Covid-19: what treatments are being investigated?
BMJ 2020; 368 doi: https://doi.org/10.1136/bmj.m1252 (Published 26 March 2020) Cite this as: BMJ 2020;368:m1252Read our latest coverage of the coronavirus outbreak
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
Dear Editor
During the past 2 decades, there has been a growing strand of viral infections from a corona-shape like viruses such as SARS-CoV, MERS-CoV, and most recently SARS-CoV-2, which is the deadliest amongst them all. SARS-CoV-2 is a newly recognized viral infection, which has spread rapidly from China to the whole world. The virus has been identified as a novel enveloped RNA betacoronavirus 2 given the title name severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2, which shares phylogenetic similarities to SARS-CoV (1). The term COVID-19 has been designated to patients who have developed clinical symptoms without apparent radiological manifestations (1).
As of July 13, 2020 the total number of global COVID-19 laboratory-confirmed cases is 12, 945, 828 with a mortality of 569, 878 mostly in the USA (2). The rate of COVID-19 infections has prompted the WHO on March 11, 2020 to declare it a global pandemic.
Duan and coworkers have evaluated the administration of convalescent plasma (CP) to 10 COVID-19 patients with severe symptoms (3). It was found that CP therapy was promising and it was well-tolerated by patients, leading to the disappearance of viremia, and improving symptoms and the clinical outcome of the disease. Other drugs were evaluated such as chloroquine, lopinavir and ritonavir (Kaletra), interferon β 1a (SNG001), remdesivir tocilizumab (Actemra), and favipiravir (Avigan), which all proved ineffective against COVID-19 (4).
Another approach might be to use plasma obtained from healthy children rather than CP or the other drugs discussed above. This stems from the fact that COVID-19 infectivity is uncommon in children and it appears that children are insusceptible to it. Pediatric studies have shown that children are less susceptible to COVID-19 and death cases are extremely rare (5). Only 2% of COVID-19 patients are younger than 19 years of age (6). Clinically, mild symptoms were observed with children without pneumonia and recovery was fast (7).
The non-susceptibility of children to SARS-CoV-2 might be related to the fact that the thymus gland and its hormones remain active during puberty where the thymus grows and reaches its maximum size and then starts to atrophy and decay (involution). Since the thymus is the primary site of de novo naïve T cell production (8), the presence of thymic hormones in the blood pool might be the reason for the resistance of children to COVID-19.
Accordingly, blood plasma obtained from healthy children administered to adult patients suffering from COVID-19 might cure the disease. However, since in most countries blood donation from children is considered illegal and unethical, an alternative approach would be to use blood from adults aged 18 to 20.
It is expected that plasma from young people enhances human thymopoiesis and treats patients suffering from COVID-19. Previously, it was found that growth hormone (GH) therapy can in fact enhance thymopoiesis, thus increasing thymic hormonal output and the production of de novo naïve and total CD4+ T cells, which in turn facilitated immune restoration in HIV-1 patients (9). The study concluded that thymic involution can be pharmacologically reversed and thymic function can be restored in immuno-deficient patients (9).
The thymus’ hormones are thymosin, thymopoietin, thymulin and thymic humoral factor all of which play vital roles in both the immune and endocrine systems. Any of these hormones, their progenitors, or chemical compounds which these hormones activate can be responsible for the resistance of children to COVID-19. One key essential hormone against COVID-19 might be the thymic humoral factor since it increases the immune system response to viral infections.
If the plasma approach proves successful, then research will focus on zooming in to pinpoint the specific agent(s) responsible for this non-susceptibility.
References
1. Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 Novel coronavirus: implications for virus origins and receptor binding. The Lancet. Issue 10224, 395, 565-574 (2020).
https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2930251-8
2. Johns Hopkins University & Medicine. Coronavirus Resource Center. https://coronavirus.jhu.edu/map.html.
3. Duan K, Li C, Zhang H, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. PNAS, Apr 2020, 202004168; DOI: 10.1073/pnas.2004168117.
4. Mahase E. Covid-19: what treatments are being investigated? https://www.bmj.com/content/bmj/368/bmj.m1252.full.pdf
5. Rasmussen S, Thompson L. Coronavirus disease 2019 and children what pediatric health care clinicians need to know. JAMA. Published Online April 3, 2010. file:///C:/Users/layla/Downloads/jamapediatrics_rasmussen_2020_vp_200009.pdf
6. Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. Published Online February 28, 2020. https://www.nejm.org/doi/pdf/10.1056/nejmoa2002032
7. Xu Y, Li X, Zhu B, et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med (2020). https://doi.org/10.1038/s41591-020-0817-4.
8. Tesselar K, Miedema F. Growth hormone resurrects adult human thymus during HIV-1. J Clin Invest. 118(3), 844-847 (2008). https://www.jci.org/articles/view/35112/pdf
9. Napolitano L, Schmidt D, Gotway M, et al., Growth hormone enhances thymic function in HIV-1-infected adults. J Clin Invest. 118(3), 1085-1098 (2008). https://www.jci.org/articles/view/32830/pdf
Competing interests: No competing interests
Dear Editor,
Since the coronavirus disease (COVID-19) and its virus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) emerged in Wuhan in the Hubei Province of China, global attention has focused on its
control and containment. Its rapid spread and the absence of an effective treatment or vaccine has caused COVID-19 to overwhelm even the most robust health systems in the world. [1] From January 2020 to
date, the cumulative number of cases is over 8.5 million with more than 450,000 deaths globally. Conceivably, therefore COVID-19 has the potential to decimate large populations especially those of low and middle-income countries with limited health infrastructure, personnel and resources, and thus a reason for the unrelenting efforts to control and prevent its spread. Among those who have died from the condition are senior government officials, policy makers and key front line health workers who are critical in the fight against the disease. [2] [3]
The virus, as has been well established, spreads through contaminated surfaces, droplets from saliva, sneezes and coughs and through aerosols (micro droplets) in breath. [4 5]. Public health measures adopted so far to contain COVID-19 have thus focused mainly on preventing the virus from entering the nasal and oral cavities. These include the isolation and quarantining of confirmed and suspected individuals, physical distancing, staying at home, regular hand washing with soap under running water, rubbing hands withalcohol-based sanitizers and the use of face masks.[6 7]. The provision of personal protective equipment for frontline staff has been key, considering their increased risk of contracting the disease.
