by Abimbola Farinde, Medically Reviewed by Dr. C.H. Weaver M.D. 4/2022
The coronavirus disease (Covid-19) is considered to be one of the greatest health crises that the world has faced to date. Since its identification in late 2019, early 2020, Covid-19 has contributed to the deaths of more than 800,000 Americans and over 5 million people worldwide.1 While the global and domestic death rates continue to decline, there are still ongoing cases of coronavirus related deaths and the emergence of new strains. In an effort to combat fatalities in the United States vaccines have been released by Pfizer, Moderna, and Johnson & Johnson, with the first two being preferred and the Johnson and Johnson Covid-19 vaccine being administered in certain situations.2 In the aftermath of these vaccines came the recommendation for booster shots to be administered to adults who are 18 years of age and older as well.2 However, there have been growing concerns about the shortening of the booster windows for these vaccines and the development of additional interventions that can be applied to curtail the negative health impacts of Covid-19.
The combination of social distancing, wearing masks, hand hygiene, and vaccine administration may help to control the spread of the virus, but an effective treatment of COVID-19 is needed.3 There has been approval for two antiviral pills to treat Covid -19 made by the Food and Drug Administration (FDA). The first approval by the FDA was for Pfizer’s, Paxlovid, which is indicated for the treatment of Covid-19 at home for those people who contract the virus prior to requiring hospitalization. 4 This antiviral pill can be viewed as a breakthrough in the fight against Covid-19. The target population for the use of Paxlovid is for those individuals who are 12 years of age of older that are considered to be high risk for hospitalization and death from the virus, and have demonstrated a positive SARS-COV-2 test.
On the heels of the approval of Paxlovid came the FDA approval of the second antiviral pill from Merck, called Molnupiravir. This antiviral pill is indicated for the treatment of mild to moderate Covid-19 in adults who have a positive SAR-COV-2 test that are at risk for more severe Covid-19 when no other treatment options are available or inaccessible. 5 In an effort to combat the impact of Covid-19 on the health status of many more Americans, the FDA has moved to provide emergency authorization for both of these antiviral pills.
With ongoing concerns of possible surges of the Omicron variant which has the capacity to significantly overwhelm the resources of various hospitals across the nation, the FDA has made the bold decision to approve these antiviral pills. It is hoped that that these pills will work to combat the virus by reducing the risk of hospitalizations and deaths, particularly among those that are unvaccinated.6
Most recently a novel medication called sabizabulin appears very effective in treating hospitalized patients and is currently under review by the FDA.42
Paxlovid is prescribed as three pills taken twice a day for five days. Both Paxlovid and molnupiravir have been shown to reduce hospitalization and death from Covid-19 if taken early on in the course of an infection. They are most effective when used within a few days of the onset of symptoms. Currently, to be eligible for Covid-19 treatment you must test positive with a PCR test and have symptoms that started within five days or fewer. You must also be at increased risk of developing severe Covid-19. Those who are asymptomatic, or who have symptoms but are not higher risk, will not be eligible. Many people in the United States have medical conditions that would qualify them for the high-risk category. That includes all adults 65 and older, as well as those of any age with certain health conditions like heart disease, cancer, diabetes or obesity.
Most people who take Paxlovid don’t experience serious side effects, though some may have diarrhea, muscle pain or an altered sense of taste. Certain medications or supplements, including painkillers, statins and even St. John’s Wort, may have adverse interactions with Paxlovid. But for some medications, like drugs that regulate heart rhythm, abstaining for a week may not be possible.
Molnupiravir has no known interactions with other medications. But possible side effects can include diarrhea, nausea and dizziness. The drug is not authorized for anyone under 18 years old because it may affect bone and cartilage growth. And molnupiravir cannot be used during pregnancy because of the potential harm to the fetus. For this reason, doctors may also recommend that sexually active men and women of childbearing age use contraception during treatment and for a period afterward (three months for men and four days for women). Those who are breastfeeding should consider pumping and discarding breast milk during treatment and for four days after the last dose.
