publication date: Apr. 9, 2020

Conversation with The Cancer Letter

COVID-19 lesson from Spain: Like the U.S., we failed to take this seriously before it came to us—we have to learn

Josep Tabernero 1

Josep Tabernero, MD, PhD

Director, Vall d’Hebron Institute of Oncology;
Head, Medical Oncology Department, Vall d’Hebron University Hospital;
Director of clinical research, VHIO;
Co-director, Research Unit for Molecular Therapy of Cancer—“la Caixa”;
Head, Gastrointestinal and Endocrine Tumors Group

 

This story is part of The Cancer Letter’s ongoing coverage of COVID-19’s impact on oncology. A full directory of our coverage is available here.

 

While the world watched the pandemic unfold in China and Italy, SARS-Cov-2 spread exponentially in Spain, killing more people faster and earlier within a month, relative to many outbreaks in other Western countries. 

Spain quickly surpassed Italy in the number of confirmed cases, even though the coronavirus began spreading rapidly in Italy a week or two earlier than in Spain. Both countries reached the “peak” almost simultaneously, as the epidemiological curves of total detected infections reach a plateau following nationwide lockdown and containment measures.

By April 10, over 157,000 cases had been confirmed in Spain, with nearly 16,000 deaths. Italy has logged nearly 144,000 detected cases, with over 18,000 deaths.

On April 10, with over 470,000 confirmed cases at this writing, the death toll in the United States, at nearly 18,000, has exceeded that of Spain—a number that is expected to continue rising.

“One of the things that we have failed, globally—and probably the United States as well—is to take this problem seriously before it came to our environment,” said Josep Tabernero, director of the Vall d’Hebron Institute of Oncology (VHIO), head of the Medical Oncology Department of Vall d’Hebron University Hospital, and director of clinical research at VHIO.

“It’s important to learn about and from others,” Tabernero said to The Cancer Letter. “If you look at how the authorities dealt with it in South Korea, actually, they didn’t confine the whole population—except for those that were positive—but they had available SARS-CoV-2 tests for the global population. 

“This was not the case in Spain. At the end, the Spanish authorities decided to shut down, to lock down the country with most of the citizens confined.”

 

Confirmed COVID-19 cases, as of April 8, 2020

 

COVID-19 deaths, as of April 8, 2020Source: 1Point3Acres, April 8, 2020

 

The Vall d’Hebron University Hospital, located at the far northwestern edge of Barcelona, is the largest hospital complex in Catalonia, which, with a population of over 7.5 million, is the second most populous autonomous community in Spain.

“Right now, we have a total of 176 patients hospitalized in the intensive care unit; around 675 patients in total, not only those in the intensive care unit, but also in the conventional wards,” “We used to have, before the COVID-19 outbreak, 130 beds in the intensive care units, and this figure has been expanded through different facilities and resources up to 320—just in case more cases were coming and they needed intensive care unit support.”

The VHIO has established separate clinics and care teams for patients with cancer to lower their risk of being exposed to the coronavirus.

“I think that it’s important in cancer care to establish independent paths for our patients, just to prevent them from getting infected,” Tabernero said. “Obviously, this is not something that we did early on, from the beginning, but learning about what our colleagues did in Italy and China was really very helpful.”

Following discussions with cancer experts with experience in Wuhan, China, VHIO has also postponed surgical procedures for patients who were scheduled for elective surgery, while including neoadjuvant therapy for some patients.

“Especially for cancer care, one of the things that was raised as a risk for infection and for patients with cancer, and also for severe evolution of the disease, was, for example, to have elective surgery for patients with cancer,” Tabernero said. “We have implemented in some diseases more new neoadjuvant treatments than we used to have.

“This is something that health authorities may consider in promoting policies like this.”

As drastic containment measures were being implemented in Spain, government health officials moved quickly to expedite research and clinical trials on COVID-19.

“Our oncologists, especially medical oncologists, are used to do clinical trials for many new therapeutic options,” Tabernero said. “So, we are used to rapidly designing and activating clinical trials.

