ALL YOU NEED TO KNOW ABOUT ‘LONG COVID’ AND ITS IMPACT ON HAEMATOLOGICAL AND CANCER PATIENTS

May 2021 Covid-19 Willem van Altena

Interview with Maarten van Herck, PhD, Maastricht University, The Netherlands

Maarten Van Herck is a PhD researcher in lung diseases and pulmonary and extrapulmonary symptoms under supervision of prof. Chris Burtin at Hasselt University and Prof. dr. Martijn Spruit at Maastricht University in The Netherlands. In May 2020, when more and more COVID-19 patients reported a vast array of long lasting symptoms, Hasselt University together with Maastricht University and the Center of Expertise for Chronic Organ Failure (CIRO) was among the first in Europe to investigate this.1 Now, almost one year later, drs. Van Herck shares his knowledge on what has become known as LONG-COVID.

Firstly, can you explain what long-covid is and what the incidence and the clinical symptoms are?

“Long-covid is a condition whereby affected patients do not recover for several weeks or months following the onset of symptoms that are suggestive of COVID-19. Clinical symptoms can vary between individuals and over time. The most common symptoms are fatigue, dyspnoea, headache, chest pain, joint pain, muscle pain, and heart palpitations. There can be also cognitive dysfunctions present, such as memory loss, brain fog and concentration problems. A very recent study that is still in pre-print identifies no fewer than 205 different symptoms that could be associated to long covid, affecting more than 10 different organ systems.2

“As for the incidence of long-covid here in Belgium, not that much research has been done yet, unfortunately. From comparable countries some data is available. What we need to realise is that long-covid is not just limited to severe cases where people were admitted to the hospital, but also concerns people who recover at home. However, it is true that long-covid is more common in hospitalized patients. Recently, The Lancet published a large cohort study3 from China showing that three out of four individuals (75%) suffer from at least one symptom six months after having been hospitalized.3

“However, around 80% of COVID-19 patients recover at home. A study from Denmark shows that around 30% of non-hospitalised patients suffer from at least one symptom four weeks after the initial infection, and this number decreases to 10 or 20% at three months, so long-covid is less prevalent in patients who recovered at home than in patients who were admitted to the hospital.4 Despite prevalence of long-covid being lower among non-hospitalized patients, we are talking about a very large group of people.”

“Long-covid is less prevalent in patients who recovered at home than in patients who were admitted to the hospital.4

It has been almost a year since you began examining long-covid together with researchers from Maastricht and from CIRO. What were positive outcomes until now?

“What I think was an important result of our study was that we were able to get recognition for these issues. Until then, patients were simply brushed aside by healthcare professionals as merely suffering from post-traumatic stress or depression. These patients, especially those who had not been hospitalized, were disbelieved and ignored. Our research created awareness among healthcare professionals, but also in the society as a whole, that there are most probably thousands and thousands of people with a mild form of covid, who didn’t fully recover. Our study1 is one of the first to highlight this problem. Patients felt abandoned to their fate in comparison to the hospitalized patients who at least got some degree of follow-up. Currently, these forgotten long-covid patients have found recognition by friends, relatives, but also by their employers, healthcare professionals and the healthcare insurance. Insurers are now more aware of these long-lasting symptoms and how they impact a person’s productivity. It’s an important first step. Next: we need to develop the right treatment for the right patient. Because basically we are faced with a pandemic after the pandemic.”

“Basically we are faced with a pandemic after the pandemic”

How does long-covid affect the quality of life of patients?

“These persistent symptoms have an important impact on their quality of life. We did a questionnaire study in two long-covid peer support groups, with a follow-up three months later. Because of the selection bias – since the participants in the support groups had selected themselves – , the result was that 40% reported an abnormally low quality of life on the EQ5D  i.e. an EQ-5D index score that was below the fifth percentile of age- and gender matched normative values.5 Three months later, this was still 27%. Of note: these results can be an overestimation of the true burden (due to the selection bias), but give us a clear indication of the impact of long-covid on individuals). What was striking is that these patients were mostly young and healthy. The median age of the respondents was 47 years and had a good self-reported health level and hardly any comorbidities. What we must also realize is that long-covid does not just have an impact on an individual level, but also on our society as a whole. For instance, these people experience a significantly lower work productivity as well as daily quality of life, and are also more dependent on care.”

“When COVID-19 emerged one year ago, it was assumed that most patients would recover at home and regain their former health level within a couple of weeks. In time, however, it became clear that some people took much longer to recover. This was definitely not like influenza. Although we do know other infectious diseases leading to patients suffering from long lasting symptoms, for instance SARS, MERS, Q-fever and Lyme disease.”

