The COVID-19 pandemic is far from over but as time passes, we’re learning more and more about the disease. Concerns over asymptomatic and pre-symptomatic transmission have received increasing consideration. A recent expert panel gathered to discuss not just this, but also the possibility of reinfection and the transmission of the virus.

Some people,once infected, maintain positive RNA for a long time [Image: Shazzadul Alam/Pixabay].

Newswise’s Thom Canalichio hosted the debate with Dr Rebecca Dutch (Professor and chair of the Department of Molecular and Cellular Biochemistry at the University of Kentucky) and Dr Luis Ostrosky-Zeichner (Professor of Medicine and Epidemiology, vice-chair of Medicine for Healthcare Quality, and director of the Laboratory of Mycology Research at The University of Texas Health Science Center).

POSSIBILITY OF REINFECTION

Commenting on the anecdotal reports about the possibility of patients getting re-infected, Prof Ostrosky pointed out that there have been accounts of patients that have been sick for a while, improved, and then gotten worse again and test positive have largely been through the media. “It’s really hard to tell from these media reports if this is just long-term shedding of the virus and sort of long-term symptoms, which we’re learning can happen, or if it’s really that people are actually getting re-infected or relapsing with the disease.

I think it’s too early to tell whether you can get re-infected or relapse. We have not seen this described in the medical literature.”

This begs the question, how do we differentiate between the two, “People who may not fully clear the virus and still test positive vs the possibility of getting sick a second time,” Canalichio asked?

“We do know that some people when they’re infected are maintaining positive RNA for a long time,” said Prof Dutch. “They can go for weeks to months. That is a good indicator for what might look like reinfection. If that’s true, one way to do this might be to watch the patient over time and see what are the viral sequences – we have the ability to sequence these viruses. Are you getting something different or does yours look exactly the same?

“The other thing is to look at is the timing between infections. This will be much more doable as time goes on. If someone who seems to have cleared the virus, had multiple negative tests and then comes back infected nine months, 12 months later, that would be more suggestive of reinfection than someone who a few months later, without being 100% sure has cleared the infection, is re-spiking sequences.”

But with mostly anecdotal reports of potential reinfection by a few people, and no actual written reports, Prof Dutch agreed with Prof Ostrosky that it’s challenging to conclusively answer the question. “We do know with some of the human cold coronaviruses, over time, people can get re-infected,” said Prof Dutch.

“However, we also know that most people infected with Covid-19 mount at least some kind of antibody response that does wane over time. And the newest report suggests that people are all mounting a pretty good T-cell response, which would suggest that they are developing protective immunity at least for a period of time.”

ANTIBODIES VS T-CELLS

“We know we mount an antibody response,” said Prof Ostrosky, “There are some reports starting to come out that this wanes over time, (over a few months). On the other hand, we have other reports mentioning that antibodies are not everything, it’s T-cell dependent as well. Your immune system cells are trained to respond to this virus. Again, it’s too early to tell (how the situation plays out), but if it behaves like other respiratory viruses and it doesn’t mutate too much, I assume that we’ll be able to have a vaccine that works for a reasonable period of time.”

PRECAUTIONS TO AVOID REINFECTION

“I think we’re all wise to assume we could catch this virus at any time until we have good evidence from the literature to prove otherwise,” said Prof Dutch. “That means  following all the precautions that we are trying widely to propagate – put your mask on, have everybody put masks on, wash hands frequently and keep social distancing – those things really matter I would assume that it’s possible to get the virus back even if you had it.

“So, just go ahead and take the precautions. I still think it’s likely that we’re generating protective response for most people. The history of respiratory viruses would suggest that’s the most likely scenario. But given how recently this has come up, and how much we don’t know, it’s always wiser to err on the side of caution.”

CAN ASYMPTOMATIC PEOPLE HAVE LUNG OR OTHER DAMAGE?

According to Prof Dutch there are some reports that sometimes, even though people don’t feel ill, if you did careful analysis of their respiratory tract you can see some damage that would be consistent with a viral infection. “Some asymptomatic people may simply not perceive that those changes are going on and not getting ill enough that they notice it,” she said. “So, you can’t rule out the possibility someone might have long-term issues they’ll have to deal with because they had the virus but weren’t aware of it.”

WHAT MAKES SOME PEOPLE ASYMPTOMATIC?

“Based on the small amount I’ve seen, in terms of things more likely to make us asymptomatic or ill would suggest, for instance, age,” said Prof Dutch. “There was a report out of South Korea that suggested younger people, just as they’re less likely to get really ill, they’re also less likely to feel ill enough to think they have anything. So, they’re more likely to be asymptomatic, older people are much more likely to have symptoms when they catch this virus. That would be one of the things that we would be looking at.

