Enlarge / Signage stands outside the Centers for Disease Control and Prevention (CDC) headquarters in Atlanta, Georgia, U.S, on Saturday, March 14, 2020. (credit: Getty | Bloomberg)

Public health experts at the US Centers for Disease Control and Prevention have leaked their recommendations on how to safely reopen businesses amid the COVID-19 pandemic—after officials in the Trump administration rejected the guidance and allegedly told CDC officials their plan would "never see the light of day."

The 17-page document (PDF found here) was initially set to be published last Friday but was nixed. Instead, it was released to the Associated Press by a CDC official who was not authorized to release it.

The guidance lays out detailed, phased recommendations for how to safely reopen child care programs, schools, day camps, faith communities, businesses with vulnerable workers, restaurants, bars, and mass transit. Though some of the general points laid out already appear on federal websites—such as an emphasis on hand hygiene—the document uniquely offers tailored recommendations for each type of business.

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Enlarge / Hospital Corpsman 3rd Class Kimberly Wyss, from Ventura, Calif., dons surgical gloves aboard the hospital ship USNS Mercy (T-AH 19). (credit: flickr)

A study observing COVID-19 patients has found no evidence that the malaria drug hydroxychloroquine, touted as a possible treatment for COVID-19, made a difference to the chance that patients would need a ventilator. The results also suggested that patients treated with hydroxychloroquine had a higher rate of death than those who weren’t treated with the drug.

The study was not a randomized clinical trial, which means that the evidence it offers is tentative and should be interpreted with caution. It was also published on preprint server medRxiv, which means it has not yet been peer-reviewed.

But interpreting the evidence with caution does not mean disregarding it completely. This study is one of a growing number telling us that we don't yet know enough about hydroxychloroquine, adding more weight to the argument that we need to wait for better-quality evidence from randomized controlled trials before we start widespread use of a drug with significant side effects.

Premature

Some small studies have given us reasons to think that chloroquine and hydroxychloroquine could have potential as treatments for COVID-19. In some cases, the findings come from experiments in cultured cells, which won't necessarily translate directly to using the drugs in sick humans. In others, the findings come from small studies that have critical flaws like using very small groups of patients, having no control group, or excluding patients who died from analysis.

“Normally, such research would be deemed hypothesis-generating at best,” wrote doctors Jinoos Yazdany and Alfred Kim in an opinion piece in the Annals of Internal Medicine. And they were released at the same time that other early studies were finding no evidence that these drugs help COVID-19 patients.

However, early hype—including repeated promotion from President Trump—led to a runaway train of enthusiasm for the drugs. The Food and Drug Administration authorized treatment of COVID-19 patients with chloroquine and hydroxychloroquine despite the lack of good evidence for their efficacy, sparking backlash from former FDA leaders.

These drugs have a range of possible adverse effects, including serious cardiac damage. Using them for critically ill COVID-19 patients therefore not only runs the risk of not helping, but also of actively harming people. The worldwide run on the drugs and resulting shortages are also a problem for patients using them for conditions like lupus, where they have been found to be effective.

A range of clinical trials are now underway to establish whether these drugs are actually beneficial. In the meantime, the FDA authorization means that there is a growing pile of data from patients who have been treated with them.

Testing on the fly

The US Veterans Health Administration is a national system of clinics, hospitals and other medical centers. Because it’s a single organization, data on patients is gathered in a consistent way, which makes it easier for researchers to compare apples with apples.

A team of researchers used VHA data to track the outcomes of confirmed COVID-19 patients at veterans hospitals who were treated with just hydroxychloroquine, hydroxychloroquine plus an antibiotic, or neither of the drugs. They found that 27.8 percent of the 97 patients treated with just hydroxychloroquine died, compared to 11.4 percent of the 158 patients who weren’t treated with hydroxychloroquine at all, and 22.1 percent of the 113 patients who were treated with hydroxychloroquine and an antibiotic. Rates of ventilation were similar across the three groups.

This evidence is weaker than a randomized controlled trial because the patients who were given different treatments may have had other important differences to begin with. In a randomized trial, patients are assigned different treatments (or a placebo) randomly, which means that different groups should all have a roughly similar mix of people who are very sick or only a little bit sick, old and young, and so on.

In a retrospective study like this one, the doctors may have given the hydroxychloroquine treatment only to the sickest patients, in which case we’d expect that group to have worse outcomes. There are ways to try to account for this lack of randomization in the statistical tests that researchers use to calculate the risks across different groups, but these adjustments require the researchers to work out what other factors might complicate the analysis—a difficult challenge with a random population like this one.

