Fang and his colleagues have suggested to investigate the genetic predisposition for an increased risk of SARS-CoV-2 infection and they’ve proposed an explanation that might be linked to its receptor ACE2 polymorphisms1. The author agrees with their suggestion and would like to discuss it in a more elaborative manner.ACE2 polymorphisms and its induced mutations have been previously linked to enhanced susceptibility of heart diseases including coronary heart disease, myocardial infarction as have been revealed both clinically and experimentally2,3. Further, The ACE2 rs4646188 variant was suggested as a potential and optimal genetic susceptibility marker for essential hypertension, dyslipidemia and its related ischemic stroke4. Similarly, three ACE2 variants (rs4240157, rs4646155, and rs4830542) were found to be associated with essential hypertension and hypertension-related atrial fibrillation and left atrial remodeling5 Further, genetic variants in the ACE2 gene have been suggested to be associated with left ventricular mass, septal wall thickness and left ventricular hypertrophy in hemizygous men6. Noteworthy, genetic variants in the ACE2 gene were significantly associated with diastolic blood pressure responses to cold stress in the Chinese female population7. The author would like to suggest that It might be probable that ACE2 polymorphisms in the lungs could be one of the causes linked to a higher morbidity and/or mortality rate encountered in some groups of COVID-19 patients rather than the drugs suggested by Fang and his colleagues which have been refuted8. Further, these polymorphisms might also be one of the answers why some young, apparently healthy adults have been deceased while some very old patients have been rescued. The author recommends examining COVID-19 autopsies, consented before death for organ transplantation, to explore this hypothesis as it might help us to develop some genetic tests to warn those more susceptible individuals and exempt vulnerable health care professionals from duty.Conflict of interests:The author has no conflicts of interest to declare.Funding:None.References:1. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? The Lancet Respiratory Medicine 2020;8:e21.2. Wang W, Patel VB, Parajuli N, et al. Heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease. Journal of Molecular Medicine 2014;92:847-58.3. Yang W, Huang W, Su S, et al. Association study of ACE2 (angiotensin I-converting enzyme 2) gene polymorphisms with coronary heart disease and myocardial infarction in a Chinese Han population. Clin Sci (Lond) 2006;111:333-40.4. Pan Y, Wang T, Li Y, et al. Association of ACE2 polymorphisms with susceptibility to essential hypertension and dyslipidemia in Xinjiang, China. Lipids Health Dis 2018;17:241.5. Luo Y, Liu C, Guan T, et al. Association of ACE2 genetic polymorphisms with hypertension-related target organ damages in south Xinjiang. Hypertens Res 2019;42:681-9.6. Lieb W, Graf J, Gotz A, et al. Association of angiotensin-converting enzyme 2 (ACE2) gene polymorphisms with parameters of left ventricular hypertrophy in men. Results of the MONICA Augsburg echocardiographic substudy. J Mol Med (Berl) 2006;84:88-96.7. Huang J, Chen S, Lu X, et al. Polymorphisms of ACE2 are associated with blood pressure response to cold pressor test: the GenSalt study. Am J Hypertens 2012;25:937-42.8. ACEIs, ARBs, Ibuprofen linked to COVID-19: The other side of the broken mirror. 2020, June 2,. at https://www.authorea.com/users/318758/articles/456017-aceis-arbs-ibuprofen-linked-to-covid-19-the-other-side-of-the-broken-mirror?commit=c85d790e9c1c2a3e698675ed1798efe534abdfa7.)
Until recently, ibuprofen has been avoided in all COVID-19 protocols world-wide. The author has been trying since March, 2020 to publish a paper that disputes this unfortunate incident and he finally managed since May 2020 to publish two manuscripts that not only prove non-steroidal anti-inflammatory drugs not harmful for COVID-19, rather they were shown to possess a potential to cure the disease based on a unique new theory suggested to explain COVID-19 pathogenesis and he suggested NSAIDs to be added to unique protocol he suggested using nitazoxanide/azithromycin to manage early cases of COVID-19. In this manuscript, considered the fourth related to the subject, the author represents the first clinical results of using NSAIDs/Nitazoxanide/Azithromycin protocol, used partly or fully, that includes relatively cheap FDA approved drugs used in seventeen Egyptian patients, whether confirmed or suspected, including children, adults and two pregnant ladies whom have been mostly symptoms-free in five days. The manuscripts also presents a road-map to illustrate how to deal efficiently with early cases of COVID-19 according to the author’s clinical experience.
