Persistent host-specific viral agents are the origin of emerging acute epidemic disease following adaptation of that virus to new host species. . . . These acute viruses have a high dependence on host population structure as described by the apparently accurate mathematical models that resemble predator-prey dynamics in which the viruses act as predators on their host prey. . . . Acute human influenza A represents a host species jump of a persisting viral agent of aquatic birds.
Luis Villarreal et al., “Acute and Persistent Viral Life Strategies and Their Relationship to Emerging Diseases”
The major animal reservoirs of Influenza A are migratory birds and the majority of all the possible combinations of HA-NA subtypes have been isolated from them.
Andrew Pekosz and Gregory Glass, “Emerging Viral Diseases”
Most of us think of the flu as a fairly minor disease, and for most of us it is. At worst we lie in bed for a week or so, feeling miserable. But for the old and the very young the flu can be deadly; it kills those with the weakest or least developed immune systems, some 30,000 people a year in the United States. But sometimes a real pandemic happens and the death rate rises. It has never risen more than it did in 1918.
The 1918 world influenza pandemic is the most deadly plague that human beings have ever experienced. It began in 1918, just as war was drawing to a close, and lasted until December of 1920. World War I (which ended in 1918) killed some 17 million people. In contrast, the influenza pandemic, spread around the world by returning soldiers, killed six times as many in half the time — perhaps as many as 130 million people. The first wave of the pandemic began in January of 1918 and it was fairly routine. People became ill but only the very old and very young died; it was, so far, a pretty typical flu. But the virus soon mutated. And the second wave? It was deadly. It killed those with the strongest immune systems. Half of those who died were between the ages of 20 and 40; nearly all were under age 65. And it killed them by the millions.
Instead of the usual respiratory infection, with death occurring as the lungs filled with fluid, massive hemorrhages took place. The infected lung cells, and those nearby, damaged by the virus-stimulated cytokine storm (see for more on cytokines), literally burst open from the inflammation. And unlike most viral influenzas this one did not stay confined to the respiratory system. It spread to the GI tract, the brain, and every mucous membrane system in the body. First it destroyed the infected mucosal epithelial cells, then the blood vessels that fed them inflamed and burst open. Bleeding was extensive from the nose, stomach, and intestines; hemorrhages from the skin and ears were common. The infected literally bled out. And nothing physicians tried would stop it.1
To understand the impact, consider the fact that, in a world reeling from war, one-third of the entire world’s population contracted the disease — over 500 million people. In some places half the population was bedridden. As troops demobilized, the ships returning them home from war stopped at hundreds of ports along the way, and the infection spread across the globe. On the islands of Western Samoa 90 percent of the population fell ill — simultaneously. Thirty percent of the men, 22 percent of the women, and 10 percent of the children died.
In an attempt to stop the infection, port quarantines were put into effect around the world. Most were too late to do any good. One out of every three persons on Earth fell ill. One out of every five of those died. Five percent of the total world population — one out of every 20 people — did not survive the pandemic. Within the first 6 months 25 million people died, more than were killed in 5 years of war. Entire towns and cities were shut down.
There were few professionals to help the sick. Doctors and nurses were the first responders and they succumbed immediately. (The morticians followed soon after.) The infected filled the hospitals, school gymnasiums, auditoriums — every large building that could hold masses of people was pressed into service. The beds and the floors were awash in blood as the people died . . . and hemorrhaged by the hundreds and the thousands while doing it. And the bodies piled up. Steam shovels were brought in and mass graves dug — row after row after row of identically sized holes stretching across empty fields in a terrible mockery of industrial expediency. Then the trucks came, the bodies piled high on the wooden beds, and the masked workers dropped them in, hour by hour, day by day, month after month. And behind them, the steam shovels covered them over . . . one by one, day by day, for the 2 terrible years of the pandemic. There were few coffins and often no headstones. The system was completely overwhelmed. Not even a full century of the Black Plague had killed like this. In the history of human habitation of Earth, never had a disease spread so quickly around the world nor killed so many in so short a time. Only one place on Earth reported no infections: the tiny island of Marajó near Brazil in South America. And then, as inexplicably as it had begun, in a 1-month period of time, between November and December of 1920, the pandemic ended, simultaneously, around the globe.
Much effort has been expended in recent years in an attempt to understand what made that particular influenza strain so much more deadly than all the others people have known. It turns out that there were two interrelated events that came together in just the right way at just the right time in a terrible serendipity of the universe. From that intermingling came the worst pandemic the human species has ever experienced.
The first event was the emergence of a new strain of influenza at just the right time in human history. An analysis of the viral genome from 1918 has revealed that a new influenza strain had jumped species (from birds) just prior to 1913. By 1915 the virus had split into two types: one infecting pigs, the other humans. The second event was the war itself, which began with perfect timing in 1914.
Normally, when people fall ill with the flu, they go home and rest. The soldiers could not and the new influenza strain rapidly spread throughout the troops on both sides of the conflict. Constrained in cramped, unhealthy conditions, in hospital tents and in trenches, the soldiers were a perfect breeding ground for the virus. And sometime between 1915 and late 1917 the virus mutated again, this time into a form that could powerfully infect just that kind of population: the young. Then, the war over, the soldiers, millions of whom were infected, were crowded together in ships (there was no air travel then) that sailed from port to port to port, infecting as they went. Once home port was reached, the soldiers took trains, buses, and cars to their individual towns and cities. And the virus went with them, infecting everyone.
Re-created forms of the strain, patiently assembled in laboratories, when given to primates, have been found to generate the same symptoms as those described, in depth, by the physicians who treated the 1918 pandemic. An analysis of the physiological damage that occurs found that the reason the disease is so severe is that the virus creates a tremendously potent cytokine cascade in the body — a cytokine storm. A perfect storm. These cytokines are immunoregulatory proteins stimulated by the body’s innate immune system in response to infection. The cytokine cascade is how the body attempts to kill off the invading pathogen. But this was much more than the usual immune response. The immune reaction was extreme, somewhere between 100 and 1,000 times what would be normal in those who were infected. And that overreaction, much more pronounced in those with strong immune systems, is what killed so many so quickly.
It is just this kind of influenza pandemic that epidemiologists and viral researchers fear will emerge once more. Given the current population density (and the crowding in prisons, nursing homes, hospitals, day care centers, and inner cities), the ecological disruptions that are occurring worldwide, the number of viruses that are jumping species, the rate of mutation, and the vast and very rapid movement of people via air travel, they say it is only a matter of time. And in spite of the many advances in medical technology, there is very little that modern medicine can do to treat a widespread pandemic of deadly influenza. Pharmaceutical antivirals are only partially effective for this kind of infection and the stocks of those antivirals are insufficient to deal with a true pandemic. And vaccines? Vaccines take time.
Flu vaccines have to be made for the specific virus that emerges in that year. This means that the disease will already be moving throughout the world before production even begins. And if it is a true pandemic of a deadly strain, by the time the vaccine is produced and shipped (normally a 3- to 6-month process), the infrastructure of the world will already be failing. The health-care workers, hospitals, and transportation workers will be the first to fall. Then the morticians and cemetery workers. The system will begin to shut down. Quarantines, forcing people to stay in their homes, will be put into effect to try and stop the spread. And people will survive as best they can, just as they always have.
The influenza virus is a member of the Orthomyxoviridae family. It is an RNA virus and that means it alters its genetic structure very quickly. That is why a new flu shot is needed every year (for those in the Western world who have such things available). The old vaccine can only help prevent infection by the strain that has emerged in that particular year. The next year, it is not the same virus, merely a similar one. Influenza viruses spread around the world every year in seasonal epidemics; 250,000 to 500,000 people die from them each time.
