COVID 5
Rick Hodes, MD, MACP JDC-Ethiopia
www.Rickhodes.org
Rickhodes@gmail.com
I am writing to give you some update on COVID-19.
First, an important announcement:
1) EMRAP:
There is an emergency medicine website called EMRAP, located at:
https://www.emrap.org/
8 May, 2020
It is an excellent, online site with live webcasts, an online textbook, and talks by expert academics and clinicians. Normally it costs $495 USD to subscribe for 1 year. For example, most recently they have an 18 minute video on COVID-19 news, higher-risk clinicians, and Kawasaki’s Disease and COVID-19. If any Ethiopians are interested in a subscription at no cost, please contact me.
Overview: We are learning more, but there is no easy answer and every week there is more complexity. We have known that this is a major pulmonary pathogen. But it is a major cause of thrombosis, and also affects the brain, kidneys, and vascular and digestive organs. And heart. And pregnancies. It causes strokes, pulmonary emboli, purple clotted toes, it enters the CSF, causes seizures, joint and muscle pain, diarrhea, and kidney failure. We don’t understand who gets it. It seems 10%-20% of those who get it become very ill, Chinese data show 5% had strokes. High levels of D-dimer correlate with poorer outcomes. And there are pediatric consequences.
2) Hydroxychloroquine: In defense of the scientific method:
Politicians openly endorsed the use of hydroxychloroquine, before there was reliable data to support its use. A well-known TV presenter said anyone questioning the drug’s efficacy is “in total denial.” She criticized the medical profession, saying they “want a double-blind controlled study on whether the sky is blue.”
Wrong!
This is not a totally benign drug. The Veterans Administration study of 368 patients actually found increased mortality in the group which got hydroxychloroquine alone. They concluded: “we found no evidence that use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with Covid-19.”
https://www.medrxiv.org/content/10.1101/2020.04.16.20065920v2
Yesterday, a study was published in the New England Journal of Medicine by the pulmonary group at Columbia University. They examined data on 1376 patients hospitalized for at least 24 hours, followed for a mean 22.5 days. They found “hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death.” While this is not the final word, they conclude “results do not support the use of hydroxychloroquine at present, outside randomized clinical trials...”
Geleris J, Sun Y, Platt J, et al: Observational study of hydroxychloroquine in hospitalized patients with COVID-19. NEJM 2020;7 May, DOI: 10.1056/NEJMoa2012410
3) Hydroxychloroquine: prophylaxis?
Some may drugs may work as prophylaxis, but not therapeutically. An expert suggested to me that hydroxychloroquine might work in prevention. This is being studied. But I asked myself: what’s happening to lupus patients who are taking hydroxychloroquine already? Are they protected?
The Lupus Foundation of America examined this. They report: “We are not able to report any evidence of a protective effect from hydroxychloroquine against COVID-19” the group said on April 4. In fact, “over 25% of patients who developed a COVID-19 were on hydroxychloroquine at the time of diagnosis.”
https://www.lupus.org/blog/are-people-with-lupus-protected-against-covid19
4) Children: Previously, I said I would write about COVID-19 and children. There have been only 3 deaths below age 15 from COVID-19 in the US. However, there have been several notable developments:
- Pediatric multi-system inflammatory syndrome: fever, extreme inflammation, evidence of one or more organs dysfunction.
- A marked rise in what seems to be Kawasaki disease
- Children have been shown to shed the virus in stool for 30 days
- Children may transmit the disease. NYTimes article attached.
5) Convalescent Plasma:
I have looked into this data, and am attaching the 1919 paper from the (future) New England Journal of Medicine and a recent analysis. We can expect better data in the coming weeks, but we are optimistic that this may be useful.
I am attaching 3 papers.
6) Remdesivir:
This may have a modest effect.
7) Ongoing studies:
I recently read through all studies listed on ClinicalTrials.gov. To my count, there are 507 studies being conducted on COVID-19. In the US, there are 138, in Europe 142, In Canada 16, in Africa 13. I have listed them here, it is a fascinating group:
Angiotensin 1,7 – a vasodilatorAnluohuaxian – a Chinese anti-fibrosis drugArbidol HCL – broad spectrum antiviral used in Russia and ChinaREGN3048 and REGN3051 – monoclonal antibodiesAnti IL-6 another monoclonal antibodyAviptadil, a drug used in erectile dysfunction. May repair lung leakages.Bevacizumab – monoclonal antibody used against cancer and wet macular degenerationBaricitinib – immunosuppressantBidirectional oxygen valve
Bromhexine Hcl – a mucolytic drugCamostat – used in Japan for reflux esophagitis and chronic pancreatitis.Carrimycin – a macrolide drug used in gram positive and also with anti-TB uses
CD24Fc - immunomodulatorClevudine – antiviral drug used against hepatitis B in S. Korea
CM4620 – small molecule inhibitor of CRAC channels, found in many cells including immune cells (calcium release-activated calcium)
Colchicine- anti-inflammatory used in gout and pericarditis. Will be tried in several ways.