“Here in Spain, actually, now that our regulatory process has been sped up for clinical trials related to COVID-19, I can tell you the approval time—the time between the clinical trial protocol is submitted and the enrollment of the first patient—can be assured in three working days. You wouldn’t have ever imagined a situation like this.”

Tabernero said Spain’s universal health care infrastructure ensures that all hospitals and community clinics can interface with each other, including through an established national telehealth program.

“Fortunately, on our side, the network was very well established before the pandemic, but this is not usually the case in all the countries,” Tabernero said. “So, each region [in Spain] is trying to do its best to organize this thing in the best manner.

“This is one of the advantages. We don’t have one single public health system, but the systems are very similar, and they are all connected. They can interface with all the electronic medical records. So, it’s easy to work with the primary physicians, and also with small community hospitals.”

With national coverage, the central and regional governments in Spain have been able to reliably track patients.

“We can follow up our patients, we can track them, if they are temporarily visited in other community hospitals or outpatient clinics by GPs,” Tabernero said. “The bottom-line message here is that there is good coverage for the whole population. Public health leaders and public health policymakers should think about how emergencies and diseases like these should be tackled in the future. We have to learn. There is no doubt about this.

“The take-home message is that we have to work more in promoting better health care systems and adequate public health policies, because in the end—especially your country, but also other countries—we’re all investing a huge proportion of the GDP in health care. 

“And then, you realize that it does not work as you would like. We need to work a little bit harder in making health systems more efficient.”

Tabernero spoke with Matthew Ong, associate editor of The Cancer Letter. 

 

Matthew Ong:

How are you doing, and what’s the situation like in Barcelona at the moment?

Josep Tabernero:

Well, actually, the situation is improving a little bit. We have probably reached the top of the peak in a way that the number of patients—that we diagnose and that come to our institution, in the emergency area and are hospitalized—it’s reducing over the last five days.

The number of patients in the intensive care unit has been stable in the last seven days. We have a total of 176 patients in the intensive care units. Actually, one thing that I have to say is that the units were increased in number. So, Vall d’Hebron University Hospital, it’s a general hospital.

We used to have, before the COVID-19 outbreak, 130 beds in the intensive care units, and this figure has been expanded through different facilities and resources up to 320—just in case more cases were coming and they needed intensive care unit support. Right now, we have a total of 176 patients hospitalized in the intensive care unit; around 675 patients in total, not only those in the intensive care unit, but also in the conventional wards.

 

MO:

And this is in your hospital alone?

JT:

Yes, this is in our hospital alone. We have a total of 1,200 beds in the hospital with a comprehensive cancer area, but the hospital is a general hospital, and now a huge number of conventional and intensive care unit beds are dedicated to COVID-19 affected patients.

 

MO:

Is the observed flattening of the curve consistent with the models as well?

JT:

I think that it is consistent with the model. In Barcelona, we have been confined at home for more than three weeks. In the rest of Spain, it’s been two weeks since the central government ordered people to be confined at home. But in the Catalonia region, actually, it’s three weeks, so we are starting to see the results of that decision.

Right now, the question is how we are going to be starting to allow people from the lockdown to start doing activities, and this has to be gradually, of course. The question is how you’re going to be selecting the population, whether it’s going to be done by age, of course, but also whether we will have good technologies to test by PCR, which percentage of the population has been infected symptomatically or asymptomatically, and also to know whether they have developed a good immune response by IgM levels and IgG levels. 

So, there’s discussion on that, because now, in two weeks, the lockdown will be stopped—I assume this is going to be the case—but gradually. It will not be the whole population, at once, but the numbers that you were referring to are consistent with the models.

The only problem is that, looking at several web pages, including, for example, the web page from John Hopkins, the Coronavirus Resource Center, actually, from the data continuously updated, it’s difficult to understand the way that different countries count the patients affected by the disease, recovered, or deceased. If you look at the numbers, it’s very clear that, right now, Spain is the second country, just after the United States, in the total number of patients that have been confirmed, something around 157,000.

But then, when you look at the number of deaths, actually, Italy, because they started a little bit earlier, they have more deaths. We are at the level of 16,000. But also, interestingly, in our country we have more patients that have recovered from the disease. The total number of patients recovered from the disease is around 55,000.

