In the winter 2003/2004 about 50.000 people died in the UK of the consequences of cold weather, over 2.500 in one week. The deaths were mostly elderly people who died of heart or breathing problems and most of them had an underlying disease.[1]
The dimension of the death toll and the profile of the victims has some similarities with the current Covid pandemic. Of course, there are fundamental differences. Cold weather will go away and protective measures like closing of boarders, social distancing, masks and disinfections are not needed, medical staff is not endangered, and people do not die alone. But despite these fundamental differences, the cold wave of Great Britain might teach us some important lessons for the disease Covid19.
The first question we have to ask is why did more people die during the cold in Britain than in Russia where the weather is colder, people are poorer and medical treatment less available? Is it simply the fact that the Russian people are more used to such kind of weather? The second question is why are mostly older people concerned?
It is quite safe to state that a lot of people had a reduced ability to adapt to changing weather conditions. They had a reduced robustness or resilience.
The concept of resilience is central in preventive medicine and the core of naturopathy. It refers to the ability of the organism to face disturbances and to stay healthy. This includes all kind of somatic and psychological stressors and, of course, infections. A functioning immune system is an essential characteristic of a good working organism.
The immune system of older people does not work that well. They suffer from different diseases and ailments. They have a reduced resilience in general. Is this a question of age? Or has it to do with life-style factors? Bad lifestyle is known to have an important impact on mortality.[2] Some say it costs 9 years of life.[3] But such calculations have been made under normal conditions, not during the challenge of a pandemic or cold wave. Then we expect more casualties among people with reduced resilience.
A healthy lifestyle is based on three pillars: exercise, healthy diet and good sleep. For each of these pillars there is an abundant literature demonstrating that they all three support the immune system. As it is difficult even for younger people to change habits, it is nearly impossible for the elder. Now in quarantine, we have the time to invest into our health. But will we take the challenge and do so? It would be important. Otherwise we are worse off during the next wave of the disease – in case it will go away this summer.
We might expect the solution in drugs or vaccination. But how good will they work? In the case of the flu both do not perform too well. Investing into the three pillars remains the most important prevention for Covid-19, and of many other diseases as well. It is also the best therapy for psychological disturbances, and it is perfect stress management
The influence of drugs
Between August 4 and 18, 2003 about 15.000 people died during a heat wave in France.[4]
The number of casualties, although rather high, is clearly less than the victims from Covid-19. But we have to stay with the question why more people died in France compared to Portugal with similar weather conditions.
But there is a further aspect.
For example, beta receptor blockers are helpful in a lot of diseases from hypertension over glaucoma to anxiety. One of its adverse reactions is that it reduces the reaction of the body during hot weather conditions, thus increasing heat-related mortality.[5]
In a society where a lot of these drugs are taken, we should expect more deaths from heat stroke during a heat wave. But the topic of medical induced susceptibility to heat stress and especially of the beta blockers had not been investigated by French authorities.[6]
Concerning Covid-19 different drugs have been accused of facilitating a severe infection. Among these had been anti-inflammatory drugs like ibuprofen,[7] cortisone, certain antihypertensive drugs (ACE inhibitors),[8] nasal sprays[9] and others. But for the moment there is no clear evidence. Even if there are certain indications that a drug might facilitate an infection, it will be difficult to find it out. Medicine in the time of the Coronavirus is often beyond its limits. Where shall such minute statistics come from?
But it is not only the action of one drug. There is another problem. It is called polypharmacy. In the United States, 44 percent of men and 57 percent of women over 65 take five or more drugs a week, and 12 percent take 10 or more.[10] Even in Sweden 74% of the elder are exposed to polypharmacy.[11] In the US often patients are released from hospital with up to 14 medicaments.[12] The situation in Greece is not different. My rule of thumb is that a person approaching the 70 takes 10 drugs a day.
This kind of polypharmacy in elder has severe clinical consequences for their health.[13] An impact onto the immune system and the regulation is very probable, but difficult to prove. How would it be possible to relate a higher mortality to one of these drugs? Firstly, everybody takes a different mixture. Secondly, when one takes more than 3-4 drugs the situation becomes unpredictable. This is called drug interaction: the combination of drugs might intensify side effects or lead to side effects not known from any of the drugs.
