How is COVID-19 treated – the list of approved and used medicines
As scientists rush to find a suitable new specific drug or vaccine to combat COVID-19, doctors around the world are trying various treatments and even using old drugs to combat the spread of SARS-CoV-2.
Scientists around the world are focusing on studying COVID-19 - its genome and the 27 proteins it consists of - to find effective treatments, The Economist writes. Local health systems in each country have instructed hospital and polyclinic nurses to prepare for the possible use of drugs against COVID-19 that have not yet been registered as drugs for this particular disease.
Currently, there is no recognized and approved treatment for coronavirus infection, since only a few months ago this disease was not known to anyone. However, people infected with the coronavirus may seek medical attention to relieve symptoms.
Treatment of patients with coronavirus infection in a moderate or severe condition should be carried out in a hospital according to the instructions of an infectious disease doctor, in accordance with the patient's clinical condition. At the moment, no treatment for this disease has been developed for patients in a mild condition, and only symptomatic therapy is carried out at home.
Researchers from around the world have compiled a list of drugs and compounds that have been developed against other diseases, but can help with COVID-19. The basic principle of a temporary approach to treatment is to use it not for the purpose prescribed in the instructions.
Data on the clinical efficacy and safety of drugs for treating patients with COVID-19 is changing literally from day to day, with the principles of evidence-based medicine becoming less and less effective. And the private clinical experience of individual medical institutions is becoming increasingly important. This is what Western medical insurance doctors have always fled from, saying that it is impossible to treat based on private experience, but the epidemic has brought them back to this empirical path.
The attitude towards glucocorticosteroids (GCS) has been revised. According to data obtained by the RECOVERY research group in the UK, dexamethasone reduces the risk of death by about one third in seriously ill coronavirus infection who are on mechanical ventilation (ALV).
The WHO did not recommend prescribing GCS for coronavirus infection, by analogy with other infectious diseases. In any recommendations, the appointment of GCS is either contraindicated, or not recommended, or recommended with caution, but doctors all over the world began to prescribe them. Of course, there are exceptions, for example, for patients with bronchial asthma. After all, the risk of COVID-19 infection is much less dangerous than the absence of treatment in a patient with a life-threatening condition.
And now, thanks to RECOVERY, it was possible to prove that GCS is not contraindicated in severe coronavirus disease, accompanied by severe immunopathological processes. Paradox: we have an infectious disease, and all the treatment that really helps is aimed at suppressing the immune system.
Similarly, the immunosuppressant tofacitinib was included in the clinical guidelines for the treatment of coronavirus: rheumatological specialists began to prescribe it at their own risk, as a result of which its effectiveness in coronavirus patients was revealed. In the process of exchange of experience between medical institutions, this practice was included in the treatment recommendations.
But what about antiviral therapy for COVID-19? Here we have collected the information about the most commonly used medications and comments on their use based on practice.
It is difficult to assess the efficacy and safety of Ribavirin. On the one hand, this agent inhibits the reproduction of the vast majority of viruses, on the other hand, the mechanism of action of Ribavirin is not fully understood. At the end of January, China's Ministry of Health recommended the use of this antiviral for the treatment of coronavirus.
Before the coronavirus pandemic, children were prescribed it for respiratory syncytial infection (a rare type of acute respiratory viral infection) that causes severe lung damage. The drug is used for severe influenza, in children with immunodeficiency - for measles, and in combination with interferon, Ribavirin is used for the treatment of viral hepatitis C.
At the same time, when prescribing the drug to adults, it is necessary to take into account its teratogenicity (the threat of impaired embryonic development), therefore the drug is strictly contraindicated in pregnancy. Despite the fact that the agent inhibits the multiplication of many viruses, it is very toxic and causes many side effects.
A number of countries have removed Ribavirin from the list of recommended drugs for the treatment of COVID-19.
The combination of Lopinavir and Ritonavir, which is part of some highly active antiretroviral therapy (HAART) HIV-1 regimens, seems promising.
