Information on COVID-19 is evolving daily. The views and perspectives shared in this article are based on information from a webinar recorded on March 23, 2020. It has been edited and condensed for clarity and accuracy. This webinar was facilitated by J. Kevin Tucker, MD, chief of nephrology at Brigham and Women's/Faulkner Hospital, faculty director of accreditation and maintenance of certification for Harvard Medical School Postgraduate Medical Education, and assistant professor of medicine at HMS.
In the final interview of our three-part webinar, Dr. Paul Sax, an infectious disease specialist at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, offers current insights into COVID-19 testing, infection control and ongoing clinical trials.
For patients who are confirmed as COVID-positive, what is your advice in terms of how long they should remain isolated from their families after symptoms have resolved?
The CDC just updated their guidance last week, but some of this is based on limitations that we have with testing and limitations they have with data. Patients are advised to be isolated from their family members until the following occur: if you’re not being serially tested, you need to be afebrile for 72 hours or until your symptoms of shortness of breath and cough are better, and it’s been at least a week since your symptoms started.
They’re hoping to get at the fact that most people seem to clear shedding of the virus by 9 or 10 days. There is also a comment that if you are getting serial testing until negative, they want you to have something similar: no fever, cough and shortness of breath are better and your test is negative two days in a row. But, there isn’t the capacity to test people in the community until they clear the virus, at least not in Massachusetts.
Given the lack of availability of testing, are there guidelines to who is eligible for repeat testing?
Right now, repeat testing is not part of standard of care management. But, there are already issues we’ve had with trying to have people placed into rehabs or nursing homes, and it’s a very big problem. There are some people who shed coronavirus in their respiratory secretions for a prolonged period of time, even after they’ve completely recovered, and it’s unknown to what extent that is contributing to this epidemic. It doesn’t take a huge stretch of the imagination that it’s that kind of asymptomatic shedding that has led to a perpetuation of the epidemic globally. That plus the very mild cases.
From an infection control perspective, we wish that we could test everyone, but we simply can’t. We don’t have the resources, and testing right now is focused on people in the hospital and exposures.
So, we’ve talked about separation from families. What about returning to work?
That’s something that we all are experiencing right now. Health care providers want to know when they can come back to work. And right now, the guidance is very similar to the advice for isolating from families that I mentioned earlier.
Are patients who have confirmed disease considered immune from reinfection? Or are there different strains of the virus so that some are at risk of getting a second infection?
There are models that show animals can generate antibodies to this virus that then appear to be protective, and that, of course, is the line of research that vaccine researchers are taking. So, I’m optimistic. But, we don’t know whether their immunity is durable enough to get us out of this spike of infections. I think one of the reasons we have this huge spike is that the community has no native immune response to the virus.
The fact that youngsters are getting mild diseases may be because they have acquired other coronaviruses that cause all the colds they get, so they’re partially immune. But, that doesn’t seem to be helping us older people. So yes, I think there will be immunity, but I don’t think anyone knows just how long it is. One thing that has been characterized is that there is a timeline for when people can generate IgM and IgG antibodies.
If a patient comes in with a febrile upper respiratory illness and has a positive test, should we be confident that he or she has influenza only? Or is there a certain percentage of patients who may be co-infected with other respiratory virus?
Great question. Co-infection data vary from study to study. Most studies describe co-infections in the order of 5 to 10 percent. Not surprisingly, respiratory viruses circulate in the community, and people getting exposed to one often get exposed to another. The highest proportion that I saw was a study out of Stanford that found 20 percent co-infection. And very importantly, it does not exclude coronavirus infection.
In some earlier guidance about testing, people had to have negative evaluation for other respiratory viruses before they could be tested. That was never something that we infectious disease doctors supported. This was based on the fact that our testing capacity was so limited. We wanted to increase the likelihood that we were identifying active cases. You won’t see that guidance any longer, and certainly, we are not acting that way in the hospital. Someone who gets evaluated for respiratory viral infection right now is going to be evaluated for coronavirus infection as well.
Are there any trials ongoing with the use of antiviral medications for patients with COVID-19?
Yes, there are. I want to mention two open studies at the Brigham and at MGH. There is an investigational drug called remdesivir that was tested against Ebola. It had in vitro activity against Ebola but unfortunately did not work in the clinical trial. However, it’s now being brought out again because it has in vitro activity against coronavirus and SARS-CoV-2, which is this virus. It has already been given to people in clinical studies and on expanded access. Given the relatively short timeline of this illness, I don’t think it will be long before we have some data on that drug. There are several other antivirals in development but none as close as remdesivir because this had been manufactured for Ebola studies.