MOUTH AND THROAT EXPOSURE
With growing numbers of asymptomatic individuals increasing the spread of the virus in communities as well as increasing concerns among dentists about its potential spread especially during aerosol generating procedures [8 9], it is extremely difficult to restrict the virus from entering the oral and nasal cavities, even with the available protective measures for clinicians especially surgeons (Dental, Oropharyngeal, ENT) not to mention anesthetists, physicians, nurses and support staff in critical care. In that regard, attention should therefore focus also on interventions that prevent viruses that have gained access to these cavities from invading host cells to cause disease. Such a measure, which is our present focus, could protect especially contacts of infected persons and at the same time, reduce viable viral load shed in saliva by asymptomatic carriers and cases.
Notably, the virus attaches to the angiotensin-converting enzyme 2 (ACE2) receptors in the most superficial cells in the non-keratinized epithelium of the oral cavity and oropharynx. It then uses its signaling and trafficking pathways to gain further access to infect the body [10]. These ACE2 receptors are also found in several other areas including the epithelial cells of the respiratory tract down to the alveoli. [11 12].
The incubation period of COVID-19 is 14 days with an average of 6.4 days. [8] How long the virus takes on entering the oral cavity and oropharynx to invade host cells is uncertain. If it is assumed that the whole of the infective process in the upper respiratory and the oropharynx regions takes 2-5 days, there is very little time, albeit a day or two, to intervene to prevent the virus from infecting an individual who has been exposed to it through the oral cavity. This demonstrates how speedily action should be taken to prevent a contact of COVID-19 from being infected.
Therapeutic mouthwashes that inactivate microbes in the oral cavity, the palatine fossa and the oropharynx include hydrogen peroxide. [13] This communication is advocating its use to limit the infectivity and spread of SARS-CoV-2 especially in countries and communities with inadequate healthcare delivery systems.
HYDROGEN PEROXIDE
Hydrogen peroxide has been used in dental practice for nearly 100 years and has been considered safe when used in low concentrations. [13] In a review on its safety, it had been noted that 3% hydrogen peroxide daily use for up to six years, showed only occasional or transient irritations in a minimal number of subjects who also had pre-existing lesions. [13 14] Even though this solution has mutagenic potential through its reactive oxygen species that could induce DNA damage, there has been no substantive evidence in the literature to support assertions that it causes cancer in humans. [14] It has been stated that “there is strong evidence for the safety of low concentrations of hydrogen peroxide products when used on daily basis and over an extended period” [14] Earlier, the International Agency for Research on Cancer also concluded after reviewing animal and human studies that “hydrogen peroxide is not classifiable as to its carcinogenicity in humans”.[15] In a recent study assessing carcinogenicity associated with exposure to hydrogen peroxide neither tissue irritation nor tumor promotion was observed in animal models. [16]
The efficacy of hydrogen peroxide has not been in doubt, especially about its capacity to inactivate corona and influenza viruses.[17] A recent review of studies on human coronaviruses has suggested that 0.5% hydrogen peroxide will inactivate SARS-CoV-2 on surfaces.[18] Furthermore, a suggestion has been made quite recently to buttress the view that 1% hydrogen peroxide may serve to prevent entry of the virus
into susceptible cells and reduce the possibility of severe disease.[19] We are proposing, therefore, that use of 1% hydrogen peroxide mouthwash and gargle, at least twice a day be added to the established WHO preventive protocols for SARS-CoV-2. This could augment protection of frontline health personnel, contacts of COVID-19 cases, and the highly vulnerable individuals such as the aged, security personnel, media staff, persons with underlying health issues and individuals in communities where the burden of COVID-19 is high.
Furthermore, since there is evidence that even 0.5% hydrogen peroxide could inactivate the SARS-CoV-2 on surfaces [18], this lower concentration could be used by individuals who may be more susceptible to tissue irritation, considering that its prophylactic use might be required over a long period. To further limit the risk of infecting others, asymptomatic individuals and mild to moderate cases could use hydrogen peroxide mouthwash and gargle to inactivate SARS-CoV-2 shed.
In conclusion, Hydrogen Peroxide that has been in use in dental practice with proven safety and efficacy could be employed in limiting the infectivity and spread of SARS-CoV-2 whilst awaiting the emergence of fail-proof prophylactic and therapeutic measures. We have planned a clinical trial of mouthwash and gargle with hydrogen peroxide compared with mouthwash or gargle with water only, in asymptomatic cases of
COVID-19.
*Andrews S. Ayettey. MB. ChB. PhD. Retired Professor, University of Ghana Medical School, College of Health Sciences. University of Ghana, Legon. Ghana. Email: seth.ayettey@gmail.com Twitter@ayettey_seth
Emerita Professor, Isabella A. Quakyi. PhD. FGA. School of Public Health, College of Health Sciences, University of Ghana, Legon. Ghana.
Hannah N.G. Ayettey-Anie. BSc (Med Sc) MB ChB FGCP, Senior Specialist, National Radiotherapy Oncology and Nuclear Medicine Centre, Korle Bu Teaching Hospital, Accra, Ghana.
Kwamena W. Sagoe. MSc PhD. Associate Professor, Department of Medical Microbiology, University of Ghana Medical School, College of Health Sciences. University of Ghana, Legon. Ghana.
Mary N. B. Ayettey-Adamafio. BSc (Med Sc) BDS FGCS FWACS. Senior Specialist, Department of Dentistry, Korle Bu Teaching Hospital, Korle Bu, Accra. Ghana.
Merley Newman-Nartey BDS MClD FGCS. Senior Lecturer, University of Ghana Dental School, College of Health Sciences, University of Ghana.
Ruth N. A. Ayettey Brew BSc (Med Sc), MB.ChB. Resident, Department of Obstetrics and Gynecology, Korle Bu Teaching Hospital, Accra. Ghana.
