Doctor suicide is a
painful reality that hospitals, clinic networks, and medical schools go out of
their way to deny.
But with the emergence of a documentary called Do No Harm, and a surge of media attention following the suicide of Dr. Lorna Breen during New York City’s first COVID peak, healthcare leaders are finally being forced to reckon with the ugly truth that in many institutions, medicine has become culture of abuse.
American physicians kill
themselves at an alarmingly high rate. A least one doctor commits suicide every
day in the US, according to research presented two years ago at the American
Psychiatric Association’s annual meeting. Investigators at the Harlem Hospital
Center in New York did a systematic literature review of physician suicides and
identified a staggering rate of 28 to 40 per 100,000––more than twice the
general population rate of 12.3 per 100,000.
The review also showed
that doctors have the highest suicide rate among all professions, including
other high-stress ones like the military or law enforcement.
Those statistics were from
before COVID-19. The pandemic is accelerating the trend. Stories of
medical professionals lost to suicide in the last 5 months are shining new
light on long-standing and dangerous shortcomings in our systems of medical
education and practice.
Hazards of duty? Part of
the deal? Comes with the territory?
Only if that “territory”
is the United States.
Medicine is a high-pressure
job anywhere. But doctors in other countries are not killing themselves at
nearly the rates of their American counterparts. According to a 2019 systematic review
by Dutheil and colleagues, US physicians are far more likely to commit suicide than their peers
worldwide. Medical suicide rates have been rising in this country over the last
decade; in Europe they’ve actually been decreasing.
Why do so many American doctors
and medical students take their own lives? And why aren’t their deaths more
She believes guilt,
bullying, and exhaustion are three leading causes of suicide in medicine. Physicians,
med students, and other healthcare personnel are often subjected to abusive,
even dangerous working conditions. Overwork is common; self care is penalized.
In many hospitals and
clinics, the inevitable pressures of medical practice are compounded by conflicting
administrative demands, hostile work environments, retaliatory office politics,
racial discrimination, and sexual harassment. It all adds up.
“‘Burnout’ is victim-blaming, and deflects attention from the hazardous working conditions that are illegal in any other industry that values safety, and the human rights violations that are rampant in medical education and beyond.”
—Pamela Wible, MD
Hazing & “Pimping”
It begins with the rigors
of medical education, and extends through insurance-based medicine’s emphasis
on volume over quality. Young physicians in training are frequently subjected
to sanctioned abuse and public humiliation in lecture halls and hospital wards.
They’re also severely sleep-deprived—itself a form of torture.
For some suicidal doctors,
the problems began when they entered medical school. Med students are typically
high-achievers accustomed to ranking at the top of their classes. Once in med
school though, some feel for the first time in their lives that they might not
really be smart enough, tough enough, or brave enough to become “good” doctors.
Within medical culture
there’s a pervasive fear of being weak, unintelligent, or incapable. That fear
drives people to hide their mistakes and imperfections, and shy away from seeking
help, even when it’s desperately needed. Perhaps you can relate.
Some level of pressure and
anxiety is to be expected in a career as demanding as medicine. But Dr. Wible sees shockingly toxic elements
in US medical culture.
Bullying, humiliation, and
hazing are tolerated, sometimes even encouraged as acceptable training strategies.
Many doctors can tell stories of getting “pimped,” –an aggressive,
rapid-fire style of testing students’ clinical knowledge by asking difficult or
intentionally unanswerable questions in class, in the clinic, and even in front
It takes its toll.
A 2016 study of med students
by the National Institutes of Health and the US Department of State found that,
“overall prevalence of depression or depressive symptoms among medical students
was 27.2%, and the overall prevalence of suicidal ideation was 11.1%.” Among those
who screened positive for depression, only 16% sought treatment (Rotenstein, L et
al. JAMA. 2016; 316(21): 2214‐2236).
“There seems to be more
mental health distress among first and third-year med students, and definitely
for unmatched graduates. In some residency programs, 75% of residents meet
criteria for major depression,” Wible says.
Med students experiencing
depression, anxiety, or suicidal thoughts avoid seeking care because they worry
they’ll be “outed,” stigmatized, and punished if they do.
The stress and
pressure––and subsequent mental health risks––only increase once they
transition into actual clinical practice.
They enter an extremely
hierarchical system in which they’re often forced to “earn their keep” by
filling the most undesirable shifts. Long hours without breaks; weekend and
holiday shifts with little time off; isolation from friends, family, and
crucial social support—these are not exceptions, these are the rule for many
Sleep deprivation is also a
big factor, says Wible.
It is not hard to find a
physician who can tell tales of falling
asleep, or witnessing colleagues
drop unconscious to the hospital floor, while making rounds, treating patients,
or conducting surgeries. Perhaps you’ve been one of them.
In other high-stress
professions–pilots, air traffic controllers, even truck drivers for
example–there are regulations and work-hour restrictions that limit shift
lengths, because everyone recognizes that sleep deprivation and overwork impair
Yet our medical system
drives doctors—who routinely deal with matters of life and death that hinge on
clear, quick judgment—to the point of exhaustion.
Current American Council for Graduate Medical Education (ACGME) requirements permit interns’ duty shifts to go for 24 consecutive hours––up from a previous cap of 16 hours––and 80 total hours per week.
Not only do we permit sleep-starved
doctors to administer potentially dangerous drugs, monitor patients on a
complex array of equipment, and perform surgeries that require great skill––we
expect them to do it all flawlessly—and to be nice about it.
In other high-stress professions…there are regulations and work-hour restrictions, because everyone recognizes that sleep deprivation and overwork impair performance. Yet our medical system drives doctors—who routinely deal with matters of life and death that hinge on clear, quick judgment—to the point of exhaustion.
Exhausted doctors are more
likely than well-rested ones to make medical errors, which sometimes kill patients.
A 2018 Mayo Clinic study found that physicians who made errors were more likely
to exhibit symptoms of fatigue, burnout, and recent suicidal ideation (Tawfik, D et al. Mayo
Clin Proc. 2018; 93(11): 1571-1580).
When Epidemics Collide
COVID-19 presented new and
unusual stressors for clinicians in viral epicenters like New York City,
Washington, DC, and Chicago, where prevalence has been highest.
physicians and nurses are particularly vulnerable. In centers with very high caseloads
they’re working under constant duress, sometimes without adequate protective
equipment, in hospitals that were understaffed even before the pandemic. As
they treat their patients, they worry about their own risk, and the potential
for carrying the virus home to their families.
Dr. Wible, who has
provided counselling for suicidal clinicians for nearly a decade, says that since
the coronavirus, she’s seen a dramatic increase in the number of calls.
“Volume doubled, and I led
group support calls on Zoom to handle the uptick in requests for support,” she
On April 26, Dr. Lorna
Breen, a well-respected ER doctor at New York Presbyterian’s Allen Hospital in
New York City died of “self-inflicted injuries” at age 49. Her story got the
media’s attention: it represented the convergence of two epidemics: COVID and
Prior to her death, Dr.
Breen had treated many coronavirus patients, and she herself had recently
recovered from the virus.
“Make sure she’s praised
as a hero, because she was,” Breen’s father, also a doctor, told the New York Times. “She’s a casualty just
as much as anyone else who has died.” The elder Dr. Breen also stressed that
his daughter, “did not have a history of mental illness.”
In its official public statement,
New York Presbyterian used similarly valiant language. “Dr. Breen is a hero who
brought the highest ideals of medicine to the challenging front lines of the
But an email to hospital
staffers did not identify the cause of Breen’s death, reflecting an attitude of
denial and obfuscation that Wible says is the rule, not the exception, among
Breen’s family and
hospital “had to use ‘healthcare hero’ propaganda on her immediately, so that
she wasn’t forgotten or thrown to the wind as weak,” Wible told Holistic
“They gave her the hero
spin because she was in New York City and had a high position in her hospital.
Her family made it clear that she never had any preexisting medical conditions
and instead tried to blame her death on the coronavirus, to distance her and
the family from the topic of mental health issues.”
This denial contradicts
evidence Wible has gathered from the nearly 1,500 cases she has recorded. She finds
that ER doctors rank among the top three medical specialists most likely to die
by suicide. Psychiatrists, surgeons, and anesthesiologists also have a higher
risk than others.
Wible believes secondary
trauma plays a big role, at least for the latter two specialties.
Breen’s family insists
that she never suffered from prior mental health challenges, but Wible says it’s
hard to imagine that a doctor who spent her entire career in the ER never
suffered a single blow to her emotional or cognitive wellbeing.
“I believe all emergency
medicine doctors have mental health wounds,” Wible said.
It is common to hear
clinicians say that experiencing or witnessing a catastrophic injury or illness
early in life is what inspired them to pursue medical careers. Wible finds that
“many EM doctors have experienced significant trauma in their childhoods––then
they go into emergency medicine and are re-traumatized every day.”
Even those who did not
experience childhood trauma will invariably incur “occupationally-induced
mental health wounds” while working in the emergency department. “If they have
not sought appropriate care, then they are still wandering around with those
wounds every day,” she said.
It’s Not “Burnout,” It’s Abuse
“This is tough work, even
on the best day,” Wible says of the medical life. “Even in the parts of
medicine that seem like they could be happy, there is unforeseen, extreme
In our current systems,
the inevitable stresses and pressures of caring for sick, injured, and
sometimes dying people, are amplified by factors unrelated to patient care.
Micromanagement by senior
doctors or hospital administrators; incessant demands for documentation; veiled
threat of punishment or legal consequences for errors; poorly managed and
understaffed clinics; incessant time pressures. All these factors leave many
physicians feeling not only emotionally exhausted, but cynical towards the
profession they once loved.
We call it “burnout.” But Dr.
Wible warns that this term obscures the abusive nature of our medical system
“‘Burnout’ is victim-blaming,
and deflects attention from the hazardous working conditions that are illegal
in any other industry that values safety, and the human rights violations that
are rampant in medical education and beyond.”
Hospitals treat physicians
in ways that “break the UN Declaration
of Human Rights,” she suggested. Other medical professionals also experience extreme
pressure, overwork, and abuse. But statistically, the suicide risk is much
higher for physicians.
Hidden in Plain Sight
Part of the problem is
physicians’ uncanny ability to hide their suffering not only from colleagues
and supervisors, but from family members and friends. Doctors who experience depression,
anxiety, or suicidal ideations often view those symptoms as flaws that must never
be exposed. Some worry that admitting psychological or emotional distress will call
into question their fitness to practice or, worse, might lead to dismissal.
There may also be
expectations from family and friends that someone who has “made it” in such a
high-status profession must surely be reaping rewards. Some doctors feel a sense
of duty not to disappoint parents, spouses, or other loved ones who’ve also invested
and sacrificed to make their medical careers possible.
As a result, few people know
when a doctor friend or family-member is contemplating suicide.
Dr. Wible—who had her own struggles
with anxiety and suicidality earlier in her career– says there are a few red
flags: “Excessively happy doctors are often hiding their
emotions and pain.” Additional warning signs may include a recent medical
liability case, medical board complaints or investigations, and major life
events like divorce.
Denial: A Double Assault
Denial by hospital
administrators, family members, and colleagues has only compounded the problem
of doctor suicide.
“We create the scenario
that takes these wonderful young people and puts them in a situation where they
can see the only way out is death––and then we bury their suicides,” Wible
said. “It’s like a double assault.”
