Respiratory Immune Support

Respiratory Immune Support

Last updated: 8/27/2020

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

1 Background

Over the last few decades, several new viruses have emerged as threats to human health around the globe. The most recent example is the 2019‒2020 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 in late 2019 when it was identified as the cause of a cluster of pneumonia cases in the city of Wuhan in Hubei province, China.1 Since then, COVID-19 has spread globally and was declared a pandemic by the World Health Organization on March 11th, 2020.2,3

Coronaviruses are a large group of related viruses that cause many common human and animal infections.4 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.5 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 in addition to SARS-CoV-2.6

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%.7,8 Current estimates of the infection-fatality rate for COVID-19 range from about 0.5% to 1%, with some researchers reporting higher rates for older individuals.148,178

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.9

2 Symptoms and Manifestations

One of the major challenges in suppressing the spread of COVID-19 has been that many cases are asymptomatic; that is, some people are infected but do not exhibit any symptoms or have only very mild symptoms and may not realize they are capable of infecting others. Estimates of the proportion of cases that are asymptomatic vary widely. Recent population-based screening studies have suggested that around 40% of people who test positive do not have symptoms at the time of diagnostic testing, though they may develop symptoms later.178-180

Among infections that do become symptomatic, the first symptoms typically manifest within about five days after exposure.178 The most common presentation of COVID-19 is fever and dry cough accompanied by flu-like symptoms. Loss of sense of smell and taste appear to be common symptoms of COVID-19 as well. Although loss of sense of smell and taste sometimes occurs with other viral respiratory diseases such as the common cold or influenza, these manifestations are thought to be much more common in COVID-19.15,16 Some reports indicate patients may experience early ocular symptoms, such as conjunctivitis (pink eye) and eye discharge.12 Emerging evidence also suggests some people may experience gastrointestinal symptoms such as loss of appetite or diarrhea in addition to—or in rare cases instead of—initial respiratory symptoms.13,14

In many cases, early symptoms of COVID-19 do not clearly distinguish it from other viral respiratory infections. However, shortness of breath that develops within a week of initial symptom onset may be suggestive of COVID-19.178

A prominent feature of severe COVID-19 appears to be a marked increase in blood clotting and vascular complications throughout the body.17-20 Importantly, infection with SARS-CoV-2 appears to cause excessive clotting in the tiny capillaries in the lungs where gas exchange takes place, impairing the lungs’ ability to oxygenate the blood.21,22 This excessive clotting tendency also underlies a pronounced incidence of ischemic strokes in younger people with COVID-19 who do not have traditional stroke risk factors.23 Other complications attributable to blood clots are also common in severe cases, including deep vein thrombosis and pulmonary embolism.181 Accordingly, anti-coagulation therapy has become a standard of care recommended by most expert panels.24

Skin manifestations such as rashes, plaque-like lesions, and painful red or purple lesions on the fingers or toes, called chilblains, have been reported in the context of COVID-19. It is not entirely clear whether these manifestations represent inflammatory effects of the SARS-CoV-2 virus, or if they arise secondarily to coagulation and clotting problems that damage the delicate blood vessels supplying the skin.130,131 Some doctors think both factors are at play given the wide variety of skin manifestations being reported in COVID-19 patients. Further research will be necessary to determine if certain skin manifestations may predict clinical outcomes or help guide treatment decisions. If you notice a new or unusual rash or skin problems, you should mention these concerns to your healthcare provider, especially if the skin issues arise along with other potential COVID-19 symptoms.

Rapid progression to acute respiratory distress syndrome (ARDS) and death is more likely to occur in older individuals and those with pre-existing conditions that increase their risk such as obesity, diabetes, or hypertension.7,25,26

Reports of lingering illness and complications lasting weeks or months after the initial course of COVID-19 began to gain attention in May and June 2020. Preliminary reports have suggested SARS-CoV-2 can infect a variety of tissues and organs such as pancreatic beta cells,149 liver cells, sweat glands, and others.150 Damage inflicted at these non-respiratory sites may have lasting consequences that researchers do not yet understand. Some COVID-19 patients are requiring rehab for extended periods after infection, and research is urgently needed to understand the long-term consequences of COVID-19.151 Imaging studies have also suggested that some patients may experience lasting cardiac effects after clinical recovery from COVID-19.182

NOTE: At the first signs of a respiratory tract infection (eg, 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.

3 Risk Factors for Severe Disease

As the pandemic unfolded around the world, researchers and clinicians identified several risk factors that predispose to more severe disease and worse outcomes in COVID-19 patients. The presence of pre-existing comorbid conditions is a strong predictor of worse outcomes, so people with any of the conditions mentioned in this section should take extra precaution to avoid infection. One analysis of 355 deaths attributed to COVID-19 found that the average (mean) number of pre-existing conditions in these cases was 2.7, and only three deaths occurred in individuals who did not have any pre-existing conditions.183

The more well-established risk factors for severe disease, as well as those that are emerging but less-well established, are summarized below.

Established Risk Factors for Severe Disease

Obesity. Obesity and greater body mass index (BMI) have emerged as very strong predictors of poor outcomes in COVID-19 patients.178 A systematic review published in July 2020 pooled data from 24 retrospective cohort studies and assessed the association of obesity and increasing BMI with poor outcomes in COVID-19 patients.184 The meta-analysis showed that obesity significantly increased the odds of being admitted to the intensive care unit (ICU) and of needing mechanical ventilation. The authors also evaluated outcomes across BMI strata and remarked that “…we found that a higher BMI always carries a higher risk.”

