2019 Novel Coronavirus (SARS-CoV-2, COVID-19)

Reviewers: Dr. Gary Gonzalez, MD; Dr. Shayna Sandhaus, PhD., Chemistry; Julia Dosik, MPH; and Andrew Roberts Jr., MPH in Global Health

  1. 1Background Over the last few decades, several new viruses have emerged as threats to human health around the globe. The most recent example is the 2019 novel coronavirus.The virus itself is called SARS-CoV-2, and the disease it causes is called COVID-19 (short for Coronavirus Disease 2019).SARS-CoV-2 came to the attention of health authorities when it was identified as the cause of a small number of pneumonia cases in the city of Wuhan in Hubei province, China (WHO 2020). Since then, thousands of cases of COVID-19 illness have been identified in China, mainly in Hubei province, and international spread has been reported as travelers coming from China carry the virus worldwide (CDC 2020b).Coronaviruses are a large group of related viruses that cause many common human and animal infections (Li 2020). In humans, coronaviruses typically cause mild respiratory infections. Responsible for an estimated 10–30% of all upper respiratory tract infections, coronaviruses are among the most frequent causes of the common cold (Paules 2020). Over the last decade, new coronaviruses that cause potentially lethal respiratory diseases have emerged. These include severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (Su 2016).The SARS pandemic in the early 2000s, which lasted about nine months in 2002–2003, affected over 8,000 people in 29 world regions and caused fatality in almost 10% of cases. MERS, on the other hand, has been smoldering mainly on the Arabian Peninsula since 2012, infecting approximately 2,400 people and having a case fatality rate of nearly 35% (Hui 2020; Killerby 2020). For perspective, the fatality rate of typical influenza viruses is much lower, reaching a maximum of about 0.2% in people over 75 years old; however, because of its high incidence, the number of deaths attributable to the flu worldwide averages between 291,000 and 646,000 annually (Iuliano 2018).Although the characteristics of COVID-19 illness are still being elucidated, those most likely to contract the disease are those in direct contact with other infected individuals. The most common presentation is fever and cough followed by flu-like symptoms, with rapid progression to fulminant pneumonia and death mainly in those over 70 years old. As of March 3rd, 2020, commonly reported estimates of the case-fatality rate range from about 1% to 3%; however, the potential for mild cases to go undetected means that the actual fatality rate may be much lower, with some suggestions as low as 0.1% (Wang 2020; Fauci 2020). Experience with other new coronavirus outbreaks suggests those at greatest risk, in addition to the elderly, are likely to be those who are hospitalized, immunocompromised, or have a chronic disease (Hui 2020; Azhar 2019). In addition, healthcare workers have historically been at increased risk of developing and transmitting coronavirus infections (Judson 2019; Otter 2016). NOTE: At the first signs of a respiratory tract infection (e.g., sneezing, coughing, feeling unwell, mild fever), contact your doctor and immediately initiate the interventions described in the Integrative Approaches section of this Protocol. The interventions described in this Protocol, though not necessarily validated as effective specifically for COVID-19, are nevertheless advisable upon onset of symptoms of respiratory tract infections.