She pointed out that a
number of doctor suicides involving ingestion of prescription drugs were misleadingly
reported as “accidental” overdoses. It is certainly possible for physicians to
unintentionally take too much medication, but this explanation stretches credibility.
MDs get extensive training in pharmaceutical use; that makes them some of the
least likely people on the planet to unknowingly over-consume a drug.
Doctors do, however, have
ready access to controlled substances, which heightens risk of abuse. According
to a 2013 study published in the Journal of Addiction Medicine, 69% of
doctors reported that they abused prescription drugs “to relieve stress and
physical or emotional pain” (Merlo, L et a. J Addict Med. 2013; 7(5): 349-53).
Physicians also possess an
intimate and detailed knowledge of human anatomy, increasing the chances that
they will complete a suicide if attempted.
Concealing doctor suicides
protects medical schools and hospitals from having to address systemic problems.
But sweeping the dirty secrets under the rug only puts other health
professionals––and their patients––at tremendous risk.
“Suicide is not the
problem; censorship is,” Wible argued. “If we would just speak openly about
this crisis, it could be easily solved.”
suicide prevention tools exist––and they can help avert the needless loss of
doctors’ lives. “We have the resources to solve this problem. But if we censor
it, we can’t make it better. We can’t solve a problem that nobody is acknowledging.”
Get Up, Stand Up
Wible says that to truly
shift medical culture in a healthier direction, “we need to normalize the
conversation about suicide risk, just like we’ve normalized conversations about
Education is also vital.
Two resources she recommends are the documentary “Do No Harm” by filmmaker, Robyn Symon, and her free audiobook of doctor suicide
notes, Physician Suicide
Letters—Answered, in which she shares her correspondence with numerous clinicians whom
she’s helped to avoid suicide.
The key, she says, is providing
a forum for self-expression without fear of rebuke or humiliation. “The system
of medical education and practice should be set up in a way where people are
able to connect with each other honestly, emotionally and spiritually, without
punishment,” Wible said.
Fixing the situation will
also require system-wide reforms to create more humane working conditions
within medical institutions. Wible believes doctors, nurses, med students,
and other health professionals need to stand up and fight for those reforms.
The book documents a spectrum
of abusive situations–from food and sleep deprivation to threatening
foreign-born doctors and trainees with deportation–that routinely occur in
American clinics. It also gives guidelines to help doctors chronicle their own
experiences of abuse, and practical action steps for confronting and resolving
Dr. Wible is certainly not
the only physician concerned with doctor suicide, and pushing for change.
Keith Frederick, an
osteopath who also served for eight years in Missouri’s House of
Representatives, introduced a bill to address mental health in Missouri medical
schools after learning that a fourth-year osteopathic student in his community
died by suicide just days before graduation.
In the film Do No Harm,
Dr. Frederick described suicide as an unacknowledged “occupational hazard” in
medical settings. During his years as a legislator (2011-2019), he also
sponsored a bill requiring hospitals to examine mental illness and burnout
Frederick’s proposal met initial resistance from Missouri medical institutions.
The deans of all six of the state’s med schools co-authored a letter urging
legislators not to pass the bill.
Ultimately, though, Frederick
and his supporters won-out. The “Show-Me Compassionate Medical Education
Act” (MO Senate Bill 52) was signed into law in
July 2017. It requires medical schools to provide incoming students with
information about available depression and suicide prevention resources. It
also granted medical institutions the authority to conduct internal research,
without penalty, on rates of depression, suicide, and other mental health
issues among medical students.
Thank a Doctor, Save a Life
In addition to raising
awareness around suicide risk and prevention, expressions of gratitude can literally help keep
Wible encourages people to
“please show appreciation and give thank you cards to your doctors, and ask
them how they are doing.”
It might seem simplistic
or even silly, but she believes it can be life-saving.
“It can be very hard to
reach doctors––they’re often so closed off emotionally. It’s important that
they feel validated, normal, and appreciated.” A thank you letter may give a
doctor some a much-needed dose of positive reinforcement that he or she may not
Verbal thanks are nice
too, but Wible says that penned messages carry an even greater and
longer-lasting power. “Thank you notes are huge––especially if they are
written. They have a lifespan that goes on for decades––doctors will read and
reread them, sit and stare and really soak in the words.”
Clinics and hospitals
might also consider setting up anonymous compliment boxes where staff and
patients alike can submit thank you notes to their doctors or colleagues.
She also urges medical
practitioners to prioritize their own health and self-care. She herself does
this by “spend[ing] a lot of time in nature, hiking, gardening, and with my
animals.” She also stressed the importance of strong social connections, like
the one she shares with her loving partner.
important,” she added, “I get therapy WEEKLY.”
She holds that all med
students and doctors should receive “non-punitive, 100% confidential
therapy” every week. Whether it’s for preventive or active treatment,
breaking down the barriers around mental health support could help avert the
tragic doctor suicides on which our current systems prefer to turn a blind eye.
Discussions about the microbiome in human health usually focus on the gut. But what about the microorganisms that reside in other parts of the body––like the vagina? The vaginal microbiome is a critical, yet largely overlooked, aspect of women’s health.
That’s in part because scientists know far more about the microbes in the digestive tract than those in the vagina. Then there are cultural factors like taboos surrounding female genitalia and sexuality that limit open, honest conversations about vaginal symptoms.
Yet some of the most common complaints women bring to their doctors are directly or indirectly related to imbalances in the vaginal flora. Many vaginal symptoms are treatable with natural therapies that rebalance the microbiome and heal symptoms just as effectively, if not more so, than conventional antibiotic or antifungal drugs.
Vaginal Dysbiosis Ups Infection Risk
Though the gastrointestinal microbiome still dominates in research circles, scientific interest in the vaginal microbiome is growing.
Recently, Virginia Commowealth University launched a major research initiative called the Vaginal Microbiome Consortium, to foster cross-disciplinary studies on the vaginal flora and how it influences women’s health, sexuality, fertility, and infant health and well-being.
The vaginal microbiota consists primarily of bacteria, yeast, and fungi. As is the case with the gut microbioe, each individual’s vaginal ecosystem is unique, and influenced by a host of factors: age, diet, environment, hormones, and genetics. The quantity and diversity of microbes in the vagina “have significant implications for a woman’s overall health,” said Liisa Lehtoranta, PhD, manager of research and development in the Global Health & Nutrition Science division at DuPont Nutrition & Biosciences.
Lehtoranta, who specializes in research on probiotic bacteria, explained that in healthy women, the vaginal microbiome is usually highly populated by a few species from the Lactobacillus genus. “As a key feature, vaginal lactobacilli produce lactic acid, which creates an acidic [low pH] microenvironment and prevents the overgrowth of potentially harmful bacteria,” she said.
But a host of environmental and lifestyle factors can upset this optimal microbial makeup. Vaginal imbalance or dysbiosis, Lehtoranta said, is a known risk factor for yeast infections and bacterial vaginosis (BV).
Vaginal dysbiosis also correlates with sexually transmitted infections like HIV, human papillomaviruses, herpes, chlamydia, and gonorrhea, she added.
Vulvovaginal infections account for millions of physician visits annually, ranking among the top conditions for which women in the US seek medical care. Treatment typically involves simple lifestyle modifications plus a course of antibiotics or antifungal drugs.
In the case of a single infection, a standard antibiotic regimen will generally alleviate symptoms. But these powerful pharmaceuticals also disrupt the delicate vaginal microbiome, potentially setting the stage for recurrent future infections that are far harder to clear.
“A classic and unfortunate 3-step sequence of events is often the starting point for people with chronic vaginal infections,” Amy Day, ND, founder and medical director of the Women’s Vitality Center in Berkeley, Calif., told Holistic Primary Care.
The pattern begins when a patient develops a urinary tract infection (UTI) which is treated with antibiotics.
Hard-hitting antibiotics “throw off the vaginal flora due to killing the good bacteria along with the bad ones that are causing the UTI,” Day explained. They may knock out the UTI, but in doing so, they create the perfect environment for fungal pathogens to grow unchecked.
As in the gut, certain microbes in the vagina are “critical for maintaining the balance of good bacteria to help fend off bad bacteria and yeast,” Day said. It is normal and even healthy for small amounts of unwanted bacteria and yeast to appear, provided there are enough beneficial flora also present to prevent pathogenic microbes from causing harm.
Lactobacilli, for instance, keep infectious yeasts like Candida albicans––the main cause of genital yeast infections––from reaching dangerous levels. Antibiotics or other forces that disrupt or destroy the Lactobacilli, create conditions for Candida overgrowth.
Rebalancing After Antibiotics
It is crucial to rebalance the vaginal flora after a course of antibiotics. Otherwise, the very medications intended to treat one infection might just end up causing another.
Day said that in her practice, it is “very common” to find that patients with long histories of chronic vaginal infection experienced their first symptoms following antibiotic treatment.
“If the pharmaceuticals always worked and didn’t have side effects, I probably wouldn’t see any of these patients because they would just get an insurance-covered prescription and be done with it.”
“That works for some people,” she acknowledged. “Diflucan can knock out a yeast infection and a patient can be fine. But it’s a hard-hitting drug and it doesn’t always work, and it often requires re-treatment and re-treatment if you’re not rebalancing” the vaginal flora.
What makes the UTI-antibiotic-yeast infection sequence even worse is that in many cases, it’s preventable.
Teaching women how to support their own healthy vaginal ecosystems can minimize the likelihood of recurrent infections.
“This is definitely an unmet need in the medical field,” Day suggested. Patients with vaginal infections are frequently, “handed a prescription without finding out first what is truly going on and what needs to be treated.” Others receive antibiotics or antifungals that do not effectively clear their symptoms, which sends them “to the internet to try and research what else they can do for themselves. It’s very frustrating.”
Fortunately, “most doctors are now being more cautious about prescribing antibiotics without first confirming the [presence of a] UTI, so that is a step in the right direction,” Day noted.
The Maternal-Infant Microbiome
Conventional medicine does recognize some additional aspects of the vaginal microbiome, particularly in the context of pregnancy and childbirth.
Take Group B Strep (GBS), a prevalent bacterial vaginal infection with potentially serious consequences for newborns. Physicians routinely screen expectant mothers for GBS in the late stages of pregnancy and provide treatment as needed to prevent mother-to-infant transmission.
During vaginal delivery, infants are inoculated with microbes from the mother’s vagina while passing through the birth canal. Exposure to healthy––or unhealthy––vaginal flora can influence a baby’s health even long after birth. Studies indicate that babies delivered by Caesarean section have distinctly different microbiomes than those delivered vaginally. C-section infants frequently carry higher levels of opportunistic pathogens at birth, as compared to vaginally delivered babies (Shao, Y et al. Nature. 2019; 574: 117–121).
Given that a mother’s vaginal flora directly influences an infant’s gut microbiome, some holistic medical practitioners recommend that expectant patients supplement with high-quality probiotics during the last trimester. Supplementation with healthy intestinal flora after birth is especially important for babies delivered by C-section.
Bacteria and yeasts thrive in damp, warm environments, so conditions like high humidity or wet clothing can promote pathogen overgrowth. Diets high in refined carbohydrates provide an ideal fuel source for sugar-loving yeasts, increasing the risk of vaginal dysbiosis.
Hormone fluctuations can also trigger infections. Some patients consistently experience monthly flares in chronic BV or candidiasis at specific points in their menstrual cycles.
