Should people be tested for antibodies before getting the vaccine?
The vaccine will be licensed specifically without a need for antibody testing, and even if you were to test positive for antibodies, I would recommend getting the vaccine.
If you’re testing everyone at an institution with a rapid antigen test weekly, do you still need a backup test?
If you’re asymptomatic and it's part of a screening assay, you have to follow whatever the screening program is at your institution: Usually it's just repeating the antigen test. If you're infected, but antigen-test negative, and retested 3 to 4 days later, it'll probably show up positive. So again, you just have to follow the protocol.
If you’re symptomatic or there’s concern that you’ve had contact with someone who is infected, you need a backup PCR test—period. The advantage of antigen tests is that they can be done quickly and aren’t much of a burden on the healthcare system.
At my institution, since the summer we’ve had huge lines of people who want to get tested. Over the summer and into early fall we were able to turn PCR tests around in less than 12 hours. Now, with the increased volume, turnaround is about 1 to 5 days. Since antigen testing isn’t as complex, it can be done much more quickly and help shorten the turnaround. However, more research is needed to determine the optimal role of antigen testing in the real world.
Is time of exposure a significant factor in contracting the virus?
Yes, the longer you’re exposed to someone who is infected, the higher the risk of contracting the virus. That’s why if you're having lunch with someone and you both don't have a mask on for about 5 minutes, the risk is much lower than if you’re both without a mask for an hour, or if you live at home with someone who is sick and you're exposed all day long.
Is wearing glasses sufficient for eye protection?
We know from studies in China that wearing glasses does seem to help. However, this is not sufficient in the context of a healthcare environment.
The general advice is that if you’re working with patients closer than 6 feet away who are possibly infected/asymptomatic, we suggest using surgical masks plus a face shield—that’s what we do at Johns Hopkins.
Can you explain a little bit about how herd immunity works, and whether it can be realized in the US?
The herd immunity concept is that there will be limited transmission of the virus if there are sufficient numbers of people who were previously exposed, because you’re just not encountering people that are susceptible as often. For measles virus—which is actually much more contagious than this current pandemic virus—estimates are you need at least 80% to 90%, some people say 92%, of the herd population to really have solid immunity so that you’re not going to transmit it.
Based on what we know about this respiratory virus, a lot of modelers are suggesting that with the transmission factors and maybe the dispersion factors, that a target of about 60% is sufficient. But we’re really still far away from that and, of course, it’s going to be very slow going. For example, in New York City, more people have been exposed than other parts of the country. So, I think it’s going to be a long, long while to reach that 60%. Unless this virus magically disappears, I believe that it will still be around with us for a while. What you can do and tell your patients to do is wear masks, social distance when you’re out in public, and so on to reduce risks for acquiring the virus.
What if someone tests negative and wants to spend the holidays with their family? What should we be telling patients?
Well, it's very simple. How will they feel if that test doesn't detect COVID-19, but they infect their grandma, and she dies?
A test that is negative just tells you at the moment that the test was drawn, there's not enough detectable virus. There's no way to guarantee that someone doesn’t become infected between that test and when they see their loved ones. There’s almost no reason I can think of why anyone should be having a holiday meal with anyone whom they don't currently live with, because doing so will place people at risk. It will burden the healthcare system further. It's been advised by the CDC that that's not a good idea. I equate it to someone not wearing a mask; it’s just not the right thing to do this year. As many people have pointed out, having a wonderful holiday this year could result in you not seeing some of those loved ones next year.
What percent of patients who tested positive for COVID-19 who lost their sense smell or taste see these senses return, and in roughly what time frame?
There have not been a lot of studies about this, but most people do experience a return of smell and taste. It typically takes 2 to 3 weeks. Studies suggest that up to two-thirds of people may have some perturbation of taste or smell. There have also been cases in which, as far as we can tell, patients have not regained their sense of taste or smell after 4 to 6 months. However, this seems to be a small number.
What is your opinion on using an N95 mask versus a regular surgical mask or a handmade/commercially made fabric mask?
Outside of the healthcare setting, I don't care what masks you wear, as long as you've got something covering your nose and mouth. Clearly, a surgical mask or a procedure mask is better than a single ply of cloth over your face, but anything is better than nothing. The one thing that's an absolute no-no that I see a lot is N95 masks with ventilation, with a little valve on the side to let the air out. That makes it a lot easier to wear the N95s, but it's unfiltered air coming out. So you're not doing anything, you might as well just take the mask off. You're not reducing the risk to others if you have asymptomatic COVID-19.