Which persons are more at risk of contracting long-covid and what are potential risk factors?

“There is evidence that having a more severe acute phase of the illness is one of the risk factors for ending up with long-lasting symptoms.3 People who are admitted to the ICU are more likely to have persistent symptoms in comparison to people who have been hospitalized outside the ICU.3 And people who had mechanical ventilation have a greater chance of long-covid than people who only had oxygen supplementation.6 Other risk factors are gender: women have a greater chance of long-covid than men, we see this in many infectious diseases. Also age and having a higher body mass index are risk factors.8 There is also evidence that patients who suffer from five symptoms or more during the acute phase of COVID-19 have a greater risk of long-lasting symptoms.1 Comorbidities also come into play, but comorbidities in general make it more likely someone is admitted to hospital.”

Are cancer patients more at risk of developing long-covid?

“What we do know about these patients is that they are more likely to be admitted to the hospital when they contract COVID-19 and have a greater chance of a more severe course of acute illness or mortality.9And as I mentioned, COVID-patients who have to be treated in hospital are more likely to develop long-covid8 We do know that cancer patients with COVID are admitted more often to the hospital than people without cancer.10 So, in my opinion, cancer is a risk factor for experiencing persistent symptoms after the acute infection phase, but this is not yet confirmed by scientific evidence.”

What is known about the effects of long-covid on patients with cancer and how long-covid may influence the outcome of treatments?

“These are important questions, and again I have to say that evidence is lacking. Cancer is indeed an important risk factor for having severe COVID and people with cancer who get infected are more likely to be admitted to the hospital and to die from COVID-19.11 But to date, we do not know if COVID-19 impacts treatment outcomes after a patient has recovered. Cancer treatments affect a person’s ability to fight COVID-19, but more research is needed. We need observational studies and follow up a cohort over a longer period of time, but for this we need a lot of patients and many centers collaborating internationally.”

Looking into the future: should long-covid, in your opinion, be considered as a separate medical, possibly chronic condition, with its own epidemiology, diagnosis and treatment?

 “Basically, COVID-19 as well as long-covid affects several organs and can be considered a systemic disease. So, in my opinion, a holistic approach is needed. So far, diagnostic assessments are too fragmented and too often seem to be quite narrow in their focus. Basically, focusing on just one organ or organ system is an outdated strategy. I think it would make sense if patients received a more holistic and comprehensive assessment of all organs involved. In some countries, like Great Britain, dedicated covid clinics are emerging. I believe this can be a good approach. Over time we may well end up with dedicated ‘covidologists’. But right now we do not even have diagnostic criteria to define ‘long-covid’ other than the common definition of having symptoms four weeks after a COVID-19 infection. Also, add to that the fact that most hospitals are overrun now, and many non-critical procedures have been scaled back.”

‘Over time we may well end up with dedicated ‘covidologists’

“As for treatment strategies for long-covid, these are mostly based on our knowledge of the treatment of other diseases, for instance multidisciplinary rehabilitation programs, energy conservation techniques and cognitive behavioural therapy. There are also pharmacological treatment strategies being proposed, such as mast cell stabilisers and antivirals. Still, good evidence for these treatments is still lacking. With long-covid it can be expected that not everyone will benefit from the same treatment strategies due to multi-organ impairment and different underlying pathological pathways. We need to find a way to provide the right treatment for the right person at the right time.”

“I hope Belgium will step up its response to long-covid, following the example of countries like the UK and Italy. In the Netherlands the RIVM has started a very large study from the end of April in which at least 1,000 Dutch who tested positive for COVID-19 are followed up during a year. Basically, it could be so simple. Just contact every person who tests positive for the virus after 1 month and again after 6 months and ask them if they have recovered.”

References

1. Goërtz M J, Van Herck M, Burtin C et al. Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome? ERJ Open Research 2020 6: 00542-2020; DOI: 10.1183/23120541.00542-2020

2. Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med. 2021 Apr;27(4):601-615. doi: 10.1038/s41591-021-01283-z.

3. Huang C, Huang L, Wang Y et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021 Jan 16;397(10270):220-232. doi: 10.1016/S0140-6736(20)32656-8.

4. Bliddal S, Banasik K, Birger Pedersen O, et al. Acute and persistent symptoms in non-hospitalized PCR-confirmed COVID-19 patients. MedRxiv Jan 25 published ahead of print. doi: https://doi.org/10.1101/2021.01.22.21249945.