Right around mid-cycle, “there’s an estrogen spike that happens as part of the ovulation process,” Day pointed out. Recurrence during ovulation is not uncommon in patients who experience frequent yeast infections. For others, infections arise shortly before the bleeding phase when hormone levels start to drop. Still others notice that symptoms return right after their periods, as menstrual blood both adds moisture and feeds vaginal microorganisms.
Low estrogen later in life can be problematic as well. “In the post-menopausal years, some people experience an increase in UTIs and vaginal infections,” Day said. Declining estrogen in the vaginal mucosa correspond with weaker immune responsiveness, likely resulting from decreased circulation. Treatment with local estrogen therapy can help boost immunity and prevent additional infections.
Medical Red Flags
Some women recognize that their symptoms appear at specific times or under specific conditions, but others do not.
You can help by asking patients to carefully track and document when their infections occur. When evaluating a patient’s flare ups, make sure to ask about dietary habits, clothing choices, menstrual cycle, and environmental conditions. Do infections occur predictably at a certain stage of the menstrual cycle, or after certain vacations or certain types of meals?
Taking the time to ask those questions may yield vital insights about a patient’s vaginal microbiome.
In cases where the infection triggers aren’t immediately apparent, dig deeper. Chronic infections of the genital tract–or anywhere else for that matter–are medical red flags for underlying problems.
“Yeast overgrowth in the vagina can occur on its own, but I do think about yeast in the gut in cases where the vaginal yeast infection keeps recurring,” Day noted. “The bowel can act as a reservoir, and even after treating a vaginal yeast infection, any remaining yeast can travel from the anus to the vagina and cause another infection.”
For this reason, Dr. Day says she often pairs local vaginal treatment with systemic oral antimicrobials .
Chronic vaginal infections may also signal a compromised immune system. Always “screen for any signs of recurring infections that may indicate an immune deficiency state.”
When treating vaginal symptoms, try to determine the exact cause of a bacterial or yeast infection and treat accordingly. It will mprove the likelihood of successful eradication, and also reduce risk of recurrence.
Unusual vaginal discharge marked by changes in color, consistency, or smell, as well as redness, swelling, rashes, and itching or irritation of the vagina or vulva, are the typical indicators of vaginal dysbiosis. But “symptoms depend on the infection in question,” Dr. Lehtoranta cautioned.
There are a number of different testing options now available–including home test kits—to characterize the vaginal microbiome and determine what type of infection may be present. One example is the Vaginosis Profile by Doctor’s Data, which patients can complete at home and send to a lab for analysis.
Testing is “a fantastic way to get more information, especially in women who struggle with chronic and recurring infections,” Day says. Results may take several days to return, so testing is somewhat less useful in acute cases requiring immediate treatment. But generally, “it’s so useful to know about [a patient’s] levels of good and bad bacteria and yeast…to help guide treatment decisions.”
A host of natural therapies can effectively treat many symptoms of vaginaly dysbiosis without causing harmful side effects.
Begin by encouraging patients to drink more water.
Supplements like d-mannose, vitamin C, probiotics, or herbs such as uva ursi and berberine are great options for patients with UTIs.
For confirmed yeast infections, Day’s go-to treatment is boric acid or Yeast Arrest, a natural vaginal suppository made by Dr. Tori Hudson’s Vitanica supplement line. The product contains a blend of boric acid, tea tree oil, neem oil, Oregon grape root, Lactobacillus probiotics, and homeopathic botanicals, in a base of cocoa butter. “It is highly effective at relieving uncomfortable symptoms and usually clears the infection completely with twice a day use for 7-14 days,” she reported. Yeast Arrest is also an effective BV treatment.
“If the infection is severe enough that antibiotics truly are needed, then the patient should always be given probiotics along with that prescription,” Day urged. Using “high dose probiotic supplements during the course of antibiotics––taken at a different time of day, two hours away from the antibiotic doses––and then for two to four weeks afterwards, can help to maintain the healthy flora and prevent a vaginal yeast infection.”
She added that vaginal probiotics make good sense “no matter what treatment is used to kill off [an] infection.”
Supplementing with oral probiotics may also help to maintain or increase healthy levels of vaginal lactobacilli. DuPont’s HOWARU® Feminine Health combines Lactobacillus rhamnosus HN001™ and Lactobacillus acidophilus La-14®, two bacterial strains offering “beneficial effects in regards to BV and vulvovaginal candidiasis recovery as an adjunct to antibiotic or antifungal therapy, respectively,” Lehtoranta said.
“Unlike antibiotics and antifungal drugs intended for killing harmful bacteria and yeast, which may be harmful to intrinsic vaginal microbiota as well, probiotic strains in HOWARU® Feminine Health are intended for maintaining the good lactobacilli balance in the vaginal tract,” she said. The probiotics in HOWARU® promote lactic acid and hydrogen peroxide production, which lowers pH levels in the vaginal environment.
Jarrow Formulas’ Fem-Dophilus is another widely used vaginal health probiotic that can be swallowed orally or inserted vaginally once a day at bedtime to help restore beneficial flora and prevent infection recurrence.
The Gut-Vagina Axis
In the same way that diet affects the intestinal microbiome, it also affects microbial diversity in the vagina.
Reducing or eliminating carbohydrates, sugars, and alcohol often alleviates vaginal symptoms and prevents them from recurring. Patients with persistent yeast infections may need to follow a strict zero-sugar anti-candida or low-mold diet. Others with less severe or less frequent infections can tolerate modest amounts of sugar or other carbs.
“There are implications that the Westernized diet and high saturated fat content may cause systemic inflammation, which may have an unfavorable effect on the vaginal microbiota composition through the so-called ‘gut-vagina axis,’” Lehtoranta warned.
Equally important as what’s removed from the diet is what stays in it. In addition to plenty of fresh or lightly cooked vegetables, it is wise for women to incease their intake of fermented vegetables, yogurt, or other Lactobacillus-containing foods.
Patients at risk for vaginal infections can further reduce the likelihood of recurrence by wearing underwear made of cotton or other breathable fabrics, and changing out of tight-fitting swim suits or sweaty workout clothing promptly after use.
It is also a good idea to avoid douching, but rather to wash the vulvovaginal area with water only.
The COVID pandemic has wrought unprecedented economic strife worldwide. Despite the public hardship, one sector profits handsomely from the pandemic: health insurance.
Healthcare plans are poised to make record profits this year. They continue to collect premiums, but their coverage of COVID care is spotty at best, and with so many clinics closed and non-COVID care deferred, their “medical losses” (aka spending on actual care) are at an all-time low.
Wendell Potter, former head of corporate communications for Cigna, understands the machinations of the insurance industry like few others could. After a long career seeing firsthand how strategic PR and lobbying unfairly tilt the scales toward corporate interests against the needs of practitioners and patients, Potter left the board room to educate people about the realities of the medical-industrial complex.
Swedish researchers recently discovered 13 unique lactic acid bacteria in fresh honey and in the honey-producing organs of bees that are strongly active against several virulent human pathogens, including Staphylococcus aureus (MRSA). The findings suggest that honeybees could be valuable allies in the human fight against MRSA.
The investigators, led by Tobias Olofsson, of the Department of Medical Microbiology, Lund University suggest that these unique microbial symbionts found in the bees’ honey stomachs and also in the honey itself could be used as an alternative for antibiotics, with “implications not least in developing countries, where fresh honey is easily available, but also in western countries where antibiotic resistance is seriously increasing.”
Dr. Olofsson’s group has been studying honeybee microbiomes for a decade. They’ve discovered roughly 40 lactic acid strains in the honey stomachs of the bees, and have characterized 13 unique Lactobacilli and Bifidobacteria that proliferate in massive amounts and are transferred into the honey itself (108 LAB per gram of honey).
They pitted these probiotic organisms from three different types of honeybees against several drug resistant pathogens cultured from chronically infected human wounds. These included methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus (VRE). They also tested a number of conventional antibiotic drugs against these same pathogens.
The honeybee microbiota showed marked activity in inhibiting the growth of the pathogens, and in most cases outperformed the antibiotics.
“We can hypothesise that the lactic acid bacteria (LAB) in this case are better than or just as effective as many of the widely used antibiotics in wound treatment today. Combined, the 13 LAB have another advantage over antibiotics: a broad spectrum against a wide variety of pathogens. As we know now, many antibiotics are active only against certain bacteria, for example, metranidazole and anaerobic bacteria,” Dr. Oloffson reported (Olofsson et al. Int Wound J. 2014.)
Of the 13 organisms tested, Lactobacillus mellifer Bin4, inhibited all 14 pathogens tested, and L. kunkeei Fhon2 showed the most potent antibiotic activity. But Dr. Olofsson stressed that it is the combined synergy of the various organisms present in honey that holds the greatest potential for wound-healing and infection control.
The antimicrobial effects of honey or honeybee-derived microbes have not yet been demonstrated in actual human studies, but they have been tested in horses with chronic, infected wounds. Ten horses were treated by topical application of honey enriched with LABs, and the investigators observed rapid resolution of the persistent wounds.
New Chapter, Old Saga
Dr. Olafsson’s work is the latest chapter in a story that is centuries old. Honey has been used around the world as a natural antimicrobial agent for millenia. Its high sugar content but low acidity and water content act as barriers to microbial activity. In numerous studies, researchers have used honey to successfully inhibit the growth of “a wide range of bacteria, fungi, protozoa, and viruses” (Tan et al. BMC Comp Alt Med. 2009; 9:34).
Previous research has suggested that one of the primary contributors to honey’s antimicrobial activity is hydrogen peroxide. When most honey types are diluted, the enzyme glucose oxidase is activated and oxidizes glucose to gluconic acid and hydrogen peroxide (Deb Mandal & Mandal. Asian Pac J Trop Biomed. 2011; 1(2): 154-160).
The Lund University work characterizing the anti-pathogenic activity of lactobacilli within the bees and transferred into the honey adds a new dimension to our understanding of this healthy and delicious food source.
Though promising, it is important to keep in mind that the amount of microbial symbionts and the antibiotic compounds they produce varies very widely in store-bought honey. As with many foods, the fresher and the less-processed the honey, the more likely it is to have potent antimicrobial properties. Highly refined, processed honey will not likely be active.
health insurers, the COVID pandemic has been a goldmine. At least so far.
Across the nation, ordinary people and small businesses struggle with both the disease itself and the fiscal consequences of prolonged economic shutdown. Healthcare plans, on the other hand, are poised to make record profits this year.
to a mid-April
seven of the biggest for-profit players—UnitedHealth Group, Centene, Cigna,
Anthem, Humana, Molina, and Magellan–are expected to turn “positive earning
surprises” in 2020. For all of them, stock performances are surpassing previous
UnitedHealth Group (UNH), the nation’s largest employer of medical professionals, saw a nearly 7% revenue rise in Q1 2020, reaching $64.4 billion. During that three-month period—as COVID spread across the country–UHG’s medical loss ratio decreased by 1% compared with Q1 2019. In laymen’s terms, “medical loss” means money spent on actual medical care.
Bull Run for Some
major insurers, UNH’s stock price remained high throughout the first months of
the pandemic. At the close of Q1, UGH was trading at $277.50 per
share, up 2.6% from the beginning of the year; it continues to generate earnings and dividends.
According to the company’s Q1 report, “Return on equity of 23.6% continued
to reflect the company’s strong overall margin profile. Dividend payments grew
19.1% year-over-year to $1.0 billion and the company repurchased 6.2 million
shares for $1.7 billion in first quarter 2020.”
right. Instead of using its Q1 windfall to reduce premiums for furloughed
workers and businesses tottering on the brink of bankruptcy, UnitedHealth
bought back its own stock, to ensure that its stock prices remain buoyant.