About one-third of people who are infected remain asymptomatic; the rest get some degree of the “flu.” The first symptoms are usually a feeling of being cold or achy and perhaps the beginnings of a fever. High fever alternating with severe chills sets in as the infection spreads. As the virus enters the lungs and sinus tissues mucous congestion begins. Coughing, body aches, fatigue, headache, and irritated eyes, nose, and throat are common. Some people will have diarrhea and abdominal pain. Vomiting. Sometimes. Yes.
The symptoms of the infection usually begin the third day after infection. But the virus is already well established by then. It starts replicating the second day, then begins “shedding” viral particles that are released in increasing numbers for the next 5 to 7 days. The higher the fever, the more viral organisms that are being released. Children are extremely infectious compared to adults, with very high viral loads. They also tend to have very high fevers.
As the virus invades the lungs it stimulates inflammation in the tissues. The lung cells, filled with viruses, soon bulge outward and explode — the essence of viral shedding. Then the virus stimulates coughing, spreading the virus to new hosts via respiratory droplets. Pneumonia, a severe inflammation of the lungs accompanied by massive fluid retention and an inability to breathe, is the main cause of death. People, in essence, drown.
There are three different groups of influenza viruses, denoted A, B, and C. Influenza A is the most virulent. Influenza B is a relatively stable virus and mutates much more slowly than A. Most people develop, in childhood, at least some immunity to it; it is much less dangerous. Influenza C is fairly rare. It does infect people, sometimes severely, but it usually causes only a mild illness, generally in children. When people talk about an influenza pandemic, what they are talking about is influenza A in one of its many genetically altered forms. The 1918 pandemic was caused by an influenza A strain.
There have been numerous pandemics of influenza over the years, each caused by a different strain of the virus. The one in 1918 was the beginning of the modern influenza pandemic era; such pandemics were much less common before then. There was a long rest after 1918. Since 1957, however, they have been occurring with greater frequency.
The most dangerous strains, currently, are H1N1, which caused the flu pandemic of 1918; H2N2, which caused the Asian flu pandemic in 1957; H3N2, which caused the Hong Kong flu pandemic in 1968; and a relatively new one, H5N1, known as avian or bird flu, which caused a pandemic in 2004. Then H1N1 came again. It was the source of the swine flu pandemic in 2009 and is a modified descendant of the 1918 H1N1 strain.
The influenza virus alters its genetic structure rather significantly every year by passing through both pigs and birds. And on that trip it exchanges genetic material with other viruses and reworks its own. Then it spreads around the world again by plane and boat, rail and car, infecting millions, causing what we call the yearly flu season. But every so often it develops a much more virulent strain, sometimes through unique genetic rearrangements, sometimes through species jumps, sometimes through both. The Asian flu pandemic in 2004 was a species jump. The swine flu epidemic of 2009 was a unique genetic rearrangement. It occurred when the virus took advantage of giant agribusiness animal crowding.
Viral geneticists have traced the lineage of the 2009 swine flu epidemic, a virulent H1N1 strain, to an H3N2 strain that emerged in 1998 in U.S. factory farms, specifically huge hog farms in which the animals are so tightly packed together that they literally cannot move. This H3N2 strain combined with another swine strain, a European H1N2 variant, rearranged genetic material into a new and very potent H1N1 form, and then emerged into the human population. The earliest infections occurred in La Gloria, Veracruz, Mexico, just adjacent to a huge hog farm. The workers became infected with the new strain, went home, infected others, many of whom traveled to other cities and towns, and the pandemic began. And it was particularly deadly for those who were infected. Among those hospitalized, depending on location, up to 31 percent were in intensive care units, and as many as 46 percent of those receiving intensive care died.
One of the main fears that epidemiologists and viral geneticists have is the possibility of a combined swine and avian flu strain. The crowding of human food animals, similar to the crowding of soldiers in trenches in World War I, continually allows for the emergence of potently virulent strains. Chicken farms, in which unique avian flu strains can emerge, and hog farms, in which unique swine strains can emerge, are perfectly positioned to allow the combination of the two into one potent, and very deadly, influenza strain. This kind of combined strain can then pass easily into farm workers and thence into the population at large.
Researchers have found that, indeed, the H3N2 swine flu virus easily combines with H5N1 strains of avian flu. When that occurs, a tremendously pathogenic form of the virus emerges. It is, they insist, only a matter of time until it occurs on its own. In fact, studies of pigs on large farms adjacent to poultry farms have found such viral combinations already infecting pigs. That combined viral strain has not infected people . . . yet.
Cytokines are physiological signaling molecules produced by the body for a variety of reasons. They are produced in the largest numbers during infections. Cytokines (and their cousins, chemokines) are generally part of the innate (rather than the adapted) immune system. They are intended to respond to incursions into our bodies by viruses and bacteria. Another way to think of them is as inflammatory molecules. They cause various sorts of inflammation in the body — they are why, when you cut yourself, the wound gets red and tender and swells. The cytokines rushing to the area create conditions in which many bacteria and viruses find it difficult to survive. Unfortunately for us, bacteria and viruses have also learned how to use our own immune responses for their purposes. They subvert them, quite often, to facilitate their infection of the body and their destruction of certain areas of the body. This facilitates their reproduction and allows them to gather nutrients. Influenza viruses love the lungs and it is where they cause the greatest damage.
Unlike encephalitis viruses, which love brain neurons but have to find their way to the brain after being injected into people by mosquitoes, influenza viruses don’t have to work nearly so hard. They are taken to the location they like best simply because we need to breathe.
Once inhaled, the viruses begin attaching to lung epithelial cells. They use a kind of agglutinin (a substance that glues things to itself — its name shares a root with the English word “glue”), a hemagglutinin, to bind to what are called sialic acid linkages on the surface of airway epithelial cells. (This is one mechanism by which plants such as Chinese skullcap and ginger stop influenza infections; they are hemagglutinin inhibitors.) All viruses do this in their own way; they have an affinity for a unique receptor on the surface of specific cells and in one way or another they get to that location and those particular cells. Once there, they attach to that part of the cells. In a sense they use that part of the host cells’ membrane as a docking port.
As soon as it is attached to a cell, the virus begins to alter the permeability of the cell wall, inducing alterations in the cell’s cytoskeleton and initiating endocytosis. In other words, it makes the cell surface more soft, causes the skeletal structure of the cell to bend apart, and tricks the cell into taking the virus inside it where it can’t be found by the immune system. It does this by using a particular kind of enzyme, neuraminidase — which is sometimes also called a sialidase because such enzymes catalyze, or break apart, the sialic acid linkages on the host cell surface. This is why neuraminidase inhibitors (such as Tamiflu, i.e., oseltamivir) are effective in the treatment of influenza; they inhibit the ability of the virus to enter host cells. This stops the infection. (Chinese skullcap, elder, licorice, rhodiola, ginger, isatis, Lespedeza bicolor, Angelica keiskei, Amorpha fruticosa, quercetin, Alpinia zerumbet, Erythrina addisoniae, and Cleistocalyx operculatus are all neuraminidase inhibitors.) Neuraminidase inhibitors are effective against both influenza A and B strains.
During the process of endocytosis, the virus stimulates the cell to create what is called a vacuole, essentially a sealed bubble that will be held inside the cell. Cells do this to sequester substances that can damage them. Microbes have learned to use such vacuoles for their own purposes, usually to protect the virus or bacteria from intracellular antimicrobial actions.
The virus uses its hemagglutinin to bind itself to the inside of the vacuole membrane, where it opens a pore to the cell’s cytoplasm, i.e., its interior spaces. To do this the virus uses what is called the M2 ion channel — ion channels are tiny pores in cells that allow charged molecules to enter and exit cells, bringing food in and allowing waste out. Using an M2 inhibitor blocks this process and literally stops the virus from replicating. (Lomatium is one of the most potent M2 inhibitors known, stronger than the pharmaceutical amantadine.) Use of the M2 channel is specific to the influenza A virus, which is why the development of blockers for it was considered crucial. Unfortunately, the extensive use of chemical M2 inhibitors such as amantadine in poultry farms has now created nearly complete resistance to them in all influenza A strains.