So, sometimes it’s difficult to understand the numbers, as infected patients have been counted in different ways. But if you look at the evolution over the last few days, I think that we start to see the light of having achieved the plateau; so, the number of patients that come to the emergency area has been reduced in the last five to seven days.

 

MO:

So, as Spain is thinking about reopening the economy, what are some strategies that are being considered? How does one warm up to regular business while preventing new spikes in infections, and a resurgence of the pandemic?

JT:

Yes, this is the discussion that we are having right now. Basically, different opening models are being evaluated. None has been taken as the right one, but, as mentioned, there are lots of discussions about whether we’d be able to screen the population, especially the young population, for those markers that I mentioned. 

One message is that it seems that the oldest population will still be confined for more time, because this is the population that, in principle, is at greater risk for developing severe complications.

 

MO:

So, at least in the U.S., it seems our lay news cycle has been focused on China, Italy, and then, of course, the exponential increase in cases here. And before we knew it, Spain appeared to suddenly climb up the charts in total cases and deaths. What happened?

JT:

I think that what happened is that the pandemic evolved very rapidly. When we look at the epidemiology of the disease, it seems that the first cases actually came from Germany and later on from Italy, of people that had been in contact with the Chinese population. 

But then, it expanded very rapidly. It seems that it’s important to enact measures as soon as possible. Different countries have evaluated these kinds of measures.

For example, if you look at how the authorities dealt with it in South Korea, actually, they didn’t confine the whole population—except for those that were positive—but they had available SARS-CoV-2 tests for the global population. 

This was not the case in Spain. At the end, the Spanish authorities decided to shut down, to lock down the country with most of the citizens confined, except those that were indispensable, like, obviously, all the health workers, but also all the food distribution workers, among others.

I don’t know whether it depends also on the behavior of the population, but at least what the authorities did three weeks ago now, it shows that we are starting seeing the result for that. Probably we should have confined the population earlier. But now, it’s easy to look back and say that.

 

MO:

What are your data on fatality rates telling you? What are the overall case fatality rates for Spain? Also, what proportion of these deaths are patients with cancer?

JT:

The fatality, actually, if you look at the numbers, it’s around 10%. It depends a little bit on the regions, but I don’t think that these numbers are correct—the denominator is wrong, because we have not diagnosed all patients that have been infected.

We only diagnose those that actually come to the hospitals or to the primary care physicians, but there are some patients with middle symptoms that have not gone to see a doctor, either in the hospital or in the primary care service. So, I don’t think that the denominator is real.

 

MO:

We can probably assume the same, over here.

JT:

Yes, probably it’s the same there. Actually, if you look at South Korea, it’s the opposite. I think that the denominator in South Korea is really good. But then, if you go to different regions, the fatality rate is a little bit different. But again, I don’t think that these numbers are correct. It’s very difficult to prove the numbers, right?

 

MO:

I’d think so. In Italy, a sample of over 900 patients that are well characterized show that 16.5% of the deceased are patients with cancer.

JT:

They have more mature data, because they started doing this one week and a half or two weeks before. Our perception, at least in the distribution of patients from our hospital, seems to be very similar.

Nevertheless, in our institution, as in other cancer institutions, we have different paths for the patients. Those patients that are visited for examinations in first visits, sequential visits, in our institution follow a different path.

We have adopted important measures, just to prevent the dissemination of the disease. And so, for example, as mentioned, we were clinically screening those patients when they came to the facilities—before they enter the offices of the physicians and the nurses.

They were asked for all the symptoms, and also, their temperature was evaluated. If cancer patients did not wear a mask, we offered masks to them. I think that this would help to separate those patients that had symptoms and then had a better diagnosis for them, preventing the others from being infected.

I think that it’s important in cancer care to establish independent paths for our patients just to prevent them from getting infected. Obviously, this is not something that we did early on, from the beginning, but learning about what our colleagues did in Italy and China was really very helpful.

 

MO:

So, keeping clinics and facilities for cancer patients separate from regular patients is best practice?