It is also noteworthy
that UnitedHealth’s president, Sir Andrew Witty, also CEO of UNH’s highly
profitable Optum division, took “a leave of absence” this Spring to work with
the World Health Organization on COVID-19 vaccine development. Prior to UNH,
Witty was CEO of the drug giant, GlaxoSmithKline.
Aetna, is also
having a bull run, despite the pandemic—or perhaps because of it. CVS—which
owns Aetna—reported a net income of $2.01 billion in the first quarter.
In his Q1 2020
report, CEO Larry Merlo stated, “Consolidated
revenues increased 8.3% year-over-year with growth coming from all segments.
Our business performance exceeded our expectations due in part to strong
execution and our ability to meet elevated consumer and member needs resulting
from COVID-19. We generated $3.3 billion of cash from operations and returned
approximately $650 million to shareholders through cash dividends in Q1.”
health insurance companies are booming. But most are doing just fine, prompting Moody’s
Investor Services to report in late May that, “Coronavirus-related costs did not “materially
impact” seven major health insurance companies’ first quarter 2020 earnings,
which increased slightly over last year.”
That’s why Moody’s predicts that the majors will remain profitable even if there is a second wave of COVID.
factors play into the insurance industry’s COVID cakewalk:
Despite the economic shutdowns, insurers continue to collect premiums from employers, the federal government (for Medicare Advantage and other privatized federal insurance plans), and insured individuals.
For most plans, the medical loss –that is, the percentage of premium revenue spent on actual care for beneficiaries—is down significantly since the pandemic. That’s because so many clinics have closed, and so much sub-acute, elective, and ‘non-essential’ care has been deferred.
Prolonged quarantines, bans on large gatherings, and travel restrictions mean fewer auto and motorcycle accidents, sports injuries, and episodes of non-COVID infectious diseases. All of this translates into fewer people racking up medical bills that insurers must pay.
The actual costs of COVID care are falling most heavily on federal payors, not private sector insurers. That’s because people with severe COVID are disproportionately elderly (Medicare), poor (Medicaid), or uninsured.
Fed Bears the Brunt
be sure, insurers face storms on the horizon. More than 40 million
Americans have lost their jobs since the pandemic began, and several big employers have declared
bankruptcy. That means significant losses in employer-based insurance revenue. It
remains to be seen how many companies rebound, and how many of those jobs are
restored once “things go back to normal”—if ever they do.
could also be a massive surge in medical spending once clinics reopen and
people who deferred office visits and non-acute care feel safe enough to
even in the face of these threats, the insurers have done much to ensure their
future profitability (they are insurers, after all).
For one, many newly unemployed people will likely end up on the federal tab—either in Medicaid or Medicare—or they will scrimp and save to buy private insurance on the open markets. Even if the big plans lose revenue from employer premiums, they’ll likely save even more on reduced medical spending for beneficiaries they no longer have to cover.
a significant chunk of federal healthcare spending will end up going to the
for-profit plans anyway, via the Medicare Advantage plans.
According to Moody’s,
COVID-related unemployment “will hurt fully insured commercial risk books of
health insurers most, because membership will decline.” But the unemployment
“will benefit the Medicaid and individual market [insurer] businesses, which
will gain members.”
“HEROES” for Whom?
industry’s lobbyist sous-chefs have made sure the House of Representatives baked plenty of
into the $3 trillion HEROES Act currently under Senate review.
In an April 28
letter to Senate and House leaders, a coalition of 32 medical organizations and trade
groups—including the US Chamber of Commerce, and several insurance industry
advocates—called on lawmakers to ensure that the employer-based coverage system
does not collapse.
The coalition states
that roughly 180 million Americans depend on job-based insurance—a frequent
insurance industry talk-point– and urges Congress to “take immediate action to
support employers and workers by protecting and expanding high quality,
affordable health care coverage.”
Subsidies to corporate employers that have lost
revenue due to the pandemic and are forced to cut employee health benefits
Full-cost offsets for COBRA coverage of people
who’ve lost their jobs
Expansion of “qualified expenses” in Health
Savings Accounts, enabling people to use their HSAs to pay their insurance
A special enrollment period allowing people to
buy insurance in the Health Insurance Marketplaces created by the Affordable
Subsidies for insurance purchased through the
Of course, it
will take heroic efforts to get HEROES through the Republican-controlled
Senate. The bill is a Democratic party initiative, and Senate Majority Leader
Mitch McConnell has already voiced his opposition.
fate of HEROES, it is a safe bet that the insurance plans will remain
one thing these companies know how to do is to make money, to assure their
shareholders of a return on investment that Wall Street expects,” says Wendell Potter, a former
insurance industry communications director turned whistle-blower.
Potter spent 15 years as the Vice President of Corporate Communications for Cigna, before a crisis of conscience obliged him to leave an industry he now sees as rapacious and only out for its own good, usually at the expense of patients and practitioners.
companies are really going to have a stellar year this year, because of the
pandemic. And one of the reasons for that is because of all the elective
procedures that have been cancelled or postponed. They’re not going to happen
this calendar year. Some of those will never be rescheduled because
unfortunately some of those individuals have died by now, or will die,” Potter
said in a recent interview with Holistic Primary Care.
experience in the corporate board rooms over decades has shown him that
insurers are quite capable of weathering social and economic storms.
“Since the ACA was passed, insurance companies have made alot of money. They’ve made record profits even with the restrictions that the ACA brought to the industry. The insurers can no longer refuse to sell coverage to people with preexisting conditions or charge people more because of their health status. But they can still charge older folks more than the younger people. And they’ve really ramped up prior authorization requirements. They’ve shifted more and more people into high deductible plans. They’re increasingly refusing to pay for coverage if you go out of network willingly or unwittingly,” says Potter, author of the 2010 book, Deadly Spin, which chronicles how the insurance industry manipulates public policy to its own advantage.
there are things they put into place that are barriers to care, that protect
their profits. Even if revenues drop next year, they will still have these
things in place: people will still be in high deductible plans, probably more
of them. And they can manage “medical expenses” in a certain way that, I would
imagine their profit margins are not going to be adversely affected. Even with
the drop-off in health plan enrollment and revenue, they still know how to convert
their revenues to profit.”
COVID & Collusion
several decades in the health insurance business, Potter says he’s rarely
surprised by the degree of collusion between the big plans and the government.
even he was taken aback when the Trump administration announced in
that it was contracting with UnitedHealth Group to oversee and disburse $26 billion
in federal relief funds to COVID-stricken hospitals.
than running the money through its usual Medicare and Medicaid payment channels,
the government chose UnitedHealth—the country’s largest private, for-profit
insurer–to administer and distribute the massive sum to hospitals and clinics
that are running aground financially, owing to the impact of COVID.
claims it is not profiting on the deal, and that the $1 million administrative
fee that the government is paying will be donated to further hospital relief.
Friends in High Places
his announcement of this arrangement, Health and Human Services Secretary Alex
Azar claimed that UNH was better positioned “to expedite” the distribution of
the money to hospitals where it is needed.
says he smells a rat.
government, through CMS, makes payments to healthcare providers every single
day. They’ve been doing it for more than 50 years. Why would you think that a
private company could do it more expeditiously when they don’t even do business
with all the hospitals in the US?
(UNH) are big. But they’re not as big as Medicare. They don’t have as many
doctors and hospitals in their networks as does the Medicare program. So why in
the world would the federal government turn to a private company that actually
has fewer doctors and hospitals in network than Medicare? There’s no logical
reason for that, except that it was a favor. It’s an example of what happens
when you have friends in high places.”
insurance industry is one of the largest sources of political campaign funding.
United, being the biggest player on the field, doles out a lot of campaign cash
on both sides of the aisle.
to the Center
for Responsive Politics’ Opensecrets.org website, UnitedHealth—through its political
action committees and through donations by individual executives—is ranked
number 126 in a list of 5,500 biggest Washington lobbyists, and 111th
in a list over 19,000 sources of campaign contributions.
Potter points out that President Trump himself, as well as Vice President Mike Pence, CMS Administrator Seema Verma, who was a close advisor to Pence, and many top officials in the administration are, “very favorable to private industry, to private insurance companies.”
Push for Privatization
strongly encourage people to enroll in Medicare Advantage plans. They want to
convert the Medicare program to a program that is entirely run by the (private)
insurance companies. That has long been an objective of a number of Republican
politicians. Over the years they just developed relationships with the
executives of these big companies, as they have sought to turn more and more of
these public programs over to private insurers.”
Steven Parente, of the White House Council of Economic Advisers, is among the people in charge of managing the hospital COVID relief program. Prior to this position, he served as a business consultant to a number of major corporations, including—guess who? UnitedHealth Group.
As reported on the Politico website earlier this year, just a few months after Trump installed Parente in his current HHS post, UnitedHealth made a $1.2 million multi-year donation to Parente’s research center at the University of Minnesota. A curious coincidence, is it not?
UNH’s involvement in distributing the money, there are other questionable
issues regarding the government’s hospital bail-out plan.
of the $26 billion is based on how much hospitals were reimbursed in 2019 under
the traditional Medicare Fee for Service programs—that is, Medicare Part A
and Part B contracts.
Critics, like Erin O’Malley, senior policy director for America’s Essential Hospitals, is concerned that the plan will direct more money into the hospitals with big private-sector Medicare Advantage contracts, and less into those with high proportions of “traditional” Medicare and uninsured patients.
that by only looking at Medicare fee for service revenues, it could tilt the
playing field against some of our members that have a disproportionate share of
uninsured as well as Medicaid patients,” said O’Malley,
in an interview posted on CNBC in April.
Wendell Potter says that in times of crisis—like the current pandemic—insurers go into overdrive trying to make themselves look like good guys, concerned with public well-being.
Case in point, Potter’s former employer– Cigna—and its announcement that it will waive “all customer cost-sharing and co-payments for COVID-19 treatment.”
customers with COVID-19 should focus on fighting this virus and preventing its
spread,” said David M. Cordani, the company’s
president and CEO, whose
personal compensation package totaled more than $19 million last year. “While
our customers focus on regaining their health, we have their backs. Our teams
of experts are working around the clock to support front line health care
workers, increase flexibility for hospitals, and deliver greater peace of mind
to those we serve.”
Several other major insurers have also waved the banner of altruism by similarly dropping co-pays and cost-shares on COVID-related care. The website for America’s Health Insurance Plans (AHIP), the industry’s biggest trade organization, has a list of all the big insurers and their official responses to COVID.
Dropping co-payments? Sounds generous. Potter says it’s little more
than corporate PR.
That’s because if you look at the fine print, you’ll see that the
insurers are allowing their corporate customers with self-insured plans to opt
out of this philanthropic display.
other words, these rules they say they’re putting in place, apply only to the
people who are in the so-called “fully ensured” health insurance plans. All
their employer customers (ie the self-insured plans) have the opportunity to
opt out. Who knows how many are opting out?! There is no way of knowing that. AHIP
will not tell you that.”
Americans get their insurance via their jobs. Most of the large employers—the big
corporations—are self-insured, which means they can opt-out of the insurance
industry’s magnanimous offer to eat the copayments.
As a result, ordinary Americans might read the statements on the AHIP site and think that the waived cost-shares apply to them, only to find out that their particular companies have opted out.
says there’s similar variability within the Medicare Advantage plans. “Cigna
might be doing it (dropping COVID co-pays). But Aetna might not be doing it.