High blood pressure. High blood pressure has been observed to be among the most common comorbid conditions in COVID-19 patients.185 In many cases, high blood pressure co-occurs with elevated glucose and obesity, forming a constellation of illness described as “metabolic syndrome.” One study found that the presence of metabolic syndrome increased death risk among black COVID-19 patients more than the presence of hypertension alone.186 Some evidence suggests that the increased risk of severe COVID-19 associated with high blood pressure may be more pronounced in males.187

Dyslipidemia. A systematic literature review published in August 2020 found that dyslipidemia (ie, elevated cholesterol and/or triglycerides) is associated with increased risk of severe outcomes among COVID-19 cases.188 Interestingly, a meta-analysis of four studies including nearly 9,000 COVID-19 patients found that use of statin drugs was associated with a 30% reduction in fatal or severe disease in COVID-19 patients. However, these findings represent preliminary evidence and need to be corroborated in a randomized controlled trial before conclusions can be drawn as to the potential utility of statins in reducing COVID-19 severity.189

Diabetes. An elevated case-fatality rate has been documented among COVID-19 patients with diabetes.178,190 Some evidence suggests elevated glucose levels may increase the expression of the angiotensin converting enzyme 2 (ACE2) receptor in lung tissue, facilitating more efficient SARS-CoV-2 infection. Experts recommend safe but stringent control of blood glucose, blood pressure, and lipids among people with diabetes as measures that could potentially decrease severity of COVID-19 illness should SARS-CoV-2 infection occur.191

Cardiovascular disease. An analysis of over 70,000 COVID-19 cases in China showed that pre-existing cardiovascular disease was associated with a 10.5% case-fatality rate, significantly higher than the case-fatality rate among otherwise healthy individuals.190

Chronic kidney disease. Chronic kidney disease (CKD) is associated with immunologic changes that predispose patients to many types of infections. In COVID-19 specifically, the risk of severe disease has been reported to be three-fold greater in people with CKD than in those without. Also, CKD is a common comorbidity among COVID-19 patients admitted to the ICU.192

Chronic respiratory/lung disease. Chronic respiratory disease, such as chronic obstructive pulmonary disease (COPD), increases risk of severe disease and death among COVID-19 patients.178,190,193 Asthma has also been linked to more severe disease.194

Smoking. Smoking has been associated with worse COVID-19 outcomes and greater need for mechanical ventilation support in COVID-19 patients.193,195

Cancer. Cancer patients have an increased risk of poor outcomes from COVID-19. This is due in part to immune system compromise caused either by cancer itself or cancer therapies.190

Emerging or Potential Risk Factors for Severe Disease

Proton pump inhibitors. Results of a preliminary online survey of over 53,000 participants published in early July suggested proton pump inhibitor (PPI) use was associated with increased odds of a positive COVID-19 test.196 PPIs are drugs used to reduce stomach acid to relieve symptoms of gastroesophageal reflux disease (GERD) and other gastroesophageal problems. These drugs are associated with increased risk of some enteric infections, which is thought to be because reduced stomach acidity allows some pathogens to survive. The findings of this recent survey suggest reduced stomach acidity may increase susceptibility to SARS-CoV-2 infection, but more rigorous studies are needed to confirm this possibility. Of note, in this same survey, use of histamine-2 receptor antagonists, which also reduce stomach acidity but are less potent than PPIs, was not associated with increased odds of a positive COVID-19 test.

*#Table 1: Laboratory Features Possibly Associated with Severe COVID-19 Illness178

Parameter

Values Possibly Associated with Severe COVID-19

Normal Value

D-Dimer

>1,000 ng/mL

<500 ng/mL

C-Reactive Protein (CRP), quantitative (not high-sensitivity [hs-CRP])

>100 mg/L

<8 mg/L

LDH

>245 units/L

110–210 units/L

Troponin

>2x the upper limit of normal

Troponin T High-sensitivity

  • Females: 0–9 ng/L
  • Males: 0–14 ng/L

Ferritin

>500 mcg/L

Females: 10–200 mcg/L

Males: 30–300 mcg/L

CPK

>2x the upper limit of normal

40–150 units/L

Absolute lymphocyte count

<800 per microL

1,800–7,700 per microL

*Values may vary between laboratories. Consult with a qualified clinician for interpretation of lab values in the context of COVID-19.

#These parameters have not yet been rigorously established to have prognostic value. Research is ongoing to more firmly establish laboratory prognosticators in COVID-19. These factors are presented here to inform readers as to the parameters that clinicians treating COVID-19 may monitor.

4 Spread

Coronaviruses are highly adaptable and known to undergo host-switching. Several established human coronaviruses have evolved from bird or mammalian coronavirus origins.29 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.26,30 Although distinct from all other known coronaviruses, SARS-CoV-2 also appears to be closely related to a bat coronavirus.31

Once adapted to the human host, coronaviruses can become transmissible between humans. There are four possible routes of transmission: respiratory droplet, contact, aerosol, and oral-fecal.32

  • Respiratory droplet. Respiratory droplets are an important route of SARS-CoV-2 transmission. In this kind of viral transmission, the virus is suspended in droplets emitted from the respiratory tract of an infected individual through a sneeze or cough, which are then inhaled by nearby uninfected individuals. Because respiratory droplets play such an important role in transmission of SARS-CoV-2, it is imperative that everyone practices social distancing whenever possible.
     
    Another possibility is that droplets may land on or near uninfected individuals, be picked up on hands, and transferred to the respiratory tract through touching the nose, mouth, or eyes.30 However, the CDC stated in mid-May 2020 that infection via contaminated surfaces is not likely to be a major route of transmission for SARS-CoV-2.
  • Aerosol. The aerosol route of transmission involves inhalation of very small, airborne viral particles, possibly at some distance from the infected person.10,33 These particles are smaller than those described above as respiratory droplets. Aerosol transmission is an especially important concern in healthcare settings.10 SARS-CoV-2 aerosols are detectable for up to three hours.34
     
    A critical issue related to aerosol transmission of SARS-CoV-2 is that loose-fitting surgical facemasks or cloth facemasks are unlikely to effectively prevent the transmission of aerosolized viral particles. It is imperative that the public understand that cloth or surgical facemasks do not provide protection to the wearer from aerosolized viral particles. Rather, these masks are intended to help capture some respiratory droplets expelled by already-infected individuals.152
  • Contact. Direct person-to-person contact is another mode of transmission for coronaviruses such as those associated with SARS, MERS, and the current COVID-19 outbreak.8 In these cases, the virus is transferred when an uninfected individual comes into direct contact with an infected person who is actively shedding virus.
  • 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.30

5 Protective Measures

Below are some basic measures to consider in order to reduce your risk of contracting COVID-19 and other viral illnesses.