Sabizabulin Cuts COVID-19 Death; Trial Stopped Early Due to Efficacy
Sabizabulin is an oral cytoskeleton disruptor that blocks microtubule trafficking with both antiviral and anti-inflammatory effects, thereby treating both the SARS-CoV-2 infection and the cytokine storm and lung toxicity.42
A phase 3 trial evaluating sabizabulin in hospitalized COVID-19 patients at high risk for acute respiratory distress syndrome (ARDS) found that sabizabulin resulted in a 55% relative reduction in death.
In the study patients were treated with either oral sabizabulin for up to 21 days or placebo in addition to treatment remedesivir, steroids, and anti-interleukin 6 (IL6) receptor antibodies.
Interim analysis the mortality rates for the sabizabulin was 20% compared 45% in placebo treated patients. Aabizabulin was well tolerated with no clinically relevant safety concerns compared with placebo. The independent Data Safety Monitoring Committee has recommended that the trial be stopped early and the Food and Drug Administration evaluate an emergency use authorization application.
What About Fluvoxamine?
Another promising medication is fluvoxamine, a pill the FDA approved in 1994 to treat obsessive-compulsive disorders. Doctors often prescribe it off-label for anxiety, depression and panic attacks. Studies show that fluvoxamine is highly effective at preventing hospitalization in Covid-infected patients, and it’s unlikely to be blunted by Omicron. A 10-day course of fluvoxamine costs $4, compared with the $2,100 the U.S. government has been paying for monoclonal antibodies, and $530 to $700 for a course of the Pfizer and Merck treatments. Multiple drugmakers manufacture fluvoxamine and could ramp up supply without much difficulty were demand to increase.7
Researchers at McMaster University in Hamilton, Ontario launched a large clinical trial in Brazil. The results from their trial demonstrated that Fluvoxamine reduced the odds of hospitalization or emergency care by 66% and death by 90% among unvaccinated high-risk patients who mostly followed the treatment regimen.9 The FDA however declined authorization of fluvoxamine for emergency use as an outpatient treatment for COVID-19 due to “insufficient data” showing that fluvoxamine “may be effective in the treatment of non-hospitalized patients with COVID-19. The request for an emergency use authorization (EUA) was based on data from the randomized placebo-controlled TOGETHER trial conducted in Brazil, which demonstrated that fluvoxamine reduced the need for among high-risk patients with COVID-19. The FDA noted that the trial met its primary endpoint but said “the results were primarily driven by a reduction in the emergency department visits lasting greater than 6 hours, and there are uncertainties about the assessment of this endpoint and whether the 6-hour time point represents a clinically meaningful threshold.”
What About Monoclonal Antibodies, and How do They Work?
Monoclonal antibodies are lab-made antibodies that work by binding to the virus the way natural antibodies do. Monoclonal antibody treatments for COVID-19 are used before a person gets really sick, usually within the first 4 - 10 days of their first symptoms to prevent hospitalization and death. The antibody treatment is given through an IV or infusion.
One monoclonal antibody therapy made by AstraZeneca (Evusheld) is authorized for preventative use, before a person is sick or exposed, but only for people who are immunocompromised or those who don't mount an adequate immune response to the COVID-19 vaccines.
Laboratory studies suggest that the monoclonal antibody treatments made by Eli Lilly (bamlanivimab and etesevimab together) and Regeneron (REGEN-COV) no longer work to prevent severe disease caused by the Omicron variant and lost their EUA from the US Food and Drug Administration.
GlaxoSmithKline and Vir Biotechnology make sotrovimab which is authorized for people 12 and up who are at risk of getting severely sick from COVID-19 within 10 days of their symptoms starting. People eligible include adults age 65 and up and people living with diabetes, asthma or other medical conditions.