Humana might be doing it, but Anthem might not. So, it really depends on what
specific plan you are enrolled in, even if they’re all “Medicare Advantage”
it’s all over the place. There’s no standardization. You cannot believe what
these health plans are saying, nor is there any reason to have certainty that
they’re going to be doing the right thing for all the people enrolled in their
To the extent
that insurers really are waiving COVID costs for ordinary Americans, this is a positive
step. But rest assured that on the insurance industry’s priority list, the
public good comes well below profitability, CEO compensation, and shareholder
Pulmonary inflammation has been in
the public spotlight since the start of the COVID-19 pandemic. Formerly obscure
immunology terms like “cytokine storm” are now common, as we learn more about
how the immune system responds to SARS-CoV-2 and other viral pathogens.
The intense immune reactions seen in severe COVID cases and other forms of Acute Respiratory Distress Syndrome (ARDS) are mediated in part by Inflammasomes–multi-protein complexes found in the cytosol of immune cells, pulmonary endothelial cells, and other epithelial cells.
What are Inflammasomes?
Inflammasomes are typically formed in response to specific stimuli including pathogenic microbes, environmental insults, or inflammatory signaling molecules. As part of the innate immune system and the body’s first line of defense, inflammasome activation leads to the release of pro-inflammatory cytokines IL-1B and IL-18. In the lungs, IL-1B is one of the most potent inflammatory cytokines, and it is a major factor in ARDS.
In ordinary circumstances,
inflammasome activation is a discrete and limited process resulting in a
clearance of the triggering noxious stimuli such as infectious pathogens,
environmental or metabolic toxins. However, the excessive activation of
inflammasomes can result in increased and prolonged cytokine release, chronic
inflammation and pulmonary and endothelial damage.
Inflammasome activation also triggers pyroptosis, a rapid form of programmed cell death. Pyroptosis is a highly inflammatory state usually triggered in response to intracellular pathogens.
The good news
is that many phytochemicals naturally occurring in certain herbs and plant
foods can down-regulate inflammasome activation.
Combined, these processes create a
highly pro-inflammatory environment, with high levels of oxidative stress and
proteolytic enzymes, predisposing to thrombus and fibrin formation. At the
cellular level, this is war.
When this response is mobilized, an
infection can be quickly neutralized. The inflammatory cascade should then turn
off, enabling the body to restore equilibrium.
In situations like we’ve seen with severe COVID
and other acute respiratory infections, this cascade does not turn off,
resulting in a prolonged cytokine “storm” that can cause serious, sometimes
fatal tissue damage.
Inflammasome dysregulation leads to
excessive cell death, tissue fibrosis, and ultimately, organ dysfunction.
Chronic diseases such as COPD, auto-immune inflammatory syndromes, Crohn’s
disease, Type 2 Diabetes, Alzheimer’s disease, atherosclerosis and cancers are all
associated with dysregulation of the inflammasomes, upregulation of NFkB, and other
Respiratory distress in the context
of inflammasome dysregulation is not always responsive to exogenous oxygen
therapy. That’s because the alveoli themselves become damaged and dysfunctional.
Further, there is also endotheliitis in the capillary beds surrounding the
alveoli, leading to hypercoagulation and thrombus formation. The net result is
that the alveoli are unable to deliver oxygen to the blood.
This creates a deadly feed-forward
cycle, because the resulting hypoxia is itself a signal for activation of the
NLRP3 inflammasome. This is a perfect storm for respiratory failure,
severe morbidity, and all too often, death.
Curcumin’s bright yellow color announces its value as a scavenger of ROS and modulator of oxidative stress. The absorption of curcuminoids from turmeric-rich foods and supplements is enhanced with the addition of black pepper. The most absorbable curcumin supplements are lipid based.
Resveratrol is a stilbene polyphenol present in
abundance in the skins of red and purple grapes, and in the plant Polygonum
cuspidatum. It is the trans-resveratrol isomer that is most
biologically active. Resveratrol has been widely studied and like
most polyphenols, it scavenges ROS and reduces oxidative stress.
Epigallocatechin-3-gallate (EGCG) is the major bioactive polyphenol found in Green Tea (Folium Camellia sinensis). It inhibits NLRP3 inflammasome activation, and also reduces the expression of NFkB, matrix metalloproteinases, IL-1B, IL-6 and TNF-α. EGCG’s antioxidant properties and ability to scavenge ROS are also well-documented. A single cup (8 oz or 250 ml) of brewed green tea contains approximately 50-100 mg of EGCG. EGCG catechin is also available in capsules.
Sulforaphane is an isothiocyanate
produced from a precursor called glucoraphanin, in the presence of the
myrosinase enzyme. It is best to lightly cook (steam or sautee) or massage
cruciferous vegetables to liberate their phytochemicals. There are a
number of supplement products now available that include Sulforaphane,
Glucoraphanin, DIM (di-indole-methane) and I3C (indole-3-carbinol) in
capsule or powder form. The highest quality products are derived from
broccoli sprouts and broccoli seeds.
Quercetin is a flavonoid commonly found in a
wide variety of fruits, vegetables and herbs. It has been shown to block
NLRP3 inflammasome activation inhibit damage from ROS and modulate multiple
inflammatory pathways and downregulate NFkB expression and IL1B
secretion. The red skin of apples and purple onions are rich dietary
sources of quercetin. Quercetin as a supplement is not highly absorbable
and is best taken with healthy fats and oils or encapsulated as a lipid
Ginsenosides are major active saponin components
of Radix Panax Ginseng. Ginsenosides attenuate NLRP3 Inflammasome
activation and NFkB expression. They also reduce IL-1B, IL-18 and TNF-α levels.
Modified Citrus Pectin (MCP) is a low molecular weight dietary fiber derived from the inner peel of citrus fruit. It is best known as a Galectin-3 antagonist. Galectin-3 is widely found in immune and epithelial cells and it promotes NLRP3 inflammasome activation and pyroptosis.
While unprocessed food pectin is a large lectin molecule that is not digested or absorbed through the intestinal epithelium, MCP is an enzyme-processed product that yields a small esterified molecule that can be absorbed through the small intestine and enter the bloodstream. By binding and inactivating Galectin-3, MCP down-regulates the activation of the NLRP3 inflammasome, reducing pyroptosis and cell death. It also reduces secretion of inflammatory cytokines IL-1B and IL-6, and matrix metalloproteinases. Further, MCP inhibits fibrin formation minimizing the hypercoagulation and thrombus formation that follows from dysregulated inflammasome activity.
The highest quality MCP nutritional
products have the smallest particle size to insure intestinal absorption.
Potassium: Due to the potassium efflux that occurs at the initiation of inflammasome activation, oral potassium repletion makes sense, according to Joe Pizzorno, ND. For patients who follow a plant-based diet, there should be no shortage of potassium ingestion. However, an elderly, very ill, or hospitalized patient who is not eating normally could be potassium-depleted.
For such at-risk patients, it is wise to monitor potassium as well as the full range of electrolytes.
Food as Medicine
Cancer is also a chronic inflammatory illness. The selected natural compounds reviewed here also form the core Materia Medica found to shift the tumor microenvironment and the cancer terrain away from inflammation, hypercoagulation, immune suppression, carcinogenesis, proliferation, angiogenesis, and metastasis.
Many of the natural compounds that influence inflammasome activation are found in plant food. These phytochemicals are pleomorphic multi-taskers and can bind to many different receptors and influence a lot of different pathways and genes at once. Therefore, encourage patients who are concerned about their immune system health to eat a plant-rich, colorful, rainbow diet that includes a variety of herbs and spices. A diet rich in phytochemicals has a powerful impact on long term health and enhances inflammation control. Remind patients that, “Our food is talking to our genes. This is why it matters what we eat.”
Nutritional status is a major determinant of COVID-19 risk. Yet public health policy worldwide has given little attention to the role that nutrition, supplementation, and herbal medicine could play in improving individual and community resilience.
The intense focus on stopping viral spread is sensible and necessary. But without a parallel effort toward strengthening immune system function, enhancing resilience, and mitigating the burden of chronic metabolic disease, people will remain vulnerable to SARS-CoV-2, and any future novel pathogen.
Pharmaceuticals and vaccines—the great hopes of political leaders, and of many citizens—will play important roles in quelling this pandemic. But they are only partial solutions—and they are still a long way off.
“A wealth of mechanistic and clinical data show that vitamins, including vitamins A,
B6, B12, C, D, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper; and the omega-3 fatty acids EPA and DHA acid play important and complementary roles in supporting both the innate and adaptive immune system,” writes UK researcher Philip C. Calder in a recent paper in the journal, Nutrients.
“Deficiencies or suboptimal status in micronutrients negatively affect immune function and can decrease resistance to infections….there can be decreases in the numbers of lymphocytes, impairment of phagocytosis and microbial killing by innate immune cells, altered production of cytokines, reduced antibody responses, and even impairments in wound healing.”
Yet none of this is even part of the international public health dialog. The World Health Organization’s massive multi-nation SOLIDARITY Trial of the “most promising therapies” for COVID includes nothing about nutritional supplementation. The study is looking at the newly-approved antiviral Remdesivir, Chloroquine, Hydroxychloroquine, and a combination of two anti-HIV drugs—lopinavir and ritonavir.
In the absence of definitive drug therapies, practitioners are experimenting with a wide range of supplements, herbal remedies and older, rarely used drugs to try and protect themselves and help their patients deal with COVID.
Here, we review the natural therapies gaining the attention of prominent holistic and functional medicine practitioners and organizations. This list is by no means exhaustive, and the evidence is drawn mostly from studies of acute respiratory distress syndrome (ARDS), and other viral and bacterial respiratory infections. Given that COVID-19 did not even exist 6 months ago, there are few nutritional intervention studies in COVID patients, though several are in the works.
Mitigate collateral damage from other therapeutic agents.
Promote resolution of collateral damage and restoration of function.
Reduce severity and duration of acute symptoms.
Support recovery and reduce long-term morbidity and sequelae.
The functional medicine approach is focused, in part, on reducing the virus’ characteristic activation of a branch of the immune system called the NLRP3 inflammasome.
VITAMIN C Vitamin C supports immune function in multiple ways: it strengthens epithelial barrier function, fosters growth and function of innate and adaptive immune cells, facilitates white blood cell migration to sites of infection, and increases phagocytosis and production of antibodies.
Deficiency is clearly associated with increased susceptibility to severe respiratory
The recent Calder paper recommends daily supplemental doses of at least 200 mg/day for healthy people, and between 1-2 g/day for those who are sick. These levels are considerably higher than the US RDAs, which are 75 mg/day for women and 90 mg/day for men, but still within the tolerable upper limit, which is 2 grams.
IFM’s guidance document suggests going up to 3 grams in high-risk individuals. The potential benefits are high, and the risk is very low.
The only COVID-specific studies have been with intravenous ascorbic acid. Data from COVID wards in Shanghai indicate that IV injections of 100-200 mg/kg per day improved oxygenation, reduced mortality, and shortened hospitalizations in COVID patients under ICU care. It also mitigates the characteristic cytokine storms seen in severe COVID cases. Expert guidelines from Shanghai advise giving the IV ascorbate in conjunction with heparin and broad-spectrum protease inhibitors.
study set the critical care world on fire when it published last January. The study involved 167 ARDS inpatients randomized to IV vitamin C (50mg/kg every 6 hours for 96 hours) or placebo infusion.