  2. Spread Contact. Direct contact is the most likely route of transmission for coronaviruses such as those associated with SARS, MERS, and the current COVID-19 outbreak (Killerby 2020). In these cases, the virus is transferred when an uninfected individual comes into direct contact with an infected person who is actively shedding virus.Droplet. In this form of viral spread, the virus is suspended in droplets emitted from the respiratory tract of an infected individual through a sneeze or cough and inhaled by nearby uninfected individuals. Another possibility is that droplets may land on or near uninfected individuals, be picked up by hands, and transferred to the respiratory tract through touching the nose, mouth, or eyes (Hui 2019).Aerosol. The aerosol route of transmission involves inhalation of airborne viruses, possibly at some distance from the infected person. Although this is less likely than direct contact or droplet transmission, studies in indoor environments and some case reports suggest this is a viable transmission route for SARS and MERS coronaviruses (Judson 2019; La Rosa 2013). Aerosol transmission appears to be an especially important concern in healthcare settings where aerosol-generating medical procedures may put healthcare workers and other patients at risk (Judson 2019).Oral-fecal. The oral-fecal route involves viruses being shed through the feces (usually in people with diarrhea), contaminating surfaces and ultimately hands that can then introduce the virus to the respiratory tract. This is an uncommon but documented route of transmission for coronaviruses such as the SARS virus (Hui 2019). Coronaviruses are highly adaptable and known to undergo host-switching. Several established human coronaviruses have evolved from bird or mammalian coronavirus origins (Corman 2018). For example, the human coronavirus associated with MERS is likely to have come from camels, though its origins may have been a bat coronavirus; the SARS coronavirus also appears to have originated in bats and was possibly transmitted by an intermediate mammalian host called a civet (Azhar 2019; Hui 2019). Although distinct from all other known coronaviruses, SARS-CoV-2 also appears to be closely related to a bat coronavirus (Chen 2020).Once adapted to the human host, coronaviruses can become transmissible between humans. There are four possible routes of transmission: contact, droplet, aerosol, and oral-fecal (Shiu 2019).

  3. 3Protective Measures Below are some basic measures to consider in order to reduce your risk of contracting COVID-19 and other viral illnesses.Avoid air travel to affected regions. Avoiding contact with infected individuals is the best way to protect yourself from COVID-19. Limiting travel to countries or areas with known community spread is advisable (CDC 2020c). In addition, all air travel is associated with exposure to people and the infectious agents they carry. Outbreaks of infectious illnesses, including measles, influenza, SARS, and many others, aboard commercial flights have been documented (Mangili 2015; Hertzberg 2016). Therefore, avoiding air travel is a reasonable precaution for reducing your risk of viral infections in general, particularly if you have other vulnerabilities.Wash your hands. Frequent hand washing is an important strategy for protecting against all types of infectious diseases. Studies in office and healthcare settings have further demonstrated strategic use of alcohol-based surface disinfectants and hand sanitizers can reduce viral spread by 85–94% (Kurgat 2019; Reynolds 2019).Strengthen immunity. Optimal functioning of the immune system is vital for defending against all types of infections, from mild colds to dangerous influenza and life-threatening pneumonia. A nutrient-dense diet, regular exercise, adequate sleep, and stress management can all contribute to healthy immune function (Zapatera 2015). .Disinfect surfaces. A study published on March 17th, 2020 by scientists from the U. S. National Institutes of Health and CDC along with UCLA and Princeton University researchers found that SARS-CoV-2 aerosols were detectable for up to three hours. The virus was detectable on cardboard for up to 24 hours and for up to three days on plastic and stainless steel (van Doremalen 2020).Fortunately, coronaviruses can be inactivated with proper cleaning and disinfecting agents. Therefore, keeping surfaces clean and properly disinfected is important to limit the spread of infectious diseases caused by coronaviruses. A study published on February 6th, 2020 found that coronaviruses on inanimate surfaces can be inactivated within one minute through disinfection with 62%‒71% ethanol, 0.5% hydrogen peroxide, or 0.1% sodium hypochlorite (eg, bleach) (Kampf 2020).As of March 6th, 2020, the United States Environmental Protection Agency (EPA) provides a list of EPA-registered disinfectant products for use against the SARS-CoV-2 virus (EPA 2020). The list is available on the EPA’s web page, here: https://www.epa.gov/pesticide-registration/list-n-disinfectants-use-against-sars-cov-2.Social distancing. The CDC and other health authorities worldwide strongly advise that citizens—especially those at increased risk—living in communities experiencing community spread of COVID-19 "[remain] out of congregate settings, avoid mass gatherings, and maintain distance (approximately 6 feet or 2 meters) from others when possible" (CDC 2020e). Should You Wear A Facemask? As of March 2nd, 2020, the CDC does not recommend that people who are well wear a facemask to reduce their chances of developing COVID-19. However, the Agency recommends that people who are sick or who have symptoms suggestive of COVID-19 wear a facemask to reduce the risk of spreading the infection to others (CDC 2020d).Facemasks are important in healthcare settings such as hospitals. One model of viral spread in a healthcare setting estimated facemasks could reduce flu (influenza) susceptibility by 3-10% (Blanco 2016).Importantly, the U.S. Surgeon General has discouraged people who are not sick from stockpiling facemasks because doing so could limit the supply available in healthcare settings where the masks can make a meaningful difference (Howard 2020).