Coronaviruses are large, enveloped, single-stranded, positive-sense RNA viruses that have been recognized as human pathogens for about 50 years, but no effective treatment strategy has been approved. This shortcoming became evident during the SARS-CoV outbreak which was the start of numerous studies and has been amplified by the recent global Coronavirus COVID-19 pandemic. Researchers are working to develop medications to both prevent and treat COVID-19 infection.
How Effective is Paxlovid?
Final analysis of the protease inhibitor antiviral Covid-19 pill, Paxlovid)shows near 90% efficacy in preventing hospitalizations and deaths in high-risk patients, and recent lab data suggests the drug retains its effectiveness against the fast-spreading omicron variant of the coronavirus. The pills are taken in combination with the older antiviral ritonavir every 12 hours for five days beginning shortly after onset of symptoms. Paxlovie will be the first oral antiviral treatments for Covid authorized in the United States. The interim analysis evaluating the investigational COVID-19 oral antiviral drug, Paxlovid (PF-07321332/ritonavir) has demonstrated a significant reduction in the risk for hospitalization or death in symptomatic adults with COVID-19. Paxlovid works by inhibiting viral replication of SARS-CoV-2 by blocking the activity of the SARS-CoV-2-3CL protease and is co-administrated with low-dose ritonavir slow the metabolism of PF-07321332 to prolong activity.36.37
The trial included 1219 patients with laboratory-confirmed diagnosis of SARS-CoV-2 infection within a 5-day period with mild to moderate symptoms. Patients were required to have at least 1 characteristic or underlying medical condition associated with an increased risk of developing severe illness from COVID-19. Patients were randomly assigned 1:1 to receive either Paxlovid or placebo orally every 12 hours for 5 days. Patients treated with Paxlovid had an 89% reduction in the risk of COVID-19-related hospitalization or death from any cause within 3 days of symptom onset compared with patients who received a placebo. Through Day 28, 0.8% of patients treated with Paxlovid were hospitalized with no deaths compared with 7% of those receiving placebo. The study has been stopped based on a recommendation from an independent Data Monitoring Committee and in consultation with the Food and Drug Administration.
Evusheld (AZD7442) for the prevention of COVID-19
Vaccination is the primary strategy to prevent sever COVID-19 disease and is highly effective however not all individuals, especially those with compromised immune systems can be effectively vaccinated. AZD7442 is a combination of 2 monoclonal antibodies, tixagevimab and cilgavimab, derived from B-cells donated by convalescent patients who were infected with the SARS-CoV-2 virus. The antibodies are designed to bind to distinct sites on the SARS-CoV-2 spike protein rendering it less dangerous.
The multicenter PROVENT clinical trial included 5197 unvaccinated participants aged 18 years and older who were at increased risk for inadequate response to active immunization or had increased risk of SARS-CoV-2 infection. Findings showed that AZD7442 achieved a 77% risk reduction of developing symptomatic COVID-19 compared with placebo. There were no cases of severe COVID-19 or COVID-19-related deaths in the AZD7442 treatment arm compared with 3 cases of severe COVID-19 in the placebo arm, including 2 deaths. Myron J. Levin, MD, Professor of Pediatrics and Medicine, University of Colorado School of Medicine, and principal investigator on the trial, noted that the “PROVENT data show that one dose of AZD7442, delivered in a convenient intramuscular form, can quickly and effectively prevent symptomatic COVID-19.34
Veklury as First Treatment for COVID-19
The Food and Drug Administration (FDA) approved Veklury® (remdesivir) for the treatment of COVID-19 in patients aged 12 years and older (weighing at least 40kg) requiring hospitalization. The approval was supported by data from three phase 3 trials in hospitalized patients with mild to severe COVID-19. The randomized, double-blind, placebo-controlled phase 3 ACTT-1 trial assessed 1062 hospitalized patients with COVID-19 who received either Veklury (n=541) or placebo (n=521) in addition to standard of care. Results showed that the median time to recovery was 10 days for the Veklury treatment arm compared with 15 days for placebo and Veklury showed a trend toward reduced mortality at Day 29 compared with placebo (11.4% vs 15.2%).14,15