JT:

Yes. And also, when we see patients that come to the emergency area, cancer patients, they are immediately separated—whether they have respiratory symptoms or symptoms that are similar to COVID-19 disease—from the others that do not have related symptoms. And the teams are different. This is another important thing, just to divide the professional teams as soon as possible.

The process here is to establish preventive measures, especially for the population of patients with cancer. As you know, a huge population of cancer patients have immuno-depression because of the disease, because of the treatments that they receive, so, this is a population at risk. So, it’s one of the populations that we should take care of more precisely, with separated paths to evaluate them.

Also, what we have done, as many other centers, of course, is to increase our telemedicine practice, so with more virtual visits, especially for the controls or workups for patients that were in follow-up. We try to do this as much as possible.

We’re also in collaboration with primary care physicians, and also small hospitals from the community. So, we try to prevent as much as possible that those patients that do not necessarily need to come to the hospital actually don’t come to the hospital. 

Of course, this needs good infrastructure and also to establish a good network. Fortunately, on our side, the network was very well established before the pandemic, but this is not usually the case in all the countries.

So, each region is trying to do its best to organize this thing in the best manner—because one of the messages that we are raising is that other peaks may come, and, unfortunately, the COVID-19 outbreak does not seem to be one single peak.

So, we have to be prepared for multiple peaks, or, at least, moderate outbreaks. We don’t know whether they are going to be peaks or not. If there are not going to be peaks, the disease is still going to be there, so we have to try to invest our resources in organizing as much digital medicine and telemedicine as possible.

 

MO:

With universal health care in Spain, do you find conducting telehealth across the country to be easier? Is it more convenient to move and refer patients, and make their records easily transferable?

JT:

Yes, I think so. This is one of the advantages. We don’t have one single public health system, but the systems are very similar, and they are all connected. They can interface with all the electronic medical records.

So, it’s easy to work with the primary physicians, and also with small community hospitals. We can follow up with our patients, we can track them, if they are temporarily visited in other community hospitals or outpatient clinics by GPs.

I have to say, also, that the whole health care professionals community has been very, very sensitive, and I’m really very thankful to all of them, because everyone has put their best to try to help our patients by different means. So, this is really very important. This is something remarkable and very reinforcing for all of us.

 

MO:

As you know, we don’t really have an interoperable telehealth infrastructure here—and many health systems, not to mention community hospitals, may not have a robust program to begin with. Reimbursement is not assured, states have individual licensing requirements for physicians, and most EMRs don’t interface, because they tend to be proprietary.

JT:

Yes. We all have to learn about what has happened. Actually, one of the many things that we can learn, the take-home message is that we have to work more in promoting better health care systems and adequate public health policies, because in the end—especially your country, but also other countries—we’re all investing a huge proportion of the GDP in health care.

And then, you realize that it does not work as you would like. We need to work a little bit harder in making health systems more efficient.

 

MO:

So, early U.S. data seems to suggest that we’re seeing high rates of severe complications, hospitalizations, and deaths across many age groups, not just in the elderly—a hospitalization profile that appears to differ somewhat from data in Italy and China, if I’m not mistaken. What can you infer from the unique characteristics of Spain’s population and how they may inform outcomes? For instance, the median age in Italy is higher, which translates into a greater number of deaths in the elderly.

JT:

Yes, actually, our population is quite aged. It’s very similar to Lombardia’s population. Again, if you look at the numbers, it’s very clear that the population that has more comorbidities, concomitant conditions, you see more severe cases and higher fatality rate. Nevertheless, we have patients—and naturally, health care professionals, without any considerable risk at the beginning—that unfortunately have died from the disease.

But if you look at the fatality rates, there is a clear trend, proportionally increasing with conditions like age and some comorbidities, like previous medical history of hypertension and other chronic diseases, and of course, in patients with cancer, it’s also the same. But one of the important points here, again, is to try to recognize those patients that have mild to severe COVID-19 disease and to provide them with the most rapid medical intervention or treatment.

If all patients come to the hospitals, then everything is more difficult. As you know, this is not only related to the infection. The infection, per se, is not the critical thing. The most critical fact appears to be the rapid onset of severe inflammation that, in some particular patients, appears in the lungs, probably related to the overactivity of the macrophages in combating the SARS-CoV-2 infection.

