Brazil advances in its research on Covid-19 in patients with autoimmune diseases

By :
    Claudia Marques
    Reumatóloga y profesora en el Hospital das Clínicas, Universidade Federal de Pernambuco, Recife, Brasil

    Estefanía Fajardo
    Periodista científica de Global Rheumatology by PANLAR.

22 June, 2021
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Dr. Cláudia Marques addresses some doubts regarding the development of the virus in patients with rheumatic diseases and talks about the studies being carried out in Brazil. 

In a dialogue with Dr. Cláudia Marques, rheumatologist and professor at the Hospital das Clínicas, Universidade Federal de Pernambuco, Recife, Brazil, different questions and research on Covid-19 and autoimmune diseases are addressed, taking as a starting point that despite the large amount of information produced in the last year on SARS-CoV-2, there are still some doubts, mainly related to the frequency of Covid-19 in patients with rheumatic diseases.

 At the beginning of the pandemic the great fear was that these patients would develop more severe forms of the disease and that, to date, is not very well established, taking into account that studies have different results in this regard.

In this new video blog we address the different concerns about the virus, its vaccination and the tests that are currently being developed in Brazil to provide an answer. 

Interview with Dr. Cláudia Marques

Estefania: Hello everyone. Welcome to a new video blog on PANLAR's Global Rheumatology. Today we meet Dr. Cláudia Marques, she is a rheumatologist, PhD, associate professor and works at Hospital das Clínicas - Universidade Federal de Pernambuco. Doctor, how are you?

CM: Hello, Estefanía. 

It's my pleasure to accept this invitation to briefly speak about this interesting topic. It's an honor to represent the Brazilian Society of Rheumatology. 

E: Let's start with what unanswered questions exist between Covid-19 and patients with rheumatic diseases, now that we are a little more than a year after the pandemic?

CM: So, there are many questions! Some have been probably clarified, but despite the vast amount of information that came in the last year, some questions remain. Specially related to the frequency of COVID in patients with rheumatic diseases.

Patients with rheumatic diseases present more COVID-19 than those without that condition. The other question is about the severity in those patients. For that reason, at the beginning of the pandemic, our fear was that those patients were going to develop more severe forms and that is still not very well established. The studies have different results in relation to this. 

The third topic is related to medication. The drugs used to treat rheumatic disease and not those to treat the COVID —that's not even the subject of our conversation here. 

Something that seems to be well established is the use of corticosteroids, and we'll talk about them a little later.

Concerning other medication, results are also something different in multiple studies. It's still early to extract conclusions about these topics.

At first, the frequency of COVID in patients with rheumatic diseases and the general population was apparently the same, but there have been studies that showed that it could be higher with rheumatic patients. 

E: What clinical questions have emerged from a rheumatologic standpoint after all this?

CM: I think that the big questions still present, relative to the rheumatological part, it's related to the disease activity, to the multiple diseases, and the interaction with the COVID. In these two aspects:

The first, if the disease is active in the patient, if it represents a stronger case of COVID-19. The other problem is after COVID. In this form, those patients with COVID release the activity of the disease in the stage where they should be recovering from COVID-19. Especially because, and perhaps you have seen this, there is a post-COVID syndrome, characterized by a series of articular, cutaneous and neurological changes. This as a result of the cytokines storm during the infection. For that reason, this question about the release of activity after the COVID is not answered either. This may be the greatest rheumatological question related to COVID, then the activity of the disease and the interaction with the infection.

E: What should a patient be aware of if he/she is positive for SARS-CoV-2?

CM: Rheumatic disease patients, who have been proved to be infected with the Sars-CoV-2, should be seen in a special way.

To keep the patient's wellbeing, and in this way, they remain in control of their disease, the recommendation is to interrupt the immunosuppressive treatment to avoid any possible development of a more serious form of the disease. Although this hasn't been completely established. 

Nevertheless, with this patient that is in an active rheumatic disease and has COVID, we must keep in mind a series of factors, because it can be that we are stopping the treatment for a rheumatic disease, making the patient more susceptible to a serious infection, since the activity of the disease is also inflammatory, combining both answers. It's because of these, that it must be evaluated individually.

But in general, with the patient under control it is possible to interrupt the treatment for 14 days approximately. This is what is indicated in most recommendations. And we could re-introduce the treatment after the 14 days or even after 10 days after the confirmation test and with a 72-hour absence of the fever. In this patient that evolved well, with a calm COVID-19, it's possible to reintroduce the treatment, but again, this must be studied individually. 

E: What would be the main aspects to consider for the triggering of a severe disease that could lead to an ICU?

CM: The studies have shown the same in relation to the consequences of the disease. So, what is well established? The age. Older patients have a higher risk; the presence of comorbidities such as hypertension, diabetes, cardiac and cardiovascular diseases. The use of corticoids; that's also present in different studies. Every study published so far on the several diseases in which corticoids are used, linked the chronic use of a dose over 20 mg of Prednisone, or its equivalent, per day, as a factor.