Nii Otu Nartey BDS MSc FAAOP MRCD FWACS FGCS Retired Associate Professor, University of Ghana Dental School, College of Health Sciences, University of Ghana.
Albert G.B. Amoah MB ChB, PhD, FWACP, FGCP, FGA. Retired Professor, University of Ghana Medical School, College of Health Sciences, University of Ghana.
Felix I D Konotey-Ahulu MD(Lond) FRCP(Lond & Glasg) DTMH(L'pool) Distinguished Professor of Human Genetics University of CapeCoast, Honorary Consultant Physician Specialist to Ghana Ministry of Health through Commissioner of Health Brigadier Odartey-Wellington 1976, and Former Consultant Physician, Korle Bu Teaching Hospital, Accra, and Phoenix Hospital Group 9 Harley St, London W1G 9AL.
*Corresponding Author Professor Seth Ayettey: Twitter@ayettey_seth
Acknowledgement: The authors acknowledge Mr. Benjamin Yankah of Accra, Ghana, for encouragement.
References
1. Preparedness, prevention and control of coronavirus disease (COVID-19) for refugees and migrants in non-camp settings. 2020. https://www.who.int/publications-detail/preparedness-prevention-and-cont...(covid-19)-for-refugees-and-migrants-in-non-camp-settings (accessed January 12 2020).
2. Thompson Adrian. OBITUARY of Amged El-Hawrani. Consultant ear, nose, and throat surgeon. (Born 1964; Qualified 1993), died from COVID-19 on 28 March 2020. BMJ 2020;369:m1658. Print Edition May 30
page 335.
3. Ali Jawad. A PERSONAL REFLECTION: Professor Jacob Plange-Rhule, BSc PhD MB. ChB. FWACP, FGCP, FRCP, Rector, Ghana College of Physicians and Surgeons (GCPS), Accra. Ghana. Born, 27th July 1957. Passed away on 10th April 2020 from COVID-19 https://www.rcplondon.ac.uk/news/professor-jacob-plange-rhule-personal-r.... (And Ali Jawad BMJ 2020; 369:m1982 (Print Edition 20 June page 461)
4. Liu J, Liao X, Qian S, et al. Community Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, Shenzhen, China, 2020. Emerg Infect Dis 2020; 26(6): 1320-3.
5. Li Q, Guan X, Wu P, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med 2020;382(13): 1199-207.
6. Wilder-Smith A, Freedman DO. Isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus (2019-nCoV) outbreak. J Travel Med 2020; 27(2).
7. Coronavirus disease (COVID-19) advice for the public. 2020. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-f... (accessed January 12 2020).
8. Wang Y, Wang Y, Chen Y, Qin Q. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures. J Med Virol 2020.
9. Peng X, Xu X, Li X, Cheng L, Zhou X, Ren B. Transmission routes of 2019-nCoV and controls in dental practice. Int J Oral Sci 2020; 12(1):1-6.
10. Cong Y, Ren X. Coronavirus entry and release in polarized epithelial cells: a review. Rev Med Virol 2014; 24(5): 308-15.
11. Xu H, Zhong L, Deng J, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci 2020;12(1): 8.
12. Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. bioRxiv 2020: 2020.01.26.919985.
13. Marshall MV, Cancro LP, Fischman SL. Hydrogen peroxide: a review of its use in dentistry. J Periodontol 1995; 66(9): 786-96.
14. Walsh LJ. Safety issues relating to the use of hydrogen peroxide in dentistry. Aust Dent J 2000; 45(4): 257-69; quiz 89.
15. Hydrogen Peroxide (group 3): International Agency for Research on Cancer, 1999.
16. DeSesso JM, Lavin AL, Hsia SM, Mavis RD. Assessment of the carcinogenicity associated with oral exposures to hydrogen peroxide. Food Chem Toxicol 2000; 38(11): 1021-41.
17. Mentel R, Shirrmakher R, Kevich A, Dreĭzin RS, Shmidt I. [Virus inactivation by hydrogen peroxide]. Vopr Virusol 1977; (6): 731-3.
18. Kampf G, Todt D, Pfaender S, Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. J Hosp Infect 2020; 104(3): 246-51.
19. Caruso AA, Del Prete A, Lazzarino AI, Capaldi R, Grumetto L. May hydrogen peroxide reduce the hospitalization rate and complications of SARS-CoV-2 infection? Infect Control Hosp Epidemiol 2020: 1-5.
Competing interests: No competing interests
Dear Editor
We know that several coronaviruses cause respiratory problems like the common cold, Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Covid-19 is the most recent disease caused by coronavirus (SARS-CoV-2) (1). Already mentioned in your editorial that there is no recommended and confirmed remedy available in the form of antiviral drugs for the coronavirus (SARS-CoV-2). All the vaccines and drugs are under clinical trials (2). Some home remedies, traditional and western remedies are used for relief of mild Covid-19. WHO is in continuous coordination with many research institutions who are involved in the development of medicine and vaccine for SARS-CoV-2. (3).
In such a situation, there should be a regimen of supportive treatments in all the three cases (Mild, Moderate, Suspected) of Covid-19, which can fulfill the below criteria.
1- There should be supportive medicine with minimum side effects and better safety.
2- There should be supportive medicines with antiviral activities, as still no antiviral drug has been confirmed against the coronavirus (SARS-CoV-2).
3- There should be supportive medicine with antioxidant activity against pre-radicals in covid-19, to protect further the respiratory membrane.
4- There should be supportive medicine which can control the release of cytokines and inflammatory mediators in Acute Respiratory Distress Syndrome (ARDS).
5- There should be supportive medicine to enhance the immunity of the body against the coronavirus (SARS-CoV-2).
Based on clinical researches in covid-19, the above targets can be achieved while adding the below supportive medicine in any of the empirical regimens for Covid-19.
Vitamin-D
There is dual action of vitamin-D in covid-19 infection. First, in the respiratory epithelium it produces the antimicrobial peptides and thus it reduces the viral infection with reduction in Covid-19 symptoms. Second, it might be helpful in the reduction of inflammation in SARS-CoV-2 infection. Based on these beneficial responses of Vitamin-D, it is suggested in this letter to administer the Vitamin-D in a loading dose at once and continue the daily requirement till the symptoms subside in patients with Covid-19 (4). It has been found that the patients with covid-19, who were in the deficiency stage of vitamin-D, were mostly effected and mortality rate was also high in them (5).
