Traveling In Pandemic Times

My parents provided me with the usual survival tactics in childhood: “don’t put your finger in the electric socket; “don’t play stickball in a busy street;” “look both ways when crossing the street;” “put a jacket on to prevent pneumonia.” But no pandemic advice. My father, born in 1921, had missed out on the Great Influenza pandemic by 3 years. He survived the depression, World War II, the Korean War, The Cold War and Stagflation, but he had no pandemic real world experience. 

Mastering COVID avoidance was easy. I didn’t go out the front door. I wiped down every delivery with Clorox wipes. I interrogated delivery workers at the front door from 6 feet away. I masked up and social distanced with friends who took science and survival seriously. My only brush with the outside world was beamed in with cable news and internet pictures.

With viral mRNA inoculated twice into my arm, the lure of travel beckoned and with it the reality and trepidation of return to the unknown. What would airports, big cities, seeing friends and family be like after a monastic-like life for almost a year?

Armed with an  N95, surgical mask and face shield barrier, I pushed the UBER request on my app for a ride to the airport. “Please roll down the front and back windows for cross ventilation,” I directed the driver, thinking viral kinetics and air exchange. He didn’t blink an eye. At the airport, Homeland Security officers donned face shields and stood behind window barriers. Driver license identity was self-swiped at a distance. The Starbuck’s line imprints on the floor were spaced 6 feet apart and baristas looked like they were part of a surgical OR team. Sipping coffee, a learned skill honed in the past, became a conundrum when faced with two masks blocking the oral route. Should I slip the masks down or up? Should I replace the mask after each sip? Should I take the masks off completely? Should I just gulp the coffee quickly and then replace the mask? Thoughts of Dr. Fauci and the CDC flashed through my head: 10 minutes of exposure, high viral load, ventilation and symptomatic patients. I headed to the far reaches of the airport terminal, separated myself from the unmasked masses, and bolted the coffee down, nearly incurring mouth burns.

Boarding the plane entered me into a strange world. The cheap seats in the back of the plane got first dibs on boarding to limit contact time. Finally, seated, I breathed a sigh of relief when the hotly debated middle seat vacancy was enforced. Anxiety returned, as the flight attendants distributed the snacks. Was it worth unmasking for a granola bar and a small package of chips? The lure of Pringles was too great and I succumbed to temptation, all the while contemplating my eulogy, “he gave his life for a a few plain potato chips.” 

The plane hovered over LaGuardia Airport awaiting the final approach. Built on a garbage dump used for Brooklyn’s excess waste, I pondered the early Queen’s denizens grappling over their microbe challenge: Salmonella and Shigella. The plane landed, the  gate opened and I marched single file, 6 feet apart, masked and into the terminal where multiple, camouflaged clad military awaited me. Did I take the wrong flight and land in Mogadishu, Somalia? No, New York City, where Andrew Cuomo’s quarantine rules were being enforced against the blasé non-Northeastern states where I was now residing. It seemed surreal to be approached by a military serviceman and servicewoman who were both armed with weapons and asked if I had a Covid 19 PCR test performed in the last 72 hours, and if so, what was the result? Things had changed.

After claiming my luggage, I entered a NYC taxi cab to the final push to Manhattan. As I gazed upon the the facial scowl of our driver, I thought it best not to bring up the cross ventilation directions again. As I entered FDR Drive, I fixated on the credit card swipe. Can COVID exist on the card? Can I Clorox the gap? “What would Dr. Fauci do?”

Walking in Manhattan, I could immediately sense the gravity and public health compliance of the borough. This pandemic was not some abstract chyron endlessly streaming on a CNN telecast. Families and friends had been stricken with serious illness and death at the beginning of the pandemic and this crystallized the importance of public health measures. Multiple restaurants had outdoor seating ensconced within a plastic dome. At night, the yellow and purple lighting from restaurant isolation tables provided an extra-terrestrial feel. 

