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Convalescent Plasma: The Unanswered Questions

https://www.medpagetoday.com/infectiousdisease/covid19/88264?xid=fb_o&trw=no&fbclid=IwAR0F6xiRAQ7ngBz4pNozJ2VqWm0-UJqGdlQojfOeyXbPJjbAeYtGL8jbAiw

“The data don’t show anything useful”

Problems with the government’s rationale for authorizing use of convalescent plasma in COVID-19 patients go far beyond the dustup over the purported 35% survival benefit cited by top officials on Sunday, numerous researchers say.

That figure quickly came under fire, leading to an apology from Commissioner Stephen Hahn, MD — but that’s not the only criticism leveled at the FDA’s analysis of the available data.

Much of it came from the Mayo Clinic and FDA expanded access program (EAP), at this point published only as a preprint manuscript. Although a large number of patients were included, the study was observational only, with no untreated control group. That makes the findings merely hypothesis-generating, and can’t offer any firm conclusions.

That’s fine for issuing an emergency use authorization (EUA), but not so much for making claims about survival benefit, independent researchers said.

“It’s not even a question of overstating,” Adam Gaffney, MD, MPH, a critical care doctor and health policy researcher at Harvard Medical School, told MedPage Today. “You can’t state much at all when you don’t have a randomized controlled trial.”

“People have made a big deal of Hahn referring to relative versus absolute risk reduction, but I think that’s less of a big deal,” Gaffney said. “The biggest problem is that the data they are citing … is not randomized. That’s the source of all the problems.”

Hahn took heat for saying that a “35% improvement in survival is a pretty substantial clinical benefit” further explaining that of “100 people who are sick with COVID-19, 35 would have been saved because of the administration of plasma.”

Critics rapidly took to Twitter, stating that the interpretation was incorrect. Hahn was referring to relative risk reduction, not absolute risk reduction. Thus, calculating the number of lives saved — which isn’t something experts recommend doing based on observational data in the first place — would have translated to somewhere more in the ballpark of 5 out of 100.

Moreover, the “risk reduction” came from a comparison of patients treated with high-titer plasma versus those receiving lower-titer preparations. The study offered no basis for concluding how many patients may have been “saved” relative to standard care.

And the 35% reduction in that analysis was for 7-day mortality; the relative reduction at 30 days was only 23%.

Hahn’s recital of the 35% figure “was just PART of the error,” tweeted Vinay Prasad, MD, MPH, of the University of California San Francisco. “The entire comparison is flawed. It is not a suitable control. The data don’t show anything useful.”

“The much broader problem here is the lack of commitment to performing large, national randomized controlled trials,” Gaffney said. “We could have done it for convalescent plasma. Instead, we did the EAP. I understand why people wanted it, but now we don’t know [if convalescent plasma works]. We have a question mark instead of a period.”

Undermining Trust in FDA?

Critics have charged that serious mistakes like Hahn’s misstatement could undermine FDA’s credibility, especially as it faces challenging decisions about potentially approving a vaccine this fall.

“This is playing out in the context of a hyper-politicized moment,” Gaffney said. “It behooves everyone to be extremely cautious in speaking about these things to avoid the appearance of politicization.”

On CBS This Morning on Tuesday, Hahn addressed concerns about politicization by offering reassurance to the “American people that this decision was made based upon sound science and data.”

In response to questions about the timing of the EUA announcement — it came just a day after President Donald Trump tweeted allegations that the “deep state” was holding back access to COVID-19 treatments with Hahn’s Twitter handle cited, and a day before the Republican National Convention got underway — Hahn said the agency had been working on the application for 3 or 4 weeks and was waiting on additional validation data, which were received at the end of last week and over the weekend.

“We’re going to continue to get data and as we’ve done with any other authorization, we will update that decision as new data come,” Hahn said on the news program. His agency initially issued an EUA for hydroxychloroquine, for instance, but later revoked it when the negative randomized trial data became available.

Lack of Access to FDA’s Data Review

Whether the public will ever see the full convalescent plasma data underlying the EUA is another matter. The “Clinical Memorandum” issued as the evidence behind the FDA’s decision glossed over the statistical analysis conducted by the agency; in particular, it made no mention of the 35% relative reduction in deaths.

