COVID-19 pill first to cut short positive-test time after infection, reduce symptoms

A new antiviral drug has proved to shorten the symptoms of mild to moderate COVID-19 by about a day, with its drugmaker claiming that the oral drug could also be used to treat long-COVID.
Ensitrelvir – which has been developed by Japanese pharmaceutical company Shionogi – is also the first drug to make a statistically significant cut in the number of days people test positive for the virus, medical journal Nature reported Tuesday.

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The drug has the potential to prevent long COVID, according to the company’s claims, although scientists remain skeptical of this assertion.
The trial of the drug, which was presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, involved roughly 1,200 people, with the main goal of determining whether the drug could accelerate recovery.
The results showed that participants who took the 125-milligram ensitrelvir pills recovered from five specific symptoms – stuffy or runny nose, sore throat, cough, feeling hot or feverish, and low energy or tiredness – about 24 hours earlier than those in the control group.
Participants who took the 125-milligram dose also tested negative for SARS-CoV-2 about 29 hours earlier than those who took a placebo. According to Shionogi, the study was the first to show a statistically significant reduction in the time to a negative test result.
The trial also investigated the drug’s potential to prevent long COVID. A subset of participants was asked about their COVID-19 symptoms three and six months after trial enrollment, as well as during their acute infection period. Those who reported two or more of the same symptoms at least twice in a row over this period were defined as having developed long COVID.
Participants who had a relatively high number of symptoms during the illness’s early stages had a 14 percent risk of developing long COVID if they took the antiviral, compared with a 26 percent risk for similar participants in the placebo group. This led Shionogi to conclude that participants who received ensitrelvir had a reduced risk of developing long COVID.
However, scientists who were not involved in the study pointed out that the trial was not specifically intended to investigate the risk of long COVID, and so the pre-trial research plan did not describe any methods for analyzing long COVID data. As a result, the definition of long COVID used in the study is unclear, and it is not possible to draw any strong conclusions about the drug’s potential to prevent long COVID.
Despite these limitations, scientists say it’s plausible that antivirals could prevent long COVID. A recent analysis found that people who took Paxlovid, another antiviral used to treat COVID-19, had a reduced risk of developing long COVID compared with those who took no antiviral drugs.
Study co-author Ziyad Al-Aly said that the ensitrelvir data made him more optimistic that attacking the virus early during an infection “seems to hold the key to reducing the risk of long COVID.”
The data that Shionogi has made public supported the idea that antivirals protect against long COVID, at least when residual virus is involved in causing prolonged symptoms. However, there is no consensus that persistent virus causes long COVID. Long COVID might be caused, for example, by the immune response to the virus.
Immunologist Danny Altmann at Imperial College London noted that the optimal study to investigate whether antivirals prevent long COVID would involve selecting only participants whose disease might be caused in part by lingering SARS-CoV-2. If scientists don’t separate out such people from those whose symptoms don’t have the same cause, trials could yield “murky answers,” Altmann said.
Ensitrelvir is the third oral antiviral used to treat COVID-19, after Paxlovid and molnupiravir. Both of these drugs are currently only used to target people who are at high risk of severe disease. But ensitrelvir was tested on people irrespective of their risk, which could have implications for its use in individuals at low risk.

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