COVID-19 is a respiratory disease caused by the new SARS-CoV-2 virus.
In December 2019, it was the first to be described in the Chinese city of Wuhan. Today it is a global pandemic due to the very high contagiousness of this virus. Intensive research into an effective remedy against COVID-19 has been underway for over a year. World health organizations analyze the flow of information and issue appropriate directives and guidelines to mitigate the effects of the epidemic. Scientists are constantly working on new preventive and therapeutic strategies and new diagnostics.
The methods of treating SARS-CoV-2 infection are only of an auxiliary nature, and the best weapon is PREVENTION, which is aimed at limiting the spread of the virus. The basic preventive measures are proper hygiene, frequent hand washing, wearing masks and keeping distance.
Due to the course of the disease, we can divide it into individual clinical states and in terms of its advancement:
Asymptomatic or with slight symptoms of Covid 19.
About 80-90% of patients infected with SARS-CoV-2 are affected. The oxygen saturation level in these patients is above 95%. At this stage of the disease, patients do not need to be hospitalized, but they remain under the care of a primary care physician. According to the recommendations, in case of symptoms they may require administration of anti-pyretics. Remember about proper hydration and rest. GKS is not recommended at this stage of the disease.
Full-blown state, SpO2 <95%.
The patient requires hospitalization if oxygen therapy is required. The use of pharmacotherapy at this stage is based on remdesivir (antiviral drug) and / or convalescent plasma. If the patient’s condition requires it, supportive treatment is implemented: symptomatic treatment, low molecular weight heparin, dexamethasone, oxygen therapy, hydration, possibly antibiotic therapy.
State with respiratory failure, SpO2 <90%.
The so-called cytokine storm, i.e. over-reactivity of the immune system and inflammation.
State of acute respiratory distress (ARDS)
It is life threatening. Requires mechanical ventilation (using a respirator).
In search of a suitable remedy, scientists conducted a series of studies based on which they assessed the possibility of using the following drugs in the fight against COVID-19:
Antiviral / immunomodulating drugs
Chloroquine and the hydroxychloroquine derivative, in addition to their antimalarial effectiveness, are important in the fight against RNA viruses such as SARS-CoV. Chloroquine (500 mg every 12 hours) and hydroxychloroquine (200 mg every 12 hours) have been proposed as immunomodulating therapy. Due to the wide spectrum of action of these substances, they are administered to newly identified viruses in the absence of effective alternatives. In vitro studies have demonstrated their ability to inhibit SARS-CoV-2 virus replication until it disappears completely. Increasing the effectiveness of these drugs was achieved thanks to the combination with macrolides (AZOTRIMYCIN), which can reduce inflammation and modulate the immune system. It should be noted, however, that the concomitant use of hydroxychloquine and azithromycin may lead to an increased risk of QT prolongation and arrhythmias. According to recent research, the FDA advises against the concomitant use of hydroxychloroquine and azithromycin in the event of COVID-19 infection, except in certain cases.
Antiviral agents
Despite the lack of an approved antiviral drug for the treatment of COVID-19 patients, several formulations have been proposed:
REMDESIWIR is a drug initially developed to fight the Ebola virus. As an adenosine analog prodrug, it is likely to interfere with viral RNA transcription and exhibits a potentially broad spectrum of activity. The drug has been tested on many aspects and concluded that it had no benefit in terms of mortality. It is presumed that its early administration accelerates recovery in hospitalized patients with severe COVID-19 cases who require oxygen. However, given the high mortality rate despite the use of remdesivir, it is clear that treatment with an antiviral drug alone is unlikely to be sufficient for all patients. Research on this drug was carried out with great interest and hope, supposedly to help reduce the multiplication of the virus in the body, but as it turned out later in one of the studies conducted by WHO, remdesivir probably did not have a significant effect on their treatment, nor did it shorten the hospitalization time or did not significantly reduce the risk of death from COVID-19. Currently, remdesivir is not recommended in patients with severe renal impairment or severe liver disease.
LOPINavir / Ritonavir is a protease inhibitor used to treat HIV infection. In March, the results of the first clinical trial on the effectiveness of these drugs in the fight against COVID-19 were published. As it turned out, unfortunately, lopinavir did not show a higher treatment effectiveness in terms of clinical improvement or viral mortality compared to standard treatment. Unfavorable pharmacodynamics and the lack of proven clinical efficacy allow the conclusion that COVID-19 is not used in the treatment.