Inside the healthcare setting, this is where you have to follow practices set in place by your institution. For most situations with patients who aren't known to be infected with COVID-19, there's no need for an N95. Really, the only situation where N95s are needed is during the first 30 to 60 minutes of aerosol-generating procedures, depending on the air flow in the room.
Can you speak to molecular testing sensitivities and specificities?
Molecular tests are currently the best option we have, though there are people who receive false negative results. That may be because, especially in younger people, the immune response is not sufficient to yield a positive test result. There’s increasing evidence that the more vigorous the immune response, the sicker you are. An analogy is Epstein-Barr Virus infection: 5-year-olds rarely get infectious mononucleosis, but teenagers do, and they’re sick because of the vigorous immune response.
It’s very interesting, and almost paradoxical, that people who are sicker tend to shed the virus for a longer period of time. So, sometimes, it’s the people who are not ill or testing positive who actually end up clearing the virus faster. We don’t know all of the details yet. For hospitalized patients, we have about an 8% false negative rate on the first test, but below a 1% false negative rate on the third test.
How likely is virus transmission via the eyes? Do glasses provide any protection?
Eyes are an avenue of transmission, although an avenue less likely than the respiratory tract. Droplets can get around regular glasses, so they aren’t sufficient. Goggles with a high top that cover above your eyebrows and over the side of your temples are recommended for protection.
What should be done for outpatients who come into ambulatory care and insist on trying different therapeutics (steroids, azithromycin, zinc, remdesivir)?
You have to be firm and say “no.” For zinc, there may not be harmful side effects. But steroids may actually cause patients harm if they don’t require oxygen. Additionally, antibiotics don’t generally help since we don’t typically see super infections in outpatients--these people still just have a viral illness and antibiotics won’t be of much help. So I’d really steer clear of giving azithromycin.
In the near-term, some modalities may turn out to be helpful for these patients. For example, there is some published evidence that if you aren’t ill enough to be hospitalized monoclonal antibodies may be helpful at stanching infection or preventing hospitalization. These are in front of the FDA now for emergency use authorization, as are some oral antivirals, but those may be further down the line.
If someone is positive for COVID—whether false negative or symptomatic but not requiring hospitalization—are there any at-home remedies we can suggest? (eg, vitamin D)
I don’t know of any compelling data. I don’t think, as healthcare professionals, we can really advocate for any particular vitamin, mineral, or nutraceutical strategy. There is a lot of controversy on vitamin D and its role in immune response. Often people with vitamin D deficiencies have more health problems, but I’m not confident it’s a cause or a marker of immune system strength against COVID.
This virus attacks virtually every organ system, from the brain to the kidneys to the heart. What else do we know about the pathophysiology?
We’re still learning about the pathophysiology. We know the ACE2 receptor for this virus is present on so many organs, endothelial cells, epithelial cells, the vasculature, and, of course, blood vessels that supply all of our organs. There is also a subset of people that get this hyper-inflammation, which also seems to cause some grave damage.
Mount Sinai has an autopsy series—which is the largest I know of, and is in a preprint—but it talks about people with extensive microangiopathic clotting, and also something like a hemophagocytic lymphohistiocytosis (HLH) process, where you have macrophage activation and a lot of tissue damage.
Can you provide more information on plasma donation? Is it helping? If so, what group of patients is it helping?
Convalescent plasma therapy has been around for a long time. It has been used in a lot of other illnesses, including the original SARS coronavirus, Ebola virus, and others. There are small case series from China that suggested it worked, and the New York Blood Bank has actually been a leader of this in the US. Mount Sinai recently put out at preprint—so it’s not yet in published press—showing that in a small, matched cohort series, convalescent plasma seemed to help patients who were not yet severely ill: These were people that needed oxygen but were not in the ICU, nor on a ventilator. It improved oxygenation and survival in that group compared to matched controls. Though it was not a true randomized, controlled trial, it is probably the best data out there so far and a promising study.
A caveat is that donated plasma contains a range of antibodies. It appears that 70% of people have lots of antibodies, 30% not so many, and 5% or 10% might actually be negative. So, rather than just one plasma unit, some places are giving two to avoid the possibility of the patient not getting a good titered plasma unit. Some centers are also trying to titer the plasma. We, at Johns Hopkins, are doing a randomized, controlled trial on early treatment—even in outpatients—before people are ill to see if it can prevent progression. A lot of trials are in progress and I think this is a stop-gap measure until we have better treatments.
