Helen Salisbury: What might we learn from the covid-19 pandemic?BMJ 2020; 368 doi: https://doi.org/10.1136/bmj.m1087 (Published 17 March 2020) Cite this as: BMJ 2020;368:m1087
All rapid responses
One parallel learning point is the issue of staff support during uncharted times. Tired staff are having to join the fray of shoppers only to find empty shelves in stores.
Perhaps hospital canteens and shops can play a more proactive role in providing a few essentials and perhaps takeaway food for tired staff who then would not have to waste time scouting for supplies.
Hospital managers could perhaps look at this.
Competing interests: No competing interests
Firstly, before the pandemic, a patient with complex co-morbidities who was unwell at home would have had a GP visit. This would sometimes be followed by a district nurse visit to check blood tests, a visit from relative who needed to fetch medication from a pharmacy, and a referral to the local Health Hub for an assessment and an increase in care visits until the patient was feeling better. Is it possible to continue with this level of activity? We need to think hard about whether patients should be visited at home by primary care teams and if so in what circumstances? Do we risk spreading the virus by visiting and doing more harm than good?
Secondly, what will get missed if we assume that the only problem a patient has is viral pneumonia aggravated by bacterial infection. Currently a lot of patients are rightly being assessed remotely as needing antibiotics, but they may well have other needs which in the current state of play are at risk of getting missed.
Patients at home may commonly develop not only pneumonia, but exacerbation of COPD or asthma, urinary tract infection, worsening of heart failure, and acute kidney injury due to medication interactions and dehydration. When we are conducting assessments in the elderly, we need to include a review of co-morbid conditions so that we can prescribe inhalers, spacers, increase diuretic medication in heart failure or stop interacting medications in suspected acute kidney injury for the duration of the illness. Creating a comprehensive Covid 19 template which includes a review of co-morbidities and a safe way of managing these by making short term adjustments in medication is something we quickly need to include in our new management pathways.
Finally, how can we integrate patient's wishes for their chosen place and style of care into the current medical model? More work needs to be done on the logistics of respecting patient's wishes so that patients have care and contact wherever they are, within the confines of what is possible and safe for patients and staff in the coming months.
Competing interests: No competing interests
At times like this, we have to make it up as we go along. There isn’t time to go through the hoops of obtaining official permission to change the way things are done. Just do it, and ask for absolution if necessary. And since we know that there are not enough doctors and nurses in the world to go round, I expect that we will find new, realistic and acceptable ways for providing good care with fewer staff.
Patients, society, management and lawyers have become less tolerant of risk. How much certainty is required of responsible medical practice? 90%? 95%? 99.5%? The cost of reducing uncertainty can be high; for the health service and sometimes for patients. My own experience of VOMIT syndrome (Victim Of Modern Imaging Technology) brought that home to me. I hope that covid-19 will help us accept that we live in an uncertain world.
Competing interests: No competing interests
The effectiveness of ACE inhibitors/angiotensin II receptor blockers and nicotine in patients infected with Covid 19
Coronavirus (2019-nCoV); It is a virus belonging to the same family that first appeared in Wuhan city of China, causing symptoms like SARS coronavirus (SARS CoV) (1). SARS CoV first appeared in 2002 and virus-cell interaction has been demonstrated by genomic studies. SARS CoV-host cell interaction is inoculated into host cell via spike protein receptor-binding domain (RBD)-host receptor angiotensin-converting enzyme 2 (ACE2).2019-nCoV RBD binds virus-host cell interaction directly to the host cell by receptor-binding motif (RBM)-ACE2 receptor interaction. With the 2019-nCoV RMB (particularly Gln493) it interacts directly with the ACE2 receptor on the human cells. 2019-nCoV RBM (particularly Asn501) has been identified as another receptor that binds to ACE2, emphasizing that it can play an important role in the transition from person to person. Phylogenetic analysis showed the bat as a source of 2019-nCoV and was defined as an intermediate host, linking the ACE2 receptor relationship to this intermediate host. Therefore source of 2019-nCoV, intermediate host-receptor relationship and ACE2 receptor-human cell interaction have been revealed and definitions have been made for epidemic disease (2,3).
