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COVID-19 in Outpatient Settings: Expert Insights on Identifying Patients Who Remain at Risk for Severe Outcomes and Complications
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Activity Information

Physicians: Maximum of 0.25 AMA PRA Category 1 Credit™

European Learners: 0.25 EBAC® CE Credit

Released: December 30, 2025

Expiration: December 29, 2026

Cristina Mussini
Cristina Mussini, MD

COVID‑19 in Outpatient Settings: Experts Insights on Identifying Patients That Remain At Risk for Severe Outcomes and Complications

 

Dr. Mussini: Yes. Good afternoon. This is COVID‑19 in Outpatient Settings, and it's Expert Insights on Identifying Patients That Remain At Risk for Severe Outcomes And Complications.

 

[00:12:17]

 

Faculty

 

I am Cristina Mussini. I'm Full Professor of Infectious Diseases at the University of Modena in Reggio Emilia, and I'm the chief of the Department of Infectious Diseases at the Modena Hospital.

 

[00:12:30]

 

Disclosures

 

These are my disclosures.

 

[00:12:35]

 

Learning Objective

 

So, the learning objective of this activity is to identify patients who continue to be at high risk for severe COVID‑19 outcomes, despite the widespread availability of vaccine. We all know that availability doesn't mean, as a recommendation, doesn't mean that the people who are at risk are really undergoing the vaccination. And this is something that we have to investigate while we see someone with some symptoms.

 

[00:13:11]

 

Timely COVID‑19 Diagnostic Testing

 

The first thing to do, if we have to do – to have an early treatment, is to diagnose. And I think that it's very clear that now what we have are very rapid testing. And if it's at home, we have a rapid antigen test for symptomatic individuals and close contacts. While at the hospital, we use PCR. For example, in my hospital, we have a combined test for flu and COVID‑19. If the antigen test is negative and the patient continues to have symptoms, we have to repeat it in three‑five days. While if it's positive, since it's very, I mean, the – the specificity is very high, it should be interpreted as definitive.

 

The problem is that you know, while at the beginning of the pandemic, we kept the patients on isolation until the – the test was negative, we all – we know now that if the antigen test continues to be positive after 10 days, it's just represent non‑infectious viral – viral particle. This is really true for immunocompetent. For immunocompromised patients, this is not really true because the problem is that when you don't have the defense, the immunological defense to protect against SARS‑CoV‑2, the risk of having a replicating virus even after 10 days it's something that is absolutely possible.

 

[00:15:12]

 

Burden of COVID‑19 Severe Disease

 

So what is the burden of COVID‑19 severe disease now, five years after the beginning of the – of the pandemic? Obviously we can have an exacerbation of underlying medical condition, if someone has – despite the fact that the new virus variants they do not replicate in the deep lung, but mostly in the upper respiratory tract making this virus now more transmissible but less severe, if you have some clinical problem, clinical issues in your respiratory tract, like if you have COPD, if you have asthma, if you have – if you underwent a lobectomy for a cancer or something like this did, you know COVID‑19 could be like the cherry on the top and there could be an exacerbation of underlying medical condition.

 

And then you have an advanced infectious process because you can have persistent viremia, long COVID, secondary bacterial infection. You can have superinfection with bacteria. And also, you know, persistent viremia is something that could be very relevant in immunocompromised because in a way, it will postpone the chemotherapy and could have an impact on the prognosis of patients affected by these diseases.

 

And then we know that with hospitalization, we have an increased risk of morbidity and even mortality, because we are talking about very fragile patients, that just because they are admitted to hospital, they could be affected by hospital‑acquired infection. So it could be really something that changes the prognosis of a patient.

 

[00:21:20]

 

Why is it important to Assess Risk of Severe COVID‑19?

 

Why it is important to assess the risk of severe COVID‑19. Obviously because it determines the hospitalization status – status. As I said, can patient be managed at home? I mean, I'm not a huge fan of telehealth, especially in someone who has symptoms, so I prefer to monitor them as inpatient for like a couple of days, and then it can be discharged. But at the beginning, I would like to admit the patient to the hospital and to provide IV treatment with remdesivir if there are drug‑drug interaction or if the symptoms dates back more than five days.

 

And when we have to think about antivirals, we have to evaluate, really, when he was vaccine – he received his last shot for the vaccine, which comorbidities has this patient. So which is the risk of this person to develop a severe disease and which is the – in – among the antivirals, the most appropriate.

 

[00:22:33]

 

Patient Case 1:

 

So let's think about a case. So this is a 78‑year‑old man that reports to his primary care physician with fever and cough. He's currently receiving chemotherapy for prostate cancer. He received one COVID‑19 vaccination five years ago.

 

[00:22:58]

 

Pretest

 

Which risk factors for severe COVID‑19 does this – does this patient have?

 

  1. Age alone;
  2. Age, cancer, and chemotherapy;
  3. Age and cancer;
  4. Chemotherapy alone.

 

[00:23:15]

 

Age Is Strongest Risk Factor for Severe COVID‑19

 

Age is really the strongest risk factor for severe COVID‑19. This was very clear from the beginning, especially from data from Italy, because we are an old country and so many, many patients with, I mean older patients were affected by the pandemic. And you see that there is a really a growth in the risk of death with the increase in age, while there is an increase with comorbidities, but not as high as with age.