The vitamin C infusion did not result in any changes in organ failure scores, c-reactive protein levels, or any of the other primary endpoints. But it did produce a marked reduction in 28-day mortality (30% vs 44%), a greater number of ICU-free days (11 vs 8), and an increased number of hospital-free days (23 vs 16). These findings were statistically significant.
Yet, US hospitals have been slow to embrace IV ascorbate. The Front Line COVID-19 Critical Care Working Group hopes to change that. This physicians’ consortium from critical care centers all over the US advocates a protocol it calls MATH (Methylprednisolone, Ascorbic Acid, Heparin, and Thiamine).
The group recommends IV ascorbate, 3 grams per 100 ml every 6 hours, for 7 days, to counteract the inflammatory damage, and the severe hypercoagulable states typical of COVID. They contend that if implemented early, MATH could save thousands of lives, reduce the need for intensive care and mechanical ventilation.
Vitamin D and its metabolites are, in essence, immunoregulatory hormones. They have direct antimicrobial effects and indirect stimulatory effects on various aspects of the immune system. Calder points out that many types of immune cells have vitamin D receptors. At sufficient levels, the vitamin promotes differentiation of monocytes to macrophages, and increases their ability to destroy pathogens. It increases antigen presentation, but tempers cytokine release, possibly preventing cytokine storms.
Leo Galland, MD, a functional medicine practitioner in New York City, points out that vitamin D is essential for normal function of the Angiotensin Converting Enzyme-2 (ACE-2), and that deficiency impairs ACE-2. This has implications for COVID, in that the virus binds to ACE-2 on the surface of alveolar endothelial cells. An overwhelming of normal ACE-2 activity is one of the hallmarks of the COVID syndrome. Vitamin D supplementation might, potentially, attenuate this.
Vitamin D metabolites prevent excessive expression of inflammatory cytokines while also stimulating expression of anti-microbial peptides from neutrophils, monocytes, natural killer cells, and lung epithelial cells (Cannell JJ, et al. Epidemiology & Infection. 2006).
On a population basis, there is a crude inverse correlation between vitamin D levels and susceptibility to COVID. In a very recent cross-sectional analysis, Petre Christian Ilie and colleagues showed that COVID prevalence and mortality were both highest in the countries with the lowest mean vitamin D. Portugal, Spain, Italy, and Switzerland were among the countries with the lowest mean vitamin D levels in COVID patients, and this was especially pronounced among the elderly.
Individual susceptibility may be partially explained by the fact that vitamin D deficiency impairs macrophage production of surface antigens, phosphatase, and H2O2, all of which play key roles in macrophage-mediated defense against pathogens (Abu-Amer Y, Bar-Shavit Z. Cellular Immunology. 1993)
Supplementation can reduce risk of acute respiratory infections (ARI), according to a massive metanalysis by Adrian Martineau of the London School of Medicine & Dentistry, who collaborated with researchers all over the globe to assess the preventive impact of vitamin D.
The Martineau paper, published in the British Medical Journal in 2017, covered 25 randomized vitamin D trials involving nearly 11,000 total patients. Irrespective of dose level or schedule, they found that vitamin D supplementation at any dose level translated into a 12% aggregate reduction in ARI incidence. There was a 19% reduction among people getting daily or weekly doses without bolus dosing.
Subjects with the lowest baseline 25(OH)-D levels benefit the most from supplementation. In people with baseline levels under 25 nmol/L, there was a 70% reduction in ARIs, compared with a 25% reduction among those with baselines above 25 nmol/L.
In reviewing the Martineau data, pulmonologist Roger Seheult notes that the number needed to treat (NNT) with vitamin D to prevent ARIs in a general population is about 33, “roughly the same as for aspirin to prevent myocardial infarction.” Among people who are deficient, the NNT is 4, making supplementation a no-brainer.
Seheult, a critical care specialist in Banning, CA, also pointed to The Irish Longitudinal Study on the Aging (TILDA), a prospective study of more than 8,000 Irish adults over age 50. The data suggest that at doses of 400 IU per day for low-risk individuals, and 800-1,000 IU per day for deficient and high-risk patients, vitamin D3 could reduce the prevalence of (non-COVID) chest infections by 50%.
Researchers at the University of Grenada recently launched a 10-week study to assess the impact of single 25,000 IU bolus dose of vitamin D in a cohort of 200 individuals with confirmed SARS-CoV-2 infections.
Calder and colleagues note that doses aimed at reducing respiratory infections are generally higher than the US RDA’s which range from 400–800 IU (depending on age). They recommend a daily intake of 2000 IU vitamin D3 per day to optimize immune function. IFM’s guidelines suggest going as high as 5,000 IU/day.
It is worth noting that the TILDA data show a strong inter-relationship between vitamin D deficiency, age, and obesity—all three are known risk factors for COVID morbidity and mortality, and they may be inter-related. Obese people were more likely than non-obese to be deficient, and this difference was more pronounced in people over the age of 70.
The IFM’s guidelines recommend supplementation with vitamin A, owing to its regulatory role in cellular and humoral immune responses. It affects T-helper cell function, production of secretory IgA, and regulates cytokine production.
In a review paper on potential interventions for COVID, researchers at the Shengjing Hospital in Shenyang Liaoning, China, point out that viral infections like measles tend to be worse in vitamin A-deficient children. Retinoids appear to, “inhibit measles replication is upregulating elements of the innate immune response in uninfected bystander cells, making them refractory to productive infection.” (Zhang L, Liu Y. J Med Virol. 2020)
Vitamin A supplementation can reduce morbidity and mortality in a range of human infectious diseases including measles-related pneumonia and HIV/AIDS.
IFM’s COVID recommendations suggest supplementation with 10,000 – 25,000 IU per day, though there are no clinical studies to support that.
Dr. Galland is more cautious. In his Coronavirus Handbook, he reminds colleagues that vitamin A (retinoids) can cause liver toxicity at high doses. He recommends supplements only if a patient shows low blood levels.
B VITAMINS & NAD+
In their recent paper, Zhang and Liu point out that people with deficiencies in B vitamins have weaker overall immune system responses to a range of pathogens.
In vitro experiments with human plasma show that vitamin B2 (riboflavin) can reduce the titers of MERS-CoV—the coronavirus pathogen that killed roughly 35% of all people infected with it back in 2012 (Kiel SD et al. Transfusion. 2016)
In mouse experiments and in vitro studies, vitamin B3 (nicotinamide) enhances the destruction of Staphylococcus aureus via a myeloid-specific transcription factor (Kyme P, et al. J Clin Investigation. 2012).
There is not a lot of specific evidence to make formal recommendations for B vitamins to prevent or treat COVID. But given their central role in hundreds of metabolic reactions, it makes sense to consider them, especially for elderly and at-risk individuals.
Several recent studies suggest that intracellular levels of nicotinamide adenine dinucleotide (NAD+), a vital metabolic co-factor, are depleted by infectious stressors, particularly by viral infections, and that supplementation to restore NAD+ may be beneficial. This phenomenon has been seen with a number of human viruses.
ARDS is characterized by a massive oxidative/nitrosative stress following viral entry into endothelial cells. This oxidative burst ultimately leads to apoptosis and necrosis due to NAD+ and ATP depletion.
In a preprint issued in March, geneticist Shirin Kouhpayeh and colleagues contend that NAD+ depletion “addresses all questions” in the COVID-19 infection process. They suggest that many of the pulmonary features of COVID, as well as the accompanying fatigue mood disorders, are due to depletion of NAD+, ATP, and serotonin—all of which depend on levels of vitamin B3, or its precursors like L-tryptophan.
Supplementation strategies aimed at boosting NAD+ might ameliorate the symptom burden. One possible approach is supplementation with nicotinamide riboside (NR)—an NAD precursor that can increase cellular NAD+ levels without causing flushing or inhibiting sirtuins.
Vitamin E compounds play a role in maintaining strong cellular immunity, particularly T-cell function, and especially in elderly people. T-cell decline is one of the most common features of immunosenescence.
“Both animal and human studies suggest that intake above currently recommended levels may help restore T-cell function which becomes impaired with aging,” reported Tufts University researchers Simin Meydani and Dayong Wu. “This effect of vitamin E can be accomplished by directly impacting T cells as well as indirectly, by inhibiting production of prostaglandin E2, a T cell-suppressing lipid mediator known to increase with aging.” (Wu D, Meydani SN. Endocr. Metab. Immune Disord. Drug Targets 2014).
Though there are not yet any COVID studies of vitamin E, data from earlier studies of other respiratory infections suggest that it might be beneficial. A randomized controlled trial of 617 residents of 33 Boston area nursing homes, daily supplementation with 200 IU vitamin E per day produced small but significant reductions in incidence of upper respiratory tract infections compared with placebo treatment (Meydani SN, et al. JAMA. 2004).
In 2009, De la Fuente and colleagues showed that at that same dose of 200 IU per day, vitamin E improved natural killer cell activity, neutrophil chemotaxis and phagocytosis, and mitogen-induced lymphocyte proliferation in elderly men and women (De la Fuente M, et al. Free Radical Res. 2009).
ESSENTIAL FATTY ACIDS
Omega-3 fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may have a role in quelling the inflammatory response following infection with pathogens like SARS-CoV-2.
At the site of inflammation, EPA and DHA are enzymatically converted to compounds known collectively as specialized pro-resolving mediators (SPMs). These are a family of naturally occurring lipid mediators that play a crucial role in switching off the inflammatory response.
They do not block the initial inflammation phase, which is a desirable and usually beneficial response to infection or sudden injury. Rather, the SPMs down-regulate the process to resolve the inflammation once it has served its purpose. They function as “resolution agonists” targeting the immune cells that mediate the inflammatory response. By binding to specific cellular receptors, particularly the types known “G-protein coupled receptors,” SPMs modify cell behavior to promote resolution.
Calder and colleagues note that omega-3 deficiencies are associated with poor resolution of inflammation. “This could be very important in the context of severe COVID-19 which manifests as uncontrolled inflammation, the so-called cytokine storm linked with acute respiratory distress syndrome (ARDS).”
SPMs formed from EPA and DHA appear to be protective, at least in animal models of ARDS.
A recent Cochrane review of 10 clinical trials involving more than 1,000 hospitalized ARDS subjects did show significant reductions in mortality, ventilator days, and ICU lengths of stay in patients given tube-feeding formulas containing supplemental EFAs versus those given standard formulas.
The trial designs, trial quality, and EFA levels were so variable across the 10 studies that the Cochrane authors dismissed the findings, stating that it is unclear whether use of omega-3s confers any benefits in this context (Dushianthan A, et al. Cochrane Systematic Review. 2019).
None the less, Dr. Calder, who was one of the Cochrane authors, recommends intake of 250 mg/day of EPA + DHA for mitigating COVID risk.
The value of zinc supplementation in preventing or mitigating viral infections is a contentious subject. Zinc is important for maintenance and development of cells in both the innate and adaptive immune systems. Deficiency impairs formation, activation, and maturation of lymphocytes, disturbs cytokine signaling, and weakens innate host defense, according to researchers at Aachen University Hospital.
The IFM COVID Task Force contends that zinc favorably modulates innate and adaptive immune system responses, and attenuates viral attachment, and replication. The guidelines advise supplementation with oral zinc acetate, citrate, picolinate, or glycinate, at levels of 30–60 mg daily, in divided doses, or as zinc gluconate lozenges.