  4. Testing and Diagnosis As is to be expected with newly emergent diseases, testing methods to confirm diagnoses are not always readily available. The CDC and other entities have been able to rapidly develop tests that can confirm a diagnosis of COVID-19. As of March 6th, 2020, the CDC and other U.S. government agencies are working to distribute enough test kits to meet demand across the country (CDC 2020a). Commercial labs such as Quest and LabCorp are also beginning to offer testing services (Hale 2020).

  5. Medications Because there are no proven medical treatments for COVID-19 or other human coronaviruses, scientists are looking to both old and new antiviral drugs in search of effective therapies. Several drugs are currently being evaluated in preliminary research. These include antiviral drugs used to treat human immunodeficiency virus (HIV) and hepatitis B and C, such as ribavirin (Ribasphere), lopinavir-ritonavir (Kaletra), and interferon beta-1b (Betaseron) (Sheahan 2020; Chu 2004; Dyall 2017). An early-stage, open-label clinical trial published in the New England Journal of Medicine on March 18th, 2020, failed to show benefit with lopinavir-ritonavir in patients with severe COVID-19 (Cao 2020).The antimalarial drug chloroquine (Aralen) has shown broad-spectrum antiviral effects in preclinical and clinical research, indicating its potential role in combined-drug approaches to treating emerging coronavirus infections (Dyall 2017). Preliminary evidence from multi-center clinical trials conducted in China suggest chloroquine phosphate has clinical efficacy against COVID-19 (Gao 2020). However, its use remains investigational until more rigorous clinical trials can be completed (Cortegiani 2020). Hydroxychloroquine, a less-toxic derivative of chloroquine (McChesney 1983), has been shown in preliminary studies to be efficacious against SARS-CoV-2. Several trials are currently underway to assess the clinical utility of hydroxychloroquine in COVID-19 patients. As of March 20th, 2020, hydroxychloroquine appears to be one of the most promising therapeutics under investigation for COVID-19 (Frieden 2020; Lecrubier 2020; Liu 2020).Remdesivir is another antiviral drug that has shown promise against SARS-CoV-2 in preliminary pre-clinical studies. It is a prodrug of an adenosine analog that has potent antiviral activity against many RNA virus families (Agostini 2018). A 2018 in vitro study showed that remdesivir was efficacious against two strains of human endemic coronavirus (HCoV-OC43 and HCoV-229E) (Brown 2019). A drug screening study published on February 4th, 2020 showed remdesivir and chloroquine were both effective at inhibiting SARS-CoV-2 in vitro (Wang 2020). The Wall Street Journal published an article on January 31st indicating that the pharmaceutical company Gilead has entered into agreement with Chinese health authorities to conduct priority clinical trials to assess the efficacy of remdesivir in patients infected with SARS-CoV-2 (Walker 2020).On Feb. 25th, 2020, the U. S. National Institutes of Health (NIH) announced the commencement of the first clinical trial of remdesivir for COVID-19 in the United States. The trial is taking place at the University of Nebraska Medical Center in Omaha. This trial will help establish whether remdesivir can offer robust clinical benefits for COVID-19 patients (NIH 2020).The utility of glucocorticoids for treating acute respiratory distress syndrome (ARDS) has been debated for some time (Hough 2014). Whether glucocorticoids are helpful in patients with ARDS depends on the severity and underling cause of ARDS. In the context of MERS, some evidence suggested that glucocorticoid use was associated with greater mortality (Alfaraj 2019). However, a study published March 13th, 2020 in JAMA suggested corticosteroid use (methylprednisolone) was associated with lower mortality in Chinese COVID-19 patients with ARDS (Wu 2020). As of March 16th, 2020, several randomized controlled trials are planned to assess the efficacy of glucocorticoids in COVID-19 patients (ClinicalTrials.gov 2020). Until more definitive evidence can be derived from these trials, the decision to use glucocorticoids should be made by the treating physician.In the face of low efficacy and challenging adverse side effects of known medications, researchers are searching for new approaches. Immunotherapy using monoclonal antibodies could have a role in treating MERS, SARS, and other emerging coronavirus infections such as COVID-19 (Jin 2017), and novel compounds with anti-coronavirus activity are currently being developed and tested (Sheahan 2017). NSAIDs (eg, Ibuprofen) and COVID-19 In mid-March, questions arose as to whether non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen would be helpful or harmful in the context of COVID-19. As of March 19th, 2020, most experts agreed that evidence was too limited to make a conclusive recommendation for or against NSAIDs, but that there was little evidence that NSAIDs would worsen outcomes in most cases (Melville 2020; NY Daily News 2020). Nevertheless, some physicians and health authorities recommended acetaminophen (Tylenol, known as paracetamol in Europe) rather than ibuprofen or other NSAIDs in the context of COVID-19.The concern with NSAIDs in the context of COVID-19 is that the drugs may mask the early symptoms of COVID-19, or possibly suppress the immune response to the virus, worsening outcomes. However, these concerns remain theoretical as of March 19th, 2020. As of this writing, there is no evidence that taking NSAIDs increases risk of infection with SARS-CoV-2 or of developing COVID-19 (Melville 2020).

