Long covid: Damage to multiple organs presents in young, low risk patients
BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m4470 (Published 17 November 2020) Cite this as: BMJ 2020;371:m4470Read our latest coverage of the coronavirus outbreak
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Dear Editor,
Symptoms are created by the brain to enable the organism to monitor its own body. Sometimes the symptoms reflect organ damage, sometimes they don't. Research has shown that medical information can both aggravate and contribute to chronification of symptoms (1).
The research article covered here by the BMJ contains information that is bound to lead to more anxiety, more symptom focus and more expectations of bodily damage and long-lasting symptoms. One should not underestimate the damage that can be caused from spreading this information uncritically.
This research has not been peer reviewed and it could not establish a clear causal link between organ impairment and infection. There are several caveats that go unmentioned:
Firstly, the research has not been replicated, and so the results may be spurious or overblown.
Second, the study does not compare the bodies of people with lasting symptoms after Covid-19 with similar patients who have no symptoms. The abnormalities found are minor, and it may well be that some of them are found in patients whether they experience lasting symptoms or not. Medicine is full of conditions where there is little connection between experience of symptoms and bodily damage. 1/3 participants had no organ system impairment. Why? What causes their symptoms?
- Third, the study doesn't compare the effects Covid-19 virus with other viral disease. Influenza may, for example, also lead to various sequelae (2). The effects observed may be nonspecific for SARS CoV-2. Covid-19 patients are probably the most heavily studied population in medical history on such a short-term basis. This is bound to lead to many findings, including false positives and findings of unknown medical significance. It is no wonder that one finds a lot when one "multi-organ MR scanning" and very extensive blood tests? What other patient groups have been subject to such attention?
- Fourth, by "impairment", the researchers meant that the "individual organ was classified as impaired if at least one of the metrics calculated for that organ was outside the reference range".
It is unclear how many people in the normal population, or in another population with viral disease, that would have at least one abnormality when subjected to this kind of medical testing. And most importantly, it is wholly unclear if these mild abnormalities can in any way explain the often significant symptoms experiences.
- Fifth, the BMJ quotes the researchers that the results “signal the need for monitoring and follow-up in at least the medium and longer term, especially for extrapulmonary sequelae”. But the research clearly does not suggest this other than in a research setting. The research has not established that the findings are significant diagnostically or that the diagnostics will benefit patients. In fact, medically initiated body-scanning may exacerbate symptoms and clinicians should protect patients from biomedical overmedicalisation.
- Sixth, the researchers claim that they have established that "Long COVID has a physiological basis". Only a medicine with a non-scientific mind-body dichotomy can assume that there are some conditions that do not have a physiological basis. All conditions do, and conditions where symptoms do not correlate with bodily changes elsewhere have a physiological basis in the brain. These researchers have not in any way established that the findings they present explain the symptoms in the population. They just assume this. This says more about the way they think, where organ impairments seem to automatically explain symptoms, than their empirical research.
Research like this mostly comes from biomedical researchers who have no inkling that the way they portray a health problem may actually exacerbate symptoms and who regularly exaggerate the significance of their findings. As evidences by their discussion, the authors of this study do not have it on their radar that the symptoms may not correlate with the bodily impairments that they find. Research on this topic needs to incorporate the effects of information, symptom focus, symptom anxiety, etc to be able to properly research the phenomenon of bodily symptoms.
The BMJ should apply its "Too much medicine" mindset to Covid-10 patients as well (3).
References:
1) Barsky, AJ. 2017. The Iatrogenic Potential of the Physician's Words. Dec 26;318(24):2425-2426. doi: 10.1001/jama.2017.16216. https://jamanetwork.com/journals/jama/fullarticle/2661032
2) Sellers, SA. The hidden burden of influenza: A review of the extra-pulmonary complications of influenza infection. Influenza Other Respir Viruses. 2017 Sep;11(5):372-393. doi: 10.1111/irv.12470. https://pubmed.ncbi.nlm.nih.gov/28745014/
3) Too much medicine. BMJ. https://www.bmj.com/too-much-medicine
Competing interests: The author has initiated and leads Recovery Norway, a nonprofit organization consisting of people who have recovered from CFS/ME and other so-called "medically unexplained" syndromes through cognitive or behavioural strategies. The goal of the organisation is to learn from their stories. This may be viewed as an intellectual conflict of interest.