The patients also weren’t representative of the wider population. They were all men and all older than 59 years, which means that the results wouldn’t necessarily be the same in younger groups or among women.

The results don’t mean that hydroxychloroquine is definitely useless or that clinical trials should be halted. Recent NIH guidance for clinicians treating COVID-19 patients says that there currently isn’t enough evidence to recommend for or against treating with hydroxychloroquine, and that remains true.

But they do offer more evidence suggesting that we don’t yet know enough to forge ahead with using the drugs as treatment. The authors of the study acknowledge the shortcomings of their own work but argue that the results nonetheless “highlight the importance of awaiting the results of ongoing prospective, randomized, controlled studies before widespread adoption of these drugs.”

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Gov. Gretchen Whitmer suggested Friday that a growing rift with the White House is affecting shipments of medical supplies to Michigan amid exponential growth in confirmed coronavirus cases.

"When the federal government told us that we needed to go it ourselves, we started procuring every item we could get our hands on," Whitmer said Friday on WWJ 950AM. "What I've gotten back is that vendors with whom we had contracts are now being told not to send stuff here to Michigan. It's really concerning."

Whitmer didn't say who has told vendors to stop sending medical supplies to the state, but strongly implied the order came from President Donald Trump's administration.

In a Friday afternoon appearance on CNN, Whitmer did not back away from her earlier claim.

"We've entered into a number of contracts and as we are getting closer to the date when shipments are supposed to come in, they're getting canceled or they're getting delayed," Whitmer said. "We've been told they're going first to the federal government."

The governor's office could not provide any additional information Friday afternoon substantiating Whitmer's allegation.

Whitmer told WWJ that she reached out to the White House on Thursday night, asking "for a phone call with the president, ironically at the same time that all of this other stuff was going on."

Trump called into Sean Hannity's Fox News program Thursday night and bashed Whitmer's handling of the coronavirus public health crisis that has claimed the lives of 92 Michigan residents as of Friday.

"Your governor of Michigan, I mean, she's not stepping up," Trump said, who referred to Whitmer as "a woman governor" and not by her name. "I don't know if she knows what's going on, but all she does is sit there and blame the federal government. She doesn't get it done. And we send her a lot."

During a Friday evening press conference, Trump said he's instructed Vice President Mike Pence, "don't call the woman in Michigan."

"If they don't treat you right, I don't call," Trump said of Whitmer. "(Pence) is a different type of person. He'll call quietly anyway."

Whitmer has made public pleas for days that the federal government has been slow to send medical supplies from its national strategic stockpile.

On Monday, Whitmer said one unnamed hospital received a shipment last weekend from the federal government of 747 N95 protective masks, 204 gowns, 40,467 gloves and 64 face shields.

"With the exception of the gloves, that allotment of PPE didn't cover one shift," Whitmer said Thursday.

Whitmer spokeswoman Tiffany Brown confirmed Friday to Crain's that the state needs 400,000 N95 protective medical masks each day for the next several weeks to keep up with demand.

Whitmer did not specify in the radio interview Friday which vendors or specific medical equipment is being blocked by federal authorities from being sent to Michigan.

"The fact of the matter remains, we need help and at the very least we don't need people standing in our way from getting," Whitmer told WWJ. "We're working incredibly hard. But these are serious times."

Crain's sought clarity from Whitmer's office midday Friday and the names of vendors under contract that the governor referenced. Whitmer's spokeswoman had no additional information.

U.S. Rep. Paul Mitchell, R-Dryden Township, said members of Michigan's congressional delegation asked regional officials from the Federal Emergency Management Agency in a Thursday conference call if vendor shipments were being redirected to FEMA. The FEMA Region 5 officials told congressional members there were no vendor shipments being diverted from Michigan and that "they would reach out (to suppliers) and try to solve the uncertainty," Mitchell said.

Mitchell called Whitmer's claim of federal diversion of medical supplies "not productive."

Whitmer, a Democrat, said she's not trying to engage in a political feud with the Republican president.

"For the doctors and nurses who are wearing one mask for the whole shift, who are worried about their own personal health but are still treating the sick and the fragile, it's crucial that everyone does their part," she said. "That includes individuals staying homes, it includes businesses that can help manufacture this (personal protection equipment) that there's too little of and it includes the federal government who we need partnership from."