COVID-19 and childhood cancer
COVID-19 is a pandemic, which is hardly a cause of illness for children, even if they are or have been treated for cancer. This means that for this group the measures cause more damage than the virus itself. Attention should also be paid to this so-called collateral damage, as well as to the damage caused by the virus itself.
A remarkable amount is said and written about this pandemic, caused by a virus that we as humanity did not yet know about. That is why so many people are becoming ill and there was a strong and sudden need for hospital and IC beds. Was, because in Europe the first peak is fortunately over. This virus is most threatening for the elderly (half of the deceased in the Netherlands are 82 years and older) and for people with one or more conditions, such as diabetes, serious obesity or chronic lung disease. Of all people under the age of 70 who died of COVID-19 in the Netherlands, almost 90% had such a disorder. All this fortunately makes children not that vulnerable, not even children with cancer. In the Princess Máxima Center, just as in similar hospitals in the Western world, the necessary measures were of course taken to ensure that the children did not become infected, nor did the staff. After all, they are desperately needed to take care of the children! All this has worked out extremely well. The Máxima's twinning program, which we support, have been partly affected. Especially the work visits back and forth are not possible at the moment. Fortunately, a lot of communication is possible with modern techniques; there is constant consultation about the most optimal treatment of individual patients. Our research projects also continue, sometimes with the necessary adjustments. However, children with cancer in hospitals in poorer countries are affected by all the measures. For example, there are hardly any blood transfusions available. Also for children with cancer in the Netherlands all measures have disadvantages, especially in the long term. If you want to read more about this, I refer you to an article of mine, recently published in Expert Review on Anticancer Therapy, available below.
Prof.dr. Gertjan Kaspers
COVID-19: what is the impact on children with cancer, now and in the future?
By prof.dr. Gertjan Kaspers, Prinses Máxima Centrum, Utrecht and Amsterdam UMC
Published in Expert Review of Anticancer Therapy, 2020
The coronavirus SARS-CoV-2 causes the disease COVID-19, that is now a pandemic. While this infection is a threat to adults, especially the elderly and those with co-morbidity, children seem at low risk for serious COVID-19 infections. This, so far, holds true for children with cancer currently being treated, even though they are known to be immunocompromised. Therefore, we should still protect them from this coronavirus, as we do for other pathogens. Children with cancer need healthcare providers to take care of them, which necessitates appropriate measures taken to avoid too many healthcare providers becoming ill in the same time-period. However, all measures taken to control COVID-19 in general will cause very significant collateral damage globally for the short- and long-term. This must be taken into account by policymakers, also for the sake of future children with cancer. The remedy should not become worse than the disease.
COVID-19 is a disease caused by a coronavirus called SARS-CoV-2, that has caused a pandemic and a global crisis. It was initially identified in Wuhan (China) in December 2019, and has spread worldwide since. While Asia was the area with most infected individuals first, including areas or countries such as Hong-Kong, Singapore and South-Korea, Europe followed and then USA and other countries and continents. This is fully compatible with our global business and touristic traveling. It has thus soon become a global infection.
There has been a large number of viruses that caused similar significant concerns worldwide, with more or less victims, being healthy initially or not, and being old and fragile or not. Well-known examples are the Spanish influenza pandemic in the years 1917-1919, smallpox in ancient times and in the 20th century, while the Asian Flu, Hong Kong flu, SARS-virus, MERS-virus and Ebola Virus infections occurred more recently. In contrast to many of these viral infections, the one caused by SARS-CoV-2 seems to mainly severely affect elderly individuals who have a co-morbidity or are obese. Clearly, there has always been and there will always be viral threats. However, what seems new is the global and immediate awareness of this pandemic, and the drastic measures taken by many governments. The latter is unprecedented, and is a threat for the care of children with cancer, now and in the future.