However, there are other factors. For example: the use of cyclophosphamide pulse therapy, or methylprednisolone corticosteroids, had a higher risk of dying or being hospitalized in intensive care.

These data were not copied in other published studies with a similar design, and it is still too early, with the initial data from our cohort, to state that. Even because it was a cross-sectional cohort that we did during that follow-up period. Still, many colleagues have seen that in clinical practice, that more immunosuppressed patients have worse outcomes.

It hasn't been the case with the use of biological drugs, mainly with anti-TNF, which has been also a repeated result, that seems to have a protective effect; therefore, those who use an anti-TNF have a lower risk of going to an ICU, or even general hospitalization. This protection only existed related to dying results. But for mechanical ventilation, ICU, and hospitalization, it also provided a possible protective effect. This has occurred repeatedly in the studies.

The other kinds of biologicals do not show, neither the protective effect nor the deleterious effect. It is a neutral effect, let's say, when we did the analysis. But if we were to list today the main factors would be these: age, presence of comorbidities and the use of corticosteroids.

E: Precisely with corticosteroids, what should patients using corticosteroids be aware of?

CM: The patient who is well, recovering, we must individualize them. This patient who is well, who is out of disease activity, ideally, should try to reduce his corticosteroid dose; if possible, withdraw it, even before he has the infection, because this will probably make a difference, if he develops COVID.

In fact, this is a recommendation that is always given to those patients with rheumatic diseases: try to keep the corticoid in the lowest possible level. 

If a patient develops COVID-19, and if possible, reduce the corticosteroid dose and do not remove it suddenly, because that is not recommended. So, just try to reduce the dose little by little; although what makes the difference is not the use of corticosteroids during the infection, but its prolonged use.

If I had to make a recommendation now, I would tell the doctors that follow-up, to try to reduce the corticosteroid dose, if possible.

If that is not possible, then they will have to manage a patient who will get infected, who will present COVID, even using corticosteroids and trying to control the other factors. But the recommendation is to try to keep the dose as low as possible.

E: How should immunosuppressants and other treatments given to these patients be managed?

CM: Well, the reasoning is similar to the corticosteroids, and because of this the recommendation is that if the patient has COVID, uses an immunosuppressant and is fine with the disease, again, in an individual manner, it should be analyzed if they can, or not, be without the treatment. So, it's fine that, outside the activity of the disease, suspend the immunosuppressant during that period. 

However, some patients need the immunosuppressant at that time, so there is no way for us to eliminate it. And they will have to use other measures to treat COVID, if the patient's case is very severe. For example, we may recommend the use of intravenous immunoglobulin so that it can resolve the disease activity, even control the COVID, and try to get the patient off of it.

Sometimes, when the immunosuppressant is removed, the activity of the disease surges, and this can be an aggravating factor of COVID-19. We have a saying in Portuguese, something like “if you run, the animal catches you; if you stay, it eats you”. We have to analyze each case, and we have to know where I should go, where I can withdraw, and how I can handle this patient.

E: How do we get more information in this population, considering that now we not only have to analyze the effect of the virus on the organism, but also the vaccination?

CM: Most of the information will come with these long-term follow-up studies. So far, the studies are still cross-sectional. There are still few studies showing follow-up results of these patients.

At the beginning of the pandemic, there were reports of cases and, in time, this improved the designs of the studies, turning them more robust. Nevertheless, more information came with this follow-up.

In the topic of vaccines, evidently similar studies have to be designed. Here in Brazil, the study that will go along with the vaccination in patients with rheumatic diseases is in the process of ethical approval. That's also the case with a study that is being sponsored by the Brazilian Society of Rheumatology. Therefore, we'll have these answers in a while. 

In our cohort, currently we have nearly 2000 patients, included in both cases and control. The controls are those patients with no COVID. And the idea is to control these patients, at least for six months; but since the epidemic has been for a long time, we will probably extend our follow-up period. Some results that we didn't expect are showing up, like the reinfection, for example, something we didn't predict. We thought that, after having it, the patient couldn't have it anymore. So, in some cases of reinfection, in a live study they are modifying it as the epidemic advances. 

So, in response to the question about better data, the most solid information will come from this long-term follow-up studies. 

E: To date, what can we tell patients who ask about COVID-19 and vaccines?

CM: I think the most important aspect is the patient’s questions, in regard to COVID, related to risk, and I think it's important to state that the risk seems to be similar to the general population. The risk of COVID in general. Nevertheless, the result may be more severe in those patients that use immunosuppressants. 

Another subject are the protection measures. This is a very important argument: the social distance, the use of facemasks, washing hands, and the use of alcohol. This shouldn't end, even with the patients already vaccinated.

Then, even more important than the information about the drug, or the severity of the disease, it's important that you insist your patient that these protective measures are much more effective. 