At this time, there are some treatment options that, when they are administered on time, they help to mitigate the severity of the respiratory insufficiency, the respiratory impairment. And then, you’ll have more opportunities for these patients to survive and to recover well. That’s why it’s important to screen and capture those patients that are at major risk to develop this severe inflammation of the lungs, and therefore at risk of respiratory insufficiency.

 

MO:

Speaking of which, what are some notable scientific efforts in Spain, both locally or as part of international collaborations? Here, I see intense focus on antiretrovirals and antiviral drugs, IL-6 inhibitors and other immunosuppresants, perhaps more research now looking at the impact of ACE inhibitors and ARBs on fatality, etc.

JT:

Yes. On top of the antiviral treatment options, as you mentioned, there’s a huge international collaboration of promoting clinical trials on this.

What is really new is the approach of treating inflammation, as you mentioned, with new therapeutics directed to IL-6 or the IL-6 receptor, and even to other macrophage receptors that are critical for the macrophage function, among others.

This needs to be the cutting-edge research that we, and other centers of course, are implementing. Because, again, the infection, per se, it’s important, but the most important thing is the secondary inflammatory reaction that the host has against the viral infection.

 

MO:

We’ve been covering this pandemic a lot, and the consensus seems to be that oncology, as a specialty, with its advanced clinical trials ecosystem and focus on immunology, is already set up to study this efficiently. I’ve also been told that cancers are way more complex than viruses, so the research should move quickly. What do you think?

JT:

There are several things to mention about that. First of all, our oncologists, especially medical oncologists, are used to do clinical trials for many new therapeutic options. So, we are used to rapidly designing and activating clinical trials.

Here in Spain, actually, now that our regulatory process has been sped up for clinical trials related to COVID-19, I can tell you the approval time—the time between the clinical trial protocol is submitted and the enrollment of the first patient—can be assured in three working days. You wouldn’t have ever imagined a situation like this.

This includes everything—IRB approval, the National Health Authority’s approval, and the completion of the contract, at least the preliminary contract. This is good for the patients, and it shows you how sensitive all the stakeholders are around this.

Also, as you mentioned, our population is a population that is at risk of having severe symptoms of infection from COVID-19, because of the immunosuppression related to the disease and related to the therapeutic options we have missed. 

So, this is a population where you can easily see results, if they are positive, in international trials aimed to, number one, prevent the worsening of the COVID-19 disease; number two, to ameliorate the symptoms and the respiratory function impairment, and number three, the use of immunotherapy and other related agents in patients with cancer and COVID-19.

Certainly, we have invested in how important it is to mitigate this immune response that these patients have, especially as it relates to the macrophage functions. We have very rapidly and easily adapted some of the therapeutic strategies in these clinical trials.

 

MO:

You’ve watched the pandemic unfold in different countries and in their respective health systems. What can you say about how the universal health care system in Spain coped with this pandemic—in terms of the development of testing capabilities, dissemination of public health messaging, contingency plans and clinical guidelines, as well as the ability to provide standard, accessible care?

JT:

This is an important factor, at least in our environment. Almost all patients are covered, by definition, by the public health system, but there are some patients that also have private insurance—around 25% of the population—that they use more or less, depending on the medical needs that you have.

For example, the uptake of private insurances for obstetrics is much higher than the uptake for severe diseases like the COVID-19 infection or myocardial infarction, or diseases like that

 But the bottom-line message here is that there is good coverage for the whole population. But the second important thing is that it’s not specifically related to the coverage, but to how comprehensive and how well public health policies are implemented in the different countries or regions. The regions where they have good public health policies, actually, have been more rapid in implementing the right measures for combating the disease.

 So, this is also something important that we have to learn for the future. Public health leaders and public health policymakers should think about how emergencies and diseases like these should be tackled in the future. We have to learn. There is no doubt about this.

 

MO:

What are your impressions of how the U.S. has handled this pandemic, especially at the national level? Also, what have you learned that you think, perhaps, we should be paying attention to as well?

