Three Questions with Dr. Michael Saag

Valerie PatmintraExpert Interviews

Associate Dean for Global Health, Director of the UAB Center for AIDS Research and Professor of Medicine at the University of Alabama at Birmingham

Dr. Michael Saag has gained national attention by participating in news conferences and speaking with reporters to share his experience with COVID-19 and encourage the public to follow basic safety precautions to protect themselves and others against the virus. He’s equally busy spending much of his time treating patients who are fighting COVID and helping colleagues who are overwhelmed and exhausted by the long battle against the pandemic.

In late October, right as news of the approved vaccines was breaking, we had a chance to interview Dr. Saag about COVID’s impact on patients’ brains, the short and long term public health implications of the pandemic and what he sees as the light at the end of the tunnel.

Q: From fuzzy thinking to brain fog and the mental impacts of social isolations and shutdown, we’ve been hearing about COVID’s potential impact to the brain. Can you tell us how the virus affects patients’ brain?

A: We are definitely seeing that COVID-19 affects the brain. The most common, universal symptom patients report is headache, while some degree of dysfunction, like fuzzy thinking and brain fog, commonly affect a lot of symptomatic people as well. 

The virus SARS-CoV-2 that causes COVID-19 is a very aggressive pathogen that enters the body through ACE-2 receptors in the respiratory track, and once there, it uses the cell as a virus factory to produce billions of copies, which go on to not only infect neighbors around person, but also burrows deeper into the cell and invade local tissue. Once it does that, it finds its way into the vascular system and spreads throughout the body using the arteries as almost a subway system. 

One of the places the virus goes is the brain and, once there, a myriad of things can happen. A lot of people stay asymptomatic, but for those who experience symptoms, it can be pretty profound. Universally people with symptoms almost always have headache, which in my opinion, can be from brain swelling, even if subtle. The way this probably happens is because once the virus gets to other sites, like the brain, it has a propensity to invade small blood cells and cause micro clots, which causes some degree of dysfunction. In addition to headache, a lot of people complain about some degree of fuzzy thinking and brain fog. I experienced this when I had COVID and it was very disturbing, 

Other less common symptoms, like strokes and some degree of more progressive cognitive dysfunction, may occur as well. These symptoms are most common among older adults and usually reverse after the virus passes, but not always. The virus progresses in stages – with the first stage lasting about three to four days, where the symptoms are often mild. Then, it progresses to more significant and severe symptoms that are associated with an immune system response. The virus is quite evil in the way that it disturbs the initial interferon response of the innate immune system, which derails the immune system’s ability to regulate itself. As the immune system starts to kick in, the normal mechanisms that tell the immune system to back off or to stand down are not operational.

So, you end up with a huge elaboration of cytokines that cause symptoms ranging from fever, to brain fog, to other things. It’s hard to sort out how much of this brain dysfunction is due to micro clots, and how much is just response to a cytokine storm. But, the thing that tells me that it’s mostly cytokines is that in my experience, the symptoms wax and wane. My mornings would be fine, but the evenings and nights were pretty horrible. For me, this went on for a total of 14 days while I was sick, but the last eight days was when what I call day phenomena happened. 

There’s also a subset of patients who get what’s called long COVID syndrome or long-haul, where the symptoms of the acute illness, which usually go away in 14 to 20 days, persist, not just for days but months. This especially is true for some people with neurologic dysfunction. The recovery from a stroke is obviously going to be long, but there is also some degree of cognitive dysfunction, some degree of headache that doesn’t seem to go away. And, this is a mysterious consequence of the infection that we really don’t know much about. And unfortunately, we don’t know much about what to do for it either.

Q: What are the public health challenges facing the nation as we look ahead to winter and are bracing for an even bigger spike in COVID cases?

A: Well, if we return to basics, we know that this virus is transmitted mostly through the respiratory route. And, if you’re in a closed space with somebody who has it, and you’re not wearing a mask and they’re not wearing a mask, the likelihood of infection is quite high. So, we know the things to mitigate.

Now with the weather getting colder, people are moving more indoors. If someone is infected, the cloud lingers around them for a much longer period of time than it might outside where it gets disturbed, or dissipated by air currents. Those air currents aren’t nearly as robust indoors, so that’s the first thing. The second thing is when people are indoors, they are crowded together a little bit more. And, that also accelerates the probability of transmission. And then, finally what’s interfering with our response now, and not just in the US, but around the world, is what I call COVID fatigue. People are very tired of putting up with this thing, and they don’t want to follow the rules anymore because they’re exhausted and craving social interaction.

To put it simply moving indoors accelerates transmission and we’re seeing our worst outbreaks of new cases currently.

There’s a great website by Georgia Tech scientists that shows county-by-county numbers across the country based on the current infection rate. Based on those numbers, you can make predictions of how many people may be infected based on a gathering of certain size. 

If you have a gathering of 10 people, the probability is around 35-40%, that one out of those 10 is infected. If you have a gathering of 25 people, there’s a probability of about 72%, that one out of the 25 are infected. If it’s 50 people, that probability is well over 90%. If it’s 100 people, the probability that one person out of the a hundred is infected is well over 99.9%. 

So, you see how that correlates so that none of us will know who in the room is infected, because most of the transmission happens when people don’t have symptoms or are pre-symptomatic and they become the super spreaders.


Q: In light of the surging case numbers, what does give you hope? You mentioned earlier that you are starting to see light at the end of the tunnel.

A: What gives me hope is the recent announcement of a vaccine. The Pfizer vaccine, just announced yesterday, supposedly shows 90% protection. And, I’m saying alleged not because I doubt the data, but haven’t seen the raw data yet. So, the purported 90%, if true, is a game changer, because it means that we can then start looking for the herd immunity that has been erroneously ascribed to the epidemic and everyone getting infected. Which is just absurd, that we would have 240 million people infected to get herd immunity. Especially, when we know that the immunity may not last more than six to 12 months. But, with the vaccine, we can actually do that without paying the price.

The vaccine gives us hope and also gives us even more reason to be extra careful now. Because, think about the raw tragedy of someone dropping their guard, becoming infected, getting sick, going to the hospital and dying. When, if we could have just made it through another six to eight months, the vaccine would start being distributed in a way that could protect everyone. So to me, the vaccine results are not only a hopeful bit of news, they are also a call to action for all of us to quadruple down on what we need to do to protect ourselves. And, that would have enormous benefit, because it would lower the overall infection rates in the community, which would then decompress the hospitals and help keep people safe.

Now, when I say six to eight months, that’s just the beginning to see more wide-spread vaccine distribution. The good news is that we have multiple manufacturers with really promising results on delivering vaccines. Hopefully they’ll all start hitting and we’ll be able to vaccinate enough people to burnout the infection rate.

I know that no one wants to go back to stringent lockdown, so the vaccines are the knights on a horse coming to rescue us, and hopefully they will be able to deliver. So, I’m hopeful now. The vaccine news was a game changer at least for me. And, I can now see a way out.

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