The current pandemic is caused by SARS-CoV-2 that was recently unknown to mankind and spreads easily. Although the most vulnerable group concerns the elderly, many people are becoming ill in a short time-period, causing a major burden for healthcare systems. In The Netherlands with a population of just over 17 million, over the past 13 weeks (update on 26 May 2020, with the first positive patient on February 27), there have been 45,578 individuals tested positive (half being 60 years of age or older, and 1.5% being below 20 years of age), 11,690 hospital admissions (half being 69 years of age or older, and 0.7% being below 20 years of age), and 5,856 persons who have died (half being 82 years of age or older, one being below 20 years of age). Globally, more than 5 million cases were identified, with 344,454 deaths due to COVID-19, up to May 26, 2020. The case-fatality rate is unknown, currently estimated to be between 0.1 and 1.0%, but likely to be much lower because of selection-bias towards persons requiring hospital-admission and intensive care.
Of all persons in The Netherlands who died being below 70 years of age, nearly 90% had one or several co-morbidities, such as cardiovascular disease including hypertension, diabetes, or a chronic lung disease. Co-morbidity very likely plays a significant role in those dying and being above 70 years old as well. The peak of actual ICU admissions was at nearly 1400 beds, in the first week of April. We have not tested all individuals with symptoms, let alone those without signs or symptoms, so the number of infected individuals will be much higher. Similarly, the number of those who died from COVID-19 will be higher (the estimate is twice as many) because, especially in the home setting and in care facilities for elderly, testing has not been routine either.
The approach in most countries worldwide in response to this pandemic has been more or less similar. First, measures are taken aimed at preventing too many individuals getting infected, reasoning that this will lead to less hospital admissions and an acceptable burden on the (limited) capacity on intensive care units (ICUs). The measures are rather drastic, entitled lock-down or variants, such as ‘intellectual lock-down’ in The Netherlands, causing a major economic crisis and collateral damage (see below). Second, within hospitals, most so-called elective care has been significantly reduced, or even halted, so that all efforts can be directed at coping with patients with COVID-19. In parallel, capacity on ICUs is being increased.
COVID-19 and children with cancer
What are the consequences for children with cancer, if any? The answer has at least three elements. First, the real physical threat of the SARS-CoV-2 virus itself for children. Second, how the risk and all measures taken by the hospital and country are being perceived by the child and their family members. And third, the impact on further treatment of current children with cancer, and of future children.
Fortunately, this particular coronavirus does not seem to affect children that much for, as yet, unknown reasons [1-4]. In fact, Lu et al.  reported that 16% out of 171 children did not even have signs or symptoms, with only 3 out of 171 (1.8%) requiring intensive care (all 3 having comorbidity, including one child with leukemia) and 1 child aged 10 months, also having intussuception and multi- organ failure, dying. Zheng et al.  reported that 2 out of 25 hospitalised children with COVID-19 needed intensive care. Yet, Sun et al.  reported on 8 children with COVID-19 being admitted to intensive care, with 2 out of 8 requiring mechanical ventilation. Shekerdamian et al.  reported on 48 children with COVID-19 admitted to Canadian and US pediatric intensive care units, with 83% having significant preexisting comorbidities, and at the time of reporting, 2 (4%) deaths. In other words, the course of the disease is not always benign. While children being treated for cancer and in the months thereafter are immunocompromised, they too seem to become ill very rarely [8,9], with only two patients reported to require intensive care treatment so far [2,10]. The child reported by Chen et al., also had febrile neutropenia and documented Influenza A infection . Of course, the relatively low incidence of (severe) COVID-19 infections in children with cancer is largely explained by how families and healthcare professionals protect them from getting any viral infection. Up to this date (May 26, 2020), we are aware of 5 children in The Netherlands being treated for cancer, who got COVID-19. Again, in a mild form.
