Thursday, March 30, 2023
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Professor of Primary Care Diabetes and Vascular Medicine
University of Leicester
Leicester, United Kingdom
This activity has been peer reviewed and the reviewer has no relevant financial relationships.
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Alessia is a 45-year old female who presents to her general practitioner complaining about fatigue and 'brain fog' following a COVID-19 infection.
Clinician: Good morning, Alessia.
Patient: Good morning, doctor.
Clinician: I understand you haven’t been feeling well lately.
Patient: No. I haven’t felt right since I had COVID.
Clinician: That was about 4 months ago?
Patient: Um...yeah.
Clinician: What are your symptoms?
Patient: Well, for one thing, I’m really tired. Exhausted. All the time. And my brain...I don’t know...it’s not working right.
Clinician: What do you mean?
Patient: I’m having a lot of trouble concentrating. I can’t focus. And I’m always forgetting things. Simple things.
Clinician: Can you give me an example?
Patient: Well, the other week, I was at a faculty meeting, and I couldn’t for the life of me remember the word “curriculum.” I’ve been a teacher for 20 years. The most important word in teaching is “curriculum”!
Clinician: Any other symptoms?
Patient: I get out of breath a lot.
Clinician: When you exert yourself?
Patient: When I do anything physical. Walking around the block...climbing a flight of stairs. This is not normal for me -- before I got COVID, I was a runner.
Clinician: Any coughing?
Patient: No, not anymore. I had a bad cough when I first had COVID, but it went away.
Clinician: Any chest pain or tightness?
Patient: No.
Clinician: Heart palpitations?
Patient: No.
Clinician: What about headache or dizziness?
Patient: I get headaches sometimes.
Clinician: What about gastrointestinal symptoms, like diarrhea...nausea...vomiting?
Patient: No.
Clinician: Any loss of taste or smell?
Patient: At the beginning, yeah, but not anymore.
Clinician: How are you sleeping?
Patient: Not particularly well. And even when I do sleep, I don’t feel rested.
Clinician: Are your symptoms the same throughout the day or week? Or do they vary?
Patient: They can vary. Some days I feel like I’m improving, you know, like I’m finally getting better. Then, a day or 2 or 3 later, I can’t get off the couch. It’s incredibly frustrating. What’s wrong with me, doctor?
Kamlesh Khunti, MD, PhD: Hello, my name's Kamlesh Khunti. I am a Professor of Primary Care Diabetes and Vascular Medicine, and I've been doing some work in Long COVID and COVID as well. So Alessia presented with symptoms that weren't present before, and they started at the time of COVID, and she's had these for about 4 months. Well, it seems that this is very much what we would class as post-COVID-19 condition. There are a number of definitions. There's a WHO definition, which is that post-COVID condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months, and cannot be explained by any other alternative diagnosis. This includes many of the symptoms that Alessia has mentioned such as fatigue, shortness of breath, they also get cognitive dysfunction, and many of these symptoms are very, very new. Patients haven't had these before, they may have started during the infection itself, or could come afterwards, and then, persist after the initial illness.
The symptoms can also fluctuate and relapse over time, so they come and go as well. There's no minimum number of symptoms that are required for the diagnosis, although the symptoms involving different signs and symptoms, and clusters have been described, and there's a number of definitions for this as well. There's also a NICE definition, and the NICE call this acute COVID-19. These are signs and symptoms of COVID-19 that last for up to 4 weeks. There are also ongoing symptoms of COVID-19. These are signs and symptoms of COVID-19 from 4 weeks to 12 weeks. And then NICE has a definition of post-COVID syndrome. This is signs and symptoms that develop during or after the infection consistent with COVID-19, and continue for more than 12 weeks, and are not explained by any alternative diagnosis.
And again, similar to WHO, these are present within clusters of symptoms, often overlapping, and fluctuate, and can change over time. In addition, NICE has also definition of Long COVID. This is commonly used to describe signs and symptoms that continue to develop after acute COVID-19. It includes ongoing symptoms of COVID-19 4 to 12 weeks, and post-COVID-19 syndromes, 12 weeks or more.
If you look at the symptoms, there's a number of studies that have been done in this area. For example, the REACT-2 study showed persistence of symptoms up to 158 days, and what we see here from this study is that one or more symptoms are very common up to 150 days, around 25% or more of patients get these. But if we look at 5 or more symptoms, this is likely to be present in about 5%. All the studies have shown the symptoms prevalence seem to be more in women than men. And again, REACT-2 has given us the symptom prevalence, and they align with many of the other studies as well. The commonest symptoms being tiredness, muscle aches, difficulty sleeping, headaches, shortness of breath is very common, and tightness of chest as well, and patients may have other mental health problems, anxiety, and depression as well.