The ordeal was worth it after ending a year absence from family. Hugging my fully vaccinated son and and elbow bumping my unvaccinated son and daughter-in-law in the social distancing expanse of Prospect Park (thank you ,Frederick Law Olmstead) was priceless.

Many years from now, when my grandchildren gather around me and ask about the Pandemic, I’ll reply, you have to carefully peel off your N-95 mask just like this, and then get the Starbucks lid under the face shield that protects your mask and..…”

COVID and Nasal Memories

Pizza in my Olfactory Dreams

The Door Dash delivery was on the top of the steps, delivered from a  pizza service in San Diego that claimed “New York Style Pizza.” After the ritual disinfection of the pizza carton, the lid was lifted and I was delivered into another time and place. Scotty, the owner of a Queens pizza restaurant 60 years ago, was ensconced in my olfactory memory. He was flipping the dough as his octogenarian mother was lovingly molding a veal parmigiana hero that could make a grown man cry. Melted mozzarella, oregano, sausage and mushroom fumes reawakened a gustatory experience that I experienced for the first time, many years ago. With hops entering my nostrils from my Dad’s 1965 Miller High life, I left the COVID virus prison and entered a happier time when New York City  was a palace of gustatory delights and my childhood garden was in full bloom.

Through my nose, to the ethmoid sinuses, onto the olfactory epithelium and 60,000 smell neurons directed my pizza delivery directly to the frontal lobes and limbic system where Scotty’s still lived in vivid memory. This ecstatic experience is being stolen from millions by a renegade virus which has shut down the world for the last year. Expunging the smell and taste in some of the 25 million who have had COVID, which may have long lasting and permanent damage of the olfactory system. Malnutrition, depression and the loss of warning symptoms to natural gas leaks or tainted foods may be the legacy of sufferers of nasal COVID injury.

The least regarded of the five senses, smell and taste have taken a back seat in medical training and in popular culture. Medical school has few lectures on the proper function and diseases of smell and taste. Medical history taking neglects inquiry of one’s nasal and lingual capabilities. Olfaction has been a butt of jokes for generations of comics from the Simpson’s “smell you later”, Hawkeye Pierce’s ridicule on food sniffing in M*A*S*H and  Mel Brooks flatulence scene in “Blazing Saddles.” 

The dismissal of this forsaken sense is belied by its prominent location. The olfactory nerve, the shortest of the cranial nerves, sits in the front of the brain and sends projections to multiple areas including the emotional hub, the limbic system. Our evolutionary ancestors and current mammalian brethren rely on scent to distinguish friend from foe and food from poison. Our beloved canine, Millie, the Jack Russell Terrier from times past would apply the sniff test and rarely made a bad decision on food or domicile choices.

Obscure medical jargon has entered the mainstream with anosmia (lack of smell), parosmia (smell that fails to correctly match the odor) and phantosmia (phantom smells) appearing on long hauler COVID social sites. “Everything smells like burnt coffee” I heard a patient exclaim. “No longer can I taste the citrus in my tea,” another laments. “I ate a hamburger and I miss the onion smell and taste.” Essential oil kits are hawked on Amazon in the hope that olfactory re-education may hasten recovery. While the long term outcomes are not apparent in so recent a disease, it appears that up to 5% of smell sufferers may not  regain perception at 6 months.

“Don’t it always seems to go that you don’t know what you’ve got ’til its gone,” Joni Mitchell’s ballad went in the ’60’s.  And so it goes with Scotty’s appetizing, fragrant pies from the same decade. Enjoy your senses and don’t forget to stop and smell the pizza.

