COVID-19 Podcast

The Future of COVID-19 and Approaches to Living With a New Endemic

Matteo Bassetti, MD, PhD; Cristina Mussini, MD


November 16, 2023

This transcript has been edited for clarity. For more episodes, download the Medscape app or subscribe to the podcast on Apple Podcasts, Spotify, or your preferred podcast provider.

Matteo Bassetti, MD, PhD: Hello. I am Dr Matteo Bassetti. Welcome to Medscape's InDiscussion series on COVID-19. Today we will discuss the future of COVID and sustainable approaches to living with something that we can't eradicate.

We know that COVID now is probably different from the COVID-19 that we faced in 2020 and 2021. But we are close to autumn and winter, and it's important to know what we have to expect from the future of COVID.

First, let me introduce my guest, Dr Cristina Mussini, who is a professor of infectious diseases at the University of Modena and Reggio Emilia, a very well-known expert in Italy and Europe, and is also a good friend. Welcome, Cristina, to InDiscussion.

Cristina Mussini, MD: Hello, Matteo. Thank you for the invitation.

Bassetti: Before beginning our discussion today, I'd like to ask you, what was it that sparked your interest in COVID-19, and what keeps you engaged today regarding this very interesting topic?

Mussini: We are both infectious disease specialists, so a pandemic is something that is related to our specialty. In our lifespan, and also the professional lifespan, we already faced one pandemic that is still here, which is HIV. Obviously, it was not a respiratory infection, so the way of transmission was completely different, and it was less of a threat for the general population. But I think that we were also preparing to have Ebola in our clinic, if you remember, so when COVID arrived, we were, I would say, the natural doctors who could take care of these patients. Not only because of our clinic's structural characteristics that allow the admittance of a patient with a respiratory contagious disease but also because of our expertise.

Bassetti: Before looking at the future, it is important, in my opinion, to look at what is happening now.

Do you think there is any difference in the presentation and the severity of COVID-19 today in comparison with the disease that we faced 2 or 3 years ago?

Mussini: Yes, I mean, it's not a mystery. It's been a long time that we have been admitting in our clinic only patients who have a positive nasal swab but no involvement of the low respiratory tract, aside from a few individuals that we will talk about later. Fortunately, the advent of vaccines and the advent of some treatment strategies that could be either in the viral phase or during the inflammatory phase have changed, dramatically, the natural course, the natural history of the infection of COVID-19. What's happening now is that the virus is still circulating. We are continuing to admit people with a positive swab because we are looking for it. We perform another swab in the emergency room, not only for those who are symptomatic from a respiratory point of view — which is something that for me would be important and relevant for the future, like we do with the flu, for example — but also for those admitted for other reasons.

For example, in my clinic, I have a person who fell in her house. Another one had heart decompensation. It's completely different because for a long period, it's been the new variants that are really more contagious, but they stay in the upper respiratory tract. I don't know what's happening with this in Genoa.

Bassetti: We are following different rules because the Liguria region was the first, in April, to release a recommendation about not using swabs in asymptomatic patients. Actually, I don't have any patients who are asymptomatic with COVID. We have only patients who are symptomatic.

This is a kind of behavior that unfortunately continues to affect the patients in Italy. I don't really know why we are swabbing so much, because I believe this is a classical respiratory tract infectious disease. And we have to only swab the patients who present symptoms of respiratory tract infections and not swab people without symptoms.

On this point, the Minister of Health, a few weeks ago, was very clear, and I hope that hospitals, emergency rooms, and doctors will follow the strict recommendation of our Minister of Health. But let me ask you in general: If you had to describe the typical symptoms that affect not a fragile or not a very old patient with COVID-19 today, what are the classic symptoms? What is the duration of the symptoms? And what are the medications that you believe are important to suggest to be used?