Veklury is an antiviral medication that was developed to treat Ebola by Gilead and works by inserting directly into viral RNA. Veklury appears to facilitate a more rapid recovery from COVID-19 infections. Preliminary study results are encouraging. According to 3 retrospective real-world studies presented at the 2021 World Microbe Forum hospitalized patients with COVID-19 who were treated with Veklury® had significantly lower risk for mortality compared with matched controls, The 3 studies found a 23% lower mortality risk in 98,654 hospitalized patients with COVID-19 who were treated with Veklury compared with controls. Patients who received a 5-day course of Veklury also had a greater likelihood of hospital discharge by day 28.33
The experimental antiviral pill molnupiravir reduced the chances that patients newly diagnosed with Covid-19 would be hospitalized by about 50%. A five-day course of molnupiravir, developed by Merck (MRK) and Ridgeback Biotherapeutics, reduced both hospitalization and death compared to a placebo. In the placebo group, 53 patients, or 14.1%, were hospitalized or died. For those who received the drug, 28, or 7.3%, were hospitalized or died. A simple oral medication to help treat Covid-19 has been an elusive goal since the start of the pandemic.35
In December 2021 the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for Merck’s molnupiravir for the treatment of mild-to-moderate coronavirus disease (COVID-19) in adults with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options authorized by the FDA are not accessible or clinically appropriate. Molnupiravir is available by prescription only and should be initiated as soon as possible after diagnosis of COVID-19 and within five days of symptom onset.
FDA Authorizes Bebtelovimab for COVID-19 Treatment
The Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for bebtelovimab for the treatment of mild to moderate COVID-19 in patients 12 years of age and older weighing at least 40kg with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19.40
Bebtelovimab is a recombinant neutralizing human IgG1κ monoclonal antibody that works by binding to the spike protein of SARS-CoV-2. The EUA was supported by data from the phase 2 BLAZE-4 trial which evaluated a single IV infusion of bebtelovimab or together with etesevimab in non-hospitalized patients with mild to moderate COVID-19. Among low and high-risk patients bebtelovimab resulted in a reduction in time to sustained symptom resolution and a reduction in viral load. BLAZE-4 was conducted prior to the emergence of the Omicron variant; no patients in the study were infected with virus of the Omicron lineage or sublineages. However, nonclinical viral neutralization data showed that bebtelovimab retained full neutralizing activity against Omicron and all other known variants of interest and concern, including BA.2.
FDA Issues EUA for Olumiant (baricitinib)
On November 2021 the US Food and Drug Administration issued an EUA for the rheumatoid arthritis drug Olumiant (baricitinib) in combination with remdesivir for treatment of patients hospitalized with suspected or confirmed COVID-19. JAK inhibitors are a class of oral medications — targeted synthetic [disease-modifying antirheumatic drugs (DMARDs)] — that inhibit a key signal-transduction pathway, the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. This pathway mediates biologic activity for a large number of inflammatory cytokines and mediators, many of which are known to be elevated in COVID-19. This is part of the rationale for using JAK inhibitors in COVID-19. There are currently JAK inhibitors approved for treatment of rheumatoid arthritis and the class of drugs is growing rapidly for treatment of a wide variety of immune-based diseases. (31)
REGN-COV2 Data Submitted to FDA for Consideration
REGN-COV2 is an antibody cocktail that consists of 2, virus-neutralizing antibodies (casirivimab/imdevimab) that bind non-competitively to the SARS-CoV-2 spike protein, thereby blocking its interaction with the host cell. On January 24, 2022, the U.S. Food and Drug Administration (FDA) amended the Emergency Use Authorization (EUA) for REGEN-COV to exclude its use in geographic regions where, based on available information including variant susceptibility and regional variant frequency, infection or exposure is likely due to a variant such as Omicron (B.1.1.529) that is not susceptible to the treatment. (28,32)