There are many reports in the lay press about patients who require hydroxychloroquine for their autoimmune diseases but are unable to get it. Can you tell us where that story came from?
This story is based on in vitro data that chloroquine and its related drug hydroxychloroquine do have activity against coronavirus. Early reports from China showed that people were receiving that drug and then improving. I don’t need to tell you that that does not mean that it actually works. There really is not a good randomized clinical trial yet. And then recently, there was another report out of France showing viral load declines with hydroxychloroquine plus azithromycin. It was a very small study highly flawed in its inclusion criteria. Some of the more severely sick people were excluded. We want to endorse what Dr. Fauci said, which is that there is no proven antiviral therapy for this infection right now, and that is something very much worth studying.
There are several studies ongoing. Hydroxychloroquine is being used as a post-exposure prophylaxis treatment in clinical trials, and one clinical trial is coming out of the University of Minnesota. You can enroll by emailing the lead investigators’ study unit, and they will send you the medicine or the placebo. And other studies are in the works right here in Boston. One of my colleagues is developing a study.
I really want to discourage people from buying hydroxychloroquine if they don’t need it because the people who really need it should be able to get it.
And what about the story about ACE inhibitors and ARBs? That’s gotten a lot of both medical and lay press.
These drugs appear to upper regulate the ACE2 receptor in the lung epithelium, which means that the target site for coronavirus is potentially in greater density. So theoretically, they could worsen it, but there are also some theoretical ways in which they could improve it.
One thing that you might have noticed is that lots of the studies of comorbidities and people with COVID-19 have listed hypertension as one of the comorbidities, and that’s led people to postulate that maybe it’s because they’re receiving ACEs or ARBs. Right now, we don’t know. We have one policy position from the American College of Cardiology: Do not stop these medications if your patients need them. There’s no evidence that it worsens the course of disease for people with COVID-19. There are also some comments about nonsteroidal drugs that have a similar effect. But again, it’s based on anecdotal data and modeling data. It’s not based on any actual studies.
What do you think the timeline is before we’ll actually have a vaccine that is available?
Way, way longer than publicly stated. We have phase one studies of vaccines going, which is great. That’s incredibly fast. Remember, this was just discovered in the end of 2019 and then mostly in January when the sequencing of the virus occurred. This is really a sensational speed for scientific discovery. The thing about vaccine studies though is that you need to demonstrate that they’re safe, that they’re immunogenic and that they can be manufactured on scale.
There are huge barriers to rapidly getting vaccines out to the public, so any estimate that is less than a year is overly optimistic to most experts in vaccine development. We have a lot of them here at Harvard, which estimates that the shortest timeline would be something in the order of 12 to 18 months.
Is this a virus that you think will wax and wane with the seasons?
The answer is we don’t know. It is true that respiratory viruses are more common in the winter; that much we’ve known since the beginning of time. So, I would suspect that COVID-19 is going to be less common when the weather warms up, but that doesn’t mean it’s going away. People may remember that the H1N1 epidemic of 2009 had a flu season in May. So, it is definitely possible that this will go on even after the weather gets warmer, but it’s also true that there are fewer respiratory viral infections in the warm weather.
Are there any final thoughts that you would like to share regarding treatment and prevention?
We’ve learned a lot already. We know how this disease is basically spread from person to person. And in places where they’ve done very aggressive testing like South Korea and very aggressive social isolation or social distancing, they’ve been able to get control of it. That is certainly what we’re after. That’s why there’s been such a dramatic shutdown. I think what we really don’t know is whether we were too late. I’d rather just let this play out as best we can and realize that these recommendations are not based on trivial estimates.
One final important note about young people. In South Korea, where they have done the most testing, they find that the rate of infection is particularly high among young people. So, when infectious disease doctors see these stories about people on spring break having a great time, it is very chilling because they are undoubtedly going to get infected. Most of them are going to be fine and recover, but some are going to get very sick.
There is definitely, just as there is with influenza, an incidence of extremely severe COVID-19 in young people. Every place that has this infection has reported young people who have gotten sick enough to require ICU care or who have even died. So, it is very concerning that people’s behavior hasn’t changed, even in the face of this epidemic. And, of course, they also potentially could transmit it to others. That’s a very, very important message.
This interview is part one of a three-part series adapted from the Treatment of Infectious Disease and Immunocompromised Patients webinar recorded on March 23, 2020.