Understanding Oxygen and the Apple Watch 6: A Primer on Oxygen Saturation 101

The tech world has had a hold on the imagination and pocketbook of Americans for decades, improving our day to day communication, entertainment and educational options, all contained in the device we hold in our hands. More recently, tech companies have entered the multi-billion dollar health and wellness market, claiming a roseate outlook on life quality by revealing a wealth of “health” data populated on our iPhone or Android phones for us to peruse. For those that majored in business, art, political science or philosophy in college, watched “Keeping Up with the Kardashians” instead of “Mr. Wizard” reruns and did not take a physiology or human biology course, these numbers may be bewildering. It is time to let some “air into this room” and provide a background for understanding tech and health devices.  After 4 decades around EKG’s and pulse oximeters attached to humans and a user of Apple products for almost as long, I will provide the introductory course on the latest Apple foray into health: oxygen saturation and the pulse oximeter.

Oxygen is a key to human health. Before it’s atmospheric debut, we had bacteria for a billion years with few tech inventions during this period, save for the flagella, a whip like structure that could take you a few inches across a scum filled pond. Queue the plants (algae and other photo-synthesizers) and oxygen enters the atmosphere allowing for multicellular organisms and ultimately us (now is the time to hug your house plant out of gratitude). What did oxygen do for us? It unlocked the ability to generate much more energy from food sources that allowed us to dig a ditch, launch a satellite or use your TV remote. As any biochemistry or medical  student knows, ATP, the powerhouse chemical we use to store and release energy, is manufactured 16 fold in the presence of oxygen (for the curious, see oxidative phosphorylation and electron transport chain for more details).

The engineering dilemma that evolution was faced with for us multicellular beings was a supply and distribution problem. How to get oxygen from the air to each of our cells?  To move a substance, you need a pressure gradient to drive the work and the atmosphere pressurizes oxygen to move from high to low pressure zones. But this does not get the prized element to deeper tissues. For that obstacle, we evolved the lungs, blood vessels, blood and heart to circulate oxygenated blood to tissues to bypass this problem. 

Yes, blood, that substance thicker than water. Oxygen can dissolve in blood but at very low concentrations. To improve on the quantity of oxygen, we inherited the red blood cell and its key constituent, hemoglobin. Hemoglobin is the main oxygen carrier in the blood and allows pick up and delivery of 02 to the tissues. Oxygenated blood is bright red (usually arterial) and less oxygenated blood (usually venous) is blue. We can exploit this light absorbing property to determine how much oxygen is bound to hemoglobin at a particular moment by shining a frequency of light at a blood vessel and checking how much is absorbed and reflected at one time in the heart beat cycle.  The ratio of oxygenated to  de-oxygenated hemoglobin is measured, and reported as  oxygen saturation.

Do you need a device that warns you of oxygen shortage? Shouldn’t you feel short of breath, breathe faster and get yourself into an emergency room in time? Not always, as your brain, highly dependent on oxygen, can go haywire with  confusion, lethargy and poor judgement as a consequence. This is why the flight attendant always directs you to put your oxygen mask on first before your children. What about turning blue (cyanosis) from low oxygen? Unfortunately, this is a late occurring sign which occurs when fully ⅓ of the hemoglobin is devoid of oxygen.

Is there an early warning device to warn us of oxygen deprivation?Cue the pulse oximeter:  oxygen saturation can be measured by a pulse oximeter, or more recently with tech watches that have similar technology. Healthy lungs at sea level usually allow for oxygen saturation over 95%. As with all technologies, certain pitfalls apply. If your hemoglobin is abnormal it may not be measured properly. Carbon monoxide poisoning, for instance, renders hemoglobin incapable of binding to oxygen but is not registered by the pulse oximeter. Yes, you can asphyxiate with a normal pulse oximeter reading. The sensors must be close to the skin and not moving or else a faulty reading could result. Even expensive devices can be subject to error. Many a time in the surgery center, a reading of 60% could appear in an awake, non sedated patient. Repositioning the sensor, recalibrating the device or wheeling a new machine into the OR solved the false reading.

