Before I begin, I would like to first thank all the doctors, doctor assistants, nurses and all the health care workers and frontline responders that have put their lives on the line during the coronavirus pandemic. They are the heroes during this crisis! Especially, in the hot zone areas, such as New York city, New Jersey, Louisiana and Michigan treating COVID-19 patients. Also, my condolences go out to all of the families that have lost their loved ones during this crisis. What’s so sad is that many times family members are tragically separated and grieving without seeing their loved ones pass on in an undignified way, dying alone because of isolation and social distancing. My prayers and thoughts go out to all of the family and friends for their tragic loss.
On April 10th my article entitled “Coronavirus Research: 500 More Clinicals! Hope On the Way!” mentioned the latest promising cutting-edge drugs and treatment and research including 500 trials since the outbreak occurred that have already commenced – a number that is growing! There are no proven miracle cures or treatment but a hydroxychloroquine or its combo provide hope that they may have anti-viral properties and lower the infection rate and spread of the virus until we have a vaccine in 12-15 months. But will the vaccine be a miracle cure? We still don’t know how successful a vaccine will be.
What if the COVID-19 virus mutates? A change in the virus genetic code. A proven vaccine long-term may not be as effective by preventing antibodies from binding to the virus. We may then have to develop another new vaccine if this occurs. This was the case with the HIV virus. It mutated so quickly we couldn’t develop a vaccine to treat it. To this very day, we don’t have a vaccine to treat AIDS patients. Anti-viral therapies and drugs have safely on their own successfully controlled the AIDS epidemic, preventing further mortality and deaths from the HIV virus.
Moving forward, we need the gold standard; double-blind randomized clinical trials to prove safety and efficacy for all of the unapproved potential drugs to treat patients with the coronavirus, which I mentioned in my last article. Unfortunately, the stringent type of clinical trials will take months. We need something now. People are dying! Hope is on the way! Many clinical trials are now taking place on these potent drugs and treatments at many medical and research centers around the world.
As I mentioned in my last article, former FDA director Scott Gottlieb, in The Wall Street Journal in “Bet Big On Treatment for the Coronavirus” (Op-Ed, April 6, 2020) said that we cannot rely solely on isolation and social distancing and urged the FDA to accelerate approval of COVID-19 drugs.
The FDA recently approved three companies including biotech company Celex and Abbott Labs under “emergency use authorization,” which allow for its new antibody test to be used prior to gaining full approval! Beware! 90 faulty tests are available that are not approved by the FDA. Also, Abbott Labs new 5-15-minute tests that had recently been approved by FDA for testing of coronavirus are vital and urgently need to be more available – even in asymptomatic people.
I can’t emphasize enough the urgency and importance of the availability of further testing for diagnosing the virus as well as further access of the antibody tests if we are going to control the spread of the infection. This is vital if we are going to open the economy and allow people to go back to work safely.
New anti-viral drugs may offer hope to control the spread of the virus. We had good news just this week, on Thursday April 16th with the anti-viral drug Remdesivir made by Gilead Sciences. I mentioned this promising anti-viral drug in my last two articles. The University of Chicago Medical Center released this week preliminary positive findings of a closely watched clinical trial with Remdesivir (Stat News.com April 16, 2020), in which researchers noted: “Seeing rapid recoveries in fever and respiratory symptoms with nearly all patients discharged in less than a week. Safety studies have been done in animals but we don’t know if it will cause side effects long-term in humans. If safe and effective, it could become the first approved treatment against the disease.”
There was more great news this week on testing! “The Food and Drug Administration branded emergency use authorization for a coronavirus test relaying on saliva samples developed by a Rutgers University-backed entity, Rutgers said Monday.” (Dan Mangan at CNBC, Monday, April 13, 2020) “The test could increase, by tens of thousands of tests per day, the number of screenings for COVID-19,” Rutgers said. The test was developed by Rutgers RUCDR Infinite Biologics and its collaborators, Spectrum Solutions and Accurate Diagnostic. Infectious disease experts are saying that such a test is enormous! A real breakthrough! The test needs to be done by a physician, or trained health professional. It is simple; the patient just has to spit in a cup and would get results in 24-48 hrs. The test is already available this past Wednesday in New Jersey.
Another immediate concern and danger with the coronavirus is that we are in a serious mist of a storm! The Cytokine Storm. It’s the biggest storm ever! We didn’t see it coming. First we thought it was going to be a minor storm and later turned out to be a world crisis and pandemic!