Multiple reports all over the world are hypothesizing a possible relationship between BCG vaccination, and a lesser incidence of and mortality from COVID-191. China is considered as one of the heavily affected countries and it was the first to report COVID-19, the author will examine this hypothesis using China as an example.According to the WHO global tuberculosis report 20192, it’s stated that in 2018, among 180 countries for which data were collected, 153 countries have properly reported administration of BCG vaccination as a standard part of childhood immunization programmes, of which 113 reported coverage of ≥90% (Figure 1). In the same report, China has accomplished a 99% BCG vaccination coverage, to be considered as one of the top countries providing this coverage rate all over the world. Moreover, the reported estimates for the global BCG coverage according to the WHO monitoring system for vaccine-preventable diseases has revealed that BCG vaccination coverage in China to be either 99% or 100% for the years 2009 to 20183. Thus, we may reasonably consider that all children, currently 10 years old or younger and living in China, are efficiently covered and immunized by BCG vaccination.Interestingly, as of the 11th of February, 2020 the Chinese Center for Disease Control and Prevention has reported 416 laboratory-confirmed pediatric cases; aged 0–9 years4. Moreover, another study, published about one month later, has researched 2143 pediatric Chinese patients who were both laboratory-confirmed as well as suspected cases, and concluded that children at all ages appeared susceptible to COVID-19 and it’s also reported that the proportion of severe and critical cases was 10.6 %, 7.3%, 4.2% for the age group of <1, 1-5, 6-10, respectively. Noteworthy, this study has suggested that the majority of COVID-19 pediatric patients were less severe in their medical condition than adults’ cases because children are usually well cared for at home and might have relatively less opportunities to expose themselves to SARS CoV-25.Thus, basing on the above analysis, the author suggests that stating that BCG vaccination could prevent COVID-19 infection should be considered as a myth. Moreover, the author considers stating that countries which have adopted childhood BCG vaccination might be the reason for a lower morbidity or mortality of COVID-19 for adults immunized at birth, should be also considered as another myth, as revealed by the incidence of adults’ morbidity and mortality rates reported in China as well as several other countries that have adopted childhood BCG vaccination. However, BCG vaccination given once a month for three consecutive months has previously showed a benefit against adult upper respiratory tract infections in the elderly6 and it might prove the same benefits against COVID-19 if administered to unimmunized adults or re-administered to previously immunized adults waiting for the results of the undergoing clinical trials7. On the other hand, BCG vaccination might or might not have some ameliorative benefits for immunized children affected by COVID-19 and this suggested positive association is highly unlikely to be properly proved because of multiple confounding factors. Finally, please keep and remain vigilant till the world finds a cure for COVID-19, this is an evidence-based medicine piece of advice.Funding:NoneConflict of interests:NoneFinancial disclosure:None
This article discusses from a pharmacological point of view, the points of weakness in a correspondence published at the Lancet Respiratory Medicine that has suggested a hypothesis relating ACEIs, ARBs and ibuprofen to be associated with a higher risk for COVID-19 infection and complications. This article also explains some unfortunate mistakes that have been made by some who have adopted this hypothesis and decided to unwisely recommend against these important drugs.
The pathogenesis of Coronavirus disease 2019 is still obscure, indeed it’s only few months since it has been first reported on December 2019, yet the need for exploration of possible mechanisms, suggestion of new drugs should never be delayed. In this communication, the author proposes an integrated pathophysiological as well as pharmacological COVID-19 approach to recommend using anti-inflammatory drugs, other than glucocorticoids, suggesting ibuprofen as an example, to be added to his recently published suggested COVID-19 early management protocol. A possible explanation for the potential failure of hydroxychloroquine for COVID-19 is also explained according to the suggested concept. The author is fully aware of the ibuprofen contradictory hypothesis; as discussed and argued against in this report.