Another problem with that is the 35% figure’s source isn’t fully clear. Although the EAP preprint manuscript is the most obvious source, Gaffney noted that HHS Secretary Alex Azar said it referred to a subgroup of patients under age 80 who were not on a ventilator. That is not found in the publicly available data. He also pointed to a tweet by FDA spokesperson Emily Miller that contains an agency slide showing a 37% reduction in mortality for non-intubated patients age 80 or under treated within 72 hours who got high-titer convalescent plasma, compared with low-titer product. Neither of those figures is reflected in the EAP manuscript.

The FDA did not return a request by MedPage Today for the full summary of data reviewed by FDA and any independent statistical analysis done by the agency.

Shmuel Shoham, MD, of Johns Hopkins University in Baltimore, said during a press briefing organized by the Infectious Diseases Society of America that “enormous amounts of data have been generated” from the EAP, in which more than 70,000 patients have been treated.

“Some data have been reported in articles and at meetings, but that’s only part of what the FDA — this is their program — has access to,” he said. “The stuff in the public domain is only a fraction of the data they have collected.”

Shoham is on the scientific advisory board of the EAP and is involved in two convalescent plasma clinical trials at Johns Hopkins.

Gaffney said Mayo researchers and FDA reviewers have noted that physicians were blinded to the dose of antibody given in plasma infusions, which he described as a “pseudo-randomization effect. We could use that to make more causal inferences about the effectiveness of antibody titers.”

However, he said there were some significant differences between those who received high-titer versus low-titer antibody, including differences in P-to-F ratio (a measure of inhaled oxygen to blood oxygen) and in those with five or more severe risk factors, suggesting the low-titer group was sicker to begin with than the high-titer group.

Also, patients in the EAP received a variety of other treatments: about half got steroids and 40% were given remdesivir.

“This is why we do randomized controlled trials,” Gaffney said. “Without them it’s very difficult to ensure that the effect you see is the result of the drug, and not the result of patient characteristics.”

Is an Answer Forthcoming?

Several randomized controlled trials of convalescent plasma are underway in the U.S., but the big concern is that wider access to convalescent plasma will limit enrollment. Will clinicians recommend that their patients enroll in a trial in which they might receive placebo? Will patients agree?

For the Hopkins studies, the prevention trial has enrolled 25 people out of a goal of 500, and its outpatient trial has enrolled 50 people of its 600-patient goal.

Liise-anne Pirofski, MD, of Montefiore Medical Center in New York, started a study at the end of April, looking to enroll 300 people. She said the team enrolled the first 150 people quickly, but “then the pandemic began to wane in New York.” With subsequent funding from the NIH, the trial has managed to enroll 190 patients, and has now expanded to four additional sites: New York University, Yale, the University of Miami, and the University of Texas Houston.

Clifton Callaway, MD, PhD, of the University of Pittsburgh Medical Center and lead investigator on the C3PO trial looking at outpatient convalescent plasma, said he hopes the EUA doesn’t discourage participation.

“To the contrary, I believe it should reassure persons considering participation that the FDA feels that convalescent plasma is safe and potentially useful and that the FDA specifically comments: ‘Current data suggest the largest clinical benefit is associated with high-titer units of CCP administered early in the course of disease.’ Giving high-titer convalescent plasma earlier (before you are sick enough to be in the hospital) is exactly what C3PO is testing.”

In addition to determining whether earlier or prophylactic treatment works, Shoham said other unanswered questions include identifying whether other components in plasma are useful therapies and whether low-titer plasma can work at all.

“What everyone agrees on is that the gaps in knowledge that exist can best be addressed by high-quality randomized controlled trials,” he said.

Pirofski said the science and data should be the focus, “rather than the decision and what drove the decision…. I don’t think anyone knows what drove that decision other than the people in that room. Hopefully they know.”

 

 

 

 

Top U.S. Officials Told C.D.C. to Soften Coronavirus Testing Guidelines

The Centers for Disease Control and Prevention abruptly changed its recommendations, saying people without Covid-19 symptoms should not get tested.

 Trump administration officials on Wednesday defended a new recommendation that people without Covid-19 symptoms abstain from testing, even as scientists warned that the policy could hobble an already weak federal response as schools reopen and a potential autumn wave looms.

The day after the Centers for Disease Control and Prevention issued the revised guidance, there were conflicting reports on who was responsible. Two federal health officials said the shift came as a directive to the Atlanta-based C.D.C. from higher-ups in Washington at the White House and the Department of Health and Human Services.