Once the pore is open, the virus disassembles itself and releases viral RNA and core proteins into the cytoplasm. (Chinese skullcap inhibits this kind of viral RNA release.) The core proteins and viral RNA form a complex that is taken into the nucleus of the cell, where the cell is stimulated to begin making copies of the viral RNA (each slightly different). The new viral RNA is combined with other newly manufactured virus components such as neuraminidase and hemagglutinin and assembled into new viruses. These attach to the inside of the host cell membrane, a bulge forms in the membrane, and the new viruses are expressed (viral budding or shedding) into the extracellular matrix surrounding the cell.
The cell is taken over by the virus in this process, its own components depleted during the creation of new viruses. Once its resources are gone, the cell dies and the newly created viruses move on to new host cells, beginning the process all over again.
The alveolar epithelial cells are specific sites for this process to occur. The alveoli are tiny sacs that are the terminal end of the respiratory tree. The air we breathe travels throughout the bronchial tree, eventually emerging into the alveoli, where the oxygen transfuses across very thin membranes into the blood. This is how our bodies remain oxygenated. In the cells lining those tiny sacs the viruses breed. They cause extreme inflammation, or swelling, of the cells in that location with resulting edema (fluid accumulation). All the infected cells burst open and die as new viruses are made. So, fewer alveoli are functional. Breathing is more difficult and the infected person has much less energy because oxygen is not making it into the blood in sufficient quantities. (This is why hospitals sometimes give the infected oxygen.) Pneumonia is when this process becomes severe, the sacs filling with increasing amounts of fluid while there are fewer and fewer functional alveoli.
Throughout the cellular infection and replication process, the virus is also stimulating the release of cytokines by the cell. These cytokines make the tight junctions between cells (and the cellular membranes) more porous and allow easier movement of viral particles through the extracellular matrix (and into the cells themselves). The cytokines are also stimulated in just such a way as to keep the parts of the immune system that can kill the viruses suppressed for as long as possible.
Toll-like receptors (TLRs) are pattern recognition receptors that can identify different types of microbes. The virus particles stimulate TLR3, which begins inducing the release of nuclear factor kappa-B (NF-κB) cytokines. NF-κB is an upstream cytokine, meaning that it is a powerful initiator of other inflammatory cytokines. NF-κB begins very specific types of cytokine cascades. Other types of initiators such as RIG-1, NOD2, and MDA5 are also released as part of the body’s reaction to a viral infection. Normally, these would strongly stimulate type 1 interferon (IFN) production (IFN-α and IFN-ß). And influenza viruses are generally very susceptible to these interferons. However, the influenza virus uses a protein, the NS1 protein, which blocks the induction of type 1 IFNs long enough to get established in the body. (Upregulating the production of type I interferons with herbs such as licorice will help reduce the severity of the infection.) The virus also inhibits dendritic cell maturation and activation, lowering the response levels of T and B cells. (Increasing T cell counts is particularly effective in reducing influenza severity. Licorice, elder, red root, and zinc are specific for this.) These cells are part of the adaptive immune response; suppressing them protects the virus from attack. The body response also stimulates the release of type III interferons, to which the virus is less susceptible and which it does nothing to suppress. These interferons have general, rather than specific, antiviral qualities and are upregulated within 3 to 6 hours of infection. This is what begins causing the general flu-like feelings that presage a full-blown flu episode. The virus itself does not make you feel “fluey.”
During this same time period, the infected airway cells (tracheobronchial and alveolar epithelial cells) begin generating specific cytokines and chemokines: interleukin-1 beta (IL-1ß), IL-6, IL-18 (which causes spikes in IFN-γ production), C-C chemokine ligand 5 (CCL5, also known as RANTES, “regulated and normal T cell expressed and secreted”), C-X-C chemokine ligand 10 (CXCL10). Then, some 12 to 16 hours later, other cytokines are produced: tumor necrosis factor alpha (TNF-α), IL-8, and CCL2 (also known as monocyte chemoattractant protein-1 or MCP-1). The expressed cytokines make the epithelial structures more porous. This assists faster viral penetration of the cells. It also stimulates the migration of immune cells to the sites of infection.
Interferon-gamma (IFN-γ) is a type 2 interferon, sometimes called macrophage-activating factor. It is this IFN that is crucial in the cytokine overinflammation that occurs during severe influenza. By stimulating it, the virus initiates a positive feedback loop in the cytokine process that leads, in severe infections, to cytokine storms.
CCL2 causes the migration of blood-derived monocytes into the alveolar airspaces. TNF-α and IL-1ß upregulate adhesion molecules (which include intercellular adhesion molecule 1, a.k.a. ICAM-1, and E-selectin) on the surface of the endothelial cells that line blood vessels. This helps the endothelial lining become more porous and stimulates the transendothelial migration of neutrophils to those locations. TNF-α induces monocyte and neutrophil movement across the epithelium through ICAM-1 and VCAM-1 (vascular cell adhesion molecule-1) upregulation. The consequence of this is increasing amounts of white-blood-cell-filled mucus in the lungs. (This is what we cough up during a flu infection.)
The size of the drainage lymph nodes in the lungs begins to increase. This helps, during a healthy resolution of infection, to drain more of the fluids from the lungs, preventing suffocation. Within those lymph nodes, areas called the geminal centers increase their size and development. The germinal centers are the sites where B lymphocytes are produced and are differentiated in order to attack the specific infection that is occurring. This is part of the adaptive humoral immune response. These lymph node locations (as well as those in peripheral tissues) can become overfull during severe infections, slowing drainage and healthy adaptive immune responses. They can also, during severe influenza infections, be specifically attacked and damaged so that they do not function at all. This is a contributor to the mortality that sometimes occurs during cytokine storms. (This is why herbs such as red root, inmortal, and pleurisy root are useful; they all support the lymph structures in the lungs and periphery. Red root — Ceanothus spp. — is particular useful in the periphery for spleen and lymph enlargement and lymph drainage; inmortal — Asclepias asperula — is specific for optimizing lymph drainage from the lungs; pleurisy root — Asclepias tuberosa — is specific for reducing inflammation in the pleurae and lungs. They can be used interchangeably to some extent.) The lymph centers in the lungs are heavily affected during influenza, much more so than the periphery.
Similarly to many viruses, while influenza viruses reproduce most efficiently in the alveolar epithelial cells, they can also infect other cells, specifically dendritic cells, monocytes, macrophages, neutrophils, T cells, B cells, and natural killer (NK) cells. In response to being infected those cells also begin releasing cytokines and chemokines: IFNs, IL-1α and IL-1ß, IL-6, TNF-α, CXCL8, CCL2 (MCP-1), CCL3 (a.k.a. macrophage inflammatory protein-1 alpha, or MIP-1α), CCL4, CXCL9, and CXCL10 through the ERK-1, ERK-2 (extracelluar-signal-regulated kinase 1 and 2), p38 MAPK (p38 mitogen-activated protein kinase), and JNK (c-Jun N-terminal kinase) pathways.
TNF-α, IL-1ß, IL-6, and IFN-γ are responsible for most of the negative effects of the cytokine cascade. Mice that are unable to produce TNF-α consistently show decreased mortality, a reduced symptom picture, and less severe course of the disease. This holds true even if they are infected with the reconstituted, and very virulent, 1918 virus. Inhibition of TNF-α (especially) and IL-1ß has been found to significantly reduce the cytokine-based inflammation that occurs during influenza, alleviating symptoms and inhibiting viral spread. (Herbs specific for inhibiting TNF-α are kudzu, Chinese senega root, Chinese skullcap, elder, ginger, houttuynia, licorice, boneset, and cordyceps. Herbs specific for inhibiting IL-1ß are Japanese knotweed, Chinese senega root, Chinese skullcap, cordyceps, kudzu, and boneset.)