Apart from the viral infection itself, children and their families are affected by the measures that governments and hospitals are taking, and by the general fear that is being generated about COVID- 19. In the Netherlands, our single national comprehensive childhood cancer center, Princes Máxima Center, acted quickly when faced with the threat of this infection. The visit of guests is limited, no family members except for both parents and in rare cases a brother or sister. Many coworkers from supporting staff services are now working from home, and nobody is allowed to enter the hospital in case of symptoms that suggest a COVID-19 infection, until the viral test is negative. Personnel that tested positive, could only start working again in the hospital after two consecutive negative tests. We temporarily closed the preclinical research activities, with the aim to minimize the risk of spread of the virus. Clinical research with a possible benefit for patients has been continued. Similarly, we temporarily postponed all follow-up visits and appointments at our late effects clinic, whenever possible without jeopardizing appropriate care for the patients. Physical contact with patients is avoided as much as possible, with social distance at 1.5 meter being the rule. The children are isolated in their hospital rooms, and many social activities had to be canceled. Of course, all oncological care is continued and appropriate personal protection equipment were otherwise maintained.
All of this is more or less similar to the recent advice for managing children with cancer by Bouffet et al.  and Sullivan et al. , while the latter authors also provide disease-specific and specialty and service-specific guidance especially for low- and middle-income countries (LMIC). However, all these measures have an obvious downside for the patients and their families. Of interest, despite similar measures taken, Casanova et al.  recently reported that a relatively large proportion of their children with cancer still personally felt at risk of severe complications, in contrast to healthy peers.
Finally, what are the consequences of this pandemic and all measures taken, for the remainder of treatment of our current patients, and for future patients. Or for that matter, what is the collateral damage? For current patients in high-income countries, it is likely that care will be as now, with some practical limitations as described, but otherwise optimal. The care for children with cancer is of the highest priority in our country, and it therefore seems extremely unlikely that e.g. intensive care facilities for children will be sacrificed for sick adults. However, children with cancer in LMIC likely already face suboptimal care. All measures being taken are worrying for future patients. This is especially true for children in LMIC, but also for our patients in The Netherlands and similar countries. What type of collateral damage might occur?
In general, we are entering a global financial recession. Governments will have less money, and consequently often less money for health care as well. Ribeiro et al. reported a strong correlation between annual government healthcare expenditure per capita and childhood-cancer survival . Individual families will have less money as well, and especially in LMIC this will lead to many more undiagnosed children, and if diagnosed, more late presentations, and more treatment abandonment. This is actually already happening, since in many of these countries there is less day-to-day work, and no work means no money. On top of that, traveling has become cumbersome, also leading to delayed presentation. If they reach a hospital it is likely that because of poverty they are even more malnourished than was the case until recently. Malnourishment is an important adverse risk factor for the cure of childhood cancer.
Another very worrying fact is the lack of blood products, that is reality already right now in countries such as Kenya and Malawi (personal communications with, Dr. Festus Njuguna and Dr. M. Huibers, respectively). A threat for all future children with cancer all over the world, is that current research is often on hold, because of the guidelines stating that most personnel must work from home, and research is not an exemption. Even more important, it is very likely than fundraising for scientific research will be significantly less successful in the coming years, ultimately causing delayed introduction of innovative treatments. This will cause unnecessary morbidity and higher mortality than would have been the case otherwise, for future children with cancer all over the world. There are other examples of collateral damage, such as the risks associated with the current interruption of screening programs and of regular “elective” healthcare, and the increased incidence of sexual abuse and child battering during a long period of lockdown, but that is beyond the perspective of this editorial. In general, it is important that policymakers take collateral damage into account, when considering prolonging current measures or even introducing novel ones.
Conclusion and warning
In conclusion, COVID-19 causes much morbidity, with an excess burden on hospitals and ICU’s. Children seem less affected, and if infected, fortunately are less ill. Although, intensive care admissions have been reported for a few children. No extremely worrying facts for children with cancer being currently treated have been reported so far. In this context, all measures causing collateral damage might be more threatening for children with cancer, especially when living in low- and middle-income countries, but also for children with cancer in high-income countries. Therefore, policymakers should take collateral damage into account in the battle against COVID-19. The remedy should not become worse than the disease.
Please refer to the article, as published in Expert Review of Anticancer Therapy, 2020