Polypharmacy is also a problem in the therapy of Covid-19. The details may be only interesting for professionals, but they are a part of the line of reasoning.
In several of his evening briefings Mr. Tsiodras, the responsible virologist for the handling of the Coronavirus pandemic, explained that patients receive the necessary antiviral drugs. However, currently (14.4.20) no proven effective therapies for this virus exist.[14] These therapies are not necessary, but experimental, mostly given by the wish to help, but without real evidence. The same is true for antibiotics that most people in China received.[15] They are given out of ‘empirical reasons’. Different drug combinations are tried. Antiviral drugs and Chloroquine together with Azithromycin. We hear about the “effective cocktail of the French professor Didier Rault.”[16] But the first studies with Chloroquine, a drug many based their hope on, had been stopped due to a high rate of deaths from cardiac complications, probably due to drug interactions.[17]
That means, it might not only be age and lifestyle factors that diminish resilience. Drug therapy might have a great share of the situation.
Public health and health service
There is another way how polypharmacy damages public health. All these drugs cost money, money that lacks the medical system. One of the outstanding examples are the ‘biopharmaceuticals’ or biologicals. They are often used, even if not absolutely necessary and where a therapy without drugs, such as improving life-style factors, physiotherapy and others, had only been superficially tried out or not been tried at all. With the money of even one therapy (lasting often for years or a lifetime) a nurse or even a doctor at a Greek hospital could be paid.
Public health service is mainly centered around providing drugs and hospital treatments. There had never been much interest in investing in public health, except with smoking, where a positive development can be seen. It is obvious that Greece had many other severe problems the last 20 years. But the lack of investment into the public health, into the actual health of the citizens and into the health institutions, will keep us much longer in quarantine. That will cost much more than any measures a government would have taken for public health earlier.
In Germany there had been always a big emphasis on public health from childhood on. Still some time ago, strong lay movements tried to improve the robustness of the people. This might be one reason why Germany does quite well during the coronavirus crisis.
The uncontrollable immune system
An interesting analysis of polytraumatised soldiers of the battles of Trafalgar, Waterloo of the United States Civil War revealed that the survival rate was then about the same as in today’s intensive care, despite all drugs and technology. The main reason for why current intensive care therapy does not prove better is the high incidence of sepsis.[18]
Sepsis is an overreaction of the immune system. It is one of the leading causes of death in Western countries and often seen in the severe cases of Covid-19, especially in the younger.[19] This explains why people in good health also die. During the Spanish flu the same motive had been seen: many mid-aged people died due to an overreaction of the immune system.[20]
This is why the study about the polytraumatized soldiers is important to us. Today polytraumatized patients get a much better care, but they die unfortunately often from sepsis, from an immune system out of control. The authors of the study attribute this high number of sepsis to the many drugs given in intensive care units, many of them have the tendency to impair the function of the immune system. They state: “The major advances of intensive care medicine in the last 20 years have been related more to the recognition and removal of harmful practices rather than to any novel pharmacological or mechanical interventions.”
One therapy, missing in their list of potentially harmful drugs, are antipyretics. The importance of fever and the potentially harmful use antipyretics will be discussed in the next article. That antipyretics might increase the severity of a viral disease had already been an issue during the Spanish flu. Aspirin, then a new and miraculous drug, that had been taken until the 60ies for every kind of ailment, had been extensively used during the Spanish Flu epidemic. It had been found in the fluid of the lungs of many people who died from pneumonia and is one reason that might have contributed to the high lethality of the disease.[21]
Conclusion
This journey through time and medicine had been necessary to show that we must have a much wider view of medicine and health in order to face the challenge of Covid-19. Viral diseases will continue to threaten our existence. Doing the best for our health is good practice. This pandemic would be a perfect opportunity to make a turn in our medical thinking, turning away from a drug-oriented approach where problems are just fixed, to a more health and joy based life.