One of the results of our study showed that, when comparing those who had COVID with those who didn't, the patients with the disease didn't comply with the social distancing in more than 60% of the cases. While among those without COVID, that number was much lower. We even had a statistical difference in our analysis. It demonstrated that the person probably contracted COVID because they were exposed, and not because they had a rheumatic disease, so I think this is very important.

About the vaccine, and this is important, people usually ask: Should I get the COVID vaccine? And the recommendation is yes, they should. Depending on the degree of the immunosuppression, perhaps the turn for vaccination, the production of antibodies is not so efficient, and for that reason higher doses of corticosteroids, some immunosuppressant, the use of some biologicals, Rituximab for example, can reduce the response to the vaccine; but there is no contradiction. The recommendation is to vaccinate everyone, and with that the benefit will be higher. 

E: How has the Brazil cohort been progressing in their research and what initial data can you share with us?

CM: As I told you, currently we have nearly 2000 patients included there are 1000 cases of COVID-19, 1090 cases of COVID-19 in patients with rheumatic disease, and about 800 without COVID-19.

We have two articles published. The first one was the protocol, and the second was the one I told you about the analysis of the first eight weeks.

We are currently preparing a working group. Several articles to be published mainly related to patients with rheumatoid arthritis, Spondyloarthritis and lupus.

It's interesting how similar the results are. We couldn't demonstrate, for example, that the patients with lupus were more serious than those with Spondyloarthritis, or rheumatic arthritis, at least in the initial analysis. Keeping in mind that this is a cross-sectional analysis, still is not a long-term follow-up of the patient. 

We did a cutoff at this point, until January, we did the survey, and we are in the analysis phase, but what I can tell you is what we already talked about, what has already been published; that corticosteroids were highly associated with the most severe outcomes; the anti-TNF that had this protective effect and this issue of social detachment that was also important, showing that the risk of COVID increased.

Another interesting fact, and probably the most informative one, is that there wasn't any effect of the hydroxychloroquine in patients that were taking chronic medication, even in another study that makes no part of the cohort, but it's a study that we made here. That study evaluated the effect of the chronic use of the hydroxychloroquine in patients with a rheumatic disease, comparing it with the home contact that was not using the hydroxychloroquine anymore, and we saw that the infection rate was similar for both groups.

So, we couldn't demonstrate this protective effect either. And one interesting thing that it's being talked about is that the patient may feel protected, but they could be even more exposed in relation to the COVID with this use of the hydroxychloroquine, similar to what happened to other medications to treat the COVID.

So, this is what I can tell you. Soon we will have more results when we finish with this analysis. But it's interesting that there was no difference in the severity of these three diseases.

We also analyzed the percentage of deaths and it was also the same in lupus, rheumatoid arthritis and Spondyloarthritis.

E: How do you perceive the pandemic in your country, in addition to the variants, do you think it may affect rheumatic patients?

CM: It's difficult here, right? I think that all of you have been following the news related to Brazil, and the way that the crisis is being handled for our people in the government, and that in fact it not only affects people with rheumatic diseases, but it affects the whole Brazil, all of us.

The number of deaths is increasing and today we account for one third of deaths worldwide. So of course, patients with rheumatic disease and other comorbidities are likely to suffer more. It's not that the frequency of infections is increasing, but if they are spread, they can have more serious consequences.

So, I think this is the big impact. And, sincerely, we don't have a perspective of improvement in the coming months. The containment measures are not effective, and they're different in the different scenarios.

We have a very poor population, with a long social disparity, and it's not possible to make this effective to everyone. 

Then, a real continental country, with continental dimensions, with several different social scenarios, that truly affects, and honestly, I can't see when this is going to end. I thought that this year it was going to end, but probably we spent the next year here, still in this situation. 

E: What can we tell physicians and patients about this issue in order to have a very clear and comprehensive approach?

CM: I think that for physicians and patients the most important thing is the recommendation to keep social distance, maintain protective measures, wear a mask, wash hands, or use alcohol. This is certainly effective in these measures to combat COVID-19. So, I think this is the message that should remain.

The other serious problem of using medication or not, is that, if it avoids the contagion, it won’t reach the need to deal with these other problems.

I think the most important issue is even if the patient is vaccinated, they need to keep the social distance and these protection measures. 

There are reports of COVID cases after the vaccine. We still don't know exactly how these vaccines work in these kinds of patients.

I think that this is the message that I would like to leave here: Wash your hands, keep your social distance, and use the mask. That's the most important.

E: Doctor, thank you very much for your participation and for sharing this very important topic with us.

CM: Estefanía, thank you! 

I appreciate the invitation from PANLAR. I feel very honored to be participating. I hope I made myself understood. 

Thank you, very much! It was a huge pleasure, and I remain at your disposition.

Here is my contact. You can make it available to everyone if necessary, alright?

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