Vitamin-C
The cytokine production in ARDS induces the release of free radicals form immune cells. In one study it has been reported that free radicals cause the damage in respiratory virus induced pneumonia, which suggests the need for antioxidants in the treatment of Covid-19 (6,7). Vitamin C is an important antioxidant and performs its vital role in many physiological reactions as an enzymatic Co-factor. These physiological reactions include immune potentiation, production of collagen and hormone synthesis. Humans need Vitamin C from outside because the body is unable to produce Vitamin C. It may act pleiotropically to control the expression of pro-inflammatory mediators and improve alveolar fluid clearance with improving of epithelial cell activities through its antioxidant role (8).
Zinc
It is known that inflammatory response, antibacterial and antiviral immunity are also modulated by Zinc. The antiviral activity by up-regulation of interferon alpha synthesis, is also regulated by zinc and improves antiviral immunity. The Cytokine storm may be limited with zinc through modulation of regulatory T‑cell functions and the inhibition of NF‑κB signaling in Covid-19. Zinc reduces the secondary infection of bacteria in the respiratory tract by improving the ability of respiratory epithelium as a barrier and enhancing the mucociliary clearance. Zinc deficiency is also linked with the severity of Covid-19 in patients with atherosclerosis, immune deficiency, diabetes, ageing and obesity (9).
Corticosteroids
In the acute respiratory distress syndrome (ARDS) there is no specifically proven pharmacological treatment. In a randomized clinical trial, an improvement in gaseous exchange, reduction in inflammatory markers, reduction in prolonged hospital stay, reduction in the duration of mechanical ventilation have been observed with the use of corticosteroid (methylprednisolone or hydrocortisone). Because of the potent antifibrotic and anti-inflammatory effect of corticosteroids, it remains an interesting entity for clinical use in ARDS, which attenuate systemic and pulmonary damage in patients. Overall mortality in patients and mechanical ventilation can be reduced with the use of dexamethasone in moderate to severe patients with ARDS. Dexamethasone can provide a long-lasting effect and therefore can be given as a single dose per day (10). Most recently after a randomized study, it has been announced that dexamethasone reduced the mortality for severe patients with Covid-19 (11).
We have suggested these supportive medicines to the registered medical practitioners, to add to their empirical treatment of mild, moderate and severe case of Covid-19 in Pakistan, especially in areas where there are limited resources for managing critical cases. Very fruitful outcomes have been reported practically, while adding these supportive medicines to the regimen of empirical therapy for Covid-19. It has been observed from adding these suggested supportive medicines that whenever the patients have used the Vitamin-D, Vitamin-C and Zinc in mild cases, the patient recovered quickly. In moderate cases these medicines have played a vital role and the patients have recovered fast without developing a severe condition. In severe cases these medicines have been added along with dexamethasone in an empirical regimen for covid-19, the patients recovered quickly from shortness of breath, fever and ARDS. The new evidence about the beneficial role of dexamethasone in severe conditions of Covid-19 (12) has supported the above suggested treatment, which we have been applied since April 2020 in communities through registered medical practitioners.
The doses we suggested after thorough study of research literature as:
• Vitamin-D: 600000 IU stat and then 400-5000 IU daily for 20 to 30 days, in all the three cases
• Vitamin-C: 500 to 1500 mg daily for 10 to 20 days, in all the three cases
• Zinc: 23.7 mg to 50 mg for 10 to 20 days, in all the three cases.
• Dexamethasone: 4-8 mg/day for 3 to 10 days in ARDS or in moderate respiratory distress with occasional shortness of breath.
In conclusion, it is suggested that further clinical trials should be officially performed on these medicines in Covid-19 to get promising outcomes.
References
1. Q&A on coronaviruses (COVID-19) [Internet]. [cited 17 April 2020]. Available from:
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/question....
2. Covid-19 care before, during, and beyond the hospital [Internet]. [cited 22 May 20
https://www.bmj.com/content/369/bmj.m2035/rr-2
3. Q&A on coronaviruses (COVID-19) [Internet]. [cited 17 April 2020]. Available from:
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/question....
4. Vitamin-D and COVID-19: do deficient risk a poorer outcome? [Internet]. [cited May 20 2020]
https://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30183-2/fulltext
5. The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality [Internet]. [cited 06 May 2020].
https://link.springer.com/article/10.1007/s40520-020-01570-8
6. Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 2012 Mar 76(1):16-32.
7. Tackle the free radicals damage in COVID-19 [Internet[. [cited 17 June 2020].
https://www.sciencedirect.com/science/article/pii/S1089860320301580?via%...
8. High-dose intravenous vitamin C treatment for COVID-19 [Internet] [cited 26 February 2020].
https://osf.io/p7ex8/?fbclid=IwAR2b67345SBs9r2QfJ23xH_0GEM771Qwww6EPpOST....
9. Anatoly VS, Lothar R, Olga PA, Michael A, Viktor AG, Svetlana IA,et al. Zinc and respiratory tract infections: Perspectives for COVID‑19 (Review). Int J Mol Med. 2020 Apr 14; 46(1):17-26.
10. Dexamethasone treatment for the acute respiratory distress syndrome: a multicenter, randomized controlled trial [Internet] [cited 7 February 2020]
https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(19)30417-5.pdf
11. Dexamethasone for COVID-19: Some US Hospitals Wait to Change Practice [Internet] [cited June 19, 2020]
https://www.medscape.com/viewarticle/932659
12. Low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19 [Internet] [cited 16 June2020] https://www.recoverytrial.net/files/recovery_dexamethasone_statement_160...
Competing interests: No competing interests
Dear Editor,
To Whom it May Concern,
I would like to propose that frontline NHS healthcare workers take the antibiotic Doxycycline (1) prophylactically to prevent COVID-19 infections in hospital and GP settings nationwide. For example, they could take 100-mg of Doxycycline per day.
