweight and obesity) are risk factors for vitamin C deficiency, and acute inflammation can quickly reduce blood levels. The risk of taking high doses of vitamin C on a short course is relatively low, although patients with kidney stones should consult a doctor – vitamin C is excreted in the form of oxalic acid and can contribute to the formation of stones.
Correcting vitamin C deficiency is essential without COVID.
Full version of the article
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