Convalescent Plasma – 24 studies in 47 places.
Corticosteroids - multiple studies of multiple drugs
Dapagliflozin is a sodium-glucose cotransporter, used in type 2 diabetes. May possibly reduce rates of respiratory failure.
Dalargin – a peptide with cytoprotective action
DAS181 – drug for influenza and para-influenza
Dexamethasone – a powerful corticosteroid
Eculizumab – a powerful immunomodulator treating terminal complement in autoimmune conditions
Etoposide –chemotherapy for various malignancies (leukemia, lymphoma, obrian and more)
Faviripavir + Chloroquine phosphate – Faviripavir is an RNA-inhibiting drug (COVID-19 is an RNA virus).
Famotidine – this drug, an H2 blocker used in gastritis, is cheap and easily available. It may work for several reasons:
Fingolimod – the first oral immunomodulator used in MSFluvoxamine - an antidepressant used for obsessive-compulsive disorder, working on
the serotonin system.
Human umbilical mesenchymal stem cells
Hydroxychloroquine 77 studies worldwideHydroxychloroquie + azithromycin – 19 studies in 54 sites worldwide
Hyperbaric oxygen – will be tried in 2 places
Interferon beta, 1a immune modulating therapy
Interferon lamba, pegylated immune modulating therapy
Intubation / extubation studies - manyLenzilumab – monoclonal antibody targeting GM-CSF
Leronlimab, a new HIV drug (not yet approved), also thought to inhibit COVID-19 entry into cells and possibly reduce cytokine storm.
Levamisole + Isoprinosine – antiparasitic drug + antiviralLopinavir + Ritonavir – 2 anti-AIDS drugs. The first boosts levels of the 2nd.
Losartan and telmisartin, both ARBs (angiotensin receptor blockers) used for hypertension. Because they bind to Ace receptors (as the COVID-19 virus), it may prevent the virus from getting into the body if the receptor is already occupied. Being tried in both prevention and treatment.
Low Dose Radiation Therapy to the lung – this is promisingMethyline Blue - Photochemical technology
Mesenchymal Stem Cell Exosomes (membrane bound extracellular vesicles) by inhalation:
Naltrexone (an opioid antagonist) + Ketamine (anesthetic)Nitazoxanide – treatment of Cryptosporidium diarrheaNitric oxide gas by inhalation
Nitrous oxide releasing solution – this is a broad-spectrum antimicrobialOral polio vaccine – proposed by Dr. Robert Gallo, not being studied yetOseltamivir – “Tamiflu” used against influenza A and B
Perfenidone – used in idiopathic pulmonary fibrosisPiclidenoson – oral, small molecule anti-inflammatory
Polymyxin in septic shock – an antibiotic
Prayer – being studied in a 1000 person, randomized study using “universal prayer” by 5 religions (Christianity, Hinduism, Islam, Judaism, Buddhism) vs standard care without prayer.
Prazosin – an alpha blocker used in hypertension
Proning – this can be a game-changer in some patients and avoid ventillation
Ravulizumab – a complement C5 inhibitor
Remdesivir – antiviral which was found to be safe but ineffective for Ebola
Ruxolitinib – used for myelofibrosis and GVH disease. It inhibits inflammation. Will be tried for immune over-reaction
Sargramostin – granulocyte macrophage colony stimulating factorSarilumab – used for rheumatoid arthritis to suppress cytokine stormsSelinexor – anti-myeloma drugSevoflurane – a fluorinated anesthetic
Sirolimus – a very interesting drug given to organ transplant patients.
Statins
Streptokinase vs unfractionated heparin nebulization – thrombolytic / anti-coagulation
Tetrandrine – calcium channel blocker
Thalidomide – powerful immunomodulator and cause of birth defects
Tocilizumab – In China, all 21 severe patients became afebrile and had decreased signs of inflammation. Lung lesions cleared in 19, all 21 were discharged alive.
TAK-981 anti-cancer drugTD-0903 a Janus kinase inhibitor used in cancer treatment
TXA – Tranexaminic acid – may help with coagulation problems. We often use TXA in our spine patients during surgery.
Winter SF, Santaguida C, Wong J, Fehlings MG: Systemic and topical use of Tranexamic Acid in Spinal Surgery: A Systemic Review. Global Spine J 2016 May; 6(3): 284-95.
Umifenovir – Russian and Chinese antiviralVaccine – 15 studies: 4 involve BCG (in 9 study sites).
Vitamin C IV – may prevent lung injury.Vitamin C +Zinc combo
Vitamin D in combo with other vitamins + meds – Vitamin D has many effects on the body.
Xiyanping – Chinese anti-inflammatory and antiviral
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Feel free to contact me with questions, comments, and suggestions. And stay healthy.
With best wishes for your success,
Rick Hodes, MD, MACP
JDC-Ethiopia
info@Rickhodes.org