On Friday, April 10, infectious diseases specialists spoke about issues around the asymptomatic transmission of the COVID-19 virus, challenges facing communities of color, and other timely issues, during a press briefing held by the Infectious Diseases Society of America (IDSA). As the association describes itself on its website, IDSA is “is a community of over 12,000 physicians, scientists and public health experts who specialize in infectious diseases. Our mission is to improve the health of individuals, communities, and society by promoting excellence in patient care, education, research, public health, and prevention relating to infectious diseases.” IDSA has been outspoken on COVID-19-related issues, urging a “continued commitment to data-driven responses to the coronavirus,” supporting the opening of access to convalescent plasma use, and urging that the federal recommendation on sheltering remain in place for the time being.
Christopher D. Busky, CEO of the IDSA, introduced the two speakers on Friday morning. Carlos del Rio, M.D. is executive associate dean at the Emory University School of Medicine at Grady, and is a professor of medicine in the Division of Infectious Diseases at the Emory University School of Medicine in Atlanta, and also a professor of global health and epidemiology at the Rollins School of Public Health. Jeanne Marrazzo, M.D., M.P.H., FIDSA, is a professor of medicine in the Division of Infectious Diseases at the University of Alabama at Birmingham; she is also a member of the IDSA’s board of directors.
Dr. del Rio spoke first. “In this epidemic,” he said, “we’re learning things every day, and things are rapidly changing and moving. And as we learn things, we have to make changes in our recommendations. One thing we suspected but have now learned,” he said, “is about asymptomatic transmission. And I like that the CDC [the federal Centers for Disease Control and Prevention] is now calling it pre-symptomatic transmission. Different studies from China, Singapore, and now one from Washington state, suggest that about 12 percent of infections occur during this pre-symptomatic stage.”
“The discussion around symptoms has been fascinating; we were treating it very much like a classical viral infection,” Dr. Marrazzo said. “A lot of people were refused testing initially because they didn’t have cough, fever, dyspnea, or myalgia. We now know that there is a wide range of symptoms, including anosmia, the loss of the sense of smell. And that’s very distinctive; I can’t think of another respiratory disease like that. The other is abdominal problems, including diarrhea including about one-third of patients. So this is a very interesting virus that seems to have the capacity of affect a lot of symptoms, beyond in the respiratory tract.”
Furthermore, Marrazzo said, “It may be up to four days when you seem to have no symptoms. But I wonder how many of those symptoms were just missed? So I think now we’re being more open to people experiencing this wider range of symptoms. So we have to be more expansive with symptoms. So we need a much lower range of symptoms and wider.”
And, said del Rio, “We’re now recommending that everyone wear a mask, to prevent them from spreading to others. Making sure something from my respiratory tract doesn’t infect someone else’s. It’s very much what happens with surgeons wearing masks. And you and I are in the South. I’m not surprised by the racial disparities here, but they’re pretty stark. Are you seeing the same thing in Alabama?”
“Yes, we are,” Marrazzo responded. “Black residents make up less than 20 percent of the population in Alabama, but 40 percent of the deaths” from COVID-19. “And Illinois, less than 15 percent of the population is Black, yet 70 percent of deaths are among Black Americans. Why? Part of it reflects the vulnerability of many urban populations, where social distancing is very challenging. I think people forget that social distancing is a luxury, and requires space,” she noted. “The other aspect of this is the lack of preventive healthcare, particularly around hypertension. If you look at the morality, hypertension keeps coming up. I’m wondering whether that’s connected to pulmonary emboli and deep vein thrombosis, blood clots.”
“We live in a country in which disparities color a lot of outcomes,” del Rio agreed. “Per hyper-coaguals, we’re seeing people present with pulmonary emboli. So this hyper-coagulable state is something we still need to understand. We’re still learning something about this every day. But that’s what makes infectious disease incredibly exciting. I wake up every day knowing I’m going to learn something.”
“Yes, I wake up every day knowing I’ll learn something, and go to bed feeling humbled,” Marrazzo said. “And I want to give a big shout-out to the science and health media for their great explanations. Per hyper-coaguals—keeping these patients well-oxygenated—I wonder two things. One is that I wonder about the rapid early decline” of some patients. “I wonder whether oxygenation is undermined by micro-emboli. And we talk about how challenging ICU care is. But we’re also now proning patients, turning people over on their bellies, and when you do that on a cycle, you get much better outcomes. But it takes a huge number of staff; it takes about ten people to prone a person. And that need for that level of staffing has not been appreciated.”