The virus can also inhibit the production of macrophages over time. This occurs because, over time, macrophages will begin producing anti-inflammatory cytokines such as IL-4 and IL-10. Once the bodily system is macrophage-depleted a prolonged inflammatory process occurs, keeping the infection going. Lung levels of IL-1ß, IL-6, and TNF-α all increase considerably at that point. Stimulating monocyte and dendritic cell maturation (cordyceps) and inducing IL-4 and IL-10 (Chinese skullcap, elder, houttuynia, licorice, cordyceps) will help counteract this.
The virus is exceptionally sophisticated in its impacts. There are three stages of chemokine stimulation. The first, 2 to 4 hours postinfection, is attended by the production of CXCL16, CXCL1, CXCL2, and CXCL3. These chemokines are specific for attracting neutrophils, cytotoxic T cells, and NK cells. At 8 to 12 hours postinfection CXCL8, CCL3, CCL4, CCL5, CXCL9, CXCL10, and CXCL11 are being produced, which attract effector memory T cells. At 24 to 48 hours post infection, when dendritic cells are most present in the lymphoid tissues, the chemokine profile changes again in such a manner as to attract naive T and B cells. The effect of all this is the virus playing the immune system as a virtuoso plays a violin. Eventually the immune system catches up (usually) and the infection is stopped as influenza-specific antibodies are created.
Plants that reduce the other main cytokines that the virus stimulates will also help lessen disease severity and prevent lung damage. I think the most important are inhibitors of NF-κB (Chinese senega root, Chinese skullcap, ginger, houttuynia, kudzu, licorice, boneset, astragalus), IL-6 (kudzu, Chinese skullcap, isatis), IL-8 (cordyceps, isatis, Japanese knotweed), RANTES (licorice, isatis), MCP-1 (houttuynia), CXCL10 (boneset), CCL2 (boneset), the ERK pathway (kudzu, Chinese skullcap, cordyceps), the p38 pathway (Chinese skullcap, houttuynia, cordyceps ), and the JNK pathway (Chinese skullcap, cordyceps, lion’s mane). The reduction of these cytokines and pathways will reduce IFN-γ.
Each type of influenza has a slightly different cytokine profile with slightly different cytokines more strongly represented. However, the protocols herein, directed to this form of cytokine profile, will be specific enough for every strain, including the low pathogenic avian strain H9N2, which strongly upregulates transforming growth factor beta 2 (TGF-ß2), a different dynamic entirely. Medicinal plants already in use in the developed protocol are, however, specific for TGF-ß2, i.e., astragalus (the strongest) and Chinese skullcap. Magnolia officinalis, Ginkgo biloba, Folium syringae, Nigella sativa, Paeonia lactiflora, and Lonicera japonica are other plants specific for inhibiting TGF-ß2. (This is why lonicera, or Japanese honeysuckle, is commonly used in the treatment of respiratory infections in China — it alleviates wind heat and expels wind heat invasion. In other words, it reduces inflammation in the lungs and expels the virus or bacteria responsible.)
Normally, influenza viruses stay in the upper respiratory tract. However, during more severe infections they will infect the lower respiratory tract as well. Pneumonia is one serious complication from that. So are cytokine storms, should the disease really take hold.
The more serious pandemic viruses (1918 H1N1, 2009 H1N1, and 2004 H5N1) cause severe pulmonary injury and inflammation. In these cases, the cytokine cascades become storms and the death rate correspondingly climbs. H5N1, for example, has around a 60 percent death rate in those who are infected, usually from acute respiratory distress and organ failure. The 1918 rate had a much lower mortality rate, around 20 percent, but the strain is much more infective, reaching about one-third of the population. (The emergence of a highly infective avian H5N1 strain is one of the things that keeps viral researchers up at night.)
While there is (usually) not a corresponding increase in viral replication during a viral storm, the cytokine increases in severe pandemic influenzas are significant and this is where the mortal damage comes from. Interferon-gamma (IFN-γ) production is usually increased, as is the expression of TNF-α, IL-1ß, CXCL10, RANTES, MIP-1α, MCP-1, MCP-3, and IL-6. The IFN-γ levels and the virus synergistically interact to significantly increase CXCL10 in airway epithelial cells. This causes a tremendous infiltration of immune cells into the airways. Blocking IFN-γ through the use of inhibitors has been found to significantly reduce airway infiltrates (houttuynia, cordyceps, Chinese skullcap, and licorice; note that licorice is an IFN-γ modulator — it inhibits its production when levels are high and stimulates its production, especially in T cells, when levels are low).
In particular, the inhibition of TNF-α, IFN-γ, IL-1ß, and IL-6 is crucial during infection with severe influenza pandemic strains. Those cytokines are found in exceptionally high levels in such instances and damage to the lungs is specific to them. If their levels rise high enough, the inflammation does not stay confined to the respiratory system but goes systemic. This kind of condition is called sepsis, essentially a whole-body inflammatory state. If severe enough it can lead to organ failure and cardiac arrest.
A particular cytokine-like protein has been implicated in sepsis-induced cytokine storms: high-mobility group box 1 protein (HMGB1). This cytokine-like protein is highly elevated in all patients who die from sepsis, including sepsis generated by influenza. HMGB1 is also unique in that once stimulated, its secretion continues for a very long time. TNF-α, in comparison, lasts at peak levels for about 90 minutes once stimulated. HMGB1 peak levels last 18 hours before they begin to decline. Once HMGB1 is released it stimulates further cytokine releases and has the additional property of being synergistic with the other cytokines already present in the body, amplifying their effects. HMGB1 release is stimulated by macrophages and monocytes when a particularly potent cytokine cascade begins, specifically with high levels of NF-κB, TNF-α, RANTES, IL-6, and IFN-γ, in pretty much that order. The amount released is directly dose-dependent. In other words, the higher the cytokine levels, the more HMGB1 is released. And the more that is released, the higher the cytokine levels go. As examples, levels of IL-6 are nearly four times higher, IL-8 nearly three times higher, and IFN-γ more than two times higher during severe infections than in milder cases. Higher IL-6 concentrations are positively correlated with prolonged illness and hospitalization. As the storm progresses levels of IL-8, MCP-1, and H2O2-myeloperoxidase also significantly increase. Endothelial cells are strongly stimulated and begin to amplify the storm’s cytokines. Hyperactivation of p38 MAPK with an accompanying inhibition of the adaptive immune system is a marker for these kinds of cytokine storms.
HMGB1 is also released when the nuclei of cells are damaged, as they are during influenza infections. HMG proteins are held in the nucleus to help in forming DNA complexes and regulating gene expression. When HMGB1 is expressed in lung tissue, as it is during severe influenza episodes, it causes massive neutrophil infiltration into the lungs and acute lung injury. As the storm progresses respiratory failure (requiring mechanical ventilation), acute renal failure, and systemic shock all occur. In severe cases such as these, antivirals (oseltamivir), antibiotics, and corticosteroids have all been found to be ineffective.
Common steroidal drugs (e.g., dexamethasone and cortisone) have consistently been found to have no effect on HMGB1 levels, and the same can be said for NSAIDs such as aspirin, ibuprofen, and indomethacin — even at superpharmacological concentrations. However, a number of herbs and herbal constituents do have direct suppressive actions against the protein.