  6. Integrative Approaches Vitamin C. Several studies have shown that vitamin C supplementation, both before and soon after the onset of symptoms of upper respiratory tract infections, may help ease symptom burden and reduce the duration of illness (Gorton 1999; Hemilä 1999; Ran 2018). However, the available evidence does not consistently support the notion that preventive vitamin C supplementation can reduce the risk of acquiring upper respiratory tract infections (Hemilä 2013; Virilhon 2019). Importantly, studies to date have not focused specifically on coronavirus infections but on upper respiratory tract infections in general such as those caused by rhinoviruses, enteroviruses, and influenza viruses. As of March 4th, 2020, a study is slated to take place in Wuhan, China to test the effects of 24-gram intravenous vitamin C infusions on outcomes in COVID-19 patients. The primary outcome will assess ventilation-free days, and one of several secondary outcomes will be 28-day mortality (Peng 2020). Previously, a 2017 case report suggested that high-dose intravenous vitamin C may have contributed to the recovery of a 20-year-old patient with acute respiratory distress syndrome (ARDS) due to a viral respiratory tract infection (Fowler 2017).N-acetylcysteine (NAC). N-acetylcysteine (NAC) is an amino acid derivative with mucolytic properties often used in the context of respiratory illnesses (Blasi 2016; Kalyuzhin 2018; Samuni 2013). A meta-analysis published in 2017 found that treatment with NAC led to shorter duration of intensive care unit (ICU) stay compared with control among patients with ARDS (Zhang 2017). In the current COVID-19 pandemic, some Chinese institutions have been using NAC as part of the standard management of patients in the hospital setting (Wu 2020), although clinical trials are needed to specifically assess outcomes in COVID-19 patients treated with NAC. Some researchers have suggested NAC could be a valuable therapeutic in COVID-19 on the basis of its potent antioxidant and mucolytic properties (McCarty 2020).Lactoferrin. Lactoferrin is a glycoprotein involved in immune response and several other functions (Baveye 1999). It is found in secreted fluids and is abundant in milk (breast and cow). Lactoferrin has well-documented antibacterial, antiviral, and antifungal properties (Malaczewska 2019; Wakabayashi 2014; Ishikawa 2013). It appears to exert antiviral effects by activating the antiviral cytokines interferon (IFN)-α/β and boosting natural killer (NK) cell activity and Th1 cytokine responses (Wakabayashi 2014). Some studies suggest that lactoferrin administration may reduce the incidence and severity of common respiratory tract viral infections, like colds and flu (Vitetta 2013; Wakabayashi 2014). In 2005, researchers reported that the gene encoding lactoferrin was highly upregulated in patients affected during the SARS epidemic that emerged in 2003, suggesting that it plays a role in the innate immune response to the infection (Reghunathan 2005). A follow-up study indicated that lactoferrin prevented the 2003 SARS coronavirus from entering host cells (Lang 2011). No data have been published as of March 10th, 2020 directly linking lactoferrin with outcomes in COVID-19 patients. Selenium. Selenium has important antioxidant, anti-inflammatory, and antiviral activities in the body, and deficiency is associated with increased risk of viral infection (Wrobel 2016). In patients with HIV infection, poor selenium status is correlated with increased mortality, and supplementation has been