 

[00:24:00]

 

Medical Conditions That Increase Risk for Severe COVID‑19

 

So there are medical conditions. As I said, the comorbidities could increase the risk of severe COVID‑19. But which one? Cancer. The – the vast majority of patients who are admitted to the hospital with COVID‑19 now have cancer. And in this case, the cancer was also in chemotherapy, so it was immune compromised. Cardiac disease, chronic kidney or liver disease, chronic lung disease, dementia, diabetes, type 1 or 2; diabetes, as obesity, were the two main comorbidities that were described even by the Chinese if you remember, also with the – with hypertension. HIV infection, but only in untreated or very advanced immunocompromise. And then mental health condition, people with disabilities. Physical inactivity, but more than physical inactivity, I would say someone who is really overweight. Pregnancy, sickle cell disease or thalassemia, smoking, solid organ or stem cell transplant, stroke, substance use disorder, and tuberculosis. So obviously, you know, if we have these diseases, we have also to take many medications. And when we have to evaluate which antiviral we have to prescribe, we have to go to the Liverpool website in order to see the drug‑drug interaction.

 

[00:26:00]

 

How do Medical Conditions Increase the Risk for Severe COVID‑19?

 

How this medical condition could increase the risk for severe COVID‑19? The reduced immunity, they are all immunocompromised. But also the chronic inflammation. Even obesity is characterized by a severe chronic inflammation. Impaired organ function. We have seen either respiratory but also kidney, also liver. Vascular dysfunction; because there is this hypercoagulability, we know that during COVID‑19, we have to prescribe also in inpatients a prophylaxis for thrombosis. And metabolic dysregulation.

 

[00:26:47]

 

Assessment of Severe COVID‑19 Risk

 

When we have to assess the severe COVID‑19, as I said, we have to evaluate the vaccine status because, you know, everybody is so stressed and so shocked by the pandemic that nobody wants to talk about COVID‑19 again. And also this, you know, there are some people who are, everywhere in the world, who are criticizing the vaccine and, you know, trying to decrease the – you know, the – how the – the efficacy of the vaccine and so the trust of the people on the vaccine, even the most in need. So age, I said, vaccine status, and comorbidities. And you see that if we consider the COVID‑19 death – death risk ratio, there is an increase on the number of comorbidities – comorbid conditions in the risk of death.

 

[00:28:02]

 

Patient Case 1

 

We know that, so on the basis of what we said until now, that the answer to the question was

 

[00:28:15]

 

Posttest

 

age; with prostate cancer, cancer; in chemotherapy, on chemotherapy; and chemotherapy, these are the three risk factors for severe COVID‑19.

 

[00:28:33]

 

Patient Case: Risk Assessment is the First Step

 

So the first thing that we have to do, we have to do the risk assessment, and is – we have to evaluate obviously, the advanced age, the lack of COVID vaccine, because five years is too much, cancer and immunosuppression with chemotherapy.

 

[00:28:52]

 

Risk of Severe COVID‑19 is Impacted Through Varying Processes

 

When we evaluate all the different comorbidities, while at the beginning of the pandemic it was the severity of the pneumonia itself that could lead to death, the patient now we have, yes, that the infectious disease process itself. So the patient who is immunosuppressed, who is unable to clear viremia and who is at higher risk for negative outcomes. But also the presence of other diseases that could lead to decompensation. So lung disease, COPD, asthma, or treatment delays with for example, chemotherapy.

 

[00:29:38]

 

Patient Case Key Points

 

So there are other – which are the patient case key points? Other impacts to patient health. So it could be, since they could not clear a replicative – replicating virus, there could be a potentially delayed chemotherapy. There could be the exposure to other infection by being hospitalized for COVID. Could be bacteria, other infection, or it could be health‑associated infection. Then decompensation of underlying disease or more severe infectious disease process itself.

 

[00:30:22]

 

Change in COVID‑19 Variants Limits the Use of Certified Therapies

 

Now, there has been, you know, in the last year, here are the data from the Italian Ministry of Health from the observatory of the variants. And you see in a few months from five – from May to October a change in the variants. They are all – they all belong to the Omicron lineage. But what we have to say is what happens is – what we have seen since the beginning of the pandemic, that there is a complete substitution of the new variants compared to the old one. So XFG started in May and then there was an increase in June, July, August, September. And in October, it has almost all – it's only – the only – it has become the only variant that is circulating. These are variants, as I said, that belong to the Omicron and so they are very infectious because they replicate in the upper respiratory tract. So they circulate a lot and this is a risk factor for the immune compromise. But on the other hand, they don't determine a severe picture of pneumonia, as for example, alpha, delta.

 

[00:31:51]

 

Key Points

 

So key points of this activity. Patient risk factors impact the risk of severe COVID‑19. Advanced age increases risk and is the most significant risk factor, but they need other risk factors in order to determine true risk. So COVID‑19 disease associated with other non‑infection‑related sequelae, because we know that we have to postpone, for example, chemotherapy. And also, management of COVID‑19 is early diagnosis and prevention through vaccination.

 

And on the basis of this, I thank you for your attention.

 

[END OF TRANSCRIPT]