Could the time of day impact the effectiveness of COVID-19 treatment?

For months, experts have warned against the use of anti-inflammatory medications, such as ibuprofen, to treat COVID-19 symptoms. But could the timing of when this drug is taken play a role in its effectiveness?

In a review report published in the British Journal of Pharmacology, researchers at The University of Texas Health Science Center at Houston (UTHealth) suggest administering anti-inflammatory medications during the right time of day could impact the bodies response to the drug without interfering with the immune system’s fight against the virus.

“When we saw the controversy surrounding the use of ibuprofen, we wanted to fully understand why this drug was beneficial to some people, but having negative effects on others,” said Harry Karmouty-Quintana, PhD, assistant professor of biochemistry and molecular biology at McGovern Medical School at UTHealth.

To help understand these differences, researchers dug deep into the idea of chronotherapy. Chronotherapy is a time-controlled treatment that is commonly used to treat those with circadian rhythm-related disorders such as jet lag, shift work sleep disorder, or irregular sleep-wake disorder. The goal of this treatment is to align the circadian clock to the preferred 24-hour cycle.

Taking the circadian rhythm into account can help target the optimal time the body can use a particular medication.

“Because we know chronotherapy works in treating circadian rhythm sleep disorders, we looked into literature suggesting how the administration of anti-inflammatory drugs given at a certain time of day would dampen the inflammatory response, such as lung inflammation in COVID-19 patients, that is often detrimental to the body,” Karmouty-Quintana said.

The timing and severity of inflammation in the body is regulated by the circadian rhythm, according to Seung-Hee Yoo, PhD, assistant professor of biochemistry and molecular biology at McGovern Medical School.

“When you have chronic inflammation or a serious disease, there is a high chance that the circadian rhythm is disturbed. The circadian clock regulates how the body responds to an illness, such as COVID-19, by controlling the timing of inflammation,” she said.

According to researchers, the different cells in our body have a unique circadian time that allows them to respond differently depending on the time of day. So, if we take into consideration the biological rhythm our body has, it can impact the body’s response to an anti-inflammatory drug.

“Based on what we know about the circadian clock of immune cells, we think that anti-inflammatory agents are most effective during the midafternoon. That is because the immune cells release cell signals associated with negative effects to the body during the mid-to-late afternoon, but release antiviral molecules during the night and into the early morning. So, this therapeutic window would be an effective time to dampen the inflammation that is bad to the body and allow the immune cells to produce inflammatory molecules to fight the virus,” Karmouty-Quintana said.

Researchers summarized that when treating COVID-19, administering an anti-inflammatory drug like ibuprofen or dexamethasone can be essential in fighting detrimental effects of the virus. Although each individual may initially respond differently to these drugs, using chronotherapy to regulate the body’s circadian rhythm may have a significant impact that could help speed up recovery or prevent long-term effects.

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