In January, however, Finnish researchers questioned the efficacy of zinc acetate lozenges. They studied 253 City of Helsinki employees who self-identified as susceptible to severe URIs. Of the total cohort, 88 (35%) developed URIs during the study period, and they were more or less evenly divided between those randomized to placebo, and those using zinc lozenges six times daily for five days, for a total zinc acetate dose of 78 mg/day.
In his Coronavirus Handbook, Dr. Galland is skeptical about routine zinc supplementation.
“Zinc has been advocated at doses of 30 to 75 milligrams per day for its alleged direct anti-vital effects and for its inhibition of certain enzymes involved in viral transport and replication. This advice ignores the physiology of zinc. Levels of zinc in plasma, even when they are low, are about 10 times greater than those needed for inhibition of viral enzymes. The concentration of zinc inside cells is over 200 times higher than needed.”
He added that, “there is no way that zinc supplementation will impact the level of free intracellular zinc. But high dose zinc supplementation will produce deficiency of copper, and copper is a natural inhibitor of Furin.” The latter is an enzyme produced by all human cells, that SARS-CoV-2 hijacks in order to bind to the ACE-2 receptors on endothelial cells. Galland added that zinc supplementation raises the risk of bowel overgrowth with Clostridum difficile.
He believes supplementation only makes sense if testing shows serum levels to be low.
NAC is a major promotor of glutathione production, and there’s some evidence that it can mitigate the severity of viral infections. IFM’s Task Force recommends 600-900 mg of oral NAC twice daily.
Italian researchers studied the impact of 600 mg NAC, twice daily for six months versus placebo in a cohort of 262 individuals, most of whom were over 65 years of age. They report significant reductions in frequency and severity of influenza episodes, as well as fewer bedridden days in the NAC group. Local and systemic symptoms were sharply reduced, and though the frequency of seroconversion was similar in the two groups, only 25% of the virus-infected NAC patients became symptomatic, versus 79% in the placebo group (DeFlora S et al. Eur Respir J. 1997).
These are simple, reasonable questions that millions of people—practitioners and patients alike—are asking every day, all over the world.
It would be nice if there were simple answers. There aren’t.
Tests to identify SARS Cov-2, and immune responses to it, are vital both for clinical decision-making and public health policy. But even with wide use of the most sophisticated tests, there would still be much variability and many unanswered questions. Testing is not foolproof nor failsafe. And it is definitely not simple.
“It is going to be frustrating at times, when you don’t have a complete answer, when there’s uncertainty around a test result. We don’t have 100% certainty, and we need to embrace that,” added Dr. Messier, an immunologist and family physician at Altum Health in San Jose, CA. “Even though we’ve learned a lot about the virus, about testing, and about the disease in a very short time, we have a lot left to learn.”
When assessing a patient who has likely been exposed, there are four key questions: Are there symptoms? If so, when did they begin? Is there detectable evidence of the virus? Is there an antibody response?
Identifying Viral Exposure
Currently, there are two main ways to determine if someone has the virus: reverse transcription polymerase chain reaction (RT-PCR) to detect viral RNA in sputum, saliva, or nasopharyngeal secretions; or viral culture of these secretions. The two methods give very different information.
RNA tests confirm that someone has been exposed, but they cannot determine if there is active viral shedding—that is, whether the person is infective. That requires a viral culture, which is seldom done outside research settings.
“Just because we see positive viral RNA on a swab does not mean that they are shedding actual infectious viral particles. If you take the swab and you can grow the virus in culture you know that it is infectious. But the viral RNA is what most people test, because setting up biocontainment labs where you can do viral cultures is very difficult. Viral RNA is much easier to study, but it is not definitive,” Messier explained.
Understand the Timeline
“The value of the test is in the context of the test,” she stressed.
The key is to understand the timeline of the infection and the body’s responses.
She and her IFM colleagues have read hundreds of papers on the immunology of SARS CoV-2, synthesizing the findings into a comprehensive graph that plots the likelihood of a positive test result against the passage of time following symptom onset.
The main point is that RNA tests and serological tests give variable results depending on when you do them.
“The span of time between exposure and development of symptoms can be very different in different people. It is anywhere from 2 days to 3 weeks. Some people will continue to be asymptomatic indefinitely. However long it is, there’s a time period during which people will likely be shedding the virus even though they don’t have symptoms, and we wouldn’t even think to test them because they’re asymptomatic,” Messier said.
Immunologically SARS CoV-2 follows a fairly predictable course, though the clinical manifestations vary widely from patient to patient.
Viral titers usually hit their peak 4-6 days after symptom onset, and then drop fairly quickly. “There’s a window in which you can test positive and capture that virus. But it is easy to miss that window,” said Dr. Messier. This is a main reason why the RNA PCR tests have a false-negative rate upward of 30%.
“By 3rd week post-symptoms, it is much less likely that someone will show viral titers. You’ll see a lot more negative RNA tests, even though people have the virus.” But it is also true that viral RNA can be present in people who are no longer symptomatic.
In other words, a positive RNA test does not mean someone is sick, or will get sick. Nor does it mean that he or she is infectious. All it indicates is exposure.
For those who do get sick, the symptomatic period is also variable. In some, it is just a few days, in others it can be up to 3-4 weeks.
One of the biggest clinical challenges is that many are not sure when they first had COVID symptoms. When they’re really sick—the point at which they become “eligible” for testing–they may not be in any condition to answer such questions clearly. Without knowing anything about symptom onset, it is difficult to put test results in context.
Viral shedding—the hallmark of infectivity– begins anywhere from 3 to 21 days following exposure. Viral particles can be detected in the nasopharynx, oropharynx, saliva, and sputum, and shedding may—or may not—go on for up to 21 days after symptom resolution. In general, it seems that shedding declines roughly 14 days after symptom onset. But again, many patients don’t know when the illness started.
Viral RNA may be detectable long after viral shedding has stopped. But beyond indicating that someone has been exposed, the clinical and public health significance of a positive RNA test after symptoms abate is largely unknown.
Assessing Immune Response
Antibody testing is the other main factor in the assessment equation. Like viral detection, this is also highly variable and time-dependent.
“Based on initial data, it looks like it (SARS-CoV2) follows the general course (for viral infections), which is that IgM, which is a more non-specific antibody class, arises first and then over time, the more specific antibodies of the IgM class will class-switch over to IgG, which is a more specific antibody. IgG levels rise later,” Messier explained.
The total antibody level—IgG, IgM, and IgA together—tends to rise first, during the first and second weeks after initial symptoms. This largely reflects the IgM response. It typically peaks between the second and third post-symptom week. Median antibody production is at about Day 15 post-symptom onset.
As the total antibody and IgM curves reach their summit, IgG production ramps up. By the 4th week, IgM drops off, but IgG remains at peak level. Presence of IgG pretty much confirms exposure. This is the general pattern, based on the best available data from observation of hospitalized patients.
The timing of these phases has significance for clinical testing, said Dr. Messier.
“You have to wait at least two weeks, sometimes up to three weeks to really be able to trust that someone has an IgG response. If you test too early, you may miss it because the patient has not mounted that IgG antibody response yet.”
What about Secretory IgA and the mucosal immune system? What does that tell about the state of the immune system?
“We know there’s IgA made against SARS-CoV-2, but I don’t know that there are any studies showing that if you have huge amounts of secretory IgA it means your immune system is able to fend off this virus. Secretory IgA fights off a lot of things. If you have other infections—oral infections for example–the secretory IgA levels may reflect the body’s efforts to block those other things.”
An IgA surge indicates that the immune system is active, but it is non-specific for SARS-CoV-2.
Dr. Messier pointed out that there’s a point on the timeline—usually around Day 7-10—where all the lines on the graph meet and cross.
“Viral RNA titers are dropping, but antibody responses are rising. If you test a patient at that point in time, they could be negative to everything even though we know there was a viral exposure, and they’re developing antibodies. The tests might all be negative just because of the timing.” But there’s also a possibility they could be positive for everything.”
Also bear in mind that immunocompromised patients—and many severe COVID patients fit that description–might not show any antibody responses. A negative antibody test does not rule out viral infection; antibodies reflect the state of the immune system, not presence or absence of the virus.
Antibodies & “Immunity”
Do any of the known antibody responses confer actual immunity? That is a big, largely unanswered question at this point.
Dr. Hanaway explained that testing labs have developed assays to detect antibodies for a wide range of potentially antigenic coronavirus proteins—the spike proteins that give these viruses their characteristic appearance, proteins on the viral envelope, proteins on the membrane. The clinical significance of having antibodies to any of these is not always clear.
“What you are measuring—whether it’s the spike protein or the membrane protein or the envelop protein—is going to affect the sensitivity and specificity of the assay. The M protein is specific and seems to be conserved in this virus over time, the S protein may change as the virus morphs. You might get a false negative simply because the spike protein varied,” he said.
Some antibodies–like antibodies to the spike protein–may be “neutralizing,” meaning that they neutralize the virulence of SARS-CoV-2. Others are not.
“Neutralizing antibodies prevent the virus from entering cells. The virus cannot enter a cell that’s covered with neutralizing antibodies,” Dr. Messier explained. “Other antibodies are binding antibodies that don’t block the viral entry into cells, but they recruit the T-cells to destroy the virus.”
In any given case, the patient’s antibody response might—or might not—be able to prevent recurrence of disease. “We are not able to assess immunity directly. But we’re making proxies of it,” Dr. Hanaway noted.
The predictive value of antibody tests for coronavirus—or any pathogen for that matter—also depends in part on overall prevalence of the pathogen in the general population, added Dr. Messier.
“If the test is 95% specific, and there’s 1% of the population that has the antibodies, you will be wrong five times more frequently than you’re right. If the prevalence is 25%, and the specificity is the same at 95%, you will be right five times more than you are wrong.”
On a total population basis, the prevalence of SARS-CoV-2 is still fairly low, meaning that from a statistical perspective there are likely to be a lot of wrong answers.
Who to test: If someone has the “classic” COVID symptom pattern, test. And then test again, said Dr. Hanaway. “Any symptoms should be considered COVID unless proven otherwise. We have to err on the side of caution, but perform the RNA test to confirm the infection. If the test comes back negative, wait 7 days or more, then do antibody tests.
Should you routinely test asymptomatic but at-risk patients? Maybe. If someone’s had a likely recent exposure, but needs to be out in the world (working at an “essential” job, for example) it is wise to do a viral RNA test. If the patient is sheltering at home, not sick, and not likely to expose others, the test may not be necessary.
If a patient had close and frequent contact with someone who has been sick with COVID, then RNA testing is strongly recommended. “But even if that test comes back negative, we still advise quarantine for 2 weeks, because we know the false negative rate is high. After that two-week period, it makes good sense to do some serologic tests to see if the patient generated antibodies.”
Obtaining test samples: Talking about testing is easy. Getting good samples is not.
Viral RNA is present in sputum, saliva, nasopharyngeal secretions, and feces. While many different testing methods claim high sensitivity and specificity, in reality most have only been validated for one or two sample types–usually nasopharyngeal swab samples–but not the others.
According to Dr. Messier, nasopharyngeal testing “has very good sensitivity. But is really awful. It’s not a great way to sample. The patient’s going to start coughing, spraying droplets everywhere, spreading the virus. It’s important for the person doing the sample to wear proper protective equipment.”
