Rationale of current COVID-19 available treatments and recommendations
Over the course of the last three months the world has gradually stopped. A pandemic caused by a coronavirus disease, now known as COVID-19, has changed the way we all live.
COVID-19 emerged as an outbreak of an initially unexplained respiratory syndrome that can progress to a lethal pneumonia in Wuhan, China, in December 2019. From China the virus has spread globally, causing an unprecedented loss of life as well as critical disruptions in the world economy. The pandemic has led to 932,605 confirmed infections with 46,809 deaths (as of April 1) and has been reported in over 203 countries worldwide.
Clinically, the most common symptoms reported are high fever, fatigue, dry cough, decreased appetite and muscle pain. The Chinese cohort reported that 80 percent of the cases are mild and less than 5 percent became critical. In the most serious cases, patients affected by this virus develop an acute, life-threatening respiratory injury that is caused by an overproduction of hormone-like substances produced by the immune system called cytokines.
The overproduction of cytokines (in extreme cases, a “cytokine storm”) causes damage in the lung cells leading to respiratory failure. In these severe cases, the respiratory failure requires intubation and mechanical ventilation with critical care staff supervision for several days to weeks.
Patients with such pre-existing conditions as cardiovascular disease, diabetes, COPD and hypertension develop more severe disease.
The significant percentage of COVID-19-infected patients who experience serious symptoms, along with the high mortality rate of this novel coronavirus thus far, has led to the institution of extraordinary measures, both socially and medically.
While there are many unanswered questions regarding treatment for this new virus, the best objective way for society to decrease further infections is to “self-quarantine” if you believe that you have been potentially exposed and especially if you are experiencing symptoms. Those who are well should adhere to social distancing in order to avoid contact with asymptomatic carriers.
Since we have no proven treatment for COVID-19 infection, the usual protocols and steps for FDA approval for clinical use of any medication in the U.S. have been bypassed to expedite the inclusion of promising therapies into our current, limited list of potential treatments.
Treatments currently being used in the hospitals range from oral medications that include the antimalarials Hydroxychloroquine and Chloroquine, antibiotics like Azithromycin, and biological agents like Tocilizumab and Sarilumab. The antimalarials and biological medications are commonly used to treat medical conditions such as lupus and rheumatoid arthritis. Now they are being used in intensive care units around the country to treat COVID-19.
We will describe the rationale for the use of the medications mentioned along with integrative recommendations that can be incorporated into our daily routine.
Why Chloroquine, Hydroxychloroquine and Azithromycin?
As you may recall, in 2002, an outbreak of the SARS virus caused numerous deaths in Asia. In the following years, studies performed in different countries led to the publications in 2004-05 of papers describing that HCQ decreased viral replication of the SARS-Cov virus in vitro. Earlier this year, Dr. Wang reported his lab experience with CQ and Hydroxychloroquine showing a significant decrease in viral replication of SARS-Cov-2 with the use of these medications. This finding led to the hypothesis that CQ and HCQ may be also beneficial in decreasing the viral replication of COVID-19.
In the past weeks, a group from France studied the use of HCQ in a small, controlled group of patients. In this study nasal swabs were performed on 26 patients and 16 controls (the controls were patients from different institutions that refused the treatment with HCQ). Among the 20 patients included in the analysis, six received Azithromycin to prevent a bacterial infection.
While the study was small and had many problems (some of the sicker patients in the study group were not included in the analysis), it revealed that the viral load in the nose cleared faster in the patients treated with HCQ and the viral clearance was even faster on the ones receiving the combination of medications (HCQ and AZ) compared to placebo. The use of biologicals (Tocilizumab and Sarilumab) is restricted to very sick hospitalized patients in whom the immune system activation has led to a “Cytokine Storm.”
A few days ago, President Trump enthusiastically endorsed the used of this combination of medications, leading to increased public awareness and demand for the two medications.
The unintended consequences of the announcement have been an increased demand from the public for use of these products and a shortage in pharmacies nationwide. I believe that recent events have led to two problems and one possible benefit.
The first problem is related to an acute shortage of HQC and AZ affecting patients who need the medications chronically. In the case of HCQ, the medication is commonly used for the management of autoimmune disorders like lupus and rheumatoid arthritis, while AZ is used in the management of acute infections.
The second problem is that the medications have side effects and the indiscriminate use of these medications without close supervision can lead to cardiac, ophthalmic and other potential complications.
On the other hand, a possible benefit of the pandemic is the increased interest in the mechanism of action of these medications and the promise of new research. Research would help us understand different ways to decrease viral replication of coronavirus. The goal is to be prepared when a new infection surfaces in a few years, allowing us to control the virus, avoiding widespread infections by the development of vaccines or other treatments.
In the last few days, the FDA gave a green light to the use of HCQ and AZ for the inpatient management of coronavirus without any conclusive clinical trials backing the recommendation.
So, what to do now?
If you have an autoimmune condition and have been taking HQC and CQ before, please continue your medications. If you have not been prescribed HCQ and AZ before, please do not ask your primary care for the medications. The increased demand and use without a clear clinical indication will worsen the shortage experienced now.
While, as mentioned above, there are no proven medications to be helpful when you have been infected with COVID-19, there are supplemental considerations to decrease your risk of infection besides regular hand washing, social distancing and staying at home.
The following recommendations are based on the published recommendations of the Integrative Health Department of the University of Arizona.
This advice is not specific for the treatment of COVID-19. The recommendations are based on publications printed regarding other viral infections and may be helpful during this pandemic.
• Stress management, including adequate sleep. Stress will not only affect your biosome but also affect your immune system. Relaxation techniques like mindfulness, prayer and journaling will help decrease stress during this challenging time. We also know that adequate sleep (at least seven hours a night) decreases the risk for rhinovirus by 350 percent compared to persons who sleep less than five hours a night.
• An over-the-counter sleeping aid is melatonin that you can take with magnesium at night. Reports indicate that melatonin reduces inflammatory cell recruitment in the lungs during viral infections. The typical melatonin dose ranges from 0.3 to 20 mg a day.
• Zinc, Coronavirus appears to be susceptible to the antiviral properties of zinc. Zinc decreases the viral entry into the cells and decreases the virulence. Typical dosing is 15-30 mg a day.
• Vitamin C, ascorbic acid inhibits the immune system activation. Vitamin C decreases the frequency, severity and duration of the common cold. The dose recommendation ranges from 500 mg to 3,000 mg a day with higher doses used at times of infection.
• Elderberry (Sambucas nigral), lab studies report that elderberry inhibits viral replication of Coronavirus NL63 (no studies on COVID-19). Is also used to prevent influenza. Is more effective preventing viral infections but needs to be discontinued if you develop symptoms of infection since it may increase inflammatory cytokines.
• Vitamin D, reports indicate that vitamin D decreases immune system activation and may be helpful as a preventive measure, but should be stopped if you have symptoms of infection. The recommended dose is 1,000 IU a day.
Our understanding and recommendations regarding the management of COVID-19 are changing rapidly. For Coronavirus updates, go to coronavirus.delaware.gov.