Now depending on which study you look at, the symptoms vary enormously, and the prevalence varies depending on the patients they've chosen, the age of the patients, the conditions they've had, whether they've been in the clinic, or they've been in the community. We've recently conducted a large systematic review of nearly 200 studies, and the pooled prevalence of symptoms was about 37% for patients who had at least 1 symptom at follow-up, and again, the commonest symptoms were exactly the same, tiredness, difficulty sleeping, fatigue, et cetera.
In terms of prevention of Long COVID, the US Department of Veterans Affairs National Healthcare Database announced of people with breakthrough infections compared no history of vaccination on COVID against infection. This showed that there was a lower risk of death in people who had their vaccination, and low risk of post-acute sequelae, or Long COVID, and this was reduced by about 15%. So vaccination is something that's really, really important to prevent post-COVID syndrome or Long COVID. The other conditions that are associated with this is people who are older, people who are more likely to get the COVID, for example, people with other healthcare conditions such as diabetes, COPD, and also people who hospitalize, they're also more likely to get this condition as well. Let's just go back to the clinic, and see what's happening now with our patient.
Clinician: Are you familiar with the term “Long COVID”?
Patient: Yeah, I’ve heard of it. Is it even real?
Clinician: Yes, it’s quite real. It’s characterized by continued symptoms long after the initial COVID infection has been cleared.
Patient: Is that what I have? Long COVID?
Clinician: Well, we can’t be sure until we run some tests to rule out other disorders that could be causing your symptoms, but you have the classic symptoms of Long COVID.
Patient: Hmm. Well, in a way, it helps to know that there may be something specifically wrong with me. I was beginning to think it might all be in my head.
Clinician: It sounds like your symptoms are severe enough that they are significantly impacting your life.
Patient: Yeah. It’s literally affecting everything I do.
Clinician: Are you able to work?
Patient: Yeah, but it’s been difficult. I’ve had to take a lot of days off. I keep trying to push through it, but the more I push the worse it seems to get.
Clinician: What about at home? You have young children, right?
Patient: Yeah, a boy and a girl. 6 and 7. Fortunately, my husband has a flexible work schedule and has been able to take on a lot of the parenting responsibilities. It breaks my heart, though, that I don’t have the energy to play with my kids or read to them.
Clinician: Alessia, I would like to discuss the option of referring you to a Long COVID clinic. They have the expertise and personnel to set you up with a management program designed to help alleviate your symptoms in both the short and long term. How do you feel about that?
Patient: I’m open to anything that will help get me through this. Do you think I’ll actually get better?
Clinician: Yes, I do. Most patients with Long COVID do get better over time.
Patient: It’s a relief to hear that there may be an end to this nightmare.
Clinician: The Long COVID clinic can also confirm your diagnosis.
Dr Khunti: So for Alessia, she just seemed to have Long COVID symptoms and so we need to really assess her. We need to ask about the history of the acute illness. Was it suspected? Was it confirmed? Did she have a positive test? Was it mild? Was she hospitalized? So the severity of when she had the condition. Also, the severity of the current symptoms. We need to ask about the timing and duration of symptoms since the start of acute COVID-19. History of other health conditions. As I mentioned, if they've got other chronic conditions, they're more likely to have Long COVID, and also exacerbation of any preexisting condition that they may have. So we need a really thorough assessment. We need to use a holistic person-centered approach, including comprehensive clinical history, appropriate examination as well.
In this patient scenario, what we need to do is we need to discuss the patient's experience as we've done of the symptoms and how their life and activities are affected. Alessia is affected quite hugely. She's a busy lady. She's working, she's got children, and it's obviously affecting her work and affecting her everyday life as well. We need to find out whether she has mobility issues, whether she's independent, and we need to also ask about her worry and distress. Psychological problems are so common. And we really need to listen to that patient, give them time, listen with empathy and acknowledge the impact that it's having on their daily living.
Once we've had a good history, we need to start thinking about possibly having tests and investigations, and we tailor these to the signs and symptoms the patient has to rule out acute or life-threatening complications and to see if the symptoms are likely to be caused by either COVID-19 or are they unrelated to COVID at all. We also need to discuss with the patient about possibly referring them if they've got severe ongoing symptoms or suspected post COVID-19 syndrome to relevant acute services. And this could be either acutely to certain specialties and we would assess in terms of the urgency of this depending on what symptoms they have.
So for example, if they've got hypoxemia, oxygen desaturation on exercise, they've got signs of severe lung disease, they've got cardiac chest pain, pediatric inflammatory multisystem syndrome, then really these are urgent referrals. I would refer these patients same day, maybe even phone the consultant and the hospital services to admit them, then same day as well. If another diagnosis unrelated to COVID-19 is suspected, then we have to offer investigations and in referral in line with whatever we would be doing as per the national guidelines.