I work in family practice. What should I look out for in patients who are post-hospitalization from COVID? Are there any tips for at-home management?
We’re still learning about this because the people that were infected in April are just now 8-weeks out. We’re seeing a subset of people that really do take a long time to recover, but the other group we’re seeing includes people who improve and then 2 to 6 weeks later develop unexplained fevers and other responses with no apparent explanation. People are also developing late secondary pneumonias, much like occurs with MRSA and influenza, but this is occurring a month or even up to 8 weeks after symptom onset, and includes not only bacteria but also fungi.
I think there is a post-infectious syndrome. I also think there’s a hyper-inflammatory syndrome with delayed onset that we’re all just learning about now, and there’s not yet any published data along these lines. It’s important to be wary if someone develops new symptoms post-hospitalization, don’t assume that it’s minor—it deserves re-investigation. I would reassure patients that even when they do have this kind of problem, they’re not infectious. It looks like you can rest assured that 2 to 4 weeks after the first onset of symptoms, people are not infectious.
What can you tell us about “long haulers”— people who had symptoms, or were asymptomatic, but tested positive, who are now experiencing long-term effects such as memory loss, weight loss, and functional decline?
“Long haul” post-infectious problems are not unique to the coronavirus—we also see them after infectious mononucleosis and Lyme disease, for example. Though we don’t see it after rhinovirus infections.
Clearly, the virus impacts the immune system in odd ways; it is likely that viral remnants that remain in the body are part of the cause. Unfortunately, we don’t have a lot of insight to the issue at the moment. Patients in the ICU may well have critical illness problems that are not necessarily unique to the coronavirus, but rather from prolonged ventilation, lung injury from ARDS, or the presence of a lot of thromboemboli. It’s curious that some people who had no symptoms or mild symptoms are now having post-infectious fatigue, muscle aches, memory loss, brain fog, etc, but again, the details and incidence of this are unclear at the moment.
Unfortunately, there is no organized approach or guideline I can point you towards. However, my approach to helping these patients is the same that I use for any infectious disease/post-infectious problem. I borrow bits and pieces of knowledge from rheumatology, fibromyalgia, chronic fatigue, anxiety, and depression, to try and figure out exactly what might help them: Sometimes it’s behavioral techniques, other times it’s neuromodulators (eg, anti-anxiolytics, antidepressants, pain modulators).
This will certainly be an active area of research in the next year or two.
How should pregnant patients with COVID be treated?
There have been a couple of studies published on this so far. What’s clear is that, in the third trimester, people can certainly acquire this and become ill, just as we know influenza can be quite severe in pregnancy. Data on first and second trimester acquisitions are a bit more uncertain. The data are not yet robust enough to know if it leads to fetal malformations any higher than baseline rates, but this is being looked at carefully. Zika virus, of course, is infamous for fetal malformations, and certainly viruses are well-known to do this, but it’s not generally seen with respiratory viruses: Most respiratory viruses don’t cause fetal malformations, so it would be surprising if that’s the finding with COVID. The general advice is to treat pregnant women as high-risk and really do your best to avoid exposures.
Should pulmonary rehab be ordered for a patient who is post-hospitalization from COVID?
I don’t think we know the answer to this yet. Certainly, we know that people who have had acute respiratory distress syndrome (ARDS) have permanent scarring or weakened lung reserves, but I can’t really tell you if pulmonary rehab is beneficial in that case—though I doubt it’s harmful. I don’t think it’s needed for everyone, though, Now we are following our patients who have been in the ICU on mechanical ventilators and gathering information to try to understand which problems they have as they step down in care. Of course, some people had preexisting lung disease, and there’s some concern that people seem to develop something like interstitial fibrosis, but again, there is still a lot to learn about the best next steps in step-down care.
Why does the CDC recommend 14 days of quarantine if people can be assumed noninfectious after 10 days?* Is the recommendation the same for someone who has been exposed to a person who is COVID-19–positive, and what is the value of testing in this case, if the exposed person is asymptomatic?
This is an important point, as people often confuse concepts. If you know someone is infected, then we’re tracking an immune response that gets rid of the virus, which is that 10-day number. Whereas if you’ve had close contact with someone who is/may be infectious, then we’re tracking an incubation period. We know the incubation period can be anywhere from 2 to 14 days, with the range of 95% to 98% of people extending all the way to 12 or 14 days, but most people will develop symptoms between 5 or 6 days.