Direct inhibition of HMGB1 with herbs such as Angelica sinensis and Salvia miltiorrhiza protects mice both before and 24 hours after infection with normally lethal influenza viruses. The licorice constituent glycyrrhizin directly binds HMGB1, inactivating its actions in the body. The green tea component epigallocatechin gallate (EGCG) also inhibits HMGB1, as does quercetin. Counterintuitively, nicotine also significantly lowers HMGB1 in the lungs. The pharmaceutical minocycline has also shown the ability to reduce HMGB1 levels; its use should be explored in hospital and pharmaceutical settings.
During severe influenza infections reducing HMGB1 is essential.
Influenza viruses specifically invade lung tissues and cause both direct and inflammatory-mediated damage. There are four primary pathological changes that occur: 1) diffuse alveolar damage; 2) necrotizing bronchiolitis; 3) intense alveolar hemorrhage; and 4) severe fluid accumulation.
The viruses infect specific cellular structures, in fact any that possess linked sialic acids (alpha-2,6 and alpha-2,3) on their surface membranes. But cells in the respiratory system express those acids differently and different influenzal strains create different infection profiles. The nonciliated cells of the lungs contain a higher proportion of alpha-2,6-linked sialic acids while ciliated cells contain both alpha-2,6- and alpha-2,3-linked sialic acid. H3N2 viruses prefer the nonciliated-cell sialic acids while the avian flu types (H5N1) exclusively infect ciliated cells. This is part of the reason that the avian strains tend to be more deadly. The cilia, when infected, are often killed and their ability to move mucus up and out of the lungs destroyed. This substantially increases mucous buildup in the lungs. The H5N1 strains prefer the alpha-2,3-linked sialic acids that are most strongly present on the ciliated cells but those acids exist on ciliated cells in higher quantities in the lower respiratory tract. So, the H5N1 strains infect not only the cilia but also the lower respiratory tract, causing a much deeper infection.
In severe cases, irrespective of strain, alveolar hemorrhage is often present, as is intra-alveolar edema and interstitial inflammation. The tissues surrounding blood vessels and lymph nodes and channels all inflame (perivasculitis). Microthrombi or tiny blood clots occur throughout the blood vessels in the lungs. IFN-γ levels are high in macrophages, alveolar epithelial cells, and vessels. TNF-α levels are high in alveolar macrophages and bronchial and vascular smooth muscle. There are massive infiltrates surrounding airways and in the alveolar walls. The spleen typically atrophies and presents with nonreactive white pulp. In the lymph nodes nonreactive follicles and sinusoidal erythrophagocytosis are common.
Protecting spleen and lymph structures and their function, cilial structures, and mucous membrane structures is essential.
If influenza is pharmaceutically treated, neuraminidase inhibitors such as oseltamivir (Tamiflu) or zanamivir (Relenza) are usually used. Sometimes adamantanes (amantadine and rimantadine) are as well; they inhibit the M2 ion channels. These pharmaceuticals are commonly referred to as antivirals but they are not, at least not in the same way that an antibiotic is an antibiotic, that is, something that specifically kills bacteria. They, more accurately, inhibit viral penetration of host cells (thus stopping or slowing the infection) or prevent the vacuole-enveloped virus from releasing viral proteins into the host cell interior (thus stopping or slowing the infection). They don’t directly kill the virus. Ribavirin, a drug that interferes with RNA metabolism, is sometimes used but its effects are mixed and it has many serious side effects.
If there is significant inflammation, corticosteriods may be used to try and reduce it — but if HMGB1 levels are in play, corticosteroids will do nothing to reduce them. Hospitalization is common in severe cases, but other than passive care and the use of oxygen, little can be done. Intravenous liquids may be given but they may have serious side effects, since the main approach has been the use of a combination nutrient solution/glucose IV in an attempt to keep the patient’s nutrient/energy levels high. Unfortunately, it turns out that the use of glucose during influenza infections significantly increases viral load and illness parameters. Insulin, on the other hand, reduces them considerably and also has the added benefit of lowering HMGB1 levels.
There is the bare beginnings within hospital settings of the use of cytokine inhibitors such as minocycline and HMGB1 inhibitors (e.g., anti-IFN-γ antibodies, intravenous immunoglobulin) but their use is not widespread. If microthrombi proliferate in the lungs then anti-coagulants may be used. Interestingly, both antithrombin III and thrombomodulin decrease HMGB1 in vitro. Very few of these HMGB1 interventions are commonly used, or known of, by practicing physicians.
To make matters worse, many influenza strains are developing resistance to the primary neuraminidase inhibitor used to treat them, oseltamivir, as well as to the primary adamantane M2 ion channel inhibitor, amantadine. Influenza virus samples from the 2007–2008 season showed 0.06 percent resistance, from the 2008–2009 season 1.5 percent resistance, and from the 2009–2010 season 28 percent resistance — a normal exponential learning curve for resistance. Research in late 2009 began finding strains resistant to the other major neuraminidase inhibitor, zanamivir. Resistance has become common as well to the other primary M2 ion channel inhibitor, rimantadine. Some areas report 100 percent resistance to amantadine and over 90 percent resistance to oseltamivir. Besides their overuse in agribusiness, there is another reason for resistance: human excretion.
Oseltamivir is immediately metabolized in the body to oseltamivir carboxylate. It is only active in this form. Unfortunately this form is the metabolized form and it is excreted out of the human body without any further alterations. It flows unaffected through wastewater treatment plants and ends up in waterways in low doses, where it comes into contact with waterfowl and thus is exposed to avian influenza strains. The avian strains develop resistance, and as the avian, human, and swine strains commingle the resistance is passed on into strains that can infect humans.
These drugs are also often used in large quantities during epidemic outbreaks. And the viruses quickly develop resistance to them. About 30 percent of those treated will develop resistant strains and will shed them for days afterward. The newly infected are then resistant to the drugs.
Less severe cases of the flu, if one sees a physician, are rarely treated (though, irresponsibly, some physicians will prescribe antibiotics, which are not active against viruses, for the flu). The usual medical advice is to “rest in bed, drink plenty of fluids, and take over-the-counter medications as needed.” In other words, it is left up to the individual’s immune system and some very limited self-care options to treat the infection. The Chinese don’t have this kind of technological bias in place. Unlike those of us in the West, they have been developing both herb-alone and herb/pharmaceutical combination approaches in their treatment protocols. And their outcomes are very good when compared to Western approaches.
There are a great many interventions that are possible with plant medicines and unlike pharmaceuticals, viruses don’t develop resistance to them.
Again, just to emphasize this: there are thousands of combinations of plant medicines that can be created to treat respiratory infections. These are just the ones I have found useful. Please feel free to experiment, combine, innovate, and find your own unique combinations. There is no one right way to the truth.
An influenza infection can run the range from extremely mild to extremely severe. I break the disease down into four types, each needing a different approach: 1) early onset; 2) mild infection; 3) moderate infection; and 4) severe infection. I will go into some of the unique aspects of treating severe infections at the end of this section.
I have found two approaches that can short-circuit a developing episode before it gets a good hold in the body: oscillococcinum and an herbal tincture combination.
I have found this homeopathic remedy to be extremely good for stopping the development of the flu if you take it at the first signs of the flu, that is, the moment you feel that first tingling sensation in your body that tells you that you are about to get sick.
Oscillococcinum comes as little sugar granules in tiny tubes. Take one tube every 6 hours, three per day, for 2 or 3 days in a row. This is often enough to stop the infection.
For many years I used a particular tincture combination: Echinacea angustifolia (now I use ginger juice — see page 44; and note: E. purpurea is useless for this; it won’t work), red root, and licorice, in equal parts. The dosage is a full dropperful of the tincture (30 drops) every hour, every day, until the symptoms resolve themselves.
I have found this useful for stopping the development of a flu infection if you take it at the first signs of tingling or soreness in your throat. The tincture mix should be held in your mouth, liberally mixed with saliva, then swallowed, slowly, letting it dribble down the back of the throat.