Another area of research is anti-inflammatory drugs that inhibit or lower cytokines in the body. In the reaction to the coronavirus infection, what’s known as cytokine storm can occur in the body. A cytokine storm is an immune reaction to infection in the body in which the immune system overproduces cytokines such as interleukin-6 which can damage the lungs and cause inflammation of the air sacs of the lung, which can inhibit oxygen in the body causing pneumonia, respiratory failure and death! This Cytokine Storm can also cause inflammation of the heart, liver, brain and other vital organs.
It was recently reported in Cancer Network.com on March 26, 2020, that “FDA has approved a randomized, double-blind placebo-controlled phase III clinical trial to evaluate the safety and efficacy of intravenous (IV) Tocilizumab (Actemra) plus standard care in hospital adult patients with severe coronavirus disease,” according to Genetech, the drug developer. “We thank the FDA for rapidly expediting the approval of this critical trial to evaluate Actemra in critically ill patients suffering from pneumonia following coronavirus infection.” Tocilizumab is already approved by the FDA for treatment cytokine release syndrome (CRS) that is severe or life threatening. It is also already approved for rheumatoid arthritis. Side effects include upper respiratory infections, hypertension, hepatotoxicity, and immune risk of certain cancers by downregulating the immune system for the most severe or acute cases and life-threatening situation which may include life or death situations. For the most severe and acute cases of COVID-19 patients, and life and death situations, the benefits probably may outweigh the risk.
Regeneron Pharmaceutical Inc. and Sanofi (Kevzara) are also testing their rheumatoid arthritis drug, which inhibits interleukin-6, which can affect inflammation. Regeneron and Sanofi started a late-stage U.S. study including 400 patients. Results are expected at the end of April or early May.
Another question often asked, why is it that some people also test positive for the coronavirus and may have limited symptoms, like a cold, or no symptoms all, while others are gravely ill with pneumonia and respiratory failure and possibly die. Is a genetic factor involved? Possibly.
We already know people over 65 years of age are at the highest risk of dying from the coronavirus. People with obesity, diabetes, heart disease and hypertension are also at a greater risk. A healthy diet such as the Mediterranean diet has been shown in the research to lower these risks along with exercise. Also, people that smoke tobacco, cannabis (marijuana), and especially vaping may be prone to severe coronavirus infections. Studies also show that air pollution can also increase the risk; it was reported in research by Harvard University. It’s the first study to show a link to exposure to pollution and breathing fine particle matter in the air. (Harvard University TH Chan School of Public Health)
Also how does the coronavirus affect and infect the cells of normal people? According to scientists and the latest research, the virus’ spike protein attaches to an ACE2 receptor on the cell’s surface of the lung and respiratory system but one more co-factor is needed to penetrate the cells! It was reported recently and published in the EMBO Journal by scientists from the Berlin Institute of Health, Germany. The article reports that certain progenerated cells and genes in the cells of the bronchi in the lungs produce coronavirus receptors that the virus attaches to and causes infection. Progenitor cells forms respiratory cells in the bronchi of the lung. These cells contain what’s called cilia, which are hair-like that normally function to remove bacteria and mucus away from the lungs. We know that older adults 65 and over are at greater risk from dying from the coronavirus. It has also been reported in the scientific literature that sex differences may play a role. Men have been reported higher mortality and death rates. Scientists have shown that in most severe cases of the coronavirus, women had higher levels of antibodies than men. In the recent study in the EMBO Journal, researchers found that ACE2 receptor density increase in older men and more so in women. Also, other scientists have reported that the coronavirus does not bind to ACE2 receptors and expressed in young children. This is a theory why children are more protected from the coronavirus. The EMBO Journal is very interesting. This is very observational study and requires further clinical studies and clinical trials in coronavirus patients. If this study is confirmed in well-designed randomized clinical trials in coronavirus patients, we can then test existing drugs or new drugs to attack the virus.
One existing class of drugs is called ACE inhibitors and ACE blockers, which are now used to treat hypertension, and a most recent study was published in the jourrnal medRxiv. The researchers found that these drugs were effective in lowering inflammation (c-reactive protein) in coronavirus patients. The study was small and needs to be confirmed in larger randomized controlled clinical trials. The mechanism of action of these drugs is controversial because in animals these drugs have been shown to enhance the expression of the ACE2 receptor and may increase the severity of the disease. Warning: if you are on ACE inhibitors or ACE blockers for hypertension, you should not stop taking them unless recommended by your physician or cardiologist.