“We think there is probably generic determinants as to your immune response to the virus that are probably going to explain why some people don’t get anything and some people land up in the ICU with white lungs,” said Prof Ostrosky. “Another explanation could be the dose, the infected dose or inoculum and I do feel that anecdotally people that have very large exposures are more likely to get the disease.”

WHAT IS THE REAL THREAT OF ASYMPTOMATIC PEOPLE SPREADING THE VIRUS?

“This has been an area of some confusion,” said Prof Dutch. “Last month, there was a report that seemed to come from the World Health Organization saying there wasn’t an issue with asymptomatic spread. They retracted that the next day because scientifically that doesn’t seem to be accurate, and it may have just been a misinterpretation.

“The evidence suggests that people who are asymptomatic, for the small number of studies where you’ve been able to follow them, are replicating the virus in their airways and have infectious particles that could spread. So far, all the evidence suggests that people with asymptomatic infections are capable of spreading the virus. If you look at when we’re most infectious, it fits with what we see for many other respiratory viruses and unfortunately, what that means is you’re actually most infectious before you even know you’re sick, which can make it really difficult.

“The same thing is true with flu. The day or so before you know you have symptoms you’re already very contagious. With this virus, it looks like the few days before symptoms show up is when you’re peaking the amount of virus in your upper respiratory tract, and that’s what you would cough or breathe out. So that would be your infectious particles. It would seem asymptomatic and pre symptomatic are likely both sources of transmission.”

Prof Ostrosky agreed that the period we’re probably most contagious is the 48 hours leading to when we become symptomatic. “If we looked at a curve, you would peak sometime around the time you actually become symptomatic,” he said.

“But those 48 hours before you’re already shedding active virus, and then your curve starts going down dramatically up to the point where at day eight or so you’re not shedding enough virus to be infectious. And if you detect RNA, it has actually translated into there not even being a virus in cell culture. This is fairly typical of respiratory viruses, nothing strange or abnormal going on here. It’s just really difficult when you are testing somebody who doesn’t have symptoms, to know if they’re in the upside of the curve or if they’re already coming down. And that makes a difference to classify them as infectious or not.

ARE ASYMPTOMATIC CHILDREN, POTENTIALLY DISEASE CONFERRING?

“This is an area of ongoing research which suggests that children who have an infection are generating infectious particles,” said Prof Dutch. “It would make sense if they’re infected, they have viral particles near the airway. Given that, it would seem most likely they could be infectious. I don’t believe I’ve seen a study that actually looked at transmission between children so the answer is most likely yes, the only thing that’s interesting is there were a few reports that I read out of Europe in particular that didn’t see a huge change in spread rates with or without school closing.

“This would suggest that maybe children are not the massive incubators of coronavirus transmission. For instance, we know with influenza, children are our major source of the spread of this virus, they just spread it like wildfire and take it home. It’s not as clear that’s the case for the coronavirus. But again, we’re really in the infancy and figuring that out.”

Prof Ostrosky agreed: “I think the way we approach children currently is that we think they’re no more or less likely to be infectious than an adult and can get as easily affected as an adult. They’re not going to be spreading it more than an adult either. And what we do know in children is that they seem to fortunately get milder forms of the disease, although there are some very severe forms in children. As a result this is all playing into this very difficult equation as to when to bring kids back to school.”

MASKS ARE A GAME CHANGER

“Unquestionably, masks are a game changer,” said Prof Ostrosky. “We’ve seen it in our hospital. Before we started universal masking, we had a lot of transmission between staff’ between patients and staff, etc. The moment we implemented universal masking, that all went away, it was very, very clear we went to a pattern where now most of the transmission we see in the hospital is between staff members that take off their masks to eat together. And then there’s a lot of research out there looking at masking in community settings, showing a significant decrease in transmission. There are a lot of really good case reports. So, in my opinion, there’s really no controversy as to whether masks help decrease the transmission of this virus.”

“I completely agree, the data is very strong that masks matter,” said Prof Dutch. “There was an epidemiology paper published about a month ago that looked at Italy and New York to measure what their transmission curves were and then put in the time point of when mandatory mask wearing was put in place. You can see a shift in the curve in both places by four and five days after that date, which would fit with the idea that when we all start to put masks on, we decrease transmission. Are we decreasing it to a 100%?

“No. But what I always say to people who are not so fond of wearing a mask, if you are about to goin a room and people were going to shoot at you, and you had the option to put something on that the data suggests is going to protect you 90% of the time, would you do it? And the answer would be yes. Same thing for your loved ones, would you have them do it? Yes. So, this is again a choice that has good scientific evidence to suggest it will really make a difference and no scientific evidence to suggest it’s causing problems.”

“I don’t particularly like wearing a mask, I’m not a huge fan of seat belts, but I wear them every singletime I get in the car. They’re uncomfortable, but I wear and one when driving. It’s the same kind of thing.”