reported to slow progression of immune dysfunction and reduce hospital admissions (Wrobel 2016; Muzembo 2019). Some researchers have proposed that lack of selenium in regional soils may have contributed to the SARS outbreak in 2003 (Harthill 2011). Probiotics. A growing body of evidence shows probiotic supplements with Bifidobacterium and Lactobacillus species can enhance antiviral immune activity and may reduce the occurrence, severity, and duration of viral respiratory tract infections such as influenza (Lenoir-Wijnkoop 2019; Mousa 2017). Epigallocatechin gallate (EGCG). EGCG is a polyphenol from green tea. Because of its broad antiviral effects, EGCG has been proposed as a promising agent for preventing and treating viral infections such as SARS and MERS (Kaihatsu 2018; Hsu 2015). There are many integrative therapies with well-established antiviral and immune-modulating properties. Details regarding these therapies can be found in Life Extension’s Influenza, Pneumonia, and Immune Senescence protocols. The interventions described in these protocols, though not necessarily validated as effective specifically for COVID-19, are nevertheless advisable upon onset of symptoms of upper respiratory tract infections.For upper respiratory tract infections in general, including those caused by some types of coronaviruses, Life Extension has long recommended swift action to help bolster your immune response and mitigate the likelihood of a severe disease course. At the first signs of an upper respiratory tract infection (eg, sneezing, coughing, feeling unwell, mild fever), make an appointment with your doctor then take the following:Zinc Lozenges : Completely dissolve in mouth one lozenge containing 18.75 mg of zinc acetate every two waking hours. Do not exceed 8 lozenges daily, and do not use for more than three consecutive days.Garlic: Take 9,000‒18,000 mg of a high-allicin garlic supplement each day until symptoms subside. Take with food to minimize stomach irritation.Vitamin D: If you do not already maintain a blood level of 25-hydroxyvitamin D over 50 ng/mL, then take 50,000 IU of vitamin D the first day and continue for three more days and slowly reduce the dose to around 5,000 IU of vitamin D each day. If you already take around 5,000 IU of vitamin D every day, then you probably do not need to increase your intake.Cimetidine: Take 800‒1,200 mg a day in divided doses. Cimetidine is a heartburn drug that has potent immune enhancing properties. (It is sold in pharmacies over-the-counter.)Melatonin: 3‒50 mg at bedtime.Do not delay implementing the above regimen. Once viruses that cause respiratory infections infect too many cells, they replicate out of control and strategies like zinc lozenges will not be effective. Treatment must be initiated as soon as symptoms manifest. Although this regimen has not been studied specifically in the context of COVID-19, there is little reason not to implement this strategy along with contacting a qualified healthcare provider as soon as possible after onset of upper respiratory tract infection symptoms.Below are a few additional integrative interventions that have shown beneficial immune-enhancing effects in the context of viral upper respiratory tract infections.

  7. Obtaining Reliable Situation Updates The CDC regularly updates their COVID-19 information portal. This is a reliable and trustworthy source of information about SARS-CoV-2 and COVID-19. The URL is: https://www.cdc.gov/coronavirus/2019-ncov/summary.html


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