15.4.20
[1] Griffiths S (2003): Reid defends winter deaths action. BBC News 23.12.03
http://newswww.bbc.net.uk/1/low/uk/3344157.stm
respectively: 2500 Kältetote in einer Woche. Spiegel online 23.12.03
http://www.spiegel.de/panorama/0,1518,279665,00.html
Wilkinson P, Pattenden S, Armstrong B, Fletcher A, Kovats RS, Mangtani P, McMichael AJ (2004): Vulnerability to winter mortality in elderly people in Britain: population based study, BMJ 329:647
[2] van Dam RM1, Li T, Spiegelman D, Franco OH, Hu FB (2008): Combined impact of lifestyle factors on mortality: prospective cohort study in US women, BMJ. 2008 Sep 16;337:a1440. doi: 10.1136/bmj.a1440
Veronese N, Li Y, Manson JE, Willett WC Fontana L, Hu FB (2016): Combined associations of body weight and lifestyle factors with all cause and cause specific mortality in men and women: prospective cohort study, BMJ. 2016 Nov 24;355:i5855. doi: 10.1136/bmj.i5855
[3] Clarke R1, Emberson J, Fletcher A, Breeze E, Marmot M, Shipley MJ (2009): Life expectancy in relation to cardiovascular risk factors: 38 year follow-up of 19,000 men in the Whitehall study, BMJ. 2009 Sep 16;339:b3513. doi: 10.1136/bmj.b3513
[4] Poumadère M, Mays C, Le Mer S, Blong R (2005): The 2003 heat wave in France: Dangerous climate change here and now, Risk Analysis 25; 6: 1483-1494
[5] Bouchama A, Knochel JP (2002): Heat stroke, N Engl J Med 346: 1978 – 1988
[6] Poumadère private email
[7] Are Warnings Against NSAIDs in COVID-19 Warranted? – Medscape – Mar 17, 2020
https://www.medscape.com/viewarticle/926940
[8] COVID-19 and Angiotensin Drugs: Help or Harm? – Medscape – Mar 25, 2020
https://www.medscape.com/viewarticle/927542
[9] COVID-19: Nasale Kortikosteroide bei allergischer Rhinitis weiterhin indiziert
[10] Saljoughian M (2019): Polypharmacy and Drug Adherence in Elderly Patients, US Pharm. 2019;44(7):33-36
[11] Wastesson JW, Morin L, Laroche ML, Johnell K (2019): How Chronic Is Polypharmacy in Old Age?, J Am Geriatr Soc. 2019;67(3):455-462
[12] Saraf, A. A., Petersen, A. W., Simmons, S. F., Schnelle, J. F., Bell, S. P., Kripalani, S., Myers, A. P., Mixon, A. S., Long, E. A., Jacobsen, J. M., & Vasilevskis, E. E. (2016). Medications associated with geriatric syndromes and their prevalence in older hospitalized adults discharged to skilled nursing facilities. Journal of hospital medicine, 11(10), 694–700. https://doi.org/10.1002/jhm.2614
[13] Maher RL, Hanlon J, Hajjar ER (2014): Clinical consequences of polypharmacy in elderly, Expert Opin Drug Saf. 2014 Jan;13(1):57-65. doi: 10.1517/14740338.2013.827660. Epub 2013 Sep 27.
[14] Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA. Published online April 13, 2020. doi:10.1001/jama.2020.6019
[15] Ding Q, Lu P, Fan Y1, Xia Y, Liu M (2020): The clinical characteristics of pneumonia patients coinfected with 2019 novel coronavirus and influenza virus in Wuhan, China, The clinical characteristics of pneumonia patients coinfected with 2019 novel coronavirus and influenza virus in Wuhan, China
Du Y, Tu L et.al. (2020): Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan: A Retrospective Observational Study, Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan: A Retrospective Observational Study
[16] https://www.enikos.gr/society/709377/koronoios-apotelesmatiko-to-kokteil-farmakon-tou-gallou-kathigiti
[17] Borba M, Almeida Val F et al. (2020): Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study), medRxiv 2020.04.07.20056424; doi: https://doi.org/10.1101/2020.04.07.20056424
Das Ärzteblatt (2020): COVID-19: Kleinere Studie mit Chloroquin wegen Komplikationen abgebrochen, 14.4.2020
[18] M, Glynne P. Treating Critical Illness: The Importance of First Doing No Harm. PLoS Med 2005;2(6):e167
https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0020167
[19] Tsiodras, evening bulletin 6.4.20
[20] Kobasa D, Takada A, et al. (2004); Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus, Nature 431: 703–707
[21] Starko KM (2009): Salicylates and Pandemic Influenza Mortality, Clinical Infectious Diseases, 2009; DOI: 10.1086/606060
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