Scientists focus on early treatment of covid-19


nbc news

posted on 1/10/2021 06:00

(credit: John Moore / AFP)

(credit: John Moore / AFP)

“If you have any symptoms, stay home for 14 days and only see a doctor if you are short of breath.” Everyone should remember one of the first recommendations of the World Health Organization (WHO), adopted globally in March 2020, at the beginning of the covid-19 pandemic. Until then, almost nothing was known about Sars-CoV-2, which, even today, has not been completely deciphered. Asking people not to go to hospitals was a way of not overburdening health systems, while imagining that mild symptoms would pass naturally, like flu.

Almost a year after the pandemic was declared, however, it is already well known that covid-19 is not just a flu. Up to 20% of patients will progress to severe cases, with critical manifestations, such as pneumonia. Studies show that, if treated from the beginning, the disease’s evolution is avoided – severe conditions, which require hospitalization and intensive care, have worse prognosis. Early interventions, as shown by research released last Thursday on the use of convalescent plasma, can halve mortality. “If you have a fever, cough or difficulty breathing, see a doctor immediately.” This became the WHO recommendation.

Now that this is known, scientists are fighting against time to find the best interventions to prevent covid-19 from evolving. “The prevention of hospitalizations and chronic sequelae of the disease will not only save lives, but also help to restore health systems and other institutions, burdened by the effects of the pandemic”, says an opinion article published in the medical journal Jama and signed by the infectologist Anthony Fauci, the head of the American task force to fight the disease. “Effective and early treatments will also mitigate gaps left by previous and current prevention strategies and reduce direct transmission. It is encouraging that effective outpatient treatments for initial covid-19 are on the horizon. These efforts deserve the full support of the medical community and the public. ”

Today, there are no specific treatments for covid-19, neither in mild form nor in severe form. However, severe conditions benefit from corticosteroids: dexamethasone has been tested in several studies worldwide, including in Brazil, and has been shown to be effective in reducing the mortality of patients who need oxygen support. However, it is not a drug indicated for mild cases. It acts with a focus on the so-called cytokine storm, when the organism triggers an exaggerated response to the presence of an invader – in this case, the coronavirus -, causing the hyperinflammatory condition that characterizes the severe covid-19.

The experimental antiviral remdesivir, originally developed for ebola, proved effective in mild to moderate cases, but it is not indicated for laboratory use, only for hospitalized patients, because it requires daily infusions for up to 10 days. In addition, it has a very high cost, which discourages the adoption of the drug. Various medications, such as hydroxychloroquine and ivermectin, initially referred to as an “anticovid cocktail” have been disapproved in clinical studies.

Currently, antivirals are approved or under development for other infections of the type, such as HIV, hepatitis C virus and ebola, under investigation for the early treatment of covid-19. Although research has not yet produced clinically promising results, there are still many clinical trials underway. An example is the MK-4482 molecule, originally developed for influenza. The flu, in laboratory tests, proved to be effective in preventing the progression of covid-19, in addition to preventing the transmission of the coronavirus. “This is the first demonstration of a drug already available, and administered orally, to quickly block the transmission of Sars-CoV-2”, celebrates Richard Plemper, author of an article on the substance recently published in the journal Nature Microbiology.

“Since the drug can be taken orally, treatment can be started early, with a potentially triple benefit: inhibiting the patient’s progress towards serious illness, shortening the infectious phase to alleviate the emotional and socioeconomic cost of prolonged isolation and silencing local outbreaks quickly, ”says Plemper.

In 24 hours

According to him, the drug acts by decreasing the amount of viral particles, which, consequently, reduces the impact of the disease on infected people, as well as the risk of transmission. The study was done on ferrets, but if the data translates to humans, patients treated with the drug can become non-infectious within 24 hours of starting treatment. MK-4482 is currently at an advanced stage in the phase 3 study, the last before a drug is authorized by regulatory agencies.

Another hope for early covid-19 therapy is the ACTIV-2 study, which investigates the action of monoclonal antibodies BRII-196 and BRII-198 and is in phases 2 and 3 of research (with humans). According to the authors, for now, everything indicates that the combination of these substances improves the effectiveness of the treatment and reduces the likelihood of the virus developing resistance.

“We are excited,” says Judith Currier, of the University of California, Los Angeles. “Although we are excited about the availability of vaccines to prevent covid-19, we will continue to need treatments for those who develop the disease. Our goal is to increase understanding of the best ways to treat covid-19 early, ”he says. Participants will be randomized to receive BRII-196 or placebo.

“Covid-19 continues to have a devastating effect on people around the world,” says Eric Daar, one of the research leaders. “We are doing everything in our power to enroll participants from the most diverse communities to ensure that treatments are safe and effective for the populations most affected by the disease.”

In three days

Another line of early treatment under investigation is the use of convalescent plasma. Since the beginning of the pandemic, the strategy has been used experimentally, but with inconclusive results. Last week, an Argentine study published in The New England Journal of Medicine showed that the technique of transferring antibodies from the blood of a person who has recovered from the disease to another is effective, if it is performed within 72 hours of the start of the symptoms.

According to the author, the infectologist Fernando Polack, within this window of time, therapy halves the risk of progression to severe conditions. “We are sure that plasma is useful in the first three days of illness, that is, you have (a period of) 72 hours of symptoms to receive it,” the scientist told Rádio Con Vos.

Three questions for

Mariana Vasconcelos, infectious disease physician at the São Francisco Xavier Foundation, in Minas Gerais

Why, at the beginning of the pandemic, was the recommendation to stay at home, unless the person felt short of breath?
These recommendations were intended to encourage distancing measures and avoid exposure of people when they attend health services more often, thus aiming to reduce contact with other patients, the risk of dissemination and the demand for care. In addition, at the beginning of the pandemic, the risks during the evolution of covid-19 were not known in detail, such as, for example, of developing signs of severity or other complications of the disease even before shortness of breath manifested.

What are the recommendations now for those who have symptoms, even if it does not include shortness of breath?
Maintain strict surveillance of these symptoms and seek medical help for other guidelines, even if using telemedicine, which is more developed today. There are danger signs in covid-19 that can occur “silently”, that is, without symptoms, and that need immediate medical evaluation and conduct. Even without experiencing shortness of breath, symptoms such as persistent fever, discomfort or pain to breathe, weakness or even drowsiness can be signs of unfavorable evolution of this disease.

What is most promising in the early treatment of covid-19?
There is still no scientific evidence to prove the effectiveness of any medication for the treatment of this disease. What is most promising for overcoming this pandemic is the search for the vaccine against covid-19 and, at this moment, maintaining the protection and social distance measures.

Scientists focus on early treatment of covid-19

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