In terms of what blood tests we do, it all depends on what symptoms the patient is having. As I said, if it's COVID related, there are certain symptoms; if it's non-COVID related, we may be doing additional investigations as well. But routinely, if clinical indicated, the blood test which we may include for Long COVID include a full blood count, kidney and liver function tests, C reactive protein. This has been shown to be associated with Long COVID from a number of studies. We look to see if the heart is affected, so we may do a B type natriuretic peptide, BNP, HBMC and thyroid function tests. These are the minimal tests that we would be doing.
When the patient's in front of us we may also want to do other examinations as well, depending on what symptoms they have. Now, I would normally routinely do blood pressure, particularly if patients have symptoms such as postural symptoms, dizziness, particularly on standing. Then I would do a lying, sitting, blood pressure check and a heart rate recording. This is the 3-minute active stand test for orthostatic hypertension, or 10 minutes if we suspect postural tachycardia syndrome, other forms of orthostatic intolerance as well. In patients who have respiratory symptoms particularly, we would offer a chest X-ray by about 12 weeks if we suspect COVID-19 only. And if they are continuing to have respiratory symptoms, then we really need to look for certain determinants on the chest area such as the ground glass opacities that have been shown in people with a Long COVID as well.
Clinician: Hi Alessia. Nice to see you again.
Patient: Hi doctor.
Clinician: How have you been?
Patient: Good. A lot better than the last time you saw me 3 months ago.
Clinician: That’s good to hear. How are things going at the Long COVID clinic?
Patient: Good. They’ve been giving me a lot of good advice on exercise...breathing techniques...sleep...things like that.
Clinician: It sounds like you’re making good progress.
Patient: I think so, yeah. I’m probably only back to...I don’t know...maybe two-thirds of my pre-COVID self. I still get out of breath and fatigued if I do too much. But I’m learning how to pace myself better...you know, adjust my expectations and be happy with small improvements.
Clinician: Are you getting regular exercise?
Patient: Yeah. I’ve been going on long walks. Lifting light weights. I’m still not nearly ready to start running again, but maybe one day. I hope soon.
Clinician: Are you still teaching full time?
Patient: No. I’ve been teaching 3 days a week.
Clinician: What about your mental state? Your mood?
Patient: Well, it’s better than before, but to be honest I’ve been feeling really anxious recently.
Clinician: Anxious about what?
Patient: Relapsing. Now that I’ve gotten a taste of my normal life back, I’m absolutely terrified of losing it. Every single symptom makes me think it’s coming back.
Clinician: Well, I can refer you to a mental health counselor, who can help you with anxiety. I can also prescribe you anti-anxiety medication.
Patient: Yeah, maybe that’s a good idea. Do you think I should get a booster?
Clinician: When was your last vaccine?
Patient: Um...about... almost a year and a half ago.
Clinician: You just had the 2-dose initial vaccination series, right?
Patient: Yeah.
Clinician: I would recommend getting a booster. New Covid variants have developed over the past year, and the booster will reduce the risk of reinfection with another variant.
Patient: Will a booster help with my current symptoms?
Dr Khunti: So seeing Alessia, it's great to see she's back. She was referred to post-COVID syndrome clinics and she's feeling a lot better. She started working. She started having her COVID jabs as well.
Now this is the normal case. If you look at all the studies that have been published, most people do improve over time. If you just look at symptoms, then many of the studies are showing that 40% to 50% of people may have symptoms at 12 months and 40% to 50% even having them at 2 years, but these are often mild. Most of the symptoms do improve with time, and the good news is majority of the patients do start back work. Usually within 12 to 24 months, they're back to work and that's what the studies have shown.
Also, vaccination is so, so important. As Alessia mentioned, she's had her vaccinations for COVID. Now this is really, really important. For example, systematic review of 11 studies has reported there are improvements of Long COVID symptoms after vaccination in many of the studies. We've shown that people who've had long COVID, the first vaccination dose is associated with about a 13% decrease in odds of Long COVID. A second dose is associated with about a 9% decrease in odds of long COVID, so it's really, really important that they are vaccinated and we need to really emphasize it at every consultation that we have.
So I hope you've learned from this case scenario, that post-COVID syndrome are common. They do affect the patients quite remarkably in all sorts of ways, not just their everyday life, daily living, mental health but other symptoms as well, but there are lots of things we can do with them. The key is taking a really proper history, examining the patient appropriately, doing the right tests and then, if appropriate, referring them to post-COVID syndrome clinics.
And as you saw with Alessia, most symptoms do improve and that's the important thing that we to need to reassure patients, that their symptoms will improve over time but we may need to refer them for certain therapies. Thank you very much for participating in this activity today. Please continue on to answer the questions that follow and complete the evaluation.
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