Another controversial study was most recently reported by Sciencedaily.com (April 2, 2020) on a new ACE2 receptor blocker that was published in the journal Cell, in which researchers concluded: “An international team has found a trial drug that effectively blocks the cellular door SARS CoV² uses to infect its host.” This ACE2 receptor blocker study is interesting but needs to be studied further and confirmed with a randomized double-blind clinical trial to assure the safety and efficacy of this new drug.
Even though cases of coronavirus are going down, we cannot take our foot off of the pedal! More testing (which includes for diagnosis and antibodies), effective anti-viral treatments, therapeutics (convalescent plasma therapy), and randomized controlled trials need to continue so we can establish safety and efficacy. We can win the war with the coronavirus with the help with all of our wonderful, heroic health care workers and leading pharmaceutical and research centers. We can recover, control and kill the virus! “Can’t” is not in my vocabulary – only can is!
- Centers for Disease Control and Prevention (CDC)
- National Institutes of Health (NIH)
- Johns Hopkins Center for Health Security
- Food & Drug Administration (FDA)
- Journal of American Medical Association (JAMA)
- New England Journal of Medicine (NEJM)
- Coronavirus War! Attack It Now: Potential Drugs and Treatment by Steve Blechman. April 1, 2020 https://advancedmolecularlabs.com/blogs/news/coronavirus-war-attack-it-now-potential-drugs-and-treatment
- CORONAVIRUS RESEARCH: 500 More Clinicals! Hope On the Way! Steve Blechman. April 10, 2020. https://advancedmolecularlabs.com/blogs/news/coronavirus-research-500-more-clinicals-hope-on-the-way
- Early peek at data on Gilead coronavirus drug suggests patients are responding to treatment.; By Adam Feuerstein @adamfeuerstein and Matthew Herper @matthewherper
April 16, 2020 https://www.statnews.com/2020/04/16/early-peek-at-data-on-gilead-coronavirus-drug-suggests-patients-are-responding-to-treatment/
- Guo T, Fan Y, Chen M, et al. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol.Published online March 27, 2020. doi:10.1001/jamacardio.2020.1017
- Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential Effects of Coronaviruses on the Cardiovascular System: A Review. JAMA Cardiol.Published online March 27, 2020. doi:10.1001/jamacardio.2020.1286
- Bonow RO, Fonarow GC, O’Gara PT, Yancy CW. Association of Coronavirus Disease 2019 (COVID-19) With Myocardial Injury and Mortality. JAMA Cardiol.Published online March 27, 2020. doi:10.1001/jamacardio.2020.1105
- Clinical Characteristics of Coronavirus Disease 2019 in China. Wei-jie Guan, Ph.D., Zheng-yi Ni, M.D. February 28, 2020. New England J. Med. DOI: 10.1056/NEJMoa2002032
- Linking Air Pollution To Higher Coronavirus Death Rates. Amanda King. Harvard TH Chan School of Public Health. April 13, 2020 https://www.hsph.harvard.edu/biostatistics/2020/04/linking-air-pollution-to-higher-coronavirus-death-rates/
- Why Some COVID-19 Patients Crash: The Body’s Immune System Might Be To Blame. April 7, 2020. Geoff Brumfiel NPR https://www.npr.org/sections/health-shots/2020/04/07/828091467/why-some-covid-19-patients-crash-the-bodys-immune-system-might-be-to-blame
- New Rutgers Saliva Test for Coronavirus Gets FDA Approval. Rutgers University. Andrew Brooks. April 13, 2020 https://www.rutgers.edu/news/new-rutgers-saliva-test-coronavirus-gets-fda-approval
- Coronavirus saliva test gets FDA emergency use approval, Rutgers University says. Dan Mangan. CNBC. April 13, 2020 https://www.cnbc.com/2020/04/13/coronavirus-saliva-test-gets-fda-use-approval-rutgers-university-says.html
- FDA Approves Phase III Clinical Trial of Tocilizumab for COVID-19 Pneumonia. Hannah Slater
- March 26, 2020 Cancer Network. https://www.cancernetwork.com/news/fda-approves-phase-iii-clinical-trial-tocilizumab-covid-19-pneumonia.