JT:

First of all, the United States is a very big country with completely different states in the way that the people behave, and also with the health systems in place. One of the messages that we have learned from what has happened in Spain and Italy is that you cannot make global decisions and actions, because there are some communities where there is not so much population concentration, and therefore, cases of COVID-19.

For example, in New York City, the population is very much concentrated, but this is not the case in Arkansas or in other places, so you cannot make global decisions for the whole community, especially in big countries.

The principle should be similar in a way that you have to protect the population. The actions that you take may be different, according to the real facts of each state or region population and the COVID-19 spread. This is something that we have to take into consideration.

Of course, there is also a balance of how these decisions may affect the economy, right? This is an important discussion that we also have in our country, but obviously, there should be a balance on that. So, some measures that have to be taken in regions or cities where the population is highly concentrated do not necessarily have to be the same ones that you have to take in other regions.

That being said, I think that one of the things that we have failed globally—and probably the United States as well—is to take this problem seriously before it came to our environment.

I think that, for the future—and this was part of what I mentioned before about public health and the policymakers—this is something that has to be taken in consideration. But it’s important to learn about and from others. Even if you may have rapid tests to screen patients for COVID-19 infection, simple things, like confinement and the use of masks and to stay at home, are really very important.

And I know how painful these decisions are, because we are not societies that are used to staying at home for four weeks, only to go outside just to get food in the supermarket—but these are important steps for mitigating the peak. Otherwise, it’s going to be very difficult to have the best medical care if all the medical resources are saturated.

 

MO:

Many reports have focused on how a number of countries and regions in Asia—notably, South Korea, Taiwan, and Singapore—were primed to move more quickly, citing experience with the first SARS outbreak as a primary reason for their proactivity, swift public health measures, and high compliance by the general population. What are your thoughts?

JT:

Yes, that’s true. I think that they have learned more about SARS, and MERS, of course. One interesting country, maybe, is Canada, because they have those sorts of experiences with SARS, because of the Chinese population in Toronto, you may remember, in 2002 to 2004.

But it seems to me that they have taken more rapid actions than other countries. And this is a country that is close to you geographically.

 

MO:

Indeed. We’ve covered a lot. Did we miss anything?

JT:

This is related to cancer care. We had discussions with some of the groups that were in Wuhan in China. Especially for cancer care, one of the things that was raised as a risk for infection and for patients with cancer, and also for severe evolution of the disease, was, for example, to have elective surgery for patients with cancer. We have implemented in some diseases more new neoadjuvant treatments than we used to have.

We learned this a lot from some of the Chinese colleagues. So, for example, in colon cancer, even in breast cancer, in patients that you would not do neoadjuvant treatment, now we are implementing more neoadjuvant protocols to treat these patients as much as possible, with chemotherapy or hormone therapy depending on the disease, and just to delay, as much as possible, surgery to a time where all the health resources come to a more normal situation.

For the time being, actually, we’re delaying some of the surgeries, especially in the big diseases—colon cancer, gastric cancer, lung cancer as well, breast cancer, and others. This is something that health authorities may consider in promoting policies like this.

 

MO:

Is this done with equal weight of consideration for health care capacity as well as for managing severe complications that may result from surgery, even more so if the patient becomes infected by SARS-Cov-2? Or does one take greater precedence over the other?

JT:

I think it’s both. If you use most of your resources in intensive care units for patients with COVID-19 respiratory function impairment, you decrease the opportunity of having the resources for patients that have complications with elective surgical procedures. But also, if you have a major surgery, you are, in a way, also in a more immune-depressed status, and you don’t want to put these patients at risk for having more severe COVID-19 infections. 

So, I think there are multiple factors that favor decisions like this. Obviously, this is not something that we’ll have to do forever. If we can delay right now, surgery for four, six weeks, this is something to consider, even if for that particular disease or for that particular patient, you were not planning neoadjuvant treatments in another situation outside the COVID-19 pandemic.

 

MO:

Thank you so much for taking the time to speak with me.

JT:

You’re welcome.

Copyright (c) 2020 The Cancer Letter Inc.