Renin angiotensin aldosterone system (RAS) plays an important role in regulating blood pressure and fluid electrolyte balance. RAS activation is mainly provided by angiotensin II and to a lesser extent aldosterone. While 10-20% of the enzymatic reaction of RAS takes place in the systemic circulation, 80-90% takes place in the tissues. The major source of circulating RAS is the kidneys that secrete renin. In the RAS, angiotensinogen is converted to angiotensin I by angiotensin converting enzyme (ACE) (4).Oparil et al. (5) emphasized that 90% of the conversion of angiotensin I to angiotensin II in physiological conditions occurs in the lungs.Studies demonstrated that local RAS autocrine and paracrine effectslead to tissue damage through immunological, metabolic and growth factors. (6) ACE has crucial tasks in the kinin-kallikrein system and RAS. On the 17th chromosome, two separate forms encoded with two separate mRNAs were found. High molecular weight ACE is mostly found in endothelial, epithelial and neuronal cells, while low molecular weight ACE is found in germinal cells. Only 10% of ACE, which is a membrane ectoenzyme, is free in plasma, while 90% of it is attached to the cell membrane.
In physiological conditions, the highest ACE activity is found in the lungs and converts angiotensin I into angiotensin II (7).The first ACE homologue shown in humans is ACE2 and is localized on the X chromosome.It is found in the coronary and intrarenal vascular endothelium, renal tubular epithelium and testicles. ACE forms angiotensin II (angiotensin1-8) by separating two amino acids from angiotensin I, while ACE2 forms angiotensin II (angiotensin 1-9) by separating leucine amino acid from angiotensin I. Angiotensin 1-9 is converted to angiotensin 1-7 with ACE and other peptidases.Angiotensin 1-7 prevents the effects of Angiotensin II by inhibiting ACE, increasing bradykinin, nitric oxide and prostaglandin 12. The inability to inhibit ACE2, a different member of RAS, with ACE inhibitors and angiotensin II receptor blockers occurs due to the different effects of the two forms. Thus, decreasing ACE2 impairs the cardiac contractility and andelevates angiotensin II levels. Increased angiotensin II leads to hypertension and tissue damage through secondary effect. ACE inhibitors and angiotensin II inhibitors can be effective in solving the problem.
Angiotensin converting enzyme 2 suppresses the production of angiotensin II with ACE inhibition. Blockage of ACE2 by COVID19 causes increase in angiotensin II and tissue destruction. ACE2 receptors blocked by Covid 19 will indirectly cause an increase in ACE-Angiotensin II. This will lead to inflammation, impaired tissue circulation with reduced levels of bradykinin, nitric oxide and prostaglandin 12. There is no treatment modality in the current literature to prevent blockage of ACE2 receptors. In a study on nicotine and RAS, Joshua et al.(8) reported that nicotine induced ACE upregulationwhile ACE2 was downregulated. It may be possible to break down the ACE2-Covid19 receptor interaction with nicotine. Nicotine replacement therapies used to quit smoking may be a glimmer of hope in the treatment of covid19. NRT forms are sold in the market as nicotine gum, transdermal patch, nicotine nasal spray, nicotine inhaler and nicotine sublingual tablets / lozenges (9). However, further randomized, prospective, controlled studies should be conducted to assess the outcome of the treatment.
Conclusion: In patients infected with COVID 19, the use of ACE inhibitors and angiotensin II receptor blockers should be effective. ACE2 receptor downregulation can be achieved with nicotine and Covid19-cell interaction may be somewhat broken. Nicotine band therapy may be a treatment option for patients who are not infected.
Giresun University, Faculty of Medicine, Department of Urology, Giresun, Turkey.