So the quarantine period is to make certain that you’re developing symptoms in the incubation period. Consequently, if you do have an infection and develop symptoms in the incubation period, then in all likelihood you’ve already included that 10-day quarantine. Some people have done sequential testing on day 9 or 10, which, if negative, lowers the probability that you will turn positive. So it largely depends on incubation period and symptom development.
So, as mentioned, in the case of someone who was exposed to a person who is COVID-19–positive, the recommended quarantine period is 14 days. Now, if you get tested 1 or 2 days after the contact, all that result is telling you is whether you had COVID-19 before the close contact. If testing is done 7 or 8 days after the contact, it is more likely that you did not acquire the virus from that contact. But remember: A negative result is not a “get out of jail free” card. If you have to return to work prior to the 14 days, wear an N95 mask and take extra precautions. And, of course, if you do break the quarantine period, you should tell the people you are in contact with that you had a possible exposure less than 14 days ago.
*Note: The CDC recommendations are continuously changing and were updated shortly after this Q&A session. For current CDC guidelines, please see: www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/quarantine.html.
Should you retest someone that you’ve diagnosed with COVID?
The CDC has moved away from retesting. If someone had tested positive, and doesn’t have a suppressed immune system, then 10 days after symptom onset you can assume they are no longer infectious as long as they’ve had a resolution of symptoms for at least a full day.
We’ve moved away from retesting because we know that viral shedding can occur for multiple weeks, but that doesn’t correlate with infectious virus. So, again, we’ve moved away from negative test being a criterion to prove that people can return to work or be transferred to a nursing home.
Which test do you recommend when asymptomatic people are being screened, as at colleges and some healthcare facilities?
To be clear, I think screening tests are used when you’re somewhat agnostic—you don’t know if people have the virus or have symptoms, you’re just mass testing. Some universities are doing this with antigen tests, though we have not seen the data on that yet.
If people are symptomatic, then that is better referred to as diagnostic testing, not screening. An antigen test can be used in that case, but they are very hard to come by unless you’re part of a university, nursing home, or other institutional setting.
Does the US appear to have a high caseload because we are testing more than other countries, or because we actually have more infections?
On a super simplistic level, doing more tests means that there are “more” cases. But if testing is very high, it may actually mean that you don’t have enough tests available, which would reflect high community virus rates. And what if there were 100 cases of COVID-19, but you only have 10 tests? Would that mean that there is “less” COVID-19? I do believe, and almost every public health authority in the US agrees, that we have very widespread disease in most communities of the US. Testing is high, and testing centers are overwhelmed by demand, and this is what happens with an astronomical rise of cases. But I think the percentage of positive versus negative tests sheds better light on the situation.
In terms of accuracy, what type of testing do you recommend to use for drive-up testing?
That depends. If you’re screening, then molecular tests are the only type that you should use. If you have access to one of the better rapid tests, such as the Cepheid GeneXpert, I would use that because I think it’s a reliable rapid test—it can give you results in less than 45 minutes. However, these rapid tests are typically reserved for EDs. I believe the best answer, and what most communities are still using, is the standard RT-PCR tests, which are done with nasopharyngeal or nasal swabs.
How long following infection are people testing positive? Are we just picking up remnant particles 5 or 6 weeks later, or are they still considered infectious?
This is still an evolving area, but I think it is highly important because the CDC had issued directions that you needed two negative tests to take you out of airborne isolation and maybe transfer you to a facility. What we’re finding is that people, even up to 80 days after symptom onset, are still testing positive for the virus and, yes, it’s only detecting a remnant of RNA. We know from small, but carefully performed, studies in people that are not severely ill that by day 10, you can’t culture a virus. Remember, culturing a virus is a pretty insensitive surrogate; you need a lot of virions to actually culture the virus.
The Korean CDC did a study where people who were hospitalized with positive COVID tests were discharged after testing negative. Two weeks later, they were tested again, cultured, and about over half were re-positives. They then did contact tracing of the homes and contacts and they didn’t find any new transmissions. To me, that’s additional evidence that if you’re about 3 to 4 weeks out—even in the hospitalized population, a sicker population—you’re not really transmitting the virus, even though the swabs are positive.
We’re still lacking data on this in the immunosuppressed population. At Johns Hopkins, we are not testing after 28 days post-acquisition of infection and onset of symptoms; we’re treating them as noninfectious.
Even though COVID-19 is principally droplet or aerosol transmission, if somebody coughs on a surface, I touch that surface, and then I touch my nose, the virus can still be transmitted, is that correct?