Adm. Brett P. Giroir, the administration’s coronavirus testing czar, called it a “C.D.C. action,” written with input from the agency’s director, Dr. Robert R. Redfield. But he acknowledged that the revision came after a vigorous debate among members of the White House coronavirus task force — including its newest member, Dr. Scott W. Atlas, a frequent Fox News guest and a special adviser to President Trump.

“We all signed off on it, the docs, before it ever got to a place where the political leadership would have, you know, even seen it, and this document was approved by the task force by consensus,” Dr. Giroir said. “There was no weight on the scales by the president or the vice president or Secretary Azar,” he added, referring to Alex M. Azar II, the secretary of health and human services.

Regardless of who is responsible, the shift is highly significant, running counter to scientific evidence that people without symptoms could be the most prolific spreaders of the coronavirus. And it comes at a very precarious moment. Hundreds of thousands of college and K-12 students are heading back to campus, and broad testing regimens are central to many of their schools’ plans. Businesses are reopening, and scientists inside and outside the administration are growing concerned about political interference in scientific decisions.

Democratic governors who were weighing how to keep the virus contained as their economies and schools come to life said limiting testing for asymptomatic citizens would make the task impossible.

“The only plausible rationale,” Gov. Andrew M. Cuomo of New York told reporters in a conference call from Albany, N.Y., “is that they want fewer people taking tests, because as the president has said, if we don’t take tests, you won’t know the number of people who are Covid-positive.”

Over the weekend, the Food and Drug Administration, under pressure from Mr. Trump, gave emergency approval to expand the use of antibody-rich blood plasma to treat Covid-19 patients. The move came just days after scientists, including Dr. Anthony S. Fauci, the nation’s top infectious disease expert, and Dr. Francis S. Collins, the director of the National Institutes of Health, intervened to stop the practice because of lack of evidence that it worked.

The move echoed a decision by the Food and Drug Administration to grant an emergency use waiver for hydroxychloroquine, a malaria drug repeatedly sold by Mr. Trump as a treatment for Covid-19. The agency revoked the waiver in June, when clinical trials suggested the drug’s risks outweighed any possible benefits.

The testing shift, experts say, was a far more puzzling reversal. Dr. Giroir said the move was “discussed extensively by” members of the White House coronavirus task force, and he named Dr. Redfield, Dr. Atlas, Dr. Fauci and Dr. Stephen M. Hahn, the commissioner of food and drugs. Notably, he did not name Dr. Deborah L. Birx, the White House coronavirus response coordinator. But he said Dr. Fauci was among those who had “signed off.”

In a brief interview, Dr. Fauci said he had seen an early iteration of the guidelines and did not object. But the final debate over the revisions took place at a task force meeting on Thursday, when Dr. Fauci was having surgery under general anesthesia to remove a polyp on his vocal cord. In retrospect, he said, he now had “some concerns” about advising people against getting tested, because the virus could be spread through asymptomatic contact.

“My concern is that it will be misinterpreted,” Dr. Fauci said.

The newest version of the C.D.C. guidelines, posted on Monday, amended the agency’s guidance to say that people who had been in close contact with an infected individual — typically defined as being within six feet of a person with the coronavirus and for at least 15 minutes — “do not necessarily need a test” if they do not have symptoms.

Exceptions might be made for “vulnerable” individuals, the agency noted, or if health care providers or state or local public health officials recommended testing.

Dr. Giroir said the new recommendation matched existing guidance for hospital workers and others in frontline jobs who have “close exposures” to people infected with the coronavirus. Such workers are advised to take proper precautions, like wearing masks, socially distancing, washing their hands frequently and monitoring themselves for symptoms.

He argued that testing those exposed to the virus was of little utility, because tests capture only a single point in time, and that the results could give people a false sense of security.

“A negative test on Day 2 doesn’t mean you’re negative. So what is the value of that?” Dr. Giroir asked, adding, “It doesn’t mean on Day 4 you can go out and visit Grandma or on Day 6 go out without a mask on in school.”

The guidelines come amid growing concern that the C.D.C., the agency charged with tracking and fighting outbreaks of infectious disease, is being sidelined by its parent agency, the Department of Health and Human Services, and the White House. Under ordinary circumstances, administering public health advice to the nation would fall squarely within the C.D.C.’s portfolio.