Bamlanivimab + Etesevimab Reduces COVID-19 Hospitalization & Deaths Eli Lilly’s SARS-CoV-2 neutralizing antibodies, bamlanivimab (LY-CoV555) plus etesevimab (LY-CoV016), also appear to significantly reduced hospitalizations and deaths among high-risk patients recently diagnosed with COVID-19. The combination of bamlanivimab and etesevimab for the treatment of mild to moderate COVID-19 is currently being reviewed by the Food and Drug Administration for Emergency Use Authorization (EUA). In November 2020, the FDA issued an EUA for bamlanivimab monotherapy for the treatment of COVID-19.33,41
Dexamethasone - Steroids
Low-dose dexamethasone used as a treatment for COVID-19 has been reported to reduce the risk for death by one-third in ventilated patients and also lowered risk in patients receiving oxygen, according to early results from the RECOVERY trial. Dexamethasone is a commonly used "steroid" medication thought to exert its benefit by reducing lung inflammation which is the main cause of mortality from the virus.20 Systemic and inhaled steroids are both known to reduce inflammation and widely used for the treatment of Asthma to reduce lung inflammation. Globally some doctors use a combination of inhaled steroids combined with zinc and an antibiotic early in the disease course and claim a high level of success. Studies have not yet been published on this combination but individuals should discuss it along with all other treatment options if they are diagnosed with COVID-19.
Ivermectin has demonstrated different mechanisms of action that potentially protect from both coronavirus disease 2019 (COVID-19) infection and COVID-19-related co-morbidities. Based on the studies suggesting efficacy in prophylaxis combined with the known safety profile of ivermectin, a citywide prevention program using ivermectin for COVID-19 was implemented in Itajaí, a southern city in Brazil in the state of Santa Catarina. The objective of this study was to evaluate the impact of regular ivermectin use on subsequent COVID-19 infection and mortality rates. Doctors followed nearly the entire city of Itajaí for six months, where 113,845 residents took small doses of ivermectin twice a month, and 45,716 did not. The sophisticated propensity score matched (PSM) analysis shows that even low-dose prophylactic use of ivermectin – with no particular treatment after infection – resulted in a 56% reduction in hospitalization and a 68% mortality improvement.38
Trials however have not found Ivermectin to be an effective treatment for individuals with COVID-19.39,42 The largest trial to date published in the March 2022, NEJM was conducted in Brazil and found no difference in hospitalization rates for placebo compared to 3 days of Ivermectin in individuals with confirmed COVID-19 infection.42
Vitamin D and COVID-19
Some but not all studies suggest that patients with lower vitamin D levels who are diagnosed with COVID-19 tend to have worse outcomes and researchers recently reported that people hospitalized for COVID-19 who were deficient in vitamin D were more likely to have severe symptoms or die from COVID-19. Dr. David Meltzer and colleagues at The University of Chicago published that patients who have lower vitamin D levels are more likely to test positive for COVID-19.4-6 Vitamin D is clearly important for a healthy immune system and research suggests it can play a role in preventing viral respiratory lung infections.7 According to Dr. Anthony Fauci “If you are deficient in vitamin D, that does have an impact on your susceptibility to infection” While ongoing research will ultimately determine the relationship between vitamin D deficiency and COVID-19 infections it makes sense to make sure individuals are at least no deficient in this important vitamin. Learn more about Vitamin D.
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Vitamin C and Zinc Appear not to Reduce SARS-CoV-2 Symptoms
Doctors from the Cleveland Clinic examined whether high-dose zinc and/or high-dose ascorbic acid reduce the severity or duration of symptoms in 214 adult patients with SARS-CoV-2. Patients were randomly assigned to receive either 10 days of zinc gluconate, ascorbic acid, both, or standard of care and directly compared. The researchers found that patients who received usual care without supplementation achieved a 50% reduction in symptoms at a mean of 6.7 days compared with 5.5 days for those receiving both supplements. The study was stopped for a low conditional power for benefit, with no significant differences seen among the groups.34
COVID-19 – Does ASPIRIN Decrease Mortality?
