June 18, 2021

“Not all patients can be diagnosed with antigen tests, the sensitivity in asymptomatic patients is lower”


Your seroprevalence study estimated that 5.2% of Spaniards had passed the disease at the beginning of May, although it showed great differences between regions. Do we have any idea how much that percentage has changed since then?

We won’t have a solid estimate until the next round, the testing of which will begin on November 16. Until then we only know that the number of confirmed cases has increased, the rest are speculations. It must be taken into account that the difference between estimated and confirmed cases was very high then. The study showed that about 2.3 million people were infected, but we only detected 10% of that number, about 230,000. That is why the fatality [observada] it wasn’t real.

In this second wave the diagnosis has greatly increased. Not only moderate and severe cases are identified, also mild and even asymptomatic. Are we detecting 100%? Surely not, the Ministry of Health estimates between 40 and 60%. The fourth round of the seroprevalence study will tell us what percentage is leaking now.

Do these studies underestimate the percentage of the immunized population, by not taking into account other factors such as cellular immunity?

Not recognizing the role of cellular immunity is a mistake, but it must be put in the right measure. This, including possible cross-reactivity with other viruses, can modulate the severity of the disease, but may not prevent infection.

Furthermore, it is not possible to have a reliable measure of cellular immunity at the population level. We measure circulating antibodies, which give us an estimate of the true magnitude of the epidemic. It is possible that there are other factors that make the degree of immunity among Spaniards slightly higher or lower, but we believe that [nuestro estudio de seroprevalencia] gives an image very close to reality.

In areas such as Madrid, seroprevalence in May exceeded 10%. Is it possible that group immunity has been achieved somewhere since then?

When they asked me in summer, I explained that it was a mistake to think about it and even to try to do it, because the cost in human lives was unaffordable. Now we have before us the answer: if there had been group immunity we would not have a second epidemic wave like the one we observe.

Yes, the opposite effect may have occurred. This would explain the rapid increase in transmission in recent weeks in some provinces with a level [previo] of lower exposure and very low seroprevalences, where there was a higher percentage of vulnerable population.

Molecular epidemiology rebuilds the history of the coronavirus and the pandemic, but runs the risk to blame. How to manage this type of investigation?

Biomedical findings are very important, especially during a pandemic. At ISCIII we have worked a lot on responsible research and innovation. Here, scientific integrity is not only that the data follow ethical commitments, but that in its dissemination truthful messages are transmitted that the population can understand. These are data that have consequences from the point of view of epidemiological surveillance and public health. So until we publish this week in a magazine an article describing the first epidemic wave we have not made a press release to explain it.

Are we confusing citizens because of the rush? I remember cases such as the pre-publication that detected SARS-CoV-2 in the waters of Barcelona in March 2019.

Totally agree, we lose credibility and get confused. It is done with good will, but they are hypotheses that when they are transferred to the population they become erroneous and dangerous simplifications. I am sure that many citizens still believe that there was coronavirus in Barcelona in March 2019, because it is very shocking news. I would not like to focus on one article, because unfortunately we see it with many. It also happened with hydroxychloroquine. There is a double reflection [que hacer], by researchers and the press.

Have we forgotten that public health information, in addition to obtaining it, must be managed well?

Effectively. [Al principio] it could be understood because quick answers were needed and there was confusion, but now it is no longer acceptable. We should have learned and take advantage of what happened these months to identify and limit the practices that harm us. The communication offices of public organizations play a key role there.

A recent example is a prepublication that suggests that the coronavirus variant that dominates Europe today emerged among foreign seasonal workers working in Aragon and Catalonia. What do you think of the national and international coverage you have received?

Is a preprint You have to go through the enrichment of the assessment. Not just by peers: in open science you expose yourself to criticism from the academic community as a whole. In this case, there has not been time for other researchers to say if the samples are representative of the country or if extrapolations are made, if there are samples from all the Autonomous Communities or are missing, if all the European countries or mainly the United Kingdom, Switzerland have been analyzed and Spain … The hypotheses that are put forward are very good as hypotheses, but let’s be cautious and first see what it means. It is also not known whether the variant has an impact on the clinical course of the disease and its transmissibility.