- Genentech Announces FDA Approval of Clinical Trial for Actemra to Treat Hospitalized Patients With Severe COVID-19 Pneumonia. March 23, 2020. AP News Wire https://apnews.com/Business%20Wire/9e97b7ad899e4bb4bcc80b0d5fc72c7d
- Why COVID-19 hits smokers harder. By Nicoletta Lanese. Life Sciences. https://www.livescience.com/coronavirus-covid-19-risk-and-smoking.html
- 16.SARS‐CoV‐2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. Soeren Lukassen et al, The EMBO Journal (April 17, 2020) e105114https://doi.org/10.15252/embj.20105114
- Obesity Exacerbates the Cytokine Storm Elicited by Francisella tularensis Infection of Females and Is Associated with Increased Mortality. Mireya G. Ramos Muniz, Matthew Palfreeman et al. Advances in Emerging and Neglected Infectious Diseases June 26, 2018. BioMed Research International. https://www.hindawi.com/journals/bmri/2018/3412732/
- Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors Usage is Associated with Improved Inflammatory Status and Clinical Outcomes in COVID-19 Patients With Hypertension
- Guang Yang, Zihu Tan, Ling Zhou, Min Yang, Lang Peng, Jinjin Liu, Jingling Cai, Ru Yang, Junyan Han, Yafei Huang, Shaobin He, medRxiv April 4, 2020.03.31.20038935; doi: https://doi.org/10.1101/2020.03.31.20038935
- University of British Columbia. “Trial drug can significantly block early stages of COVID-19 in engineered human tissues.” ScienceDaily, 2 April 2020. www.sciencedaily.com/releases/2020/04/200402144526.htm.
- Vanessa Monteil, Hyesoo Kwon, Patricia Prado, Astrid Hagelkrüys, Reiner A. Wimmer, Martin Stahl, Alexandra Leopoldi, Elena Garreta, Carmen Hurtado Del Pozo, Felipe Prosper, J.p. Romero, Gerald Wirnsberger, Haibo Zhang, Arthur S. Slutsky, Ryan Conder, Nuria Montserrat, Ali Mirazimi, Josef M. Penninger. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Submitted to Cell, 2020 DOI: 10.1016/j.cell.2020.04.004
- Decoy ACE2 receptors could be promising COVID-19 infection-preventing drug. April 3, 2020 Drug Target Review. https://www.drugtargetreview.com/news/59290/decoy-ace2-receptors-could-be-promising-covid-19-infection-preventing-drug/
- Gautret et al. (2020) Hydroxychloroquine and azithromycin as a treatment of COVID‐19: results of an open‐label non‐randomized clinical trial. International Journal of Antimicrobial Agents – In Press 17 March 2020 – DOI: 10.1016/j.ijantimicag.2020.105949
- French study finds anti-malarial and antibiotic combo could reduce COVID-19 duration. Darrell Etherington@etherington/March 19, 2020.
- Shen C, Wang Z, Zhao F, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. Published online March 27, 2020. doi:10.1001/jama.2020.4783
- Roback JD, Guarner J. Convalescent Plasma to Treat COVID-19: Possibilities and Challenges. JAMA. Published online March 27, 2020. doi:10.1001/jama.2020.4940
- Arturo Casadevall, Liise-anne Pirofski. The convalescent sera option for containing COVID-19. Published April 1, 2020; First published March 13, 2020. Citation Information: J Clin Invest. 2020;130(4):1545-1548. https://doi.org/10.1172/JCI138003.
- Effectiveness of convalescent plasma therapy in severe COVID-19 patients Kai Duan, et al. Proceedings of the National Academy of Sciences Apr 6 2020, 202004168; DOI: 10.1073/pnas.2004168117
- Pfizer PinPoints An Early Drug Candidate. Wall Street Journal. Jared S. Hopkins. April 10, 2020
- On Developing New Drugs to Treat Covid-19. Binh Nᴳᴼ & Stephen Ditmore. Friday, April 10, 2020 Wall Street Journal.
- Eric J. Rubin, M.D., Ph.D., Lindsey R. Baden, M.D., and Stephen Morrissey, Ph.D. Audio Interview: New Research on Possible Treatments for Covid-19. March 19, 2020. N Engl J Med 2020; 382:e30. DOI: 10.1056/NEJMe2005759
- COVID-19 treatment might already exist. Nevan Krogan – Professor and Director of Quantitative Biosciences Institute, University of California, San Francisco. March 26, 2020. Live Science.
- Anthony S. Fauci, M.D. et al. Covid-19 – Navigating the Uncharted. March 26, 2020 N Engl J Med 2020; 382:1268-1269 DOI: 10.1056/NEJMe2002387