“Absolutely,” del Rio said. “We’re learning new tricks, right? Our ICU nurses are having to be trained on PPE and on ventilation-based proning. And that’s incredibly taxing and challenging. But my hat is off to everybody in hospitals working on this. They’re working extremely hard. These are not easy patients to care for. And they’re also caring for them personally. They’re holding hands, providing comfort, listening to them. So it’s not just medical care, but the care of the patient that’s coming out loud and clear. I’m just so impressed. It’s absolutely amazing.”
Compassionate care and the use of non-proven medications
One specific issue that the two physicians agreed was a moving target was the development of more consistent algorithms and protocols around the use of drugs and treatments that are beginning to be used in the pandemic, but for which the evidence has not yet emerged in the clinical literature—for example, around the administering of hydroxychloroquine, sometimes in conjunction with azithromycin. Hydroxychloroquine, an anti-malarial drug, has long been prescribed for those living with lupus, rheumatoid arthritis, and other chronic illnesses. There is only anecdotal support for its prescribing to COVID-19 patients, but the Food and Drug Administration (FDA) on April 7 approved the administration of hydroxychloroquine to COVID-19 patients.
“We’re all developing our own treatment algorithms and protocols,” del Rio said. “Do we use hydroxychloroquine? Azithromycin? Remdesivir? IDSA is putting together some guidelines for diagnosis and treatment, and our colleagues in IDSA are doing such a good job. And by Monday, we’ll have IDSA guidelines, which will be changing over time. But it will be nice to have one document that we all look at.”
Marrazzo agreed. “Yes, we have a biweekly call, and everybody reviews what you’re saying, what Seattle’s saying, etc.,” she said. “And what’s amazing is that everybody’s remarkably consistent. And lots of media folks are asking what we think about hydroxychloroquine. And the reality is that we live and die by the evidence. And one issue is the argument about whether it’s even ethical to use these treatments when we don’t have the evidence. But I would get back to the compassionate use argument. When you have a patient who’s dying, you have to use what you can, what’s available.”
“And you and I cut our teeth on HIV; we were doing things when there was nothing else to do,” del Rio noted. “But we did it in a protocolized way. I’m not opposed to giving new treatments, but I don’t want to do it willy-nilly. I want to do it in an organized way. That’s how we advance.”
In response to a question from the press on what Black communities should be asking of their leaders, del Rio said, “One, we need to expand access to testing in those communities. It reminds me of HIV. Testing has to come into those communities. We have to address these healthcare disparities. And we need to go back to our roots in our communities. We have to have the community involved in the decision-making.”
And, added Marrazzo, “We need to identify and work very closely with and develop relationships with key spokespeople in the communities. When it really comes to explaining to people why we don’t want them to come to Easter Sunday services, which is the high point of the year for many people, spiritually, we need to be partnered with the faith leaders in communities. And we can’t just open things up and have everyone go to a belated Mardi Gras in the streets. In some communities that did a nice job like Singapore, you’re going to see spikes coming up again. So it’s going to take an intense, collaborative dialogue with groups who don’t necessarily come to us.”
Many unsolved questions around serologic testing
In response to a question from the press about how we will all know when antibody tests can ascertain for certain that individuals have immunity to COVID-19, Marrazzo said that “A lot of people think about antibody detection as being as simple as doing a mono-spot test; in some cases it is. But the challenge is that we don’t have a pre-developed antibody test to for this disease. The FDA has approved the idea. But I think in the next month or two, we probably will have a good test we can deploy widely. How would you use that? What you’ll need to do is more widespread screening to see who’s become immune. You could then develop interventions in communities. In some places in Italy, you could well have more than 50 percent who are immune. That’s the idea of how we could roll out serology, but we’re not ready yet; it will also be very expensive.”
What’s more, said del Rio, “Antibodies will tell us who’s infected and not. But we still need to understand the correlates of immunity. We may have a vaccine that develops antibodies but doesn’t develop immunity An antibody test will tell us who’s infected. I can see in HC testing all employees to see who’s already had the disease, and that will help as we try to reopen the economy.”