  1. Social distancing. Avoiding contact with infected individuals is the most effective strategy to protect yourself from COVID-19. Because SARS-CoV-2 has become pervasive throughout the world, you should assume the people you come in contact with may be infected and stay at least six feet away from them. The Centers for Disease Control and Prevention (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".35 In some places where the virus has become more widespread, more stringent measures have been taken such as closing public parks, limiting activity outside the home to "essential" tasks, and urging people to remain at home as much as possible. Such strict measures can help further limit the spread of infection.
  1. Avoid non-essential travel. Avoiding travel to areas with known community spread is advisable.36 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.37,38 Therefore, avoiding air travel is a reasonable precaution for reducing your risk of viral infections in general, particularly if you have other vulnerabilities.
  1. 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%.39,40
  1. 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.41 Other strategies for strengthening immunity and reducing risk of viral infections in general can be found in Life Extension’s Influenza, Pneumonia, and Immune Senescence protocols.
  1. Disinfect surfaces. A study published in March 2020 by scientists from the U.S. National Institutes of Health (NIH) and CDC along with UCLA and Princeton University researchers found that SARS-CoV-2 was detectable on cardboard for up to 24 hours and for up to three days on plastic and stainless steel.42
     
    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 in February 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).34
     
    The United States Environmental Protection Agency (EPA) provides a list of EPA-registered disinfectant products for use against the SARS-CoV-2 virus.43 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.

Should You Wear a Facemask?

Yes, you should wear a facemask when in public.

Beginning in early April 2020, the CDC and other health authorities recommended that everyone use cloth face coverings in public. N95 respirator masks should be reserved for healthcare workers.44

The recommendation for widespread cloth facemask use is to help reduce the spread of COVID-19 in the population. Cloth facemasks are unlikely to offer protection against the transmission of aerosolized SARS-CoV-2 viral particles and are not a substitute for social distancing. However, they may help prevent the spread of infection by infected individuals by reducing the dispersion of respiratory droplets into the environment.45 This is critical because many people infected with SARS-CoV-2 show no or mild symptoms and may not realize they have it.46-49

The CDC provides instructions on making homemade facemasks.

The U.S. Surgeon General has a video demonstrating how to make a homemade cloth face covering.

NOTE: It is essential to understand that the facemasks typically worn by the general public—cloth face coverings and surgical masks—have not been shown to protect the wearer from infection via the aerosol route. These masks may offer some protection against infection via the respiratory droplet route, but wearing cloth or surgical masks does not ensure protection in circumstances where social distancing cannot be practiced.152

6 Know the Facts Video

Our Director of Education Dr. Michael Smith debunks common misperceptions about COVID-19 and offers guidance for staying well.

7 Testing and Diagnosis

In general, there are two testing priorities that both the public and private sectors are working to optimize in the United States:

  1. Establish widespread availability of accurate, rapid point-of-care diagnostic tests for COVID-19; and
  2. Establish widespread and accurate serological (blood serum) tests to determine who has been exposed and subsequently recovered, possibly establishing immunity. Importantly, it is not yet clear whether the presence of antibodies against SARS-CoV-2 confers long-term immunity against COVID-19; research is ongoing to clarify this crucial question.50

If you have symptoms such as fever, dry cough, fatigue, lack of appetite, and muscle pain and think you might have COVID-19, but do not have urgent symptoms such as shortness of breath, you should call your doctor or local health department for further guidance. Do not go to the doctor’s office or hospital for testing unless you feel your condition is severe and/or rapidly worsening. Because there is currently no effective treatment for COVID-19, and interacting with other people risks transmitting the infection, people with mild symptoms should rest at home.

Diagnostic Testing

Diagnostic testing for SARS-CoV-2 consists primarily of a type of test called a nucleic acid amplification test (NAAT). These tests typically use a procedure called reverse-transcription polymerase chain reaction (RT-PCR) to replicate large quantities of certain parts of SARS-CoV-2 genetic material.197 This step is necessary because the absolute amount of viral genetic material in a diagnostic swab sample is generally very small, especially soon after infection.

As of late August, accuracy and reliability of some available diagnostic tests remain a concern. SARS-CoV-2 testing remains plagued by false-negative results, which occur when a test result is negative but the person being tested actually is infected with the virus. False-negative rates have been reported to be as high as 40% for some tests.52,197

Therefore, initial test results should ideally be repeated and confirmed with additional testing conducted by a healthcare professional trained in proper sample collection techniques; this is especially important if a symptomatic person tests negative or if an asymptomatic person tests positive.

Results of SARS-CoV-2 testing may take several days, depending on the testing methodology.

Serology (Antibody) Testing

Serology testing to detect antibodies to SARS-CoV-2 is a different type of testing and is used for a different purpose. Antibody tests are not used to diagnose a current SARS-CoV-2 infection. These tests are used to identify individuals who have been exposed to SARS-CoV-2 in the past, and whose immune system has fought off the infection in part by producing antibodies, which persist for some time in the blood.197 SARS-CoV-2 serology tests typically detect IgG antibodies.