I think that’s true. You have to realize there’s a lot that, in real world experience, we don’t know yet. The feeling is that droplets are the predominant transmission method, but there is probably some aerosol spread as well and, in fact, the World Health Organization (WHO) just recently relented and said universal mask wear is the way to go—which is very interesting because they’ve been a holdout on masks for a while, mainly because they wanted to limit use of PPE among shortages.
In terms of surfaces, the issue is that all the studies that have been done just look at viral RNA by molecular analysis, and it’s very hard to know if that correlates with infectivity of a contagious or culturable virus. We know the virus can be found on surfaces by its RNA hours, or even days, later in ideal conditions, but it does not seem to be the major mode of transition. We still want to encourage hand hygiene: We want to be careful, wash our hands, and not touch our faces, especially in public restrooms and after coming in contact with high-touch surfaces in the office. Surface transmission does not seem to be a major issue, but I would still be very cautious.
Is transmission (both aerosol and droplet) dependent on proximity and duration of exposure? For example, a teacher in a classroom spending an hour with a student versus 3 minutes.
Yes, this is definitely the case. Some people think you only need to inhale one virus particle and you’ll become infected, but the reality is that you probably have to inhale a fair amount of virus for the infection to statistically take hold. That’s why it’s not only proximity, but also the duration of exposure. This is why being across a small table from someone who is infected during a 3-hour restaurant meal is bad news, because even speaking, some virus is going to be transmitted within 3 to 6 feet. This would also be true in classroom environments, because there is a large group of people in a small room which may not have enough ventilation for proper air exchanges.
Is coronavirus heat sensitive? Why haven’t we seen numbers drop in states like Arizona, where temperatures can be more than 100⁰F?
Most of the virus transmission is by respiratory droplet. I think if you’re speaking about environments with high heat, the virus particles that land on hard surfaces in those environments may have a harder time surviving. But, we are not seeing cases drop in hotter states and countries because what happens is when it gets too hot outside, people go indoors to their air conditioning, which creates the perfect environment for the virus to survive: 68⁰F to 70⁰F with a humidity level of 40%.
What is your advice regarding international and domestic travel during the pandemic?
The short answer: don’t travel right now. There are a lot of considerations at the moment. First, you have to take a look at where you want to go. Many states and countries have restrictions and/or may require testing beforehand, afterwards, and a quarantine upon arrival. Secondly, you have to consider the safety of air travel. In general, short-haul domestic travel is relatively safe—at least on the airplane, as the air is HEPA filtered. There isn’t a lot of evidence of outbreaks on these short flights. However, transmission is pretty well characterized on long-haul flights. If your flight is 10 or more hours where people need to eat, get up to use the bathroom, or stretch their legs, this is where we see clear documentation of virus transmission.
Are any of the vaccines in development live vaccines?
Yes, some of them are. I don’t know of a vaccine that’s a weakened novel coronavirus vaccine. Instead, components—genes like the spike protein—are inserted into weakened viruses. The ones that are under development are an adenovirus vaccine that’s weakened, a vaccinia vaccine that’s been weakened, a modified vaccinia virus, and a lentivirus. So, there are a number of live vaccine candidates, which may mean that severely immunosuppressed people would not be eligible for that vaccine.
There is a claim from one Italian physician that the virus is getting weaker. Are there any data to support that?
This is an RNA virus, and RNA viruses are not nearly as free of mutability as DNA viruses, because RNA polymerases just doesn’t have the fidelity of a DNA polymerase. It does accumulate mutations, but in the world of RNA viruses, this coronavirus is actually a little more stable than others and people have postulated that perhaps it will become weaker.
The more successful a virus is, the less likely it is to make people sick so it can be transmitted rather than medicated. For example, a quarter of the US population has genital herpes, but most people don’t know they have it, so they spread it. If people know they are sick, they won’t go outside, and they’re less likely to transmit the virus to others. There are some fitness reasons why this virus could mutate and become less virulent, but I doubt that’s going to occur in the next year or two. It’s always possible, but from what we know, the changes are not that apparent yet to really indicate that the virus is currently getting weaker.
Is it recommended to wear gloves while out in the community? What about in the hospital setting?
Gloves do offer a little more protection. While wearing them, you may not be as likely to touch your face; but I think the usual suggestion to focus on hand hygiene, making sure you wash your hands and don’t touch your face, is enough. Wearing a mask is also another reminder for people not to touch their face in case they may have virus on their hands as a factor in that method of transmission.