Conflicts of Interest: The author declares no conflict of interest.
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Competing interests: No competing interests
During the last several months the world has watched as CoVid-19 spread. With countries imposing various degrees of containment and quarantine, pandemonium set in before the announcement of a pandemic by the WHO on 11 March 2020 - as fear spread faster than the virus.
Let us take a moment to reflect on what we know and what we can learn from this virus.
FIRST – What we know about CoVid-19.
This Coronavirus is behaving exactly like a virus. This means it is transmitted in specific ways: it attaches to certain tissues within the body and its goal is not to kill its host but to survive within the host.
If we knew nothing more, that should be enough to calm our fears and promote cooperation among all of us. That should be enough to halt the run on store products and stop the price gouging of toilet paper, tissue, hand cleaner, and other items, while calmly promoting restoration of the stock market, the world economy, and our countries.
This virus is transmitted by people sneezing or coughing on you. Masks are for those people who are coughing and sneezing—for them to wear to reduce their coughing or sneezing their virus upon you—not for you to wear when you’re not the one coughing or sneezing. This behavior of everyone wearing masks doesn’t stop the spread; in fact, it may increase the potential for warm moist areas for the virus to survive and it promotes unnecessary fear.
(1) A major method of spreading the virus includes touching your face with your hands and then spreading the virus by touching others, as well as increasing the likelihood of further infecting yourself with more of the virus.
(2) The virus attaches itself to the lungs and GI tract, where IgA is primarily responsible for addressing immunologic responses. This means we know what to look for and what to treat, allowing those who are sickest to be best taken care of. This is why we see the immune-compromised elderly and those with heart and lung problems most susceptible.
(3) Viruses don’t try to kill their host: if they were successful at that, it would prevent them from reproducing themselves and surviving.
SECOND – What we can learn from CoVid-19.
CoVid-19 presents us with a unique opportunity to learn and potentially develop new treatments for IgA disorders, CAD, and cancer.
While this virus is clearly harmful—especially to those whose health is already limited (including the “elderly” and people with serious health problems)—it is important to note even in the face of this adversity what we can learn from this virus.
(1) First, CoVid-19 is primarily a virus that attacks the pulmonary and gastrointestinal systems of the body. Although the emphasis has been placed on the development of pneumonia, it can also cause diarrhea. The significance of this, at least initially, is the importance IgA plays in the immunologic defense of our bodies. Thus, CoVid-19 presents us with a unique opportunity to better understand the role of IgA. The potential discoveries—as with most—may hold the key to understanding and treating other life-threatening diseases [1-3].
(2) Secondly, coronary artery disease (CAD) is an inflammatory process and as explained by the first author; bacteria, viruses and other infectious diseases can be involved in the development or progression of CAD [4,5]. It is possible that not only are some of the deaths associated with CoVid-19 due to pneumonia... but also due to CAD, especially given the increased incidence of deaths in the elderly and individuals with co-morbidities. Therefore, an understanding of CoVid-19 may hold potential insights and treatment options for CAD.
(3) Thirdly, Coronaviruses get into the cells of our bodies via a receptor on our cells coded for by the ACE2 gene. This gene is involved in the angiotensin converting enzyme (ACE) pathways involved in high blood pressure. We also have information suggesting that vitamin D may be important in regulating this by reducing the renin-angiotensin system (RAS) itself [6-8]. It is also true that CoVid-19 pneumoniae may respond favorably to certain anti-malaria drugs, which appear to increase the production of interferon and inhibit stimulation of toll-like receptors [9-11]. This information may provide treatment options for those who are most critically ill at this time.