So what can you glean from the result? High altitude can lower oxygen saturation due to lower oxygen pressures. Altitude sickness can result with headaches, shortness of breath and in extreme circumstances, flooding of the lungs with fluid. Severe pneumonia can lower oxygen saturation and in the case of COVID 19, may not result in air hunger which would normally warn you of severe lung infection. Severe asthma could also cause a drop in oxygen saturation. Apple has started a research trial examining the usefulness of the Apple Watch 6 in this circumstance.

 The most important use of this technology may be in screening for obstructive sleep apnea. This condition is quite common in the U.S with a prevalence up to 30% of males and 15% of females).  Celebrities such as Rosie O’Donnell, Shaquille O’Neal,  William Shatner, (aka Captain Kirk of Star Trek fame), Quincy Jones, Randy Jackson (of American Idol fame) are afflicted. Luminaries whose death may have been influenced by sleep apnea include William Howard Taft (former 27th President), Jerry Garcia (of the Greatful Dead), Justice Antonin Scalia, Carrie Fisher (of Star Wars fame) and James Gandolfini (of Sopranos fame). Sleep apnea has severe health consequences and has acceptable, effective therapy. With the increase in risk factors such as adult obesity and sedentary nature of the population, obstructive sleep apnea is becoming epidemic, resulting in upper airway obstruction at night with snoring, interruption of breathing and dangerous reduction in oxygen saturation. This condition often results in headaches, daytime fatigue, hypertension, acceleration of cardiac disease and premature death. A continuous positive pressure mask can ameliorate this condition. A convenient, readily available screening tool such as a reliable pulse oximeter for nighttime use could potentially save multiple lives by directing those into the office of sleep specialists for definitive diagnosis and treatment.

So should you climb on board the day and night pulse oximetry tech train?  With certain caveats (a device that has reproducible results and matched to gold standard testing, FDA approval and  that works for night-time monitoring) this metric may benefit you when hitting the ski slopes and when your significant other has had it with your snoring and asks you to “do something about it.” Take a deep breath and ponder that.

The Battle Against Fake Science

The fates of Dr. Li Wenliang and Dr. Anthony Fauci will be irrevocably linked in our current times. Both physicians were muted by their respective political overlords:  Dr Wenliang sacrificed his life in the pursuit of warning the world of a deadly airborne virus originating in Wuhan, China and Dr Fauci, by the Trump Administration in thwarting his public health efforts in limiting morbidity and mortality. In these unsettling times, the assault on medicine and public health is not only lethal, but tolerated by industry, public opinion and political factions. 

When capitalism and profit intersect with human health, the American experience has often been in the favor of the former. American medicine in the 19th century was profit driven, fueled by several hundred medical schools that had no legitimate science curricula, no formal training programs and no criteria for competent professors. US medical students, desiring a top flight education, would journey to Paris to get state of the art instruction. Snake oil salesmen who peddled dangerous potions for multiple ailments thrived in the 19th century. 

The 20th Century provided some sanity and sanctity in the pursuit of science and healthcare. Abraham Flexner, an American educator, at the request of the Carnegie Foundation, reported in 1910 on quack medical training that resulted in the closure of multiple schools and began the scientific basis of medical education in the U.S. The Food and Drug Administration, established in 1906,  provided an oversight of drug therapy and provided a safety net to the general public.

Greed and the pursuit of profit in healthcare today still cannot be denied.  Popular entertainment reinforces the profit motive. Mr. Wonderful, on Shark Tank, when reviewing a vitamin and herbal supplement, gleefully queried the proprietor, “I don’t care if it works, what are your yearly sales?” Gordon Gecko, in the 1980’s movie “Wall Street”, uttered “Greed is good.”  Even in the 1950’s, Jim Anderson,  the iconic principled father in “Father Knows Best” sitcom during  the Eisenhower era, readily endorsed the Springfield snake oil salesman’s request for a business license because he was good to his dog and family. 