Unfortunately, several issues with serology (antibody) testing persist. The accuracy of many of the tests (sensitivity and specificity) are questionable and there are the important issues of cross-reactivity to other common coronaviruses that are not COVID-19. The rate of false-positive results (when an uninfected person tests positive) may be up to 15% in some cases.53 Moreover, serology tests must be interpreted with caution in areas with a low prevalence of infection in the population. This is due to the effect of diminishing positive predictive value with diminishing prevalence. In other words, positive serology test results in an area with low prevalence of infection have an increasing tendency to reflect false-positive results than true positive results.197

The implications of the presence of IgG antibodies to SARS-CoV-2 are not yet fully understood. As of late August, it is not clear to what extent antibodies to SARS-CoV-2 confer immune protection against a future re-infection or infection with a different strain of the virus. More research is underway to clarify these critical questions.

Serological antibody testing is now available from patient service centers with a physician’s order. LabCorp and Quest Diagnostics both offer qualitative IgG antibody tests under Emergency Use Authorization at their patient service centers. In addition, LabCorp and Quest Diagnostics now offer direct-to-consumer tests for the COVID-19 antibody IgG test. Please see their dedicated websites for details and limitations of the test:

8 Medications and Treatment Approaches

Dexamethasone

On June 16th, researchers at the University of Oxford announced preliminary results from the RECOVERY trial, a large randomized open-label controlled trial, which showed that the common glucocorticoid steroid drug dexamethasone reduced mortality in COVID-19 patients requiring supplemental oxygen or mechanical ventilation.147 The results were subsequently summarized and published in the New England Journal of Medicine on July 17th.198

The trial randomized 2,104 patients to receive standard of care plus 6 mg dexamethasone daily (orally or via intravenous infusion) and 4,321 patients to receive standard care alone. Among patients receiving invasive mechanical ventilator support, dexamethasone reduced deaths by 36%, while the death rate was reduced by 18% in those who did not need a ventilator but needed supplemental oxygen. There was no mortality benefit among patients who did not need any respiratory support or supplemental oxygen.

The researchers remarked, “Based on these results, 1 death would be prevented by treatment of around 8 ventilated patients or around 25 patients requiring oxygen alone.”

The researchers went on to state, “Dexamethasone is the first drug to be shown to improve survival in COVID-19. This is an extremely welcome result. The survival benefit is clear and large in those patients who are sick enough to require oxygen treatment, so dexamethasone should now become standard of care in these patients. Dexamethasone is inexpensive, on the shelf, and can be used immediately to save lives worldwide.”

An observational study published in late July suggested that levels of C-reactive protein (CRP) may help identify patients more likely to benefit from glucocorticoid therapy.176 The study found that hospitalized COVID-19 patients whose CRP level was >20 mg/dL had significantly decreased odds of needing mechanical ventilation or dying when they were treated with glucocorticoids within 48 hours of hospital admission. In contrast, patients whose CRP level was <10 mg/dL were more likely to need mechanical ventilation or die when treated with glucocorticoids. These results derive from a retrospective observational study, which does not have the ability to prove causality. Therefore, prospective studies are needed to fully elucidate the potential of using CRP level to guide glucocorticoid treatment decisions.

Remdesivir

Remdesivir is an antiviral drug that showed promise against SARS-CoV-2 in preliminary studies. It is a prodrug of an adenosine analog that has potent antiviral activity against many RNA virus families.55 In late April, 2020, data began to emerge from controlled clinical trials testing the efficacy of remdesivir in the United States and elsewhere around the world.

In late May, results of a large randomized controlled trial (called ACTT-1) conducted by the U.S. National Institute of Allergy and Infectious Disease (NIAID) were published in The New England Journal of Medicine. The trial randomly assigned 1,059 COVID-19 patients to a 10-day course of remdesivir plus standard of care or standard of care plus placebo. The time to clinical recovery improved with remdesivir treatment: those who took remdesivir recovered in a median of 11 days, whereas those who received a placebo recovered in a median of 15 days. There was a suggestion of reduced mortality with remdesivir in the trends in the data, but there was no statistically significant reduction in mortality with remdesivir.134

Although remdesivir improved time to recovery in the ACTT-1 trial, overall mortality remained high. The researchers remarked, “… given high mortality despite the use of remdesivir, it is clear that treatment with an antiviral drug alone is not likely to be sufficient. Future strategies should evaluate antiviral agents in combination with other therapeutic approaches or combinations of antiviral agents to continue to improve patient outcomes in Covid-19.

Importantly, not all remdesivir trials have shown clear benefit. For instance, a smaller clinical trial conducted in China did not find a statistically significant effect of remdesivir on time to clinical recovery.57

At the same time the preliminary results from the ACTT-1 trial were announced via NIAID press release on April 29th, Gilead Sciences, Inc., the maker of remdesivir, announced the results of a trial that suggested a 5-day treatment course may deliver similar results as a 10-day treatment course in patients with severe COVID-19.58

Research is ongoing and will help clarify which patients may benefit most from remdesivir, and with which other drugs remdesivir should be co-administered.

Convalescent Plasma

When a person is exposed to viruses like SARS-CoV-2, their immune system responds by producing antibodies, which facilitate the recognition and elimination of the virus. After the patient recovers, antibodies typically remain in their blood and can help the immune system respond again if the patient is re-exposed to the virus in the future.

Researchers are currently investigating whether administering the antibody-rich blood plasma of people who have recovered from COVID-19 to patients who become ill with SARS-CoV-2 infection can improve their outcomes. This antibody-rich blood plasma is called convalescent plasma and may help the immune system of people with active COVID-19 respond to the virus. This approach has been used for many decades to combat infectious diseases—similar approaches were even used during the 1918 influenza pandemic.87,88

A randomized controlled trial published in early June found that convalescent plasma did not improve time to clinical improvement within 28 days overall. However, the trial did find that patients with severe (but not critical) disease experienced more frequent and faster clinical improvement compared with controls. This trial was limited by early termination, and the benefit in severe patients was derived from a secondary outcome analysis, so further trials are needed. Nevertheless, this preliminary evidence suggests that convalescent plasma administered earlier in the course of the disease may provide more benefit than if administered later when the patient is already in critical condition.154

Interim results of another study published in August provided additional support for the notion that convalescent plasma may provide a mortality benefit if administered early in the course of COVID-19 illness (ie, within 72 hours of hospital admission).199

The FDA has granted emergency use authorizations and expanded access programs for convalescent plasma.89

If you have recovered from confirmed COVID-19 and are interested in potentially donating plasma, you can contact a local hospital or visit the American Red Cross website.