Corticosteroids are a group of anti-inflammatory drugs that are effective in the treatment of various conditions such as asthma, allergic conditions, autoimmune diseases, septic shock and cancer. Due to their mechanism of action, they weaken the immune response, which creates a greater risk of infection, and also causes side effects such as hyperglycemia, abdominal obesity, osteoporosis, glaucoma and hypertension. Since the COVID-19 outbreak, corticosteroid treatment has been used in over 45% of those infected in China. In patients with acute respiratory distress syndrome (ARDS) COVID-19, steroid treatment is associated with a reduced risk of death compared with patients who are not receiving steroids. Methylprednisolone can be given short term in patients with rapid disease progression or in severe cases, but should be used at the lowest dose possible and the benefits and risks of steroids should be assessed. This group of drugs also includes dexamethasone, which has been shown to reduce deaths by a third of patients in critically ill COVID-19 patients. The Polish Society of Epidemiologists and Doctors of Infectious Diseases has opted for the use of low doses of GCS in stage 2, provided that antiviral drugs are also administered – remdesivir. Questions regarding the dosage of corticosteroids remain unclear and research is ongoing.
TOCILIZUMAB, SARILUMAB Tocilizumab (Actemra®) is a recombinant humanized monoclonal antibody against the human IL-6 receptor. A Chinese study showed that tocilizumab significantly reduced fever within days after treatment in patients with severe or critical COVID-19, and also observed a reduced need for supplemental oxygen. Scientists concluded that tocilizumab is an effective treatment for critically ill patients. Another IL-6 receptor antagonist that has the potential to combat pulmonary symptoms in critically ill patients is sarilumab (Kefzara®)
Although no published clinical trials are known, preliminary analysis of the study showed that sarilumab was effective in critically ill patients.
PLASMA OF HEALTHIANS
The potential methods of treating people with a severe course of COVID-19 include recalculating plasma. This is the plasma of patients who have been cured of COVID-19. They contain antibodies to SARS-CoV-2. By administering convalescent plasma to infected patients, it was thought to shorten recovery time and also to reduce the severity of the disease. However, there is still no adequate evidence to support the thesis about the effectiveness of plasma treatment for convalescents. From the latest reports published in The New England Journal of Medicine, we learn about the studies that have been carried out, which would undermine the effectiveness of plasma transfusion so far. The authors of the experiments made it clear that the plasma of convalescents did not cause significant differences in treatment, condition, course of the disease, or mortality in the studied patients. These studies are in great contradiction to the current beliefs about the effectiveness of plasma in the treatment of COVID-19 patients. The issues of continued administration of convalescent antibodies remain in question and await further reliable research.
FLUOXAMINE
A widely used drug called fluvoxamine has recently been tested as a drug for COVID-19 in the United States. Fluvoxamine is a selective serotonin reuptake inhibitor or SSRI. SSRIs are the first-line drugs of choice for the treatment of depression. The studies carried out have a small number of trials, and the most severely affected by COVID-19 has been eliminated. However, on their basis it was established that its administration in the early stages of the disease (fever, cough) may reduce the risk of developing the disease, characterized by a cytokine storm and subsequent lung damage. Fluvoxamine may be useful in helping to keep mild COVID-19 from getting worse.
ANTICOAGULANTS
COVID-19 patients are at risk of developing thrombosis. Anticoagulants are of particular importance in patients treated in the intensive care unit, as it has been suggested that patients on thromboprophylaxis have shown reduced mortality.
Currently, WHO guidelines focus on supportive care and the management of complications in line with the general guidelines. Remdesivir is recommended by most countries in severe cases. Currently, intensive clinical trials are underway in China on new drugs – mainly preparations of traditional Chinese medicine and antiviral drugs. Thanks to such innovative targeted therapies, maybe soon we will see the “golden mean” that the whole world has been waiting for so long.
Sources:
- Davidson, Why an antidepressant could be used to treat COVID-19, theconversation,
- Nowakowska, S. Sulimiera Michalak, COVID-19 – a disease caused by infection with the sars-cov-2 virus, a global threat to public health,
- Recommendations for the diagnosis and therapy of SARS-CoV-2 infections of the Polish Society of Epidemiologists and Doctors of Infectious Diseases of October 13, 2020,
- Features, Evaluation, and Treatment of Coronavirus, M. Cascella, M. Rajnik; A. Cuomo, S. C. Dulebohn, R. Di Napoli,
- Update on treatment of COVID-19: ongoing studies between promising and disappointing results, S. Esposito, S. Noviello, P. Pagliano
- G. Rizk, K. Kalantar-Zadeh, M. R. Mehra, C. J. Lavie, Y. Rizk & Donald N. Forthal, Pharmaco-Immunomodulatory Therapy in COVID-19