(4) Finally, and not the least important, CoVid-19 has an unusually large amount of ribonucleic acid (RNA) compared with most viruses. It is thought that viruses tend to have less RNA due to problems associated with replication of the RNA. The greater the amount of RNA, the greater the potential for errors in replication and self-extinction of the virus. CoVid-19 is unique! What we have started to learn is that CoVid-19 appears to have within this additional RNA the genetic information to correct the errors in replication, thus avoiding this extinction process. CoVid-19 appears to have the ability to correct errors introduced and restore the correct original genetic code. The ability to correct transcription and translation errors in human cellular genetic material - resulting from insults to the genome, causing mutation changes  resulting in increased metabolism and regional blood flow differences [4,14] eventually resulting in cancer [8,13-15] – by understanding how CoVid-19 is able to do this, could provide us with a unique opportunity to better understand and potentially treat cancer and CAD .
Humanity is scrambling to address an invader attacking our very immunologic system. This very invader—if we don’t lose sight of the forest for the trees—presents us with the potential to better understand and treat CAD, Cancer and our immunologic system–including, but not limited to, IgA disorders.
As the United States and other countries allocate money for testing, containment, and treatment—including potential vaccination—let us not lose sight over the possible lessons and knowledge being provided to us by CoVid-19. Let us hope and ask that our governments will look at both the forest and the trees and provide money to investigate what CoVid-19 has to teach us about CAD, Cancer, and these IgA disorders, and not merely do a knee reflex and miss the opportunity to investigate this evolutionary information being presented to us by CoVid-19.
Hope and knowledge, after all, is very contagious—more contagious than this virus.
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4. Fleming RM. Chapter 64. The Pathogenesis of Vascular Disease. Textbook of Angiology. John C. Chang Editor, Springer-Verlag New York, NY. 1999, pp. 787-798.
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7. A. Kaparianos and E. Argyropoulou, “ Local Renin-Angiotensin II Systems, Angiotensin-Converting Enzyme and its Homologue ACE2: Their Potential Role in the Pathogenesis of Chronic Obstructive Pulmonary Diseases, Pulmonary Hypertension and Acute Respiratory Distress Syndrome”, Current Medicinal Chemistry (2011) 18: 3506. https://doi.org/10.2174/092986711796642562.
8. Jia H. Pulmonary Angiotensin-Converting Enzyme 2 (ACE2) And Inflammatory Lung Disease. Shock 2016;46(3):239-248.
9. Arpaia N, Barton GM. Toll-like Receptors: Key Players in Antiviral Immunity. Curr Opin Virol. 2011;1(6):447-454.
10. Schrezenmeier E, Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nature Reviews Rheumatology 2020;16:155-166.
11. Colson P, Rolain J-M, Lagier, et al. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents 2020. https://doi.org/10.1016/j.ijantimicag.2020.105932.
12. Yao X, Ye F, Zhang M, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020; doi: 10.1093/cid/ciaa237
13. Fleming RM, Fleming MR, Chaudhuri TK, McKusick A. Cancer: Our Body’s Global Warming Warning. Biomed Research. Open Acc J Oncol Med 2019;3(1):238-239. DOI: 10.32474/OAJOM.2019.03.000154
14. Fleming RM. Angina and coronary Ischemia are the result of coronary regional Blood Flow Differences. J Amer Coll Angiol 2003;1:127-42.
15. Fleming RM, Fleming MR. The Importance of Thinking about and Quantifying Disease like Cancer and Heart Disease on a “Health-Spectrum” Continuum. J Compr Cancer Rep 2019;3(1):1-3 (Article ID 100011).
16. Fleming RM, Fleming MR, Chaudhuri TK. FMTVDM provides first patented Quantitative Method to accurately Measure both Heart Disease and Breast Cancer on the “Health-Spectrum”. J Cardiovasc Med Cardiol 2019;6(2):019-020. DOI:10.17352/2455-2976.000084.
Acknowledgments: FMTVDM is issued to the first author. The first author authored the Theories on “Inflammation and Heart Disease” and “Angina.”
Competing interests: Acknowledgments: FMTVDM is issued to the first author. The first author authored the Theories on “Inflammation and Heart Disease” and “Angina.”