Physicians who care for COVID-19 patients have considered the possibility that individuals might have a better chance of survival if they had taken medicines that would counteract this risk of blood clots prior to coming to the hospital Over-the-counter aspirin is a drug taken by a number of individuals for a variety of reasons including prevention of heart attacks and for musculoskeletal pain.
In a study of 412 COVID-19 patients 314 did not receive aspirin, while 98 received aspirin within 24 hours of admission or 7 days prior to admission. Aspirin use was associated with a decreased risk of being put on a ventilator (35.7% aspirin vs. 48.4% non-aspirin) and admission to the ICU (38.3% aspirin vs 51.0% non-aspirin) - aspirin was independently associated with decreased mortality.
Although interesting the study but does not prove the benefit of aspirin. A double-blind, randomized controlled study with an adequate number of patients would need to be done before proving the benefit of aspirin in more severely ill COVID patients.19
Individuals with more severe COVID-19 infection experience shortness of breath and cough and respiratory complications are the main cause of death. If the immune system is excessive in its response to a lung infection, a cytokine storm may occur. A cytokine storm occurs when immune factors that initiate and maintain an immune response are not inhibited. This excessive response will cause extensive lung tissue damage. Membranes will become swollen and impair oxygen exchange. With that change in lung function, individuals need to be placed on ventilators to produce positive back pressure to allow the membranes of the lung to work.
Interleukin (IL) – 6 is a cytokine identified to be a major factor in the immune process. IL-6 activates T cells, B, cell, macrophages, osteoclasts, and the production of liver factors that result in fever. IL-6 is thought to be one of the prime mediators of cytokine storm. Inhibition of IL-6 in COVID-19 patients with respiratory distress has the potential to quiet the storm and allow the lungs to heal.
IL-6 is a cytokine that also mediates the inflammatory response in rheumatoid arthritis. Therapy of rheumatoid arthritis includes Anti-IL-6 biologic drugs. These are currently available for the treatment of RA but may also be of use in the treatment of COVID -19 infection.
Tocilizumab (Actemra) is a humanized anti-human IL-6 receptor antibody that can be administered intravenously or subcutaneously. In severe cases of COVID -19 pulmonary involvement, intravenous Actemra has been utilized with some success.18 Results from the first clinical trial evaluating Actemra in COVID -19 pneumonia were published in early May.
The preliminary report suggests that Actemra may benefit COVID-19 hospitalized patients with moderately-to-severely ill COVID-19 pneumonia. Patients were enrolled if hospitalized for moderate or severe COVID-19 pneumonia. The primary endpoint was the combination of the need for ventilation (mechanical or non-invasive) or death on D14. Patients were randomized to received Actemra + standard-of-care (SOC) treatment (65 patients) or SOC alone (64 patients). The primary objective was met with Actemra treated patients having significantly fewer deaths or ventilation, compared to the SOC arm. The results will be submitted for later publication, but the " researchers and the sponsor felt obliged, from an ethical point of view, to communicate this information, while awaiting peer review while continuing the longer follow-up of these patients"17
Unfortunately, research reports offer conflicting views on the potential benefits and adverse outcomes of Actemra therapy in patients with severe COVID-19 infection. A recent Italian study grabbed the headlines with a press release stating Actemra did not improve respiratory symptoms and a report last month from Sanofi also showed no beneft, while higher doses were potentially beneficial. Preliminary reports of several other studies may suggest benefit when TCZ was given to SARS-CoV-2 patients.21,22,23
The vast majority of individuals with COVID -19 infection will be asymptomatic or will be mildly ill. About 20% will have a noticeable infection and may require medical care. A lower number will be hospitalized. In these individuals with more severe disease, the use of anti-IL6 antibodies has the potential to prevent lung damage and result in decreased mortality from this illness.
Regeneron is testing an approved drug, called Kevzara, against COVID -19. The drug, targets inflammation, not the virus itself. A similar drug from Roche, Actemra, showed early promise in a study in China. Answers from that study might be available in weeks to months, if patients respond quickly.