Exogenous Interferon Treatment

Interferons (IFNs) are a class of cytokines released by cells, including immune cells, in response to viral infection. They induce an antiviral response and help activate and regulate antiviral immune activity.161 There are three main groups of interferons: types I, II, and III. Type I IFNs, mainly IFN-alpha [α] and IFN-beta [β], are crucial during early viral infection because they stimulate many key steps in the immune response against viral pathogens.162,163 A grossly inadequate type I IFN response to infection with SARS-CoV-2 has been observed in severe and critical patients, accompanied by persistent viral load and an exaggerated cytokine response.164

Evidence published in early 2020 showed that SARS-CoV-2 was susceptible to in vitro inhibition by treatment with recombinant type I IFNs α and β.165 An open-label trial in China in medical staff exposed to SARS-CoV-2 infection yielded some preliminary evidence that IFN-α nasal drops may be effective as a preventive therapy.166 Previous in vitro evidence suggested that the original SARS coronavirus is susceptible to treatment with IFN-β.167,168 Several studies have examined using type I IFN-based therapies, and particularly IFN-β-based targeting of SARS-CoV-2 in the hope that it can become a clinically effective treatment for COVID-19.169-173

In late July 2020, Synairgen, a UK-based biotech company, announced positive preliminary results from an early-stage clinical trial of a nebulized (inhaled into the lungs) IFN-β drug, SNG001.174,175 Results have not yet been published in a peer-reviewed journal, only announced via press release, so they should be interpreted with caution. Nevertheless, the company reported that treatment with SNG001 reduced the odds of developing severe disease by 79% compared with placebo treatment (although the 95% confidence interval was very broad: 0.04–0.97). Moreover, the study found that patients treated with SNG001 were more than twice as likely to recover during treatment than those given placebo. (Recovery was defined as “no limitation of activities" or "no clinical or virological evidence of infection.")

The study of SNG001 also found that the IFN-β-based treatment significantly reduced a measure of breathlessness compared with placebo. Median time to hospital discharge was six days among those treated with SNG001 and nine days for those who received a placebo. Patients treated with SNG001 also had nearly 4-fold greater odds of having recovered by day 28 compared with placebo-treated patients.

The completion of larger ongoing trials of IFN-based therapies is needed to bolster confidence in this treatment approach. Nevertheless, these early results are based in sound biological science and appear promising.

Immunotherapies and “Cytokine Storm” in COVID-19

As the COVID-19 pandemic unfolded around the globe, doctors and scientists suggested that an exaggerated immune response could play an important role in the pathology of severe and fatal SARS-CoV-2 infections. Subsequently, research was undertaken to investigate whether therapies targeting certain inflammatory mediators could mitigate the excessive immune response and improve the clinical course of advanced COVID-19.

When a person’s airways become infected with SARS-CoV-2, the body must mount a robust innate immune response to prevent rapid viral replication and prevent the infection from spreading to other organs and tissues. In some cases, however, the immune response to the virus may spiral out of control and do more harm than good. Evidence suggests that if the immune system does not detect SARS-CoV-2 infection early, it may respond instead in an exaggerated fashion once the virus has begun replicating in the body and the viral load is high.156 Too many immune cells infiltrate tissues where the virus is replicating and release too many pro-inflammatory signals called cytokines. These cytokines recruit even more immune cells, and the cycle propagates throughout the body. Ultimately, multiple organs and tissues become damaged or impaired due to the buildup of immune cells and their inflammatory detritus. This phenomenon is referred to as a “cytokine storm”—a fitting metaphor given the ominous and rapid clinical decline that typically accompanies this immunopathology.157

Previous studies have documented clinical manifestations of ARDS cytokine storm that resemble the progression seen in some COVID-19 cases. As of late July, the role of cytokine storm in COVID-19 is not entirely understood. Research has revealed differences in the inflammatory milieu between advanced COVID-19 and ARDS due to some other causes. One inflammatory mediator thought to contribute to cytokine storm is interleukin-6 (IL-6).59 Unfortunately, data available as of late July have suggested that targeting IL-6 may not be as effective as initially hoped.

Drugs that block IL-6 signaling received considerable attention for several months following the initial revelations that advanced COVID-19 patients experiencing cytokine storms typically had very elevated levels of this cytokine. Two drugs that target IL-6 signaling, tocilizumab (Actemra) and sarilumab (Kevzara), both of which target the IL-6 receptor, underwent extensive testing but unfortunately did not show benefit in randomized controlled trials despite promising results in early observational studies.

On July 29th, Roche, the pharmaceutical company that makes Actemra, announced preliminary results of a large Phase 3 randomized controlled trial that showed that the drug failed to improve clinical status or reduce mortality in patients hospitalized with severe COVID-19 pneumonia. 177 The results have yet to be published in a peer-reviewed journal, and Roche said they will continue to study Actemra in different settings, including in combination with antiviral drugs in patients with COVID-19.

Research on sarilumab has been similarly disappointing. A large clinical trial first showed in April that sarilumab did not benefit patients with severe (but not critical) COVID-19.159 That same trial was continued in patients with more severe disease until early July, when it was halted due to lack of efficacy. On July 2nd, Regeneron and Sanofi, the pharmaceutical companies sponsoring the study, announced that sarilumab did not significantly improve clinical status in patients with severe COVID-19 requiring mechanical ventilation.160 Other trials of sarilumab are ongoing.