Experts have called the revisions alarming and dangerous, noting that the United States needs more testing, not less. And they have expressed deep concern that the C.D.C. is posting guidelines that its own officials did not author. A former C.D.C. director, Dr. Thomas R. Frieden, railed against the move on Twitter on Wednesday:

Dr. Tom Frieden
@DrTomFrieden
Two unexplained, inexplicable, probably indefensible changes, likely imposed on CDC’s website. * Dammit, if you come from a place with lots of Covid, quarantine for 14 days * If you’re a contact, get tested. If +, we can trace your contacts and stop chains of spread. A sad day.

Later, in an interview, Dr. Frieden elaborated. He noted that the C.D.C. had recently dropped its recommendation that people quarantine for 14 days after traveling from an area with a high number of cases to one where the virus was less prevalent. And he reiterated that testing the contacts of those infected was an important means of curbing the spread of the virus.

“We don’t know the best protocol for testing of contacts: Should you test all contacts? That’s the kind of study that frankly needs to get done,” Dr. Frieden said. But absent the answer to that question, he added, “I certainly wouldn’t say, ‘Don’t test contacts.’”

Democrats, including Speaker Nancy Pelosi and two governors — Mr. Cuomo and Gavin Newsom of California — were outraged by the changes. Mr. Newsom said California would not follow the new guidelines, and Mr. Cuomo blamed Mr. Trump.

Representative Frank Pallone Jr. of New Jersey, a Democrat and the chairman of the House Energy and Commerce Committee, also chimed in on Twitter: “The Trump Admin has a lot of explaining to do. #COVID19 testing is essential to stopping the spread of the pandemic. I’m concerned that CDC is once again caving to political pressure. This simply cannot stand.”

Mr. Trump has suggested that the nation should do less testing, arguing that administering more tests was driving up case numbers and making the United States look bad. But experts say the true measure of the pandemic is not case numbers but test positivity rates — the percentage of tests coming back positive.

As Dr. Giroir denied that politics was involved, he encouraged the continued testing of asymptomatic people for surveillance purposes — to determine the prevalence of the virus in a given community — and said such “baseline surveillance testing” would still be appropriate in schools and on college campuses.

“We’re trying to do appropriate testing, not less testing,” he said.

Still, the revisions left many public health officials scratching their heads. They might have made sense when the United States was experiencing a shortage of tests, some experts said, but that no longer appears to be the case. Dr. Frieden, however, said it was possible the administration was trying to conserve testing in case of another surge.

“The problem is we have too many cases, so there is basically no way to keep up the testing if you have a huge outbreak,” he said.

Jennifer Nuzzo, an epidemiologist at Johns Hopkins Bloomberg School of Public Health, said she was “not as up in arms about the content of the guidelines” as she was about the idea that the C.D.C.’s own experts did not write them — and that C.D.C. officials were referring all questions about them to the health department in Washington.

“These guidelines are clearly controversial, and many are calling on C.D.C. to explain its rationale for them, but C.D.C. is unable to comment,” she said in an email. “This is really dangerous precedent, and I fear it will erode public trust in C.D.C.”

 

 

 

 

Walmart files plans for standalone clinic in Florida

https://www.beckershospitalreview.com/capital/walmart-files-plans-for-standalone-clinic-in-florida.html?utm_medium=email

Walmart Health: A Deep Dive into the $WMT Corporate Strategy in Health Care  | by Nisarg Patel | Medium

Walmart plans to open a 6,500-square-foot standalone clinic in Middleburg, Fla., according to the Jacksonville Record & Observer, which cited plans filed with the local water management district. 

The new clinic is part of the expansion Walmart Health announced July 22. The new health center will offer primary care, urgent care, labs, imagining, counseling, optical and hearing services, according to the report. A timeline for when the clinic will open has not been released.

In addition to expanding into Florida, Walmart Health is also planning to open a few clinics in the Chicago market. The company already has freestanding health centers in Georgia and Arkansas. 

 

 

 

 

CMS to require positive COVID-19 test results for Medicare pay boost

https://www.beckershospitalreview.com/finance/cms-to-require-positive-covid-19-test-results-for-medicare-pay-boost.html?utm_medium=email

CMS to Pay For Hospital COVID-19 Care Furnished in Other Settings

CMS recently released guidance that includes a new requirement for hospitals to get a Medicare payment boost for caring for patients diagnosed with COVID-19. 