Doxycycline is widely and readily available in the United Kingdom and world-wide. The cost would be minimal, less than 10 pence a day per person. Since it is already MHRA-approved for bacterial infections, it can also be prescribed legally by consultants and GPs, in an off-licence fashion.
Doxycycline has previously been shown to inhibit the replication of other viruses, such as the Dengue virus (2), among others, because it is an inhibitor of protein synthesis. It also inhibits the production of inflammatory cytokines, such as IL-6 (3), that are activated in COVID-19 patients.
Doxycycline is a very safe drug, which was first FDA-approved in 1967, over 50 years ago. It is already used for the prevention of acne and malaria, as well as many other bacterial infections. Bacterial super-infection is a major complication of viral infections and was the major cause of mortality during the influenza pandemic of 1918 (4, 5).
Also, NICE has already designated Doxycycline as the treatment of choice for community acquired pneumonia, during the COVID-19 pandemic:
https://www.nice.org.uk/guidance/ng165/chapter/4-Managing-suspected-or-c...
Thank you for considering this inexpensive approach to preventing ongoing viral transmission during the COVID-19 pandemic, using Doxycycline prophylaxis.
Best wishes,
Professor Michael P. Lisanti, MD-PhD, FRSA, FRSB
Chair, Translational Medicine
University of Salford
Supporting Evidence
1. COVID-19 and Chronological Aging: Senolytics and Other Anti-Aging Drugs for the Treatment or Prevention of Corona Virus Infection?
https://pubmed.ncbi.nlm.nih.gov/32229706/
2. Inhibitory Effect of Doxycycline Against Dengue Virus Replication in Vitro
https://pubmed.ncbi.nlm.nih.gov/24142271/
3. Dengue Patients Treated with Doxycycline Showed Lower Mortality Associated to a Reduction in IL-6 and TNF Levels.
https://pubmed.ncbi.nlm.nih.gov/25858261/
4. Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness.
https://www.ncbi.nlm.nih.gov/pubmed/18710327/
5. Bacterial Pneumonia Caused Most Deaths in 1918 Influenza Pandemic (Press Release from NIH by Dr. Anthony Fauci in 2008)
https://www.nih.gov/news-events/news-releases/bacterial-pneumonia-caused...
Competing interests: No competing interests
Dear Editor
According to recent papers and major health organizations, asthma, along with other diseases, is a condition that makes it more vulnerable to becoming severely ill with COVID-19 (1-4). Nevertheless, despite it being a common chronic respiratory disease with around 235 million people living with asthma (5), current evidence does not support that asthma increases the likelihood of experiencing more severe SARS-CoV-2 infection.
A study on the clinical characteristics of 140 COVID-19 patients admitted to 7 hospitals in Wuhan (China) with pneumonia did not find asthma in any of the patients (6). Data regarding 1099 patients with laboratory-confirmed COVID-19 from 552 Chinese hospitals in 30 provinces did not report asthma among coexisting disorders (7). In China, the first nationwide investigation on a large sample size and extensive coverage of the geographic regions across the country systematically evaluated the impact of comorbidities on the clinical characteristics and prognosis in patients with COVID-19 on hospital admission; the authors did not find asthma among the comorbidities (8). A report on 3200 COVID-19 positive deceased patients in Italy does not mention asthma among coexisting diseases (9). Finally, no patient with asthma was reported in a study on 113 patients who died of SARS-CoV-2 infection (10).
The reasons asthma, a chronic respiratory disease, does not appear to increase the risk of more severe SARS-CoV-2 infection as happens with influenza is unknown. However, an analysis of therapeutic targets for SARS-CoV-2 by computational methods showed that montelukast, formoterol, and reproterol, commonly used drugs for the prevention of asthma symptoms, might have anti-viral activity (11,12); further in vivo and in vitro anti-viral experiments must be conducted to confirm this activity. Nevertheless, montelukast along with a potential anti-viral activity may exert anti-inflammatory effects not only by directly blocking leukotriene receptors but also by inhibiting cytokine and chemokine expression in alternatively activated macrophages (13).
In COVID-19, a protective effect from long term inhaled steroids is very difficult to be demonstrated because no association between corticosteroid therapy and outcomes in patients with moderate or severe disease without acute respiratory distress syndrome has been reported (14).
The asthma patient population with or without prior symptoms suggestive of COVID-19 infection should receive an antibody test and those positive for SARS-Cov-2 should have current asthma treatment recorded. A protective effect of montelukast and/or formoterol or reproterol could be confirmed or excluded.
In conclusion, to date, people with asthma being at increased risk of getting the SARS-CoV-2 or having more severe illness have not been identified, and the possibility that some antiasthmatic drugs could attenuate the severity of the disease should be investigated.
References
1) Do chronic respiratory diseases or their treatment affect the risk of SARS-CoV-2 infection? Halpin DMG, Faner R, Sibila O, Badia JR, Agusti A. Lancet Respir Med. Published online, April 03, 2020. DOI:https://doi.org/10.1016/S2213-2600(20)30167-3 2) Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 — United States, February 12–March 28, 2020. MMWR Morb Mortal Wkly Rep 2020;69:382–386. DOI: http://dx.doi.org/10.15585/mmwr.mm6913e2
3) Asthma and Allergy Foundation of America. Who Is at Risk From the Coronavirus? https://community.aafa.org/blog/coronavirus-2019-ncov-flu-what-people-wi.... Accessed April 15, 2020. 4) U.S. CDC, Coronavirus disease 2019 (COVID-19). People with moderate to severe asthma. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/asthma..... Accessed April 15, 2020. 5) WHO. Asthma, Global prevalence. 24 November 2019. https://www.who.int/news-room/q-a-detail/asthma Accessed April 15, 2020. 6) Zhang JJ1, Dong X1, Cao YY2, Yuan YD3, et al. DOI: 10.1111/all.14238 Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020 Feb 19. DOI: 10.1111/all.14238 [Epub ahead of print].
7) Guan W, Ni Z, Hu Y, Liang W, Ou C, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. NEJM. February 28, 2020. DOI: 10.1056/NEJMoa2002032 [Epub ahead of print]. 8) Guan W, Liang W, Zhao Y, Liang H, Chen Z, et al. Comorbidity and its impact on 1590 patients with COVID-19 in China: A Nationwide Analysis. European Respiratory Journal 2020. DOI: 10.1183/13993003.00547-2020.