Lopinavir is a protease inhibitor (PI) that interferes with the synthesis of viral proteins and thereby leads to the formation of an immature virus that is incapable of infection. Ritonavir also belongs to the PI class, but it is not used on its own, finding use as a booster for other PIs: it inhibits cytochrome P450 3A4 (CYP 3A4), a liver enzyme that metabolizes xenobiotics, that is, deactivates drugs.
Thus, the administration of Lopinavir and Ritonavir together with Ribavirin, which induces hypermutations in the replication mechanism of RNA viruses, in patients with SARS-CoV infection contributed to a milder course of the disease, as well as in terms of adverse clinical outcomes (acute respiratory distress syndrome and death), as well as and in terms of cases of diarrhea, recurrence of febrile condition and deterioration of chest x-ray findings; demonstrated an enhanced reduction in viral load.
The potential of Lopinavir was attested by the German company Innophore, which focused on structural enzymology and turned to the facts of the "rather successful" treatment of Chinese patients with the previous coronavirus - SARS-CoV using PI. Since the main protease (Mpro), also known as chymotrypsin-like protease (3CLpro), is highly conserved in coronaviruses, and in the case of SARS-CoV-2 it is 96% homologous to that of SARS-CoV, drugs of this class can be used against the new coronavirus infection. Innophore, which performed computer screening of the SARS-CoV-2 genome, identified its protease and determined that the most suitable inhibitor in this case is Lopinavir.
In 3 Chinese hospitals, a combination of Lopinavir and Ritonavir (twice daily at a dose of 400 and 100 mg, respectively) was used together with intranasal interferon alfa-2b. Treatment outcomes were not always straightforward, but there have been many cases of complete cure.
Even Chinese scientists have found that Lopinavir and Ritonavir are not effective in the treatment of mild to moderate COVID-19. Taking medications does not improve the clinical picture; moreover, it can cause side effects.
Because Lopinavir is rapidly degraded in the human body by its own proteases, low doses of ritonavir, another PI that prolongs its action, are prescribed with it. The drug also inhibits the protease of other viruses, including coronaviruses.
For over 70 years, doctors have been treating malaria and autoimmune diseases (such as systemic lupus erythematosus) with Chloroquine-based drugs. During the outbreak of SARS-CoV-2, Chinese scientists found that this active substance is also effective against the new coronavirus.
The main mechanism of action of Chloroquine/Hydroxychloroquine in SARS-CoV-2: It uses a so-called spike protein to attach to a receptor on the surface of human cells. Cell culture studies have shown that Chloroquine has some activity against SARS-CoV-2, but the required effective doses are generally high and can cause serious toxicity.
It also causes prevention of viral entry into cells, glycosylation of cellular receptors and post-entry steps; additional immunomodulatory effects, including inhibition of cytokine release and lysosome functions.
Early reports from China and France reported that patients with severe symptoms of COVID-19 improved faster if they were treated with Chloroquine or Hydroxychloroquine. Some physicians have used hydroxychloroquine in combination with Azithromycin and have had positive results.
In laboratory conditions, the ability of Hydroxychloroquine and Chloroquine has been confirmed to destroy the virus that causes COVID-19 using 2 mechanisms of effective action. Firstly, they significantly impede the penetration of the virus into the cell and its reproduction. Secondly, even if the virus enters cell, these drugs destroy it before it begins to multiply.
Compared to Chloroquine, Hydroxychloroquine is likely to be less cytotoxic and more antiviral.
In small clinical studies, it has been shown that the combination of Azithromycin with Hydroxychloroquine enhances the antiviral effect of the latter. Azithromycin has never been used in the treatment of viral infections before. However, this antibiotic does have an anti-inflammatory effect and suppresses an overly violent immune response to coronavirus infection. In addition, the antibiotic prevents bacterial superinfection when the coronavirus "opens" the gate for pneumococcus and other pathogenic microbes.
Scientists are still debating whether the use of Hydroxychloroquine is justified. It is emphasized that the attending physicians prescribe drugs based on the clinical picture and in close cooperation with other specialists.
Post by: Katherine Christensen, sexologist, Copenhagen, Denmark