Mussini: We are in Italy, and so the holiday season just stopped. The problem is that many people, even if they had symptoms related to COVID, did not undergo a swab. So now we are seeing the numbers rising because people are starting to use the swabs again because the symptoms are really similar to that of a common flu or common cold. Many times, you don't even have a fever; you just have a runny nose. You could sometimes have a sore throat, but you are not even coughing or something, because it hasn't involved the lungs. So, that's why the symptoms are so non-severe — I would say, so light — that you could think that it's a common cold. And this is important. But on the other hand, we have no idea, for now, of how much the virus is circulating because nobody underwent the nasal swab because everybody wanted to go on vacation, and if they have just a cold or runny nose, they said, "Okay, it's a cold" and they didn't do the swab.

Bassetti: Yes, this is exactly what happened during July and the end of June in the United States, with a very important circulation of SARS-CoV-2. And the phenomenon is going down rapidly without any type of intervention and without any consequences on hospital admissions and severe forms (of disease). But this is one side of the coin. Looking at the other side of the coin at the fragile and the elderly patients, are you still seeing severe disease, and what do you think will be the future? Next autumn or next winter, fragile, elderly, and very elderly patients will be affected by more severe forms (of disease). What do you suggest for them?

Mussini: This is something that we actually do not know because fragile patients, especially hematology patients or terminally ill patients, are people who are affected by many other causes of lung involvement in many cases. So it's complicated to understand if it's really a COVID pneumonia because the clinical picture really differs from the one that we were used to seeing during the early phase of the pandemic. What I can say is that our future will depend on the variants. It seems that now we have Eris and Pirola. In Italy, we don't have Pirola now; we have Eris and Eris has, in the animal model, affinity to the lung. And it seems like Pirola, which is more prevalent in the United States for now, could affect the lungs more. So this could make a difference, but still the only weapon that we have for these fragile people is to recommend vaccination, especially the most recently developed vaccines. This would be very important because we are running after the virus, but we are never there because the virus changes, and the vaccine takes some time to develop. And so, when the vaccines arrive, they are always for the old variant, not for the present variants. It's the same for monoclonal antibodies. So it's important to maintain the efficacy of antivirals, like nirmatrelvir/ritonavir or remdesivir, because these are the real weapons that we have for patients. In many cases, these people already had an infection and were not well when they were admitted to the hospital, but they could not mount an immunologic response.

Bassetti: Talking about the new variants, particularly the Eris variant, I read the article about the possibility of higher pathogenicity for the lung. However, honestly, we have to remember that the research was based just on 10 hamsters and is not already published; it is just in the preprint.

I would be a bit cautious about saying that Eris is more virulent for the lungs than the other variants because we are talking about a subvariant of Omicron. We will see what happens in the future, but this is my question for you: After November 2021, when the Omicron variant began its course from South Africa, we have not seen any increase in virulence, more contagious disease, but probably less virulence. Do you agree with that?

Mussini: Absolutely, yes. And also about Eris. Already in Italy, 40% of the swabs that we have, have this variant, and actually, we didn't see any increase in lung disease. The only caution is that I know that the number of swabs is so low that it could happen that we could see some lung disease (in the future), but we have also seen that Omicron really does not affect the lung. And even in patients who are admitted for pneumonia, in the vast majority of the cases, they have a bacterial pneumonia and a positive nasal swab. I don't know your experience, but what we have seen even in hematology patients is that with Omicron, we don't see severe lung involvement by SARS-CoV-2.

Bassetti: Honestly, with Eris and in general, during the summer, we have seen cases with a shorter duration in terms of positive swabs compared with the past. In the past, the average duration was between 7 and 10 days, sometimes even more than 2 weeks. Now we have infections that have a duration of no more than 4 or 5 days, and sometimes 7 days — except for the fragile patients who are hematology patients and the immunocompromised.

So my question now is about strategies. First of all, if you had to decide who is the target population to be vaccinated with the monovalent vaccine, which was approved by the European Medicines Agency a few days ago and will be approved soon for Pfizer and for Moderna, who would be the target population for vaccination, age, and underlying conditions?