For Echinacea angustifolia to work for a cold or flu the herbal tincture must touch the affected membranes. Echinacea is antiviral; it’s been found active against HIV and influenza H5N1, H7N7, and H1N1 (swine origin). However, in order to inactivate the influenza strains, it needs direct contact with the affected cells just prior to or right at the moment of infection. Echinacea inhibits the receptor cell binding activity of the virus, interfering with its entry into the cells while at the same time strengthening the protective power of the mucous membranes through hyaluronidase inhibition. In essence, it strengthens the cellular bonds in the mucous membranes and makes it harder for a virus to penetrate. If the virus does penetrates deeper into the body, the herb just won’t work because direct contact is not possible.
Goldenseal has some similar actions on mucous membranes, which is why the deplorable echinacea/goldenseal combinations are so common. They are only effective at the first signs of infection. (I reiterate: They are only effective at the first signs of infection. If the infection is full-blown, you are just wasting your money.) Again, E. purpurea (in the form in use in most of the West) will not work. The Germans use only the fresh, stabilized juice of the stalks, not the root, and it is the root that nearly every American herbalist and company use in their products. (Capsules, of any species, are completely useless for viral and bacterial infections.)
If you do get sick but have a relatively mild case developing, then the following protocol, composed of two parts, will usually get rid of it.
Ginger is useful for the flu only if the juice of the fresh root is used. Dried ginger is useless.
At the first signs of an infection that is not going to stop, juice one to two pounds of ginger. (Squeeze the remaining pulp to get all the juice out of it, and keep any leftover juice refrigerated.) Pour 3 to 4 ounces of the juice into a mug, and add one-quarter of a lime (squozen), a large tablespoon of honey, 1⁄8 teaspoon of cayenne, and 6 ounces of hot water. Stir well. Drink 2 to 6 cups daily.
This will usually end the infection within a few days. If it does not it is still tremendously useful as it will thin the mucus, slow the spread of the virus in the body, and help protect mucous membranes from damage.
Comment: Some people find that an elderberry syrup will provide the same effects.
A number of other plants have been found effective for influenza during in vitro, in vivo, or human studies:
Tincture combination of 2 parts lomatium, 2 parts red root, 2 parts licorice, and 1 part isatis (e.g., 2 ounces of each of the first three, 1 ounce of the latter). Dosage: 30–60 drops each hour until the condition improves.
I treat moderate and severe influenza infections similarly, though with severe infections there needs to be a great deal of focus and persistence. The doses often need to be higher as well and additional formulations used as symptoms develop.
The primary interventions are:
Treatment of moderate to severe influenza is composed of three main formulations, to which others can be added if necessary. These are an antiviral tincture formulation, an antiviral ginger juice tea, and an immune complex tincture formulation.
Equal parts of Chinese skullcap, isatis, licorice, houttuynia, lomatium, red root, yerba santa (Eriodictyon spp.), elephant tree (Bursera microphylla), osha (Ligusticum porteri), and either inmortal (Asclepias asperula) or pleurisy root (Asclepias tuberosa).
This formulation contains potent antivirals, specifically Chinese skullcap, isatis, licorice, houttuynia, lomatium. These are designed to kill the virus and inhibit its entry into the body. And of course many of them have alternate actions as well. Licorice, for example, is mucoprotective, strongly anti-inflammatory, and expectorant. Chinese skullcap is potently anti-inflammatory for the cytokine cascades that influenza creates, provides splenic protection and activation, will help lower fevers, and is an expectorant. All of these antiviral herbs have multiple functions in respiratory diseases.
The four herbs added to this protocol that are not discussed in depth in this book (yerba santa, osha, elephant tree, and inmortal or pleurisy root) do not have to be included in this formulation, though they do help considerably, primarily through helping with the tastiness of the formulation, thinning the mucus, stimulating expectoration, and promoting lymph drainage from the lungs.
For nearly 30 years I tended to use formulations that contained only three herbs, occasionally five. With the emergence of more intense forms of influenza, and my increasing age, I have found that a more complex formulation works better. I do think a major factor in that is aging. There are, in myself and in many of the people I help, considerable age-related alterations in our physiology. There are preexisting inflammations in many parts of our bodies, from age-related memory dysfunction to arthritis. Our bodies are wearing out, biodegrading, and that deterioration makes them more susceptible to infections such as influenza, and in more severe forms. Further, our immune systems are not as vital as they once were and have a great deal more trouble counteracting the infection.
Both yerba santa and osha are added for taste as well as their medicinal actions (isatis really does taste foul to me). Osha is a relative of lomatium and has its own antiviral and expectorant actions. It has strong impacts on inflammation in the lungs and increases the degree of oxygen intake during respiration. It also has the added benefit of anesthesizing the throat tissues, helping reduce throat soreness. Yerba santa is a very good expectorant, bronchial dilator, and decongestant. Elephant tree is anti-inflammatory, thins and softens bronchial mucus, and stimulates expectoration. It is a major source of copal and a close relative of myrrh. (Myrrh can be substituted for elephant tree in this formulation if the tincture is stabilized with 20 percent glycerin.) I consider all three of these herbs to be specific for maintaining the mucous membranes of the lungs, thinning the mucus, and increasing expectoration. Inmortal (or, as an alternative, pleurisy root) improves cilia function and is a bronchial dilator, an expectorant, a febrifuge (lowering fevers), and most especially a potent medicinal for stimulating lymph drainage from the lungs.
Dosage needs to be high for two reasons. The first is that there are so many herbs in the formulation that each herb has a reduced presence in the formulation. The second is the nature of moderate to severe influenza infections. As the disease progresses up the scale of severity, the cytokine cascade increases in intensity. The body needs to be bathed in the plant compounds in high enough quantities that the cytokine cascade is potently inhibited. In addition, the body needs to be suffused with enough of the antiviral compounds that the viral entry into host cells and its presence in the body are severely curtailed.
For moderate influenza: 60 drops or 3 ml (a little over 1⁄2 teaspoon) every hour.
For severe influenza: 1–2 teaspoons every hour.
Dividing the formulation: You can if you wish divide the formulation in two. The first would contain Chinese skullcap, isatis, licorice, houttuynia, and lomatium and would be primarily an antiviral formulation (and would taste from okay to bad). The second would contain red root, yerba santa (Eriodictyon spp.), elephant tree (Bursera microphylla), and either inmortal (Asclepias asperula) or pleurisy root (Asclepias tuberosa) and would taste very good. (I would skip the osha if the formulation is split in two.) This second formulation would primarily be for lymph and spleen optimization and protection, expectorant and decongestant actions, mucus thinning, cilia protection, and lymph drainage from the lungs. The dosage for each would be half the dosage as when combined.
This is the same as discussed earlier, in essence: ginger juice tea, hot. Again, ginger is useful for the flu only if the juice of the fresh root is used. Dried ginger is useless.
Juice one to two pounds of ginger. (Squeeze the pulp to get all the juice out of it.) Keep it refrigerated. Pour 3 to 4 ounces of the juice into a mug, and add one-quarter of a lime (squozen), a large tablespoon of honey, 1⁄8 teaspoon of cayenne, and 6 ounces of hot water. Stir well. Drink 4 to 6 cups daily.
Ginger in this form is potently antiviral for influenza. The fresh juice tea will also thin the mucus, help protect mucous membranes from damage, and act as a potent diaphoretic, lowering fever during the infection.
Equal parts of the tinctures of astragalus, cordyceps, and rhodiola. All of these herbs are active against influenza viruses. They are also potently adaptogenic, that is, they increase the resistance of organisms to stressors, whether microbial or external. Additionally, astragalus and cordyceps are highly specific for the cytokine cascades that are initiated by influenza. These herbs will help through their antiviral actions, modulate the overactive immune response, lower cytokine levels, and enhance a healthy immune response to the infection.