Dear Editor
It is surprising that in a young, low-risk population with ongoing Long Covid symptoms almost 70% of 67 individuals had impairment in one or more organs four months after initial symptoms of 68 SARS-CoV-2 infection. Also 70% of 201 individuals were women and 87% were white. The age range was 33 to 55 years, mean age 44 years. [1]
At least 80% of women now use or have used hormonal contraception. Therefore, the age group 33-44 years would include both recent or long-term past users of combined progestogen/oestrogen or progestogen only contraception. Also from age 44 to 55 years up to 55% of women are given these hormones again as HRT.
Hormone use causes numerous illnesses and many biochemical perturbations including zinc and magnesium deficiencies. Does taking hormones increase the risk of Vitamin D and Vitamin C deficiencies which are known increase the risk of more severe and long lasting Covid-19 complications?
1 Dennis A, Wamil M, Kapur S, Alberts J, Badley AD. Multi-organ impairment in low-risk individuals with long COVID. https://www.medrxiv.org/content/10.1101/2020.10.14.20212555v1.full.pdf.
2 Grant ECG. The pill, hormone replacement therapy, vascular and mood over-reactivity, and mineral imbalance. J Nutr Environ Med 1998;8:105-116.
Competing interests: No competing interests
Dear Editor
The worrying findings of Dennis and colleagues [1] in relation to extra-pulmonary sequelae and multiple organ damage are all the more concerning when combined with recent cardiac MRI investigations of recently “recovered” cases in Germany [2].
As in the former pre-print paper which your news item reports, the Frankfurt based cardiac MRI study selected cases of relatively low symptomatic severity in that none had been hospitalised, yet their results revealed cardiac involvement in 78% and ongoing myocardial inflammation in 60%. Given that the number of ‘milder’ cases will always inevitably far outweigh the numbers hospitalised or tragically do not survive, the sheer scale of potential public health morbidity and potentially mortality if cardiac health is undermined, begins to look very concerning.
While every applause must be accorded to the tremendous, unprecedented and very encouraging progress with vaccine development, we must not lose sight of what could potentially be an even greater challenge to come in terms of health service burdens and premature mortality. It remains vital therefore to redouble research efforts at furthering our understanding of long-COVID and how those affected might be most effectively treated: might they benefit from vaccination for instance, or would that risk further harms from what appears to be an immune-triggered pathway?
For these reasons, the UK Governments announcement of 40 long-COVID assessment centres in England [3] is only to be welcomed. It will be interesting to note if other UK governments follow suit as the cumulative incidence of long-COVID disease continues to rise across all parts of the UK affecting many previously healthy adults with no underlying health conditions or known risk factors.
References:
1. Dennis A, Wamil M, Kapur S, Alberts J, Badley AD. Multi-organ impairment in low-risk individuals with long COVID. https://www.medrxiv.org/content/10.1101/2020.10.14.20212555v1.full.pdf.
2. Puntmann VO, Carerj ML, Wieters I, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol. Published online July 27, 2020. doi:10.1001/jamacardio.2020.3557
3. NHS News: NHS to offer ‘long covid’ sufferers help at specialist centres. Published online October 7, 2020. https://www.england.nhs.uk/2020/10/nhs-to-offer-long-covid-help/
Competing interests: No competing interests
Dear Editor,
COVID-19 long term effects are not yet known with certainty. However, there are many hypotheses and, recently, some symptoms have been identified that appear to be frequent in COVID-19 patients even after the termination of the infection (1). The mechanisms underlying the onset of these symptoms are still unknown. Dennis A et al. highlighted the possibility of developing multi-organ impairment in low-risk individuals with long COVID (2). The results of the research, although preliminary, are still very worrying.
The risk that COVID-19 may cause long-term effects, even severe ones, is becoming particularly concrete. At this point, some issues arise in relation to the management of the pandemic by the various world governments. In fact, especially in this second phase of the health emergency, the public health policies of many countries are characterized by a reduction of preventive strategies (e.g. closure of business activities, maximum use of smart working, limitation of travel between cities, etc.). In the majority of world countries, in fact, until the National Health Systems resist, rigid measures are not implemented to reduce the spread of the COVID-19.
It is considered that - in view of the current lack of knowledge of COVID-19 long term effects - stricter public health strategies should be put in place not only with the aim of reducing pressure on National Health Systems, but above all with the aim of reducing the simple spread of the virus and the number of infected, even if asymptomatic. In fact, even in asymptomatic subjects, we do not know if they will develop long-term complications in the future. So it is crucial that we not only monitor the number of admissions and the level of saturation in hospitals, but also the number of people infected. This should be the basic parameter for deciding whether it is necessary to stiffen public limitations (up to total lockdowns). Obviously the immediate consequence of rigid public health policies is immediate economic damage. However, in the long term, this strategy could encourage a faster recovery of the economy, because it prevents that, in the future, a large number of people with serious post-COVID diseases can saturate the National Health Systems and, therefore, also induce economic collapse.