The initial enthusiasm for these IL-6-targeted drugs early in the pandemic on the basis of observational studies was not borne out in more rigorous randomized controlled trials. These circumstances represent an important lesson in the context of COVID-19 and medicine in general: it is critical not to become over-enthusiastic about potential therapies on the basis of early studies with weak methodological quality. Observational studies cannot establish a causal link between an intervention and an outcome. They only establish correlations or associations. Randomized controlled trials, on the other hand, can establish causality, but they take longer to complete. As we continue to move forward through the pandemic, the medical community and the public in general must remember that good quality scientific studies take time and that we need reliable data to inform treatment decisions.

Hydroxychloroquine

The antimalarial drugs chloroquine and hydroxychloroquine received attention early in the pandemic when anecdotal reports and preclinical evidence suggested these drugs might benefit COVID-19 patients.62,63 However, as evidence continued to accumulate through May and June, enthusiasm waned and concern about side effects and lack of efficacy mounted.

On June 3rd, the first rigorous study testing whether hydroxychloroquine could prevent development of COVID-19 was published in The New England Journal of Medicine. The 821 trial participants were randomly assigned to either hydroxychloroquine or placebo and took their first dose within four days after exposure to someone known to have COVID-19. There was no statistically significant difference in incidence of COVID-19 illness in the two groups. In addition, among subjects in either group who chose to take vitamin C or zinc supplements after their exposure to someone infected with SARS-CoV-2, there was an increased risk of developing COVID-19 illness.138 Side effects were more common among those who took hydroxychloroquine, but there were no serious adverse reactions reported.135

On June 15th, the U.S. FDA revoked the emergency use authorization (EUA) it had earlier issued for hydroxychloroquine and chloroquine. The agency stated that “The totality of scientific evidence currently available indicate a lack of benefit,” and that “...in light of ongoing serious cardiac adverse events and other potential serious side effects, the known and potential benefits of chloroquine and hydroxychloroquine no longer outweigh the known and potential risks for the authorized use.”146

Subsequent trials have also shown that hydroxychloroquine does not provide clinical benefit in the context of COVID-19.200,201

Colchicine

Preliminary evidence published in late June 2020 suggested that colchicine, an older anti-inflammatory drug normally used to treat gout and inflammation of the tissue surrounding the heart, may improve time to clinical deterioration in hospitalized COVID-19 patients.153

Colchicine piqued the interest of doctors and scientists working in inflammation research after a 2019 study showed that, in low doses, it reduced the risk of cardiovascular events in people who had recently had a heart attack.73

Preliminary evidence suggests that SARS-CoV-2 infection may trigger inflammation in cardiac tissue. The virus is thought to damage the heart by other mechanisms as well, such as triggering endothelial dysfunction, promoting blood clotting, and impairing the lung’s ability to supply the oxygen demanded by the hard-working cardiac tissue. Some researchers think these events may be triggered in part by activation of inflammatory pathways that colchicine can inhibit, namely the NLRP3 inflammasome.74-76

As of late June 2020, several clinical trials are enrolling patients to test the effects of colchicine in COVID-19.72,74

Although colchicine is generally well tolerated, it may cause problems in people with kidney impairment. This is important in the context of COVID-19 because SARS-CoV-2 infection has been shown to cause kidney damage in some cases. This is a potential safety concern that will be clarified in the ongoing trials.

Camostat Mesylate

An enzyme called TMPRSS2 facilitates a necessary step in the process by which SARS-CoV-2 and other coronaviruses enter cells.77 Therefore, inhibitors of this enzyme have been suggested as potential modalities to limit the pathogenicity of SARS-CoV-2. Some preclinical evidence suggests the drug camostat mesylate, a TMPRSS2 inhibitor developed in Japan in the 1980s, blocks viral entry of SARS-CoV-2 and might be a viable therapeutic option.78,79

As of early May, at least three clinical trials are recruiting subjects with confirmed COVID-19 to test whether camostat mesylate can improve clinical status or time to recovery. Camostat mesylate is approved in Japan for the treatment of chronic pancreatitis and postoperative gastric reflux. It is generally well tolerated, but there have been rare reports of serious side effects.80

Other 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).62,81,82 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-19.83

Another antiviral drug, favipiravir (Avigan), is also undergoing studies to determine if it is efficacious in COVID-19 patients.84,85 Preliminary results from a phase 3 trial conducted in India showed that favipiravir led to faster viral clearance and offered more clinical benefit for patients compared with standard of care. Moreover, subjects who deteriorated clinically despite taking favipiravir did not need oxygen support as soon as those not receiving favipiravir.202 However, some safety concerns have arisen related to potential for the drug to cause birth defects.86

Prone Positioning in Awake, Non-Intubated COVID-19 Patients

Although mechanical ventilation can be lifesaving in some COVID-19 patients suffering with ARDS, it is not a pleasant experience and most patients would prefer to avoid intubation if possible. One strategy that may delay or avert the need for mechanical ventilation in some COVID-19 patients is as simple as adjusting the position in which they lie on their hospital bed.

For some hospitalized but non-critical COVID-19 patients, switching from lying on their back to lying on their stomach may help their lungs absorb more oxygen and keep their blood oxygen saturation at sufficient levels to avoid intubation. The strategy calls for patients to lie on their stomachs for several hours daily while receiving supplemental oxygen via a nasal cannula. Patients lying on their stomach are said to be in the “prone position,” and those lying on their back are in the “supine position.”