The Coronavirus Aid, Relief and Economic Security Act provided a 20 percent add-on payment to the inpatient prospective payment system diagnosis-related group rate for treating patients diagnosed with COVID-19. Until now, a physician’s documentation that a patient has COVID-19 was sufficient to receive the add-on payment. However, recent guidance from CMS adds the requirement to have a positive COVID-19 laboratory test documented in the patient’s medical record for the claim to be eligible for the add-on payment. The new requirement applies to admissions occurring on or after Sept. 1.

To receive the payment boost under the new guidance, the COVID-19 test must be taken within 14 days of the hospital admission. Only the results of viral testing that are consistent with CDC guidelines can be used. Tests performed by an entity other than the hospital, such as a local government-run testing center, can be manually entered into the patient’s medical record, CMS said.

Meeting the new requirement for the add-on payment could be difficult for hospitals, Ronald Hirsch, MD, vice president of the regulations and education group at R1 Physician Advisory Services, told Becker’s Hospital Review

“There is no way to indicate on a claim for a hospital patient that a test was positive or negative,” he said. “First, the hospital will manually need to go into every record for a patient with U07.1 as a diagnosis and look for a positive test in their own lab system. If one is not found, they will need to search the notes to see if the patient had a test in the 14 days prior to admission and if that test was positive. If there is a note the patient self-reported that they had a positive test, the hospital must decide if they must go through due diligence and attempt to get that actual test result for their records.”

In cases where there isn’t a positive test noted in the medical record, hospitals would need to notify the Medicare audit contractor that they are submitting a claim for a COVID-19 diagnosis that was made clinically, Dr. Hirsch said. The MAC would need to make the appropriate adjustment to ensure the 20 percent add-on payment is not made.

The “undue burden” that the new requirement will place on hospitals was one of the concerns the American Hospital Association highlighted in an Aug. 26 letter to CMS Administrator Seema Verma. The group is also concerned that requiring a positive COVID-19 test will lead to unnecessary additional testing.

“Basing the COVID-19 diagnosis code on clinical judgment alone — in line with coding rules — continues to be an important approach given that test accuracy may not be reliable, re-testing is unnecessarily onerous, and some communities face persistent testing shortages.” 

The AHA is urging CMS to drop the new requirement and allow provider documentation of a COVID-19 diagnosis to be sufficient for the add-on payment if the test result is unavailable. 

 

 

 

 

2020 Health Care Legislative Guide

https://unitedstatesofcare.org/resources/2020-health-care-legislative-guide/

Pennsylvania 2020 Health Care Legislative Guide - United States of Care

ABOUT THE UNITES STATES OF CARE

United States of Care is a nonpartisan nonprofit working to ensure every person in America has access to
quality, affordable health care regardless of health status, social need or income. USofCare works with elected
officials and other state partners across the country by connecting with our extensive health care expert
network and other state leaders; providing technical policy assistance; and providing strategic communications
and political support. Contact USofCare at help@usofcare.org

Health care remains one of the most important problems facing America.

Voters are concerned about access to and the cost for health care and insurance.

Health Care During the COVID Pandemic
The COVID-19 pandemic has illuminated the need for effective solutions that address both the immediate
challenges and the long-term gaps in our health care systems to ensure people can access quality health care
they can afford. Americans are feeling a mix of emotions related to the pandemic, and those emotions are
overwhelmingly negative.*

In addition, the pandemic has illuminated deficiencies of our health care system.

People feel that the U.S. was caught unprepared to handle the pandemic and our losses have
been greater than those of other countries.

People blame government for the inadequate pandemic response, not health care systems.

Health Care During the COVID Pandemic

The COVID-19 pandemic has illuminated the need for effective solutions that address both the immediate challenges and the long-term gaps in our health care systems to ensure people can access quality health care they can afford. In the wake of COVID, policymakers have a critical opportunity to enact solutions to meet their constituents’ short- and long-term health care needs. The 2020 Health Care Legislative Candidate Guide provides candidates with public opinion data, state-specific health care information, key messages and ideas for your health care platform.

Key Messages for Candidates:

  • Acknowledge the moment: “Our country is at a pivotal moment. The pandemic, economic recession, and national discussion on race have created a renewed call for action. They have also magnified the critical problems that exist in our health care system.”
  • Take an active stance: “It is long past time to examine our systems and address gaps that have existed for decades. We must find solutions and common ground to build a health care system that serves everyone.”
  • Commit to prioritizing people’s needs: “I will put people’s health care needs first and I’m already formalizing the ways I gather input and work with community and business leaders to put effective solutions in place.”
  • Commit to addressing disparities and finding common ground: “The health care system, as it’s currently structured, isn’t working for far too many. I will work to address the lack of fairness and shared needs to build a health care system that works for all of us.”