Asked about the various projections on when peaks in infection will occur in different places across the United States, del Rio responded that “I tell people, when you look at different projections and models, the peaks are different in different places, of course. But I tell people, reaching the peak just means you’ll reach maximum use of resources; it’s not the end. You’ll still have a lot of patients coming in and disease happening, and deaths. And we want to blunt the curve. It will be different in different places and influenced by two factors: primarily by social distancing in your community. New York is obviously driving a lot of what’s happening in this country. It will change dramatically, because if you have an outbreak in a community. I’m worried about Easter, about people here in the South saying, OK, I’m going to go to church. I don’t want 500 people in a megachurch; we could potentially see a major problem.”
“A great example of the comment that ‘all models are wrong but some are useful,’” Marrazzo said, “is that last week in Alabama, I got a lot of questions because the IHME model [the model of COVID-19 evolution created by the Seattle-based Institute for Health Metrics and Evaluation] in Seattle predicted that Alabama would experience its peak around April 19 and we would have at least 300 deaths on that day. Of course, the press was freaking out; but they never revised that model. And models depend on so many factors that I think it’s really important to remind people that they’re designed to help you plan for the worst. The IHME model didn’t really have the data on the kinds of hospitals we have here or account for the fact that much of the state is quite rural. And the third thing on the models, you can plan everything you want, but if you have an isolated outbreak in a jail or nursing home or large gathering, all models are off.”
Asked about the administration of hydroxychloroquine in their hospitals, Marrazzo said, “We are using it in our hospital. We’re using it for a range of patients including when patients are beginning to deteriorate. It is an oral drug, so we do want to give it to people when they can still take that drug.” Added del Rio, “We’re not doing it in the outpatient setting, but when [COVID-19 patients] are hospitalized, it’s a good option,” and are administering the drug in the inpatient setting. “And especially when you combine it with azithromycin, you don’t want to do that in an outpatient setting,” Marrazzo added.
A member of the press stated that she had spoken with a dermatologist, who is seeing rashes in some COVID-19 patients. Could that be a new coronavirus symptom?
“Yes, it could; there’s been a lot of discussion in the medical forums on that,” Marrazzo said.
What about the percentage of patients needing very intensive care? “Only about 10-12 percent of people need hospitalization,” and the increasing intensity of illness “starts with desaturation, a drop in oxygen concentration,” del Rio commented. “If the oxygen saturation continues to drop, we consider additional therapies. And if they need intubation or more aggressive care, you put them into the ICU, which happens to be 3-5 percent of patient, you have different modalities. People go to the ICU—about 70 percent end up on a ventilator. But most people actually recover. But once you get onto a ventilator, the course is very rough. And our critical care colleagues are doing a yeoman’s job on this.”
“Our experience is pretty similar,” Marrazzo said. “But the reason our ICUs are having relative success in getting people out is because they have the ability to do the intensive respiratory therapy, including the proning. In Italy, they were completely overwhelmed, and the mortality in the age range of 60-80 was very high, around 25 percent, in a JAMA [Journal of the American Medical Association] article this week. So my guess is that if you have an ICU as overwhelmed as those places are and in New York, it may be impacted by how intensively you can provide care.”
“And that’s why we need to flatten the curve, because you need not only beds and ventilators, but you really need staff,” del Rio commented.
What about new reports of rebounding infections in South Korea? “I think there’s a question about what these infections are,” Marrazzo said. “Are these really people who were infected previously and are getting reinfected, or who had not been infected previously? I haven’t seen enough of the data to know which is which. And it gets back to the question of, do we really know how good the serology was? Those are the kinds of things that I’d really like to dig into before making an assessment.”
“We really need to understand the correlates of immunity,” del Rio added. “Just because you have antibodies doesn’t mean you have immunity.”
And, a member of the press asked, what about the possibility of second and third subsequent waves of mass infection later this year? There continues to be a broad debate about the impact that the pandemic, and the partial shutdown of activity, are having on the country; and a premature full reopening of activity could be dangerous. “We have a policy dichotomy here,” del Rio said. “Believe me, those of us in public health do care about the economy. But it’s not a switch that you can turn on, and it’s not going to go back to the way we were. It will be a new way of living. And what you do in NY will be different form in Brim or SD. It depends on how much infection you have. And we need a lot of access to testing; because if you can diagnose people right away, you can diagnose them, do contact testing. I want to stop small outbreaks, and do rapid testing, identification, and contact tracing, and for that, we’ll need a much bigger public health workforce. If we do those things, we can start to get back to a new normal. Can we do events with 100,000 people? No. But we all want to get back to some sort of normal.”
