Encyclopedia
COVID-19 is a dangerous disease that has been treated with dangerous and ineffective drugs like chloroquine and hydroxychloroquine. Nonsteroidal anti-inflammatory agents may also be dangerous in the disease due to embolism formation. Safe and potentially effective alternative medicines are proposed.
- COVID-19
- embolism
- alternative medicines
- inflammation
- NSAIDS
1. Introduction
In about 70% of people, COVID-19 damages the lungs causing coughing, shortness of breath and pain with breathing [1]. D-Dimer blood levels increase, perhaps due to pulmonary microembolisms [1].
2. COVID-19 Mechanisms of Lung Damage and Treatment
Computed tomography shows peripheral distribution of lung damage with ground glass opacity and bilateral patchy shadowing [1]. Macrophages invade into the lungs and become inflammatory dendritic cells [2]. These cells contain cyclooxygenase-2 that makes prostaglandins that interact with prostaglandin receptors and transient receptor potential cation (TRP) channels to induce pain and inflammation [3]. Inflammatory dendritic cells activate T cells, including Th2 and Th17 cells that produce cytokines and chemokines. Chemokines can attract neutrophils and more macrophages into the lungs. Neutrophils are probably involved in lung damage. High blood levels of neutrophils are associated with severe illness in COVID-19 [1]. Neutrophils secrete leukotrienes, such as leukotriene B4 [4] that activate TRP channels causing pain and inflammation [5]. Monoterpenoids such as camphor, cineole and menthol inhibit TRP channels [6][7][8]. Administration of small doses of monoterpenoids to COVID-19 patients may help with pain and inflammation in the lungs. Monoterpenoid preparations are available that can be applied inside the lower nostrils with cotton swabs. Evaporation of the monoterpenoids leads to inhalation into the lungs. Inhibition of inflammatory dendritic cell activity might also help with pain and inflammation in the lungs. Chloroquine and hydroxychloroquine are known to inhibit inflammatory dendritic cell activity [9][10]. Echinacea preparations and Sambucus nigra flower preparations can also inhibit inflammatory dendritic cell activity [11][12]. S. nigra might additionally increase tumor necrosis factor levels [13] and should be used only very early in disease progression to avoid cytokine release syndrome.
Embolism is an important feature of COVID-19 including prominent pulmonary embolism in 30% or more of patients [14]. The use of nonsteroidal anti-inflammatory agents such as aspirin, ibuprofen, naproxen and acetaminophen should be discouraged in the disease since these drugs increase embolism formation and may increase the incidence of heart attacks, strokes and other coagulation events.
References
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- X. Li, M. Geng, Y. Peng, L Meng, S Lu, Molecular immune pathogenesis and diagnosis of COVID19. J. Pharmaceutical Anal. in press (2020).
- T. Taylor-Clark, B. Undem, D. MacGlashan, S. Ghatta, M. Carr, M. McAlexander, Prostaglandininduced activation of nociceptive neurons via direct interaction with transient receptor potential A1 (TRPA1). Mol. Pharmacol. 2008, 73, 274-281.
- B. Robinson, D. Rathjen, N. Trout, C. Easton, A. Ferrante, Inhibition of neutrophil leukotriene B4 production by a novel synthetic N-3 polyunsaturated fatty acid analogue, β-Oxa 21:3n-3. J. Immunol. 2003, 171, 4773-4779.
- S. Vigna, R. Shahid, J. Nathan, D. McVey, R. Liddle, Leukotriene B4 mediates inflammation via TRPV1 in duct obstruction-induced pancreatitis in rats. Pancreas 2011, 40, 708-714.
- H. Xu, N. Blair, D. Clapham, Camphor activates and strongly desensitizes the transient receptor potential vanilloid subtype 1 channel in a vanilloid-independent mechanism. J. Neurosci. 2005, 25, 8924-8937.
- T. Masayuki, F. Fumitaka, U. Kunitoshi, Y. Satoshi, S. Maki, H. Chihiro, S. Mayumi, T. Makoto, 1,8cineole, a TRPM8 agonist, is a novel natural antagonist of human TRPA1. Mol. Pain 2012, 8, 86-98.
- J. Abe, H. Hosokawa, Y. Sawada, K. Matsumura, S. Kobayashi, Ca2+-dependent PKC activation mediates menthol-induced desensitization of transient receptor potential M8. Neurosci. Let. 2006, 397, 140-144.
- P. Gautreta, J. Lagiera, P. Parola, V. Hoang, L. Meddeb, M. Mailhe, B. Doudier, J. Courjone, V. Giordanengo, V. Esteves Vieira, H. Tissot Dupont, S. Honoré, P. Colson, E. Chabrière, B. La Scola, J. Rolain, P. Brouqui, D. Raoult, Hydroxychloroquine and azithromycin as a treatment of COVID19: results of an open-label non-randomized clinical trial. Int. J. Antimicrobial Agents in press 17 March (2020).
- R. Thome, L. Issayama, R. Digangi, A. Bombeiro, T. Alves da Costa, I. Ferreira, A. Rodrigues de Oliveira, L. Verinaud, Dendritic cells treated with chloroquine modulate experimental autoimmune encephalomyelitis. Immunol. Cell Biol. 2013, 92, 1-9.
- C. Wang, M. Chiao, P. Yen, W. Huang, C. Hou, S. Chien, K. Yeh, W. Yang, L. Shyur, N. Yang, Modulatory effects ofEchinacea purpureaextracts on human dendritic cells:A cell- and genebased study. Genomics 2006, 88, 801-808.
- G. Ho, H. Wangensteen, H. Barsett, Elderberry and elderflower extracts, phenolic compounds, and metabolites and their effect on complement, RAW 264.7 macrophages and dendritic cells. Int. J. Mol. Sci. 2017, 18, 1-17.
- V. Barak, T. Halperin, I. Kalickman. The effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines: I. Inflammatory cytokines. Eur. Cytokine Netw. 2001, 12, 290-296.
- I. Leonard-Lorant, X. Delabranche, F. Severac, J. Helms, C. Pauzet, O. Collange, F. Schneider, A. Labani, P. Bilbault, S. Moliere. Acute pulmonary embolism in COVID-19 patients on CT angiography and relationship to D dimer levels. Radiol. April 23, 2020.