9) Istituto Superiore di Sanità. Characteristics of COVID-19 patients dying in Italy Report based on available data on March 20th, 2020. https://www.epicentro.iss.it/coronavirus/bollettino/Report-COVID-2019_20...
10) Chen T, Wu D, Chen H, Yang D, Chen G, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: a retrospective study. BMJ 2020;368:m1091. doi.org/10.1136/bmj.m1091. (Published 26 March 2020)
11) Xie J, Tong Z, Guan X, Du A, Qiu H. Clinical Characteristics of Patients Who Died of Coronavirus Disease 2019 in China. JAMA Netw Open. 2020;3(4):e205619. DOI:10.1001/jamanetworkopen.2020.5619. 12) Tien H, Haoran W; Binquan L. In Silico Exploration of Molecular Mechanism and Potency Ranking of Clinically Oriented Drugs for Inhibiting SARS-CoV-2’s Main Protease. 2020. ChemRxiv. Preprint. https://doi.org/10.26434/chemrxiv.12045549.v1
13) Lin YC, Huang MY, Lee MS, Hsieh CC, Kuo HF, et al. Effects of montelukast on M2-related cytokine and chemokine in M2 macrophages. Journal of Microbiology, Immunology, and Infection. Volume 51, Issue 1, February 2018, Pages 18-26. https://doi.org/10.1016/j.jmii.2016.04.005
14) Zha L, Li S, Pan L, Tefsen B, Li Y, et al. Corticosteroid treatment of patients with coronavirus disease 2019 (COVID‐19). The Medical Journal of Australia. April 8, 2020. https://doi.org/10.5694/mja2.50577
Competing interests: No competing interests
Dear Editor,
Diltiazem may be useful to treat hypertension linked to COVID-19
Hypertension was one of the common comorbidities seen in COVID-19 infected patients (1). According to the recent US report, 49.7% of patients had hypertension in 178 patients (1). In China, 25% to 50% of patients came to the hospital with hypertension. In Italy, 76% of patients had high blood pressure (2).
Diltiazem is a calcium channel blocker to be used to treat hypertension, which works by relaxing the muscles of the heart and blood vessels. Diltiazem is an alternative medicine to treat hypertension instead of using ACE inhibitors. As ACE2 is the receptor of SARS-CoV2, the ACE inhibitors have the potential to increase the level of ACE2 (3). Furthermore, Diltiazem was reported to ameliorate the acute lung injury by the suppression of neutrophilic oxidative stress (4), which may relief acute lung injury in COVID-19 patients.
It is reported that inhibiting NF-kb pathway may be improving the immune response to the virus (5). Diltiazem was reported as an inhibitor of NF-kb signaling pathway (6). Overall, Diltiazem plays dual effects on hypertension linked COVID-19 treatment by lowering high blood pressure and inhibiting NF-kb signaling pathway related inflammation.
References:
1. Garg S, et al "Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 -- COVID-NET, 14 States, March 1–30, 2020" MMWR 2020.
2. Coronavirus and High Blood Pressure: What’s the Link? WebMD link https://www.webmd.com/lung/coronavirus-high-blood-pressure#1
3. Zheng, Y., Ma, Y., Zhang, J. et al. COVID-19 and the cardiovascular system. Nat Rev Cardiol 17, 259–260 (2020).
4. Jang YS , Lee YM , Ahn WS , Lee SC , Kim KC , Hyun DS. Pretreatment of Diltiazem Ameliorates Endotoxin-Induced Acute Lung Injury by Suppression of Neutrophilic Oxidative Stress. Tuberc Respir Dis. 2006 Apr;60(4):437-450
5. Alex Swanson COVID-19: Genetic Research and a Novel Pathway. Nutrition Genome. Mar.2020
6. Gilmore, T., Herscovitch, M. Inhibitors of NF-κB signaling: 785 and counting. Oncogene 25, 6887–6899 (2006).
Competing interests: No competing interests
Competing interests: No competing interests
Dear Editor,
We read the article in the BMJ “COVID-19: what treatments are being investigated?” by Elisabeth Mahase on 4th April 2020 [1]. Several treatment options have been cited including but not limited to chloroquine/hydroxychloroquine, Kaletra (Lopinavir + Ritonavir combination), Remdesivir, Tocilizumab and Interferon β 1A. These drugs work by stopping/reducing viral multiplication and, in the case of chloroquine, altering the pH of the intracellular compartment.
Changes in the pH of the environment has been shown to alter/reduce the infectivity of sexually transmitted chlamydial infections (an obligatory intracellular organism) [2]. Combination therapies have been well established in the treatment of infectious diseases, due to their ability to achieve efficacy with lower doses and the synergistic effects of combined therapies. We hypothesise that a treatment paradigm that combines these drugs to alter pH and another drug(s) to reduce the multiplication of the virus is the best way to treat this extraordinary infection.
We propose to treat patients with a confirmed diagnosis of COVID-19 and moderate to severe symptoms with hydroxychloroquine for 24 hours, and then randomise the patients into 3 groups [3]. Group 1 continues with hydroxychloroquine, Group 2 hydroxychloroquine + Kaletra and Group 3 hydroxychloroquine + Kaletra + INF-β 1A. The primary outcomes for this study should be time to recovery in each group and percentage progressing to require invasive ventilation. The secondary outcomes should be symptom relief and patient wellbeing. This, we believe, is a starting point for a randomised controlled trial with currently available medication. We can start this trial without delay as these treatments have been previously approved with known safety profiles.