References.
1. CDC. Long-Term Effects of COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects.html
2. Dennis A, Wamil M, Kapur S, Alberts J, Badley AD. Multi-organ impairment in low-risk individuals with long COVID. https://www.medrxiv.org/content/10.1101/2020.10.14.20212555v1.full.pdf.
Competing interests: No competing interests
Dear Editor
The findings of Multi organ damage in Young people after 140 days of Sars Cov 2 Infection are alarming and a serious cause of concern because of several reasons namely, the disease Long covid doesn’t spare the even the young people with relatively low/no associated co-morbidities, secondly multiple organ damage could be noticeable even after 4 to 5 months of primary illness, thirdly it affects the vital organs like Heart, Lung, Liver, Kidney and Pancreas but most unfortunately the changes in these vital organs can’t be picked on routine clinical blood tests(1).
However, all the patients detected to have organ dysfunction continued to have one or more symptoms of fatigue, muscle aches, headache, shortness of breath suggesting that low grade inflammation has been continuing in the body of such patients. Unfortunately, routine markers of like hsCRP and ESR was found raised only in 13 % patients making them unreliable as screening tool. It calls for studies with other markers of inflammation like Serum Ferritin which have been reported high in 33% patients(2). D Dimer/ IL- 6 levels could be additional possibilities for monitoring purpose. Probably, the ongoing endothelitis as reported by some authors could be the pathogenetic mechanism in such cases(3).
It is matter of serious concern and all efforts be made to halt the progression of disease to save the young from long term morbidity. It calls for further discussions on the use of anti-inflammatory agents be it NSAID or low dose steroids in patients who continue to have symptoms. Though further studies will provide answers many questions. But till than the preventive measures like masks, physical distancing, testing and tracing remain the key.
References
1. Dennis A, Wamil M, Kapur S, Alberts J, Badley AD. Multi-organ impairment in low-risk individuals with long COVID. https://www.medrxiv.org/content/10.1101/2020.10.14.20212555v1.full.pdf.
2. Respiratory Research volume 21, Article number: 276 (2020)
3. https://www.eurekalert.org/pub_releases/2020-10/fefu-sma103020.php
Competing interests: No competing interests
Dear Editor,
I have a couple of comments on this study:
1 - The study assumed that all measurements before participants were infected were reference measurements, which is not a valid assumption. I know it will require a large cohort study with tens of thousands of participants to measure the state before and after the infection, but this will be the best way to quantify the exact damage done by the infection excluding any unknown issues. Because with 20% hospitalization rate in the participants, it is not really reasonable to assume that individuals were in perfect condition before infection.
2 - In order to plan health care resources that may be needed in the future, it will be helpful if the study can classify the effects based on how much health care is needed. Some mild symptoms may not require any health care resources while others may require a lot. Also quantifying the rate of long-covid per infection in the general population will be very important in planning health care resources.
Competing interests: No competing interests
Dear Editor,
The extent and dimensions that the Pandemic has assumed are unfathomable. The duration, with no end in sight, the number of people it has infected and the number of people it has affected without infecting them, the number of deaths it has caused, the economic, social, educational and family life aspects it has affected were never thought of in recent times.
The article outlines the damage CoVID-19 causes to various organs in the majority of people and how multiple organs may be involved simultaneously, as well as how long the anomalies may persist beyond the acute stage.
It is going to be really a daunting task to plan around care for the victims of CoVID-19, and it will have to encompass the near ones and dependants of these people as well.
Arvind Joshi MBBS MD FCGP FAMS FICP.
Competing interests: No competing interests
Re: Why do women account for 70% of patients with Long COVID in this study?
Dear Editor
How strange that this article on Long COVID did not discuss the point that 70% of the patients were women. As suggested by Dr Ellen Grant in her rapid response, this could mean a possible association with use of hormonal contraceptives or HRT. Her comment about the known biochemical abnormalities associated with use of these hormones is important. Magnesium deficiency from hormonal contraception may be relevant as magnesium is necessary for vitamin D absorption. Vitamin D is an anti-oxidant which is recommended by many authorities as prophylaxis for COVID-19 and as part of the treatment for this condition. Zinc can also be lowered by use of sex steroid hormones and zinc has also been suggested for COVID-19 prophylaxis.
This surprising sex incidence needs further investigation.
Competing interests: No competing interests