Mussini: I think that the age should probably be older than 75 or 80. I would not say for those who are 65 years old. I will go older. I think 80 years old and fragile patients, especially hematology patients, much more than oncology patients, but also oncology patients with severe diabetes or severe cardiovascular comorbidities. We should also not forget that we have a population that not only received at least three vaccine doses but also experienced a lot of positivity for SARS-CoV-2 because they had several infections. I think that I had two — Delta and Omicron, for example — on top of the vaccination. In the general population, in people who can mount a normal immune response, the antigen has been seen many times; it's easy to recall it. So that's why the duration of symptoms that you were mentioning before is due to the fact that our immune system — the memory — says to just jump in because we have seen this virus many times. This probably is the best defense that we have.

Bassetti: People cannot see us because they are just listening to us, but when you said that you suggest the vaccination in patients over 75 years old, I applauded you because obviously 60 years old is a very young population. And I prefer to have one 80-year-old patient vaccinated than 100 people who are 60 years old vaccinated.

In the end, for the health system, for our public health system, it is much better to have all or more than 75% of the 80-year-old patients vaccinated than having 25% of all the people over 60 years old vaccinated. It is much more important.

The other question I have is regarding the fragile and the elderly patients. Do you believe that there is any type of new strategy, particularly for patients who [have hematologic conditions] or are immunosuppressed, who present with a long course of positive swab testing? Do you know if there are any particular strategies for this type of patient?

Mussini: We have all been artists in this setting. So what we do is we use everything that we have: all the antivirals — if we have monoclonal antibodies also, we know that a few of them can retain some activity. But just think of a cake: I think that each of these strategies could represent slices that all together make a cake. We don't have one single strategy that could help us in this. We are re-treating patients, for example, with a longer period of remdesivir; we are re-treating patients with Paxlovid; we are using, for example, sotrovimab; we are trying to combine different strategies, but nothing is really written in guidelines. When I say that we are artists, it's because of this. But what is your experience now?

Bassetti: We are using the combination of at least double antivirals. Unfortunately, we cannot use the third antiviral anymore because molnupiravir has been stopped in Italy by the Italian Medicines Agency. And we usually and routinely treat hematology patients with remdesivir plus Paxlovid in combination.

I hope that in the future we will have new monoclonal antibodies that maybe should help us in the cocktail. But before closing this episode, I'd like to ask you what advice you would share with clinicians treating COVID, and what is your advice for the future with COVID? Do we have to live with COVID, or do we have to live terrified by COVID?

Mussini: I always think of the data that we have. I don't like when people try to predict the future. What we know for now is that the virus is less virulent, and it's more contagious, but it's part of our differential diagnosis. An important mutation in COVID that makes it as pathogenic as before has the same chance as having a flu pandemic. For now — maybe I will be a terrible predictor; we will see — there are no data, no reason to think that it will change soon.

Bassetti: Thank you very much. Today we have talked with Dr Cristina Mussini about the future of COVID and about sustainable approaches to living with something that we know we can't eradicate. Thank you for tuning in. Be sure to download the Medscape app and share, save, and subscribe if you enjoyed this episode. This is Matteo Bassetti for InDiscussion.


Barriers to and Strategies to Address COVID-19 Testing Hesitancy: A Rapid Scoping Review

Factors Associated With Mortality Among Elderly People in the COVID-19 Pandemic (SARS-CoV-2): A Systematic Review and Meta-Analysis

COVID-19 and Lung Pathologies

Editorial: A Rapid Global Increase in COVID-19 Is Due to the Emergence of the EG.5 (Eris) Subvariant of Omicron SARS-CoV-2

Covid-19: Scientists Sound Alarm Over New BA.2.86 "Pirola" Variant

Recommendations for the Management of Drug-Drug Interactions Between the COVID-19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications

Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients

Characterization of an EG.5.1 Clinical Isolate in Vitro and in Vivo

Omicron: The Pandemic Propagator and Lockdown Instigator - What Can Be Learnt From South Africa and Such Discoveries in Future

Systematic Lung Ultrasound in Omicron-Type vs. Wild-Type COVID-19

Sospensione di Utilizzo del Medicinale Lagevrio® (Molnupiravir)

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