References
1. Mahase E. Covid-19: what treatments are being investigated?. BMJ. 2020:m1252. doi:10.1136/bmj.m1252
2. Das S, Sabin C, Allan S. Higher vaginal pH is associated with Chlamydia trachomatis infection in women: a prospective case–controlled study. Int J STD AIDS. 2005;16(4):290-293. doi:10.1258/0956462053654221
3. Liu J, Cao R, Xu M et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020;6(1). doi:10.1038/s41421-020-0156-0
Competing interests: No competing interests
Dear Editor,
Immunizing Camels with SARS-CoV-2: A promising Strategy in the Fight Against COVID-19
Camels are well-known hosts to harbour different strains of the coronaviruses and were shown to produce effective neutralizing antibodies to these viruses [1]. Although camels may be involved as a source of the human infection with the Middle East respiratory syndrome coronavirus (MERS-CoV), they can still be used as an important source to generate strong immune responses against different strains of the coronaviruses [2]. Hence, immunising lactating female camels with an inactivated form of the current coronavirus strain (SARS-CoV-2) the causative agent of the current COVID-19 pandemic, will steer a strong immune response against the virus components with the generation of specialized small camel IgG antibodies both in camel serum and milk [3].
These small antibodies are able to gain access to tissues and neutralise SARS-CoV-2 viruses outside and inside infected cells [4,5]. These Nano molecules were demonstrated to be stable at high temperatures, resist stomach enzymes digestion and can pass into the bloodstream as intact antibody molecules [6,7]. They are less immunogenic than most mammalian IgGs, and when administered intravenously they are less inclined to prompt serum sickness and anaphylactic adverse reactions [8]. This has already been demonstrated in a similar strategy that we have invented and implemented in phase I clinical trial for the treatment of HIV patients, with a patent being granted by the US Patent Office [5].
Studies on camelid antibodies provide a rationale for the development of such a promising strategy of an antibody-based approach for the neutralization and inactivation of SARS-CoV-2. This strategy is based on the fact that camelid IgG lack light chains and the 15 kDa antigen-binding domain of the heavy chain (VHH) is significantly smaller than papain-cleaved Fab fragments of conventional human IgG [3]. Moreover, antigens-specific VHH, intravenously injected into mice, were shown to penetrate and bind the deep-tissue located target antigens within two hours and were retained in tissues for more than eight hours after administration [4]. This rapid tissue-ingress of intravenously injected VHH has obvious potential for the treatment of viral infections [9].
Camel milk has its own remarkable nutritional composition and is rich in minerals, vitamins, low sugar and cholesterol and has a significant antioxidant effect [10]. In addition to the secretory IgA and IgM antibodies as well as the small IgG molecules, camel milk also possesses numerous non-antibody components with their scientifically proven effective antimicrobial activity, especially antiviral [11]. We predict that using lactating female camels to generate antibodies including the “VHH” will potentially and selectively neutralise SARS-CoV-2 [12].
The neutralizing antibodies in the milk of immunised camels will give passive immunity to those with COVID-19 as a treatment or as a means of prophylaxis to prevent those at risk of SARS-CoV-2 infection. Moreover, the strategy involves the isolation and purification of the raised antisera against SARS-CoV-2. Once confirmed its efficacy and safety, the purified antisera can be transfused directly into the bloodstream of the infected patient. This is in the same manner where current anti-snake venoms are generated and used.
Currently, there is no vaccine or cure for COVID-19. Therefore, such a promising treatment/prevention proposed strategy should be first tested in vitro and in vivo and then confirmed in clinical trials, as per international standards and ethics before being made available to all in need [12]. We invite and encourage researchers to test and confirm the proposed strategy using camels, with their unique immune system, as live factories to synthesise the desired antibodies, not only to prevent SARS-CoV-2 infection, yet additionally to confirm the use of this strategy against other viral and microbial infections.
References
[1] Lau SKP, Chan JFW. Coronaviruses: emerging and re-emerging pathogens in humans and animals. Virol J (2015) 12. https://doi.org/10.1186/s12985-015-0432-z
[2] Killerby ME, Biggs HM, Midgley CM, Gerber SI, Watson JT. Middle East Respiratory Syndrome Coronavirus Transmission. Emerg Infect Dis. (2020) 26(2):191-198.
https://dx.doi.org/10.3201/eid2602.190697
[3] Hamers-Casterman C, Atarouch T, Muyldermans S, Bendolman N, Hamers R. Naturally occurring antibodies devoid of light chains. Nature. (1993) 363: 446-448.
[4] Cortez-Retamozo V, Lauwereys M, Hassanzadeh Gh G, Gobert M, Conrath K, Muyldermans S, De Baetselier P, Revets H. Efficient tumor targeting by single-domain antibody fragments of camels. Int J Cancer. (2002) 98(3):456-62.
[5] Hasson SS & Al-Jabri AA. Therapeutic composition. US10336817B2, filed by SULTAN QABOOS UNIVERSITY. Being granted by the US Patent Office in 2016 (Priority to ZA16/7084 2016-10-14).
[6] Van der Linden RHJ, Frenken L, de Geus B, et al., Comparison of physical chemical properties of llama VHH antibody fragments and mouse monoclonal antibodies. Biochim. Biophys. Acta (1999); 1431, 37–46.
[7] Jason VS & Burnett BP. Survival and digestibility of orally-administered immunoglobulin preparations containing IgG through the gastrointestinal tract in humans. Nutr. J. (2015) 14, 22.
[8] Herrera MG, Leon A, Segura F, Meneses B, Lomonte J, Philippe JP, Chppaux P, Gutierrez JM. Factors associated with adverse reactions induced by caprylic acid-fractionated whole IgG preparations: comparison between horse, sheep and camel IgGs. Toxicon. (2005) 46:775-781.
[9] EL-Fakharany EM, Abedelbaky N, Haroun BM et al. Anti-infectivity of camel polyclonal antibodies against hepatitis C virus in Huh7.5 hepatoma. Virol J (2012) 9, 201. https://doi.org/10.1186/1743-422X-9-201.
[10] el Agamy EI, Ruppanner R, Ismail A, Champagne CP, Assaf R. Antibacterial and antiviral activity of camel milk protective proteins. J Dairy Res. (1992) 59(2):169-75.
[11] Shamsia SM. Nutritional and therapeutic properties of camel and human milks. International J Genet Mol Biol. (2009) 1, 052-058.