5. Grochtdreis T, Dams J, König H H, Konnopka A. Health-related quality of life measured with the EQ-5D-5L: estimation of normative index values based on a representative German population sample and value set. Eur J Health Econ. 2019 Aug;20(6):933-944. doi: 10.1007/s10198-019-01054-1.

6. Halpin S J, McIvor C, Whyatt G, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol. 2021 Feb;93(2):1013-1022. doi: 10.1002/jmv.26368.

7. Arnold D T, Hamilton F W, Milne A, et al. Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: results from a prospective UK cohort. Thorax. 2020 Dec 3;76(4):399–401. doi: 10.1136/thoraxjnl-2020-216086. Epub ahead of print.

8. Sudre C H, Murray B, Varsavsky T, et al. Attributes and predictors of long COVID. Nat Med. 2021 Apr;27(4):626-631. doi: 10.1038/s41591-021-01292-y.

9. Vijenthira A, Gong I Y, Fox T A et al. Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients. Blood. 2020 Dec 17;136(25):2881-2892. doi: 10.1182/blood.2020008824.

10. Passamonti F, Cattaneo C, Arcaini L. et al. Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study. Lancet Haematol. 2020 Oct;7(10):e737-e745. doi: 10.1016/S2352-3026(20)30251-9.

11. Clift A K, Coupland C A  C, Keogh RH, et al. Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality from coronavirus 19 in adults: national derivation and validation cohort study. BMJ. 2020 Oct 20;371:m3731. doi: 10.1136/bmj.m3731.

Further reading recommended by Maarten van Herck:

Alwan N A, Johnson L. Defining long COVID: Going back to the start. Med (N Y). 2021 Mar 25. doi: 10.1016/j.medj.2021.03.003.

Barker-Davies RM, O’Sullivan O, Senaratne KPP, et al. The Stanford Hall consensus statement for postCOVID-19 rehabilitation. Br J Sports Med 2020;54:949–959.

van den Borst B, Peters J B, Brink M, et al. Comprehensive health assessment three months after recovery from acute COVID-19. Clin Infect Dis. 2020 Nov 21:ciaa1750. doi: 10.1093/cid/ciaa1750.

Davis H E, Assaf G S, McCorkell L et al. Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact. MedRxiv 2020, doi: https://doi.org/10.1101/2020.12.24.20248802

Gloeckl R, Leitl D, Jarosch I, et al. Benefits of pulmonary rehabilitation in COVID-19 – a prospective observational cohort study. ERJ Open Res 2021; in press https://doi.org/10.1183/23120541.00108-2021.

Khandait H, Gandotra G, Sachdeva S, et al. COVID-19 and Hematology-What Do We Know So Far? SN Compr Clin Med. 2020 Oct 27:1-6. doi: 10.1007/s42399-020-00607-3.

Kingstone T, Taylor AK, O’Donnell CA, et al. Finding the ‘right’ GP: a qualitative study of the experiences of people with long-COVID. BJGP Open. 2020 Dec 15;4(5):bjgpopen20X101143. doi: 10.3399/bjgpopen20X101143.

Norton A, Olliaro P, Sigfrid L et al. Long COVID Forum Working Group. Long COVID: tackling a multifaceted condition requires a multidisciplinary approach. Lancet Infect Dis. 2021 May;21(5):601-602. doi: 10.1016/S1473-3099(21)00043-8.

Roberts L N, Whyte M B, Georgiou L, et al. Postdischarge venous thromboembolism following hospital admission with COVID-19. Blood. 2020 Sep 10;136(11):1347-1350. doi: 10.1182/blood.2020008086.

Salisbury R, Iotchkova V, Jaafar S et al. Incidence of symptomatic, image-confirmed venous thromboembolism following hospitalization for COVID-19 with 90-day follow-up. Blood Adv. 2020 Dec 22;4(24):6230-6239. doi: 10.1182/bloodadvances.2020003349.

Townsend L, Fogarty H, Dyer A, et al. Prolonged elevation of D-dimer levels in convalescent COVID-19 patients is independent of the acute phase response. J Thromb Haemost. 2021 Apr;19(4):1064-1070. doi: 10.1111/jth.15267.

Vaes A W, Goërtz Y M J, Van Herck M et al. Recovery from COVID-19: a sprint or marathon? 6 months follow-up data of online long COVID-19 support group members. ERJ Open Research 2021; DOI: 10.1183/23120541.00141-2021

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