There’s an added problem: many clinics are running out of swabs and unable to order more. “Some people have begun 3-D printing them,” she said.
Sputum sampling is easier, but it will only provide reasonably accurate results if you can get a first morning sample of mucus from the lungs and the back of the throat. Saliva testing is more practical, and is being widely used in some countries. But saliva tests have not been fully validated.
Stool testing is possible in principle. It is being used at the public health level to assess viral loads in sewage in various communities, said Dr. Hanaway. Clinically, it is not yet relevant. “We know viral RNA is present in stool but they’ve never been able to culture virus from stool. All it really tells you is that someone has been exposed.”
Point-of-Care and Home Test Kits: Widespread testing requires easily accessible tests. That has been problematic in most countries, including the US. The biotech and diagnostic testing industries are in overdrive right now, developing and releasing new point-of-care tests, and DIY home test kits, at a rapid clip.
“To stop the virus spreading…will take a massive effort to scale up the production of easy-to-use POC tests and then to deploy them widely,” wrote Cormac Sheridan, in a recent article in Nature Biotechnology detailing some of the emerging methods. Sheridan points out, however, that quickie tests to detect antibody responses have been faster to emerge than simple tests to detect the virus itself.
Hundreds of new COVID-related tests have hit the market in the last few weeks, prompting the FDA in May to impose a new rule requiring test-makers to apply for emergency-use authorization and FDA review when launching new tests. Previously, the FDA allowed companies to do their own validation testing and to market COVID tests without prior FDA evaluation of sensitivity and specificity.
Many new tests are modeled on home pregnancy tests. They require just two drops of blood, and promise low cost, convenience, and privacy–appealing attributes. But the validity of these tests is questionable.
“The results were all over the place,” said Dr. Messer. “There were only three that came even close to getting it right. There were a lot of false positives. And with convalescent plasma, it was like rolling the dice. The test that gave the fewest false positives, also missed about 10% the true positives.”
According to the IFM reviewers, the jury is definitely still out on the role of these tests.
Cross-Reactivity & Test Validation: There are at least four other types of coronavirus circulating in the general population, besides SARS-CoV-2. From both a clinical and public health perspective, they can cloud the testing picture.
The widely used RT-PCR methods have been validated against the other four coronavirus types, as well as other common viruses. But many of the other types of tests—especially the antibody tests—have not.
When a test comes back positive, you want to assume this reflects a recent or current infection with SARS-CoV-2. But unless you are certain that the specific method has been assessed for cross-reactivity, you cannot rule out other coronavirus strains.
“Maybe your patient had a cold recently. Owing to this cross-reactivity, that may show up as a false positive for SARS-CoV-2,” Dr. Messier said.
She challenged the “100% specificity” claims made by many test marketers. “I’ve not seen any lab—and I have looked at quite a lot—that has done their validation studies looking at that cross-reactivity with the other coronaviruses. Many will look for other respiratory viruses, but they don’t test for those other coronaviruses.”
Practitioners have a big role to play in driving improvements in test validity. The IFM strongly encourages all clinicians who do COVID testing to insist that labs provide complete analytical and clinical validation data. The organization has created a standard question set for communicating with labs (see Evaluating COVID Serology Tests).
When is someone “safe”? How do we know for sure that someone who has tested positive for SARS-CoV2 is non-infectious and safe to go back into life? We don’t.
But Dr. Messier said there are basic minimum criteria: “We don’t want to see any more viral RNA in respiratory droplets. If you see no viral RNA, and you also have antibodies, you’re probably safe to go back to work. But the viral RNA test should be done twice because the false negative rate is high.”
Testing for SARS-CoV-2 and COVID is a rapidly evolving field. New studies and new testing systems are emerging nearly every day. We may never reach a point of 100% diagnostic certainty. But wider testing, good clinical judgment, and honest communication will help us move in the right direction.
The COVID pandemic has put viruses and virology front and center in public consciousness. It has also triggered an unprecedented surge in viral research, with hundreds of new papers posting every day.
All that we are now learning underscores how little we really know about the virome—the fascinating and vast world of viruses.
What is known about viruses is both fascinating and unsettling. Here are some viral facts that many people do not know:
Viruses are the most abundant biological entities on Earth: There are an estimated 10,000,000,000,000,000,000,000,000,000,000 (10 quintillion) viruses on earth, making them the most abundant form of life on the planet. In aggregate, they number far more than all other types of organisms combined.
There are an estimated 380 trillion viruses inside the average human body. Read that again. There are around 380 trillion viruses in (and on) your body. That’s ten times the already staggering number of bacteria in the typical human microbiome, according to an article by UC San Diego’s David Pride, and Rockefeller University’s Chandrabali Ghose, on the EarthSky website.
Most viruses are entirely harmless: Viruses have a justifiably bad reputation among us humans. Smallpox, AIDS, Dengue Fever, Polio, Ebola, and now COVID…these are just a few of the horrendous human diseases in which viruses play a central role. But the vast majority of viruses—and the operative word here is ‘vast’—cause no harm to humans whatsoever.
Fifty years ago, prior to the discovery of probiotics and the microbiome, bacteria were similarly vilified as pathogenic “germs.” Today, we understand that while some bacteria are indeed harmful, others are beneficial. We’re starting to learn the same thing about viruses. Most are harmless, some are helpful.
The virome is a key component of the microbiome: The microbial ecosystem in and on our bodies is a complex universe of bacteria, fungi, protozoa, and viruses. The majority live in the gut, particularly the large intestine. Viruses are more likely to “infect” other microorganisms than human host cells, and they play an important role in regulating bacterial populations, in some cases destroying bacterial pathogens.
The widely celebrated CRISPR-Cas gene editing process that transformed the biotech world was initially developed by bacteria, as a way of ridding themselves of viruses.
In a 2012 paper entitled, Emerging View of the Human Virome, Kristine M. Wylie and colleagues at the Washington University School of Medicine point out that prokaryotic viruses that infect bacteria, “can also influence human health by affecting bacterial community structure and function.” Wylie stresses that “analysis of the human virome is critical as we aim to understand how microbial communities influence human health and disease.”
Viral DNA comprises roughly 10% of our “human” genome: Many different types of viruses or viral genetic sequences have become integrated within our human genetic material. To some extent, viruses make us who and what we are. According to researchers at the University of Heidelberg, genes from viruses known as HERVs (human endogenous retroviruses) account for up to 9% of the total human genome. They’re transcribed routinely in many different human tissues, and they cause no harm.
Viruses mutate and evolve—very quickly: Practically since early microbiologists discovered viruses, there’s been a long-running debate about whether viruses are truly alive. That debate continues to this day. Some argue that because they cannot survive and cannot replicate outside the cells of an animal, plant, or microbial host, they are not really living organisms. Others argue that no organism is entirely self-dependent; we all rely on a host of some sort.
But nobody can dispute the fact that viral genomes change and evolve. And they do so far more rapidly than bacterial, plant, or animal genomes.
Viruses are constantly morphing, either through recombination in which two viruses infect the same host cell simultaneously which results in the release of a new virus with mixed genetic materials; or through mutation, where an error occurs in the transcription process during replication.
Viral virulence is often species-specific: Only a tiny fraction of the virome is pathogenic, which begs important questions: What is different about the viruses that cause harm and the quadrillions that do not? Did pathogenic viruses originate as harmless ones that somehow became more harmful?
The answer to that second question is, Yes. But the key factor is the host species.
Many human viral pathogens originated in other animals—bats, birds, pigs, other primates—in which they cause no harm. That’s because the immune systems of the animals of origin in which the virus evolved, are able to keep them under control. But if a virus makes an inter-species jump, it’s another story.
Interspecies infectivity is itself a major evolutionary step for a virus.
“When a virus enters a new host, there’s often a brief period of acclimation, a little span of time when it’s mutating a bit and finding ways of better existing within that new type of body,” explained science journalist Ed Yong, in a recent interview on National Public Radio.
“And that’s what we saw with SARS classic. It took a little while before the virus became very good at infecting humans. That doesn’t seem to be the case with this new coronavirus. It seems to have been a really good human pathogen right off the bat, so to speak.”
It is important to also keep in mind that host susceptibility to any viral pathogen is influenced by overall health status, nutritional status, environmental conditions, and immune system health.
Bats are very good at fending off viruses: Some of the worst viral disease outbreaks in recent years (SARS, MERS, Ebola, SARS-CoV-2) have been linked to bats—the second largest order of mammals after rodents.
What is it about these generally harmless nocturnal animals that makes them hosts to such deadly viruses? The answer is, their immune systems.
According to researchers at UC-Berkeley, bats have extremely strong immune systems, particularly for fighting off viruses. But this puts tremendous selective pressure on the virome.
“Some bats are able to mount this robust antiviral response, but also balance it with an anti-inflammation response,” said Cara Brook, a postdoctoral Miller Fellow at UC Berkeley and the first author of the study. “Our immune system would generate widespread inflammation if attempting this same antiviral strategy. But bats appear uniquely suited to avoiding the threat of immunopathology.”
Bat immune systems are constantly primed to respond to viruses, and this drives viruses to greater virulence at a faster rate. The increased potential virulence does not necessarily harm the bats. But if one of those viruses makes an interspecies leap into humans or other animals, it can wreak havoc.
Viruses that look similar may be very different: To a child, whales and fish seem like the same sort of animal: they share similar bodily forms, and they live in the water. We know that beyond their outer shape, they are so different physiologically, metabolically, genetically and behaviorally, that they are totally unrelated.
According to virologist Nathan Wolfe, Founder and Chairman of Metabiota—a company specializing in epidemic tracking systems–our understanding of viruses is often just as child-like.
Two viruses that appear to be very similar, and that have been categorized in the same family based on morphology, often have almost nothing in common genetically. That’s because many viruses are polyphyletic—they look much alike, but genetically they are unrelated, and do not share common progenitors.
The virome contains “dark matter”: In the last decade, virologists have discovered a tremendous amount of genetic material that they describe as “viral dark matter.” These gene sequences seem to be viral in nature, but are so different from the sequences of well-known viruses that they can’t be detected with most conventional analytic methods.
The neologism echoes the astronomical term, dark matter, which describes gravitational perturbations that astronomers have observed, though the entities causing them are not themselves detectable.
In a fascinating QuickTake video by Bloomberg News, National Cancer Institute researcher, Mike Tisza says this is a good analogy for what today’s virologists have discovered. “We can’t detect it with any of our reference viruses, but we know it exists, we can see it, and it has features that are vaguely like a virus.”
NCI senior investigator, Christopher Buck, who directs the Laboratory of Cellular Oncology, says the viral dark matter came to light as he and other virologists sought to characterize polyomaviruses, papilloma viruses, and other viruses that might play a role in human cancers. In that process, they found large numbers of never before seen viruses, virus-like entities, and genetic sequences that nobody had ever seen before.
The clinical significance of these discoveries is still largely unknown. But today’s researchers have a host of incredibly powerful data processing tools to help them identify and characterize viruses that contribute to human disease—and human health.
Anita Teresa Boeninger and Val Elefante are writers and practitioners in the realms of integrative health, human sexuality, and the interplay between science and embodied wisdom. With the advent of the novel coronavirus named Covid-19/SARS-COV 2, we became curious about the nature of viruses, and how viruses interact with the human species. We began asking the question: is there another way to relate with viruses besides viewing them as dangerous enemies lurking in the corners, waiting to attack us? As this is still a new area of science, there is much to learn about these ancient precursors to all biological life on earth.