Regeneron said in a press release that its scientists have isolated hundreds of virus-neutralizing antibodies from mice, and patients who have recovered from COVID-19. It will choose two of these based on their potency and other qualities like to be manufactured easily, and durability in the body. The antibodies target a protein on the virus’ outer shell, called the spike protein. Having two antibodies targeting the spike protein in the treatment, not one, should mean that it is more difficult for the virus to mutate in a way that will allow it to evade both antibodies.
Creating antibody drugs against the COVID -19 virus is seen as one of the more promising approaches. Teams of researchers at Biogen, Regeneron, Gilead, Eli Lilly and others have all announced plans to develop antibody drugs against the virus.
The Food and Drug Administration (FDA) said the drugs hydroxychloroquine and chloroquine are unlikely to be effective in treating the novel coronavirus on June 12, 2020 Citing reports of heart complications, the FDA said the drugs' unproven benefits “do not outweigh the known and potential risks”. In addition based on a non-clinical laboratory study in which remdesivir was administered with either chloroquine phosphate or hydroxychloroquine sulfate, the FDA revised its fact sheet for health care providers so that co-administration of these drugs is no longer recommended. The change in recommendation is based on the suggestion that co-administration diminishes remdesivir’s antiviral activity.
A World Health guideline panel conducted a systematic review and network meta-analysis using 6 trials with 6059 participants to produce a recommendation based on the evidence surrounding the use of hydroxychloroquine. Of these studies, 3 enrolled people with known exposure to SARS-CoV-2 infection, and 3 enrolled people who did not have known exposure.32
They found that hydroxychloroquine had little or no effect on mortality or hospital admission, and there was little or no evidence of the drug having an effect on laboratory-confirmed SARS-CoV-2 infection. More than 80 trials planning to enroll 100,000 individuals are registered or ongoing to assess hydroxychloroquine and chloroquine for COVID-19 prophylaxis.
Additional information on registered and ongoing trials for COVID-19 therapeutics and prophylaxis are available from the Infectious Diseases Data Observatory
On July 7, 2020 researchers from the Henry Ford Medical Group reported that there was clear benefit to using Hydroxychloroquine as a treatment for sick, hospitalized patients with COVID-19. Doctors at Henry Ford analyzed 2,541 COVID infected patients hospitalized between March 10 and May 2 and found that 13% of the patients treated with hydroxychloroquine died compared to 26.4% of the patients who did not receive the drug.
The Henry Ford protocol required the drug to be given soon after admission and 91% of patients were treated within 48 hours of which is different than many other reports where the drug was utilized much later.
Regardless of treatment, mortality was highest in:
· Patients older than 65
· Patients who identified as Caucasian
· Patients admitted with reduced oxygen levels
· Patients who required ICU admission.
Patients who died commonly had serious underlying diseases, including chronic kidney and lung disease, with 88% dying from respiratory failure.
The study results should be interpreted with some caution as we still await prospective, randomized controlled trials that rigorously evaluate the safety and efficacy of hydroxychloroquine therapy for COVID-19.23
Hospitalized patients in Brazil with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen were randomly assigned to receive standard care, hydroxychloroquine or hydroxychloroquine plus azithromycin for 7 days. When directly compared no benefit from hydroxychloroquine treatment was identified.24
Chloroquine is a clinically approved drug effective against malaria, and it is known to elicit antiviral effects against several viruses including human immunodeficiency virus type 1, hepatitis B virus, and herpes simplex virus type 1.3-10 Chloroquine is also reported to inhibit the replication of some HoCov10 and SARS-CoV (11) in vitro. Chloroquine can affect virus infection in many ways. Besides having a direct antiviral effect, chloroquine is endowed with immunomodulatory activity, suppressing the production and release of tumor necrosis factor alpha and interleukin 6, which mediate the inflammatory complications of several viral diseases.13
Physicians routinely use FDA approved medications to treat conditions for which they are not approved if it's in their judgement that the medication might benefit their patient, especially in "life threatening" situations. Hydroxychloroquine is are already FDA approved and has been in use for decades - the side effects at recommended doses are well documented. Patients with certain autoimmune conditions have been routinely taking hydroxychloroquine medications for years. In oncology patients are often treated with non FDA approved treatments because the "available" data suggests the treatment may benefit an individual patient and following a discussion a shared decision can be made between a patient and their physician.