Click to access USC_Generic_CandidateEducationGuide.pdf

 

 

Promising State Policies to Respond to People’s Health Care Needs

In the wake of COVID, policymakers have a critical opportunity to enact solutions to meet their constituents’
short- and long-term health care needs. Shared needs and expectations are emerging in response to the
pandemic, including the desire for solutions that:

Ensure individuals are able to provide for themselves and their loved ones, especially those worried about
the financial impact of the pandemic.

• Protect against high out-of-pocket costs.
• Expand access to telehealth services for people who prefer it to improve access to care.
• Extend Medicaid coverage for new moms to remove financial barriers to care to support healthier moms
and babies.

Ensure a reliable health care system that is fully resourced to support essential workers and available when
it is needed, both now and after the pandemic.

• Ensure safe workplaces for front-line health care workers and essential workers and increase the capacity to
maintain a quality health care workforce.
• Support hospitals and other health care providers, particularly those in rural or distressed areas.
• Expand mental health services and community workforce to meet increased need.

Ensure a health care system that cares for everyone, including people who are vulnerable and those who
were already struggling before the pandemic hit.

• Adopt an integrated approach to people’s overall health by coordinating people’s physical health, behavioral health
and social service needs.
• Establish coordinated data collection to quickly address needs and gaps in care, especially in vulnerable
communities.

Provide accurate information and clear recommendations on the virus and how to stay healthy and safe.
• Build and maintain capacity for detailed and effective testing and surveillance of the virus.
• Resource and implement contact tracing by utilizing existing programs in state health departments, pursuing
public-private partnerships, or app-based solutions while also ensuring strong privacy protections.

 

BY THE NUMBERS

The pandemic is showing different impacts for people across the country
that point to larger challenges individuals and families are grappling.

A disproportionate number of those infected by COVID-19 are Black, Indigenous, and people of color. According to recent CDC data, 31.4% of cases and 17% of deaths are among Latino residents and 19.9% of cases and 22.4% of deaths were among Black residents.ix They make up 18.5% and 13.4% of the total population, respectively.

Seniors are at greatest risk. According to a CDC estimate on August 1, 2020, 80% of COVID-19 deaths were among patients ages 65 and older. In 2018, only 16% of Americans were in this age range.

Access to health care in rural areas has only become more challenging during the pandemic and will likely have lasting impacts on rural communities.

The economic fallout of the pandemic has caused nearly 27 million Americans to lose their employer-based health insurance. An estimated 12.7 million would be eligible for Medicaid; 8.4 million could qualify for subsidies on exchanges; leaving 5.7 million who would need to cover the cost of health insurance policies (COBRA policies averaged $7,188 for a single person to $20,576 for a family of four) or remain uninsured.

 

Children might play a bigger role in COVID transmission than first thought. Schools must prepare

https://theconversation.com/children-might-play-a-bigger-role-in-covid-transmission-than-first-thought-schools-must-prepare-144947?utm_medium=email&utm_campaign=Latest%20from%20The%20Conversation%20for%20August%2028%202020%20-%201715916573&utm_content=Latest%20from%20The%20Conversation%20for%20August%2028%202020%20-%201715916573+Version+A+CID_8719e3ecf842bc9762e48ce42f2ba6ad&utm_source=campaign_monitor_us&utm_term=Children%20might%20play%20a%20bigger%20role%20in%20COVID%20transmission%20than%20first%20thought%20Schools%20must%20prepare

Children might play a bigger role in COVID transmission than first thought—schools  must prepare

Over the weekend, the World Health Organisation made an announcement you might have missed.

It recommended children aged 12 years and older should wear masks, and that masks should be considered for those aged 6-11 years. The German Society for Virology went further, recommending masks be worn by all children attending school.

This seems at odds with what we assumed about kids and COVID-19 at the start of the pandemic. Indeed, one positive in this pandemic so far has been that children who contract the virus typically experience mild illness. Most children don’t require hospitalisation and very few die from the disease. However, some children can develop a severe inflammatory syndrome similar to Kawasaki disease, although this is thankfully rare.

This generally mild picture has contributed to cases in children being overlooked. But emerging evidence suggests children might play a bigger role in transmission than originally thought. They may be equally as infectious as adults based on the amount of viral genetic material found in swabs, and we have seen large school clusters emerge in Australia and around the world.