A May article advised against “Overinterpreting genomic data during the pandemic”. When explaining the current situation, do we give too much importance to the virus itself and its mutations, when the key is found at the social and political level?

Totally agree. It is something that is part of the simplistic messages. Citizens are used to the idea of ​​a virus that mutates, becomes very bad, circulates more and that is why we are worse off. It even gives us some peace of mind. It is much more difficult to convey complex messages with the factors that affect the transmission and development of the disease. It has more to do with the social and health structure, personal characteristics, the patient’s comorbidity, the management of the care process, the situation of the residences …

The coronavirus was already adapted to humans from the first moment and no mutations are necessary to improve that.

I have no doubt that the role that the mutability of this virus has played has been minor in the consequences of the pandemic. It is a young virus and the degree of mutation that it has had so far has not been very important. The difference between variant and strain is so difficult to explain that even doctors do not understand this terminology and, in any case, it is of minor importance regarding the course of the disease.

The National Center for Microbiology has coordinated studies to validate the reliability of antigen tests. What do you think of these tests that are gaining so much relevance?

Reliability is high, but most people who have been tested under real conditions have symptoms. In patients with symptoms, and within the first five days, the reliability is very high both in sensitivity and specificity, which is around 100%. They are an advantage that allows an active infection to be diagnosed outside hospitals quickly and without complex equipment, provided it is used in the right conditions.

What are those “right conditions” that we must take into account?

Antigenic tests can have associated problems, because not everything can be diagnosed with them and they have limitations. We know that the sensitivity in asymptomatic patients and between contacts is lower. This is possibly linked to several factors such as viral load, which decreases detection capacity if it is low. Also to the difficulty of identifying that five-day period in which they work very well.

Do you think it is a good idea that they are accessible to the point of being sold in pharmacies?

The pharmacy thing is very complex. First, the required removal of the nasopharyngeal swab is neither straightforward nor immediate. Second, there has to be coordination and clinical diagnosis. [El test] It must be indicated in close coordination with the health and public health services, and [dejando claro] who is responsible for a positive and instructions to patients. Also evaluate and other issues such as the impact of false positives and negatives.

It should be thoroughly analyzed before making the quick decision to use them outside of the healthcare settings for which they are designed. It goes beyond what can be done: they have to integrate into the health system and think about the repercussions it will have on it.

Will there be flu this year and, above all, will we be able to detect it?

The possibility [de que coincidan ambos virus en la población] It’s on the table. Some researchers indicate that measures against covid-19 may reduce other respiratory diseases, but it remains to be seen if this is true. We must be prepared. That is why a reinforced flu vaccination campaign is being carried out, because you always have to put yourself in the worst case scenario.

When identifying the [temporada de] flu there is a risk that I want to point out. Until now we had an epidemiological surveillance network for influenza that was working remarkably well. In March, with the dismantling of primary care and the relocation of resources, this sentinel network also suffered a major disruption. At this time, work is being done to start it up again, that it works as before and also serves to monitor covid-19.

As a cardiologist, what do you think of the studies that suggest that the coronavirus can damage the heart?

I think there is enough data to say there is something. The robustness of the data and the number of patients is small, but what has been published points to a tropism of the virus in cardiac tissue. When systemic inflammation occurs, something that does not happen in all covid-19 infections, the heart can be involved like any other tissue. We still do not know what effect it may have in the medium and long term, but in some patients there is a cardiac involvement that must be studied.

The question you are tired of hearing: what is going to happen in the weeks and months to come?

I’m bad at making predictions, I avoid it. We must learn from the past months when some wrong predictions were based on hypotheses rather than data. To make predictions we need data: right now they show a very rapid increase in transmission, but in some parts like Madrid they tell us that we are getting better.

You always have to prepare for the worst case scenario, but do not close your eyes to the possibility that the measures may work and, in some cases, we are seeing that they do. Always with the exception of whether the data show us reality and be prudent with it. You have to see them not day by day, but weekly or every fourteen days, taking into account all the notification exceptions that we know.

If we look at the impact of the flu in previous years, and the very rapid increase that we see in many Autonomous Communities and European countries, the situation is very worrying. On the other hand, if data like those of Madrid are showing us the reality, it would be much more optimistic. There is a huge fork in which all the options are still open.

The Conversation

East Article was originally published in The Conversation. You can read it here.

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