[12] Hasson SS, Al-Jabri AA. Immunized Camels and COVID-19. Asian Pac J Trop. Med. (2020) (In Press)
Authors
Sidgi Syed Anwer Hasson, MSc, PhD
Immunology Unit,
Department of Microbiology and Immunology,
College of Medicine & Health Sciences,
Sultan Qaboos University,
Muscat, Oman
Ali A. Al-Jabri, Ph.D., FRCPath
Head of Immunology Unit,
Department of Microbiology and Immunology,
College of Medicine & Health Sciences,
Sultan Qaboos University,
Muscat, Oman
Competing interests: No competing interests
Dear Editor,
We really appreciated the terrific work that Elisabeth Mahase recently published in The BMJ. Beside antiviral molecules, only some immunomodulatory agents have been cited. To this regard, we would like to add a note regarding the possible role that sphingolipids, a class of lipid molecules with well-known immunomodulatory properties and not only, may have in the context of treatments that are currently investigating for managing COVID-19 infection.
According to the WHO, the most common diagnosis in severe COVID-19 patients is a serious and difficult to cure pneumonia (1). Patients are classically at risk for acute respiratory distress syndrome (ARDS) due to an exaggerated inflammatory response. Emerging evidence, however, also points out that the clinical picture of these patients is exacerbated by a high incidence of thrombotic complications (2). Thus, acting on several levels would potentially mean to avoid the rapid clinical deterioration of patients with COVID-19.
Over the past years, it has been demonstrated that sphingolipids play a crucial role in protecting lungs from pulmonary leak and lung injury and, the modulation of their pathways may represent a strategy therapeutic interventions (3-4).
Modulation of sphingolipids has a plethora of beneficial effects (5). Of note, their anti-inflammatory (6), neuroprotective (5-6) and anti-coagulant (7) properties are particularly intriguing and, today, they could likely be all exploited to counteract the associated complications of COVID-19 infection.
In this context, the FDA-approved immunomodulator FTY720 (Fingolimod), one of the best characterized “sphingomimetic” drug (8), is now an ongoing Clinical Trial (NCT04280588 -ClinicalTrials.gov-) for the management of COVID-19 pandemic (9).
From our perspective, moreover, beside the recognized immunomodulatory properties that made Fingolimod suitable as possible therapeutic strategy (9), its less known anti-coagulant and anti-thrombotic actions would make the drug more useful and promising for the treatment of COVID-19 patients.
However, we believe that other “sphingomimetic” and “sphingomodulating” compounds, some of which are already in clinical trials for other pathological conditions (10), might be easily repurposed and conceivably provide further therapeutic options for the management of this global health emergency.
Thus, in our opinion, while waiting for a vaccine, it is imperative to consider all the available options and taking advantage of the therapeutic properties of drugs that are normally used in clinical practice, to counteract complications associated with COVID-19, would mean to widen the range of therapeutic opportunities against this new and devastating infection.
Sincerely,
Vittorio Maglione, PhD
IRCCS Neuromed
Pozzilli (IS), Italy
E-mail: vittorio.maglione@neuromed.it
Alba Di Pardo, PhD, Medical Geneticist
IRCCS Neuromed
Pozzilli (IS), Italy
E-mail: dipardoa@hotmail.com
References
1. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 Novel Coronavirus–Infected pneumonia in Wuhan, China. JAMA 2020;323:1061. 9. doi:10.1001/jama.2020.1585.
2. Klok FA, Kruip MJHA, van der Meer N.J.M. et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thrombosis Research. 2020, in press. doi:10.1016/j.thromres.2020.04.013.
3. Ghidoni R, Caretti A, Signorelli P. Role of Sphingolipids in the Pathobiology of Lung Inflammation. Mediators Inflamm. 2015;2015:487508. doi:10.1155/2015/487508.
4. Chakinala RC, Khatri A, Gupta K, Koike K, Epelbaum O. Sphingolipids in COPD. Eur Respir Rev. 2019 Nov 6;28(154). pii: 190047. doi: 10.1183/16000617.0047-2019.
5. Cartier A, Hla T. Sphingosine 1-phosphate: Lipid signaling in pathology and therapy. Science. 2019 Oct 18;366(6463). doi:10.1126/science.aar5551.
6. Hannun YA, Obeid LM. Sphingolipids and their metabolism in physiology and disease. Nat Rev Mol Cell Biol. 2018 Mar;19(3):175-191. doi:10.1038/nrm.2017.107.
7. Zhao Z, Wang R, Huo Z, Li C, Wang Z. Characterization of the Anticoagulant and Antithrombotic Properties of the Sphingosine 1-Phosphate Mimetic FTY720. Acta Haematol. 2017;137(1):1-6. doi: 10.1159/000448837.
8. Huwiler A, Zangemeister-Wittke U. The sphingosine 1-phosphate receptor modulator fingolimod as a therapeutic agent: Recent findings and new perspectives. Pharmacol Ther. 2018 May;185:34-49. doi:10.1016/j.pharmthera.2017.11.001.
9. Lythgoe MP and Middleton P. Ongoing Clinical Trials for the Management of the COVID-19 Pandemic. Trends in Pharmacological Sciences (TiPS). In Press, Corrected Proof, Available online 9 April 2020. doi:10.1016/j.tips.2020.03.006.
10. Chew WS, Wang W, Herr DR. To fingolimod and beyond: The rich pipeline of drug candidates that target S1P signaling. Pharmacol Res. 2016 Nov;113(Pt A):521-532. doi: 10.1016/j.phrs.2016.09.025.
Competing interests: No competing interests
Re: Covid-19: what treatments are being investigated?
Dear Editor,
Re BCG: I have no idea if this will be of interest in assessing this vaccine. I am simply describing our family situation:
When I was a teenager and tested to have the BCG I did not need it. I was sent for X rays and was found to be okay. To my knowledge I had never had TB. However, my mother had had TB when she was a small child. I presumed I had inherited immunity. When I married we found that, by chance my husband was also 'immune'. We were told this was impossible. However, our elder son (but not our second son) was also found to be 'immune' and did not have the BCG. Although we are told this cannot happen it seems that my husband and I both inherited 'immunity' and that our first son inherited it from both of us. I am only detailing this in case it is of any help re the use of TB / BCG and the Covid-19.
Yours faithfully,
R.E. Richardson.
Competing interests: No competing interests