How likely are children to be infected?

Working out how susceptible children are has been difficult. Pre-emptive school closures occurred in many countries, removing opportunities for the virus to circulate in younger age groups. Children have also missed out on testing because they typically have mild symptoms. In Australia, testing criteria were initially very restrictive. People had to have a fever or a cough to be tested, which children don’t always have. This hindered our ability to detect cases in children, and created a perception children weren’t commonly infected.

One way to address this issue is through antibody testing, which can detect evidence of past infection. A study of over 60,000 people in Spain found 3.4% of children and teenagers had antibodies to the virus, compared with 4.4% to 6.0% of adults. But Spain’s schools were also closed, which likely reduced children’s exposure.

Another method is to look at what happens to people living in the same household as a known case. The results of these studies are mixed. Some have suggested a lower risk for children, while others have suggested children and adults are at equal risk.

Children might have some protection compared to adults, because they have less of the enzyme which the virus uses to enter the body. So, given the same short exposure, a child might be less likely to be infected than an adult. But prolonged contact probably makes any such advantage moot.

The way in which children and adults interact in the household might explain the differences seen in some studies. This is supported by a new study conducted by the Centers for Disease Control and Prevention. Children and partners of a known case were more likely to be infected than other people living in the same house. This suggests the amount of close, prolonged contact may ultimately be the deciding factor.

How often do children transmit the virus?

Several studies show children and adults have similar amounts of viral RNA in their nose and throat. This suggests children and adults are equally infectious, although it’s possible children transmit the virus slightly less often than adults in practice. Because children are physically smaller and generally have more mild symptoms, they might release less of the virus.

In Italy, researchers looked at what happened to people who’d been in contact with infected children, and found the contacts of children were more likely to be infected than the contacts of adults with the virus.

Teenagers are of course closer to adults, and it’s possible younger children might be less likely to transmit the virus than older children. However, reports of outbreaks in childcare centres and primary schools suggest there’s still some risk.

What have we seen in schools?

Large clusters have been reported in schools around the world, most notably in Israel. There, an outbreak in a high school affected at least 153 students, 25 staff members, and 87 others. Interestingly, that particular outbreak coincided with an extreme heatwave where students were granted an exemption from having to wear face masks, and air conditioning was used continuously.

At first glance, the Australian experience seems to suggest a small role for children in transmission. A study of COVID-19 in educational settings in New South Wales in the first half of the year found limited evidence of transmission, although a large outbreak was noted to have occurred in a childcare centre.

This might seem reassuring, but it’s important to remember the majority of cases in Australia were acquired overseas at the time of the study, and there was limited community transmission. Also, schools switched to distance learning during the study, after which school attendance dropped to 5%. This suggests school safety is dependent on the level of community transmission.

Additionally, we shouldn’t be reassured by examples where children have not transmitted the virus to others. Approximately 80% of secondary COVID-19 cases are generated by only 10% of people. There are also many examples where adults haven’t transmitted the virus.

As community transmission has grown in Victoria, so has the significance of school clusters. The Al-Taqwa College outbreak remains one of Australia’s largest clusters. Importantly, the outbreak there has been linked to other clusters in Melbourne, including a major outbreak in the city’s public housing towers.

Close schools when community transmission is high

This evidence means we need to take a precautionary approach. When community transmission is low, face-to-face teaching is probably low-risk. But schools should switch to distance learning during periods of sustained community transmission. If we fail to address the risk of school outbreaks, they can spread into the wider community.

While most children won’t become severely ill if they contract the virus, the same cannot be said for their adult family members or their teachers. In the US, 40% of teachers have risk factors for severe COVID-19, as do 28.6 million adults living with school-aged children.

Recent recommendations on mask-wearing by older and younger children mirror risk-reduction guidelines for schools developed by the Harvard T. H. Chan School of Public Health. These guidelines stress the importance of face masks, improving ventilation, and the regular disinfection of shared surfaces.

The changing landscape

As the virus has spread more widely, the demographic profile of cases has changed. The virus is no longer confined to adult travellers and their contacts, and children are now commonly infected. In Germany, the proportion of children in the number of new infections is now consistent with their share of the total population.

While children are thankfully much less likely to experience severe illness than adults, we must consider who children have contact with and how they can contribute to community transmission. Unless we do, we won’t succeed in controlling the pandemic.