Although rigorous evidence is not yet available to clarify to what extent awake prone positioning can help avert deterioration in COVID-19 patients, many hospitals now implement proning in COVID-19 patients. Early, anecdotal reports92 and observational data in ARDS due to other causes93 are encouraging. At least two clinical trials are underway to formally evaluate the potential benefit of prone positioning with high-flow nasal cannula in moderate-to-severe COVID-19 patients.94,8

Angiotensin-II Receptor Blockers (ARBs), ACE inhibitors, and COVID-19

The SARS-CoV-2 virus enters the human body by interacting with a receptor on the outside surface of cells called angiotensin converting enzyme 2 (ACE2). ACE2 is a component of the renin-angiotensin system, which plays a critical role in maintaining homeostasis. Popular blood pressure medications—angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs)—modulate this system to control blood pressure. Examples of ACE inhibitors are lisinopril (Prinivil, Zestril) and enalapril (Vasotec); ARBs include losartan (Cozaar) and telmisartan (Micardis).

When it became widely reported that ACE2 served as the receptor site for SARS-CoV-2, many people taking ACE inhibitors or ARBs grew concerned that these drugs could increase their risk of COVID-19. However, cardiology societies around the world have issued statements urging patients not to discontinue their blood pressure medications, and stating that there is no compelling evidence that these drugs increase risk of COVID-19.95,96 It is important to keep in mind that stopping a blood pressure medication does have known risks and is not advised.

A systematic review published on May 15th, 2020 found that observational and retrospective data available as of mid-May did not suggest that ACE inhibitors or ARBs were associated with increased risk of infection with SARS-CoV-2 or more severe COVID-19.132 The analysis included data from two retrospective cohort studies, one case-control study, and 14 observational studies. The researchers concluded that “High-certainty evidence suggests that ACE inhibitor or ARB use is not associated with more severe COVID-19 disease, and moderate-certainty evidence suggests no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients.”

Emerging, preliminary evidence suggests ARBs may actually be linked with improved outcomes in COVID-19. While it is crucial to acknowledge that these findings are preliminary, a retrospective study presented (pre-peer review) in late March suggested that people who had been taking ARBs prior to developing COVID-19 were less likely to develop severe disease than people who had not been taking ARBs.97 Other preclinical and preliminary evidence supports the potential beneficial effects of ARBs in COVID-19 as well.98 As of mid-May, at least four randomized controlled trials are planned to evaluate the use of ACE inhibitors or ARBs in the treatment of COVID-19.132


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. Most experts have agreed that evidence is too limited to make a conclusive recommendation for or against NSAIDs, but that there is little evidence that NSAIDs would worsen outcomes in most cases.101 Nevertheless, some physicians and health authorities recommend 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 are theoretical. As of late June, there is no evidence that taking NSAIDs increases risk of infection with SARS-CoV-2 or of developing COVID-19.102

9 SARS-CoV-2/COVID-19 Vaccine Development

The development of a SARS-CoV-2 vaccine is among the most pressing issues facing the medical and scientific communities during the COVID-19 pandemic. Many experts believe that COVID-19 will remain a global health concern until a safe and effective vaccine has been developed and administered to much of the world’s human population. Given the urgency and magnitude of the situation, global research collaborations have initiated unprecedented efforts to develop a safe and effective vaccine against SARS-CoV-2. However, the process of developing a vaccine is inherently time consuming and, critically, safety and efficacy trials must be long enough to allow thorough outcome and safety assessment.

There are several general types of vaccines being developed for SARS-CoV-2/COVID-19, some of which utilize tried and true technologies, while others are building upon unproven novel technologies. 139,140 The kinds of vaccines being studied as of mid-June include:

  • Live attenuated or inactivated virus vaccines
    • These kinds of vaccines aim to use modified variants of the SARS-CoV-2 virus that do not cause disease but can nevertheless cause the human immune system to mount a defense against future SARS-CoV-2 exposures. Many traditional familiar vaccines such as those for influenza and measles are of this type.139,141
  • Viral vector vaccines
    • Viral vector vaccines would incorporate SARS-CoV-2 genes into a different, non-pathogenic virus. When the non-pathogenic virus containing SARS-CoV-2 genes is administered in a vaccine, it does not cause illness but arms the immune system to be able to mount a defense against SARS-CoV-2 upon future exposure.
  • Subunit vaccines
    • Subunit vaccines are meant to deliver specific proteins or antigens unique to the SARS-CoV-2 virus that can prime the immune system to respond against a future SARS-CoV-2 infection. Familiar vaccines of this type include hepatitis B and whooping cough.141
  • Nucleic acid vaccines
    • This is a new kind of vaccine technology that delivers the genetic material (DNA and/or RNA) that codes for the viral antigens. The vaccine recipient’s own cells then use the genetic material to manufacture the antigens, alerting the immune system to be on the lookout for future exposures to SARS-CoV-2. No vaccines of this type have been approved as of mid-June 2020.

In mid-June, public-private partnerships to conduct large phase 3 trials of at least three vaccine candidates were reported.142 The trials are set to start during the summer and into the early fall of 2020 and will test vaccine candidates being developed by Moderna, AstraZeneca, and Johnson & Johnson. AstraZeneca and the University of Oxford have already begun a phase 3 trial in 10,000 participants in the United Kingdom.143 Other biotech firms are launching phase 3 trials of vaccine candidates during the summer months as well, including a private partnership between Pfizer and BioNTech SE. As of mid-May, there were over 160 vaccine candidates in various stages of development.140

Vaccines must have an outstanding safety and efficacy profile given that they are administered to, ideally, most of the population. This differs from therapeutic drugs, which are given to far fewer individuals. Any risks associated with vaccines are amplified because they are generally administered to large numbers of healthy people. Therefore, long-term clinical trials are essential to ensure that any vaccine candidate is not only effective in preventing its target disease, but also safe.

Phase 3 vaccine trials take a long time because vaccinated trial subjects must be followed-up for many months so researchers can determine whether they become sick upon exposure to the virus circulating in the population. It is also important that phase 3 trials follow subjects for a long time to help determine how long the immunity granted by the vaccine lasts, which will inform vaccination schedules in such matters as if and how often booster shots are needed.

