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Using hydroxychloroquine (HCQ) to treat COVID-19 has been surrounded by more hype than data, with too little known about how the virus affects the immune system, investigators said.

"[T]he known and potent immunomodulatory effects of [HCQ and its close cousin chloroquine] which support their use in the treatment of autoimmune conditions, and provided a component in the original rationale for their use in patients with COVID-19, may, in fact, undermine their utility in the context of the treatment of this respiratory viral infection," wrote Mark Poznansky, MD, PhD, of Massachusetts General Hospital in Boston, and colleagues

Poznansky said his own clinical experience was one of the reasons he wanted to look into the literature, as when he was on clinical service, there were a lot of COVID-19 patients on hydroxychloroquine and they "weren't doing very well."

"It wasn't a 'wow, this drug is keeping patients out of the ICU'-type feeling," he told 乌鸦传媒 separately.

Widespread use of hydroxychloroquine, an immunosuppressive agent, struck Poznansky as unusual, he said, noting that clinicians should be thoughtful about this particular drug in the context of acute viral infection.

"There's a lot of literature on the fact that hydroxychloroquine is quite drastically immunosuppressive. Even a paper in an immunology journal said it drastically reduces immune functions. And I said, 'wait a minute, we're using this in patients with acute viral infection,'" Poznansky noted.

He wasn't the only one who observed this phenomenon, as the group's paper noted, "initial anecdotal reports out of China led to the initial wide uptake of HCQ and to a lesser extent [chloroquine] for many hospitalized patients with COVID-19 around the globe."

Indeed, Michael Liu, AB, of the University of Oxford in England, tracked Google searches including the words "buy" and "order," or retail sites such as Amazon and Walmart, in combination with hydroxychloroquine and chloroquine, from Feb. 1 to March 29. In a , they identified key dates including eccentric businessman Elon Musk's endorsing use of the drug on March 16, President Trump's widely publicized encomium on March 19, and the first reports of chloroquine-related poisoning on March 22.

The researchers found the largest spikes came after well-known public figures spoke highly of the drug: searches about purchasing hydroxychloroquine were 1,389% higher and those for chloroquine were 442% higher than the prior 6 weeks, and searches remained high even after news reports about poisonings related to the drug.

Liu and colleagues observed that "findings about the clinical efficacy of chloroquine and hydroxychloroquine were inconclusive at the time these drugs were promoted."

Poznansky and colleagues also pointed out the lack of clinical evidence about the drug -- for example, the "wide-ranging secondary effects" of hydroxychloroquine, namely "potent immune modulation" -- and said that while the effect of modulating the immune system is favorable for treating autoimmune conditions, "it is not clear how these effects of HCQ may affect a person with acute COVID-19."

"We do not fully understand the immune response to COVID-19, and it's only been around a few months," Poznansky said. "We don't fully understand the immune response to HIV and it's been around for decades. We're applying an immune modulator to a disease where we don't understand what role the immune system has in combating the virus."

Moreover, he said, the key immune functions you would say would be important in combating a virus seem to be suppressed by hydroxychloroquine: "They've never directly tested if hydroxychloroquine down-regulates immune response in COVID-19. That's a gap that needs to be bridged here," he noted.

Clinical trials addressing the use of hydroxychloroquine hope to provide some of these answers. Poznansky said research needs to determine hydroxychloroquine's effect on clinical progression of illness, and that researchers "don't completely understand what they need to measure in the context of hydroxychloroquine as it relates to immune function."

"Does it curtail the cytokine storm? Do patients on hydroxychloroquine have lower levels of cytokines than patients not on hydroxychloroquine?" Poznansky asked. "This sort of thinking needs to be applied to the use of an immunomodulator for COVID-19."

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