Again, dosage levels should be highish, for the same reasons as outlined above.
For moderate influenza: 1⁄2 teaspoon of the tincture 3x daily.
For severe influenza: 1–2 teaspoons of the tincture 6x daily.
There are a few additional things that can be very helpful during acute influenza episodes. These are treatments for high fever, severe headache, cough, high HMGB1 levels during cytokine storms, and protecting cilial structures and mucous membranes in the lungs. Two supplements have also been found to be helpful (in a number of studies). And essential oil inhalants can help with the infection in the lungs, coughing, and mucous flow and secretion.
There are a number of interventions that can help. The ginger juice tea previously described (page 49) can often lower the high fevers that occur during influenza, but if you want more:
I make a cough syrup every fall just before the flu season. It comes in handy. The recipe varies all the time, depending on what I have on hand and what I have wild-harvested in any particular year. But the recipe below gives you a good idea of what kinds of herbs are in it. I do keep it refrigerated though it will last awhile if it is not.
Combine the horehound, cherry bark, elderberries, elecampane, licorice, mallow, elm bark, vervain, and half of the lomatium in 7 pints of water in a large pot. Bring to a boil. Stir frequently as it heats to prevent sticking. Once it boils, reduce the heat and let simmer, stirring constantly. Cook until the liquid is reduced by half. Remove from the heat and let cool. (You can put the pot in a bath of cold water to cool it faster. Don’t let it tip over.) Strain the liquid, pressing the marc (the spent plant matter) through a cloth to get as much liquid as you can.
(With mucilaginous herbs — the licorice, mallow, and elm bark — as part of the mix, it can be hard for the liquid to pass through the weave of the cloth you are using. So, alternatively, you can keep the mucilaginous herbs out of the mix and once the marc is pressed, heat all the liquid again, adding the licorice, mallow, and elm to the pot in a muslin bag to keep them out of the liquid. Bring to a boil and simmer, stirring constantly, for 30 minutes. Remove the bag, let it cool, then squeeze out the liquid as best you can.)
Warm the liquid again, just enough to dissolve the honey and glycerin. Add the glycerin, then the honey to taste. Grind the remaining lomatium (or osha) to a fine powder—a nut or coffee grinder or mortar and pestle is good for this—then add it to the liquid. Let the mix cool, then add the mullein and yerba santa tincture. (Keep in mind that you can substitute similar herbs for any used in this recipe.)
The honey, glycerin, and two tinctures help stabilize the syrup, keeping it from going bad. I do keep the whole thing in the refrigerator though. It will last a year very easily. Generally, it is best to make this kind of a syrup in the fall, after the berries are ripe and ready for harvest, and just before flu season. It is very effective.
I keep this by the bed and take as desired. Really, none of that 1-tablespoon-at-a-time stuff, that won’t help at all. Just drink it as needed, right out of the bottle. It will help soothe the mucous membranes, reduce coughing, and ease the aches and pains that come with the flu.
The herbs that are already being used will help this considerably. However, if the condition significantly worsens then the following specific intervention is warranted. Take both formulations.
Formulation 1: Tincture combination of Angelica sinensis and Salvia miltiorrhiza, in equal parts. Dosage: 1 tablespoon every hour. Or . . .
Formulation 2: Strong infusion of the two herbs, 4 ounces of each in 1 gallon of just-boiled water. Remove from the heat, let sit 4 hours, and strain. Dosage: Drink 12 ounces every hour.
There are a number of herbs that are specific for protecting the cilia: cordyceps, olive oil and leaf, the berberine plants, and, my favorite, Bidens pilosa. Bidens is a very strong systemic antibiotic that is used in Asia and Africa for systemic bacterial infections (including respiratory) and influenza (though it has not been tested against that virus). If the mucous membranes have been infected by a microbe and you start to get well, relapse, start to get well, relapse, this is the herb to use. The herb is specific for healing and protecting mucous membrane structures, including the cilia. Tincture of the fresh herb should be used. The dry herb is not as antimicrobial though it will still help the mucous membranes’ tone. Dosage: 1⁄4–1⁄2 teaspoon up to 6x daily.
When people become severely ill with influenza, they often present with high fever, extreme lethargy, and significantly reduced vital energy. They are usually bedridden and very, very afraid.
The interventions in such cases need to be highly focused and attentive. It takes a lot of work. They need to be nurtured continuously, fed if they will eat (chicken broth is very good), helped to the bathroom (if they can even get out of bed), and ministered to. The fever will often need to be brought down and you will have to monitor the plant medicine intake. It needs to be constant (every hour at minimum), and in fairly high dosages in order to lower the cytokine cascade, reduce the viral load, and get the immune system back online. It will often take a week to begin to turn the situation around, and several more weeks before the person really begins to get well. It can be done. Of all the herbs useful for this, lomatium, licorice, Chinese skullcap, and cordyceps are the most essential.
Zinc and selenium are very helpful during influenza infections. Both have been found to protect mice from severe influenzal strains. Dosage: 200 mcg daily of selenium; 25–40 mg daily of zinc.
Essential oils of thyme, eucalyptus, rosemary, and sage can all help. They are all antiviral for influenza (to varying extents), will help reduce the coughing reflex, thin and help expectorate mucus, and improve airflow in the bronchial tract. To use: Bring a gallon of water to a boil in a pot on the stove. Turn off the heat, add 20 drops of each of the essential oils to the pot, and bring the pot to a comfortable location where you can sit with your head over it. Hold your head over the pot and breathe in the steam for as long as you can take it, every few hours.
SARS is, in its impacts in the body, very similar to acute influenza and at first was thought to be an emerging influenzal strain. However, SARS (sudden acute respiratory syndrome) is a new, emerging viral pathogen that appeared suddenly in 2002 in China. The disease is characterized by fever followed by respiratory symptoms and, ultimately for some of those infected, progressive respiratory failure. The nature of the virus, at the time, was unknown but eventually it was found to be a coronavirus that had jumped species. Into us.
Coronaviruses are enveloped, positive-stranded RNA viruses. They possess the largest genome of all the RNA viruses. The viruses in this group engage in a very high frequency of RNA combinations, continually producing new variants. Of the dozen or so coronaviruses only three infect people. Among them, SARS is the most serious.
The virus takes about 6 days to develop in the body and, like influenza, is primarily spread by respiratory droplets — though direct contact with body secretions can also transmit it. The virus sheds particles in feces and urine, often for several weeks, and cleaning up after the severely ill can spread the infection. Fever, cough, and difficulty breathing are the first symptoms of the disease. Headache, muscular stiffness, myalgia, loss of appetite, malaise, chills, confusion, dizziness, rash, night sweats, nausea, and diarrhea occur for many.
With increasing age comes increasing fatality. Those under the age of 24 are not very susceptible. For those aged 25 to 44 the fatality rate is 6 percent. It is 15 percent in those 45 to 64 and greater than 50 percent in those over 65.
SARS, unlike influenza, attaches not to sialic acid linkages but to angiotensin converting enzyme 2 (ACE-2). This is an integral membrane protein on many cells throughout the body, including the heart, vascular cells, and kidneys. It is intimately involved in regulating the renin-angiotensin system (RAS). The RAS is intimately involved in vascular constriction and renal electrolyte homeodynamis, which is where its primary impacts were thought to be. But the RAS is also crucial to the functioning of most organs, including the lungs, spleen, and lymph nodes. ACE-2 converts angiotensin II to less potent molecular forms. Among other things angiotensin II is a potent vasoconstrictor but it also is highly bioactive along a range of cellular actions.