Aside from the medical and scientific challenges that SARS-CoV-2 vaccine developers must overcome, there are tremendous logistical and manufacturing hurdles that will influence the availability of shots once one or more are approved.144 In theory, most people on Earth should be vaccinated, which means distributing and administering over seven billion doses of vaccine.

These are just some of the substantial hurdles standing in the way of rapid vaccine development for SARS-CoV-2. One potential difficulty is that vaccines that are shown to work in younger individuals may not confer the same degree of immunity to older adults. Another is that the track record of vaccine development suggests that success is not common: less than 10% of vaccines make it through clinical trials. Not least, the problem of trying to compress what is ordinarily a very lengthy process into a shorter time period creates multiple potential scientific, medical, and logistical challenges. Still, many experts are optimistic that the urgent and global nature of the current situation, along with the many remarkable recent innovations in multiple scientific disciplines, will allow successful vaccine development on a shorter-than-usual timeline.140,142,143,145

Most experts expect that the first vaccine(s) will become available in mid-to-late 2021 at the earliest, with ongoing efforts to vaccinate the world population extending beyond 2021.

10 Integrative Approaches

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 severe viral illness resulting in ARDS or SARS, are nevertheless reasonable upon onset of signs and symptoms of respiratory tract infections to provide optimal support for the respiratory tract and/or immune system.

For respiratory tract health and immune support, Life Extension has long recommended swift action to help mitigate the likelihood of an evolution of respiratory tract infection to a more serious course. During the initial signs and symptoms of respiratory illness, contact your personal healthcare provider as soon as possible, and strongly consider the following options to support your respiratory health and the health of your immune system:

  1. 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.
  2. Garlic: Take 9,000‒18,000 mg of high-allicin garlic each day until symptoms subside. Take with food to minimize stomach irritation.
  3. 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.
  4. Cimetidine: Take 800‒1,200 mg a day in divided doses. Cimetidine is a heartburn drug that has potent immune support properties. (It is sold in pharmacies over-the-counter.)
  5. Melatonin: Take 3‒50 mg at bedtime.

Avoid delay. Once microbes (eg, bacteria, viruses) that cause respiratory infections are allowed to multiply, they can replicate rapidly and strategies like zinc lozenges may not be effective. Interventions should be initiated as soon as signs and symptoms manifest. Although this regimen has not been studied specifically in the context of severe viral illness resulting in ARDS or SARS, implementation of this strategy along with contacting a qualified healthcare provider as soon as possible after onset of upper respiratory tract infection symptoms is advisable.

Several additional integrative interventions to help provide functional support for the health of the respiratory tract and immune system in the context of viral upper respiratory tract infections are provided below.

  • Vitamin C. Several studies have shown that vitamin C, 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. 103-105 However, available evidence does not consistently support the notion that vitamin C can reduce the risk of acquiring upper respiratory tract infections.106,107 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 twice-daily 12-gram intravenous vitamin C infusions on outcomes in patients with SARS-type viral respiratory illness. The primary outcome will assess ventilation-free days, and one of several secondary outcomes will be 28-day mortality.108 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 ARDS due to a viral respiratory tract infection.109 On April 1st, 2020, the American Association of Naturopathic Physicians issued a recommendation in favor of the use of intravenous vitamin C as supportive care for patients with severe, SARS-type viral respiratory illness. Their recommended dosing regimen is 100 mg/kg as a 24-hour continuous infusion for general supportive care, and 200 mg/kg (24-hour continuous infusion) for patients with severe SARS-type viral respiratory illness also experiencing a profound inflammatory immune response known as “cytokine storm.”110
  • N-acetylcysteine (NAC). N-acetylcysteine (NAC) is an amino acid derivative with mucolytic properties often used in the context of respiratory illnesses.111-113 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.114 Based upon some positive observational data during late 2019 and early 2020, some Chinese institutions have initiated using NAC as part of the standard management of patients in the hospital setting,70 although clinical trials are needed to specifically assess outcomes in patients with severe, viral respiratory illness treated with NAC. Some researchers have suggested NAC could provide valuable functional support for the health of mucous-producing cells lining the respiratory tract in some types of patients suffering from SARS-type viral respiratory illness on the basis of its potent antioxidant and mucolytic properties.115
  • Lactoferrin. Lactoferrin, a glycoprotein involved in immune response and several other functions,116 is found in secreted fluids and is abundant in milk (breast and cow). Lactoferrin has well-documented antibacterial, antiviral, and antifungal properties.117-119 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.118 Some studies suggest lactoferrin administration may reduce the incidence and severity of common respiratory tract viral infections, like colds and flu.118,120
     
    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.121 A follow-up study suggested that lactoferrin interfered with the ability of the 2003 SARS virus from breaching the functional and structural integrity of host cells.122
  • Selenium. Selenium has important antioxidant, anti-inflammatory, and antiviral activities in the body, and deficiency is associated with increased risk of viral infection.123 In patients with HIV infection, poor selenium status is correlated with increased mortality, and selenium has been reported to slow progression of immune dysfunction and reduce hospital admissions.123,124 Some researchers have proposed that lack of selenium in regional soils may have contributed to weakened immunity and the associated SARS outbreak in 2003.125
  • Probiotics. A growing body of evidence shows Bifidobacterium and Lactobacillus species can support the health of the host’s immune response and may reduce the occurrence, severity, and duration of viral respiratory tract infections such as influenza.126,127
  • Epigallocatechin gallate (EGCG). EGCG is a polyphenol from green tea. Because of its broad immune-benefiting effects, EGCG has been proposed as a promising agent for supporting the host’s immune response in the context of viral infections such as SARS and MERS.128,129

11 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/index.html

Disclaimer and Safety Information

This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the therapies discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.

The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. Life Extension has not performed independent verification of the data contained in the referenced materials, and expressly disclaims responsibility for any error in the literature.

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