Researchers have investigated the anti-corona viral properties of chloroquine and demonstrated that it inhibit some HCoV replication. Chloroquine has also been shown to prevent HCoV induced death in newborn mice. These results have led to recent testing of chloroquine and hydroxychloroquine in humans impacted with the current COVID-19 strain implicated in the global pandemic with encouraging results.13 Clinical trials are ongoing and results are being reported.
A report released by Chinese researchers on April 2 suggests hydroxychloroquine helped to speed the recovery of a small number of patients who were mildly ill from the coronavirus. Cough, fever and pneumonia all recovered quicker, and the disease seemed less likely to become severe in people who received hydroxychloroquine than in a comparison group not given the drug. Another recent study in Brazil has raised concerns about toxicity to the heart however the dose of the drug utilized was higher than the approved dose. Results from other recent larger observational trials have not been supportive of the early trial results. It's important to remember however that none of the published trials are well controlled comparative trials evaluating the medication in comparison to a placebo. Comparative trial results will be available soon and will help determine whether these medications ultimately have a role in management of COVID-19.
- Wu J & Chiwaya N. Coronavirus deaths: US maps show the number of fatalities compared to confirmed cases. NBC News. January 5, 2022, Accessed January 5, 2022. https://www.nbcnews.com/health/health-news/coronavirus-deaths-u-s-map-shows-number-fatalities-compared-confirmed-n1166966
- Center for Disease Control and Prevention. Covid-19 vaccine booster shots. January 4, 2022. Accessed January 5, 2022.
- Chiu NC, Chi H, Tai YL, et al. Impact of wearing masks, hand hygiene, and social distancing on influenza, enterovirus, and all-cause pneumonia during the coronavirus pandemic: Retrospective National Epidemiological Surveillance Study. J Med Internet Res. 2020;22(8):e21257. Published 2020 Aug 20. doi:10.2196/21257
- Gumbrecht J & Howard J. FDA authorizes second antivirual pill to treat Covid-19. CNS Health. December 24, 2021. Accessed January 5, 2022.
- Tin A. FDA authorized second Covid antivirual pill, from Merck, if no alternatives available. CBS News. December 23, 2021. Accessed January 5, 2022.
- Beusekom M. Merck’s Covid-19 pill cuts hospital use, deaths in unvaccinated. Center for Infectious Disease Research and Policy. December 17, 2021. Accessed January 5, 2022.
- Antiviral Activity of Chloroquine against Human Coronavirus OC43 Infection in Newborn Mice
- Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia
- Kouroumalis, E. A., and J. Koskinas. 1986. Treatment of chronic active hepatitis B (CAH B) with chloroquine: a preliminary report. Ann. Acad. Med. Singapore 15:149-152.
- Pardridge, W. M., J. Yang, and A. Diagne. 1998. Chloroquine inhibits HIV-1 replication in human peripheral blood lymphocytes. Immunol. Lett. 64:45-47.
- Rubin, M., H. N. Bernstein, and N. J. Zvaifler. 1963. Studies on the pharmacology of chloroquine. Recommendations for the treatment of chloroquine retinopathy. Arch. Ophthalmol. 70:474-481.
- Savarino, A., J. R. Boelaert, A. Cassone, G. Majori, and R. Cauda. 2003. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect. Dis. 3:722-727.
- Savarino, A., L. Gennero, K. Sperber, and J. R. Boelaert. 2001. The anti-HIV-1 activity of chloroquine. J. Clin. Virol. 20:131-135.
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