SARS viruses attach to ACE-2 on the surface of lung, lymph, and spleen epithelial cells. (Licorice, Chinese skullcap, luteolin, horse chestnut, Polygonum spp., Rheum officinale, and plants high in procyanidins and lectins such as elder and cinnamon block attachment to varying degrees.) Once the receptors on these cells are compromised there is enhanced vascular permeability, increased lung edema, neutrophil accumulation, and worsened lung function. In essence, once the virus begins attaching to ACE-2, ACE-2 function begins to be destroyed. ACE-2 function also tends to be less dynamic as people grow older, hence the more negative the effects of SARS infection on the elderly. (Kudzu, Salvia miltiorrhiza, and ginkgo all upregulate and protect ACE-2 expression and activity and lower angiotensin II levels.) ACE (in contrast to ACE-2) inhibitors increase the presence of ACE-2 and help protect the lungs from injury. (Hawthorn and kudzu, for example.)
Upon infection by the SARS virus, similarly to influenza, inflammatory cytokines are strongly upregulated. IFN-γ, CXCL10, IL-1ß, TNF-α, and IL-6 are primary, IL-6 particularly so. RANTES, MCP-1, and IL-8 are elevated in about half of those who are infected. The p38 MAPK pathway is highly stimulated and as the infection progresses levels of PGE2 (prostaglandin E2) and TGF-ß both rise (with a later elevation of IL-2). Lowering TGF levels is very helpful (Angelica sinensis, Astragalus mongholicus). HMGB1 levels during SARS cytokine cascades are high, especially in those who die. During the infection, the cytokine cascade initiates a massive immune cell migration, infiltration, and accumulation into lung tissues. The older the infected animal (human or otherwise), the greater the cytokine upregulation and the worse the outcome. Sharply reducing IL-1ß has been found to significantly decrease the impact of the disease on the infected and to inhibit mortality (Japanese knotweed — i.e., Polygonum cuspidatum — Chinese senega root, Chinese skullcap, cordyceps, kudzu, and boneset). Severe hypoxia occurs in the cells that are affected (and in the person so afflicted). The RAS-stimulated cellular hypoxia generates high levels of free radicals through the rapid increase of angiotensin II, i.e., a hypoxia-reoxygenation injury cycle. In essence an abundance of hydrogen peroxide and superoxide radicals is generated. The high levels of angiotensin II stimulate free radical formation from endothelial cells, vascular smooth muscle cells, and mesangial cells as well. In short the excessive angiotensin II levels (due to the destruction of ACE-2 cells by the virus) cause massive damage to the lung, lymph, and spleen tissue. Protecting the cells from the induced hypoxia significantly reduces the damage in the lungs. (Rhodiola is specific for this. It prevents hypoxia-induced oxidative damage, increases intracellular oxygen diffusion, and increases the efficiency of oxygen utilization.)
The virus specifically targets (and replicates within) ciliated cells, destroying the cells and their capacity to move mucus up and out of the lungs. (Cilia-protective herbs are cordyceps, olive oil and leaf, the berberine plants, and Bidens pilosa.) Autoantibodies are produced that begin to attack host epithelial and endothelial cells, increasing the destruction. Reducing the autoimmune response (rhodiola, astragalus, cordyceps) and protecting endothelial cells (Japanese knotweed) is crucial.
Autopsies of those who died revealed that the alveolar damage in the lungs was severe. There was massive damage to the lymph nodes in the lungs, as well as severe necrosis in the white pulp and marginal sinus of the spleen, destruction of the germinal centers in the lymph, apoptosis of lymphocytes, and an infiltration of monocytic cells. Protection of the spleen and lymph is essential (red root, poke root, Chinese skullcap).
SARS replicates primarily in ciliated epithelial cells but also in infected dendritic cells, both mature and immature. Dendritic cells exist abundantly just under the epithelium layers in the lung tissue. The cytokine upregulation makes the endothelium much more porous, allowing the virus to penetrate and infect the dendritic cells. It does not kill the dendritic cells but merely stops them from stimulating an effective adaptive immune response. The virus very powerfully upregulates IL-6 and IL-8 in the epithelial cells. These particular cytokines concentrate around the immature dendritic cells and strongly inhibit their maturation.. This in turn inhibits mature dendritic cells’ ability to prime the production of active T cells and allows the virus to enter and severely damage the lymph organs in the lungs. Stimulating dendritic cell maturation (cordyceps) and increasing T cell counts (licorice, red root, elder, and zinc) will reduce the symptom picture and disease severity.
Ribavirin is only marginally effective against SARS but is still used in spite of the side effects. Corticosteroids are used to try and reduce inflammation. The nonsteroidal anti-inflammatory drug indomethacin has shown potent antiviral activity against the virus and should be used. Rimantidine and lopinavir have both been found active in vitro.
The plants found specific for the SARS virus are Chinese skullcap, houttuynia, isatis, licorice, Forsythia suspensa, and Sophora flavescens.
I would use the exact same protocol as for influenza, outlined earlier, with two exceptions:
Other plants found active against SARS are:
The main ones that people encounter are the adenoviruses, parainfluenza viruses, respiratory syncytial virus, and rhinoviruses.
Adenovirus infections tend to be mild and are generally easy to treat. However, acute conditions such as pharyngoconjunctival fever, acute respiratory disease, pneumonia, and meningitis can also occur.
Adenovirus 14 is an emerging serotype that can cause serious infection, essentially acute respiratory disease, which can sometimes lead to death. Conjunctivitis, high fever, pneumonia, and gastrointestinal involvement can all occur. The virus sheds in both respiratory droplets and feces and can remain highly infective in feces for long periods.
The herbs specific for adenovirus infections are astragalus, Chinese skullcap, elder, isatis, and licorice. Other herbs that are active are Ardisia squamulosa, Artemisia princeps, Boussingaultia gracilis, Caesalpinia pulcherrima, Ocimum basilicum, and Serissa japonica.
Treatment: The same as for mild influenza. If it becomes serious, the same as for moderate to severe influenza.
Parainfluenza viruses generally cause what is called croup. It is an acute infection of the upper respiratory tract accompanied by barking cough (the croup part) and hoarseness. The throat is often swollen, which can interfere with breathing. The herbs specific for parainfluenza are Chinese skullcap, elder, and licorice. Allium sativum and Cicer arietinum have also been found active.
Treatment: Tincture combination of elderberry, Chinese skullcap, and licorice tinctures, in equal parts. Dosage: 30 drops every hour.
Respiratory syncytial virus is also a single-strand, enveloped RNA virus with high variation in its genome. It is a very common infection, especially in young children, throughout the world. It causes bronchiolitis and other types of respiratory infections, especially in the lower respiratory tract. It generally presents as a common cold but can sometimes become serious, turning into pneumonia if left untreated.
The herbs specific for respiratory syncytial virus infections are Chinese skullcap, Eleutherococcus senticosus, elder, isatis, licorice, and Sophora flavescens. Other herbs found active are Barleria prionitis, Blumea laciniata, Elephantopus scaber, Laggera pterodonta, Markhamia lutea, Mussaenda pubescens, Narcissus tazetta, Selaginella sinensis, Scutellaria indica, and Schefflera octophylla (in vitro).
Treatment: The same as for mild influenza. If it becomes serious, the same as for moderate to severe influenza.
These viruses cause the common cold. The herbs/supplements specific for rhinovirus infections are ginger, Echinacea angustifolia, elder, Eleutherococcus senticosus, quercetin, Papaver pseudocanescens, and Raoulia australis. A Japanese traditional formulation, hochu-ekki-to, has been found highly effective, as has Prunus mume.
Treatment: I have found the use of an E. angustifolia, licorice, and red root tincture combination, as outlined earlier (see page 43), and the prolific use of the ginger juice tea, also discussed earlier (see page 44), to be very effective.