Congress got into the act of greed and greenbacks in response to a potential flood of pharmaceutical lobbyist money, further sacrificing the principles of science and public safety. Utah Senator Orin Hatch orchestrated potential legislative medical malpractice with The Dietary Supplement and Health Education Act of 1994 (DSHEA) which decreed that over the counter supplements and herbal products did not need to prove safety data prior to their release to the public and any complications would only need to be voluntarily reported. The supplement companies could not claim to treat a “disease” but misleading euphemistic claims such as “supporting health, “wellness,” or supporting a biologic system could be used in advertising without any scientific data to confirm the claim. What was the result? The OTC industry money profits increased from $9 billion to $50 billion,  Salt Lake City, Utah became a destination for the supplement companies. Hatch’s family became lobbyists for the industry and he and other members of Congress had a reliable flow of campaign donations.  What did the consumer get? The answer is clear: A flood of products that resulted in liver injury, life threatening drug interactions and occasional cardiovascular deaths. Product labeling was often misleading or wrong. Probiotics, living bacteria that can contribute to health, were often non viable or absent when analyzed by microbiologist/scientist scrutiny (R. Knight, UC San Diego). Families put themselves into financial jeopardy by spending hundreds of dollars per month on bogus supplements hawked by salesmen and health providers. This was a legislative fiat that legally supported medical quackery.

Now the technology industry is attempting to expand their profits by tapping into our health obsession and circumventing health law. Products that evaluate sleep hygiene, pulse and heart rhythm and oxygenation are entering watches, phones and bracelets. When developing a new technology, the rational response is to compare your experimental device to a gold standard that accurately measures the outcome you are looking at. For sleep analysis this is polysomnography, a medical test that looks at EEG, respiratory rates, eye movements among other data; oxygenation gold standard is the transmission pulse oximeter. Tech companies, such as Fit Bit and Apple, for instance, bypass the gold standard test and support their device results with an opaque “secret artificial algorithm.”  In the few studies that compare products to their gold standard, they are often shown to be inaccurate. The companies, unable to get FDA approval, then take guidance from the supplement industry by using “wellness” as the reason for the biometric. With no reproducibility and no public direction on the meaning and actionable explanation for the results, we are left with tech company advertising babble to encourage their purchase. 

It has been the pandemic of 2020 that has shown the stark reality of science deniers. Trump’s effort to undermine science and mask wearing and the infiltration and destruction of our beloved NIH, CDC and FDA autonomy has been an armageddon moment in healthcare. Pushing hydroxychlorquine, megavitamins and experimental medications that have not been fully vetted in randomized controlled studies as effective cures is unacceptable to the medical community and cannot be recommended as treatments to the public at large. Furthermore,  anti-vaxers, and proponents of the deadly “Herd Immunity” strategy are further evidence of our dilemma.

I am reminded of Dr. John Snow, a British obstetrician in the mid 19th century, who observed his London patient washing her infant’s diapers in a common water pump in town that spread cholera throughout the community. Snow’s work established the water-borne source of cholera and his urging of removing water pump handles. His pleas went unheeded by the public and scientists of his time leading to the death of thousands of additional victims in the cities around the globe. Accepting well designed investigations and their conclusions are our only way to avoid a “Dark Ages” outcome of health goals.

Our hope for the future lies in the investment of science teachers, high quality training of physicians and allied health providers, debunking and removing dangerous healthcare products on our social networks and providing the public with political leaders who want to move away from the past and into the evidenced based medical world of the present. 

Gut Punch Against COVID-19

“You are what you eat.”Jean Anthelme Brillant-Savarin, a French lawyer, epicurean and father of the low carbohydrate diet, penned these words in the 18th century. As we struggle through the COVID-19 pandemic, we search for personal ways to influence our health and our immune system to combat this pestilence. Food choices are an overlooked variable that may alter our fate.

Our human engagement with infections is played out daily through our immune system. Ironically, we are dependent upon our commensal microbes that happily reside in our bodies to assist in the fight against environmental, viral and bacterial invaders.  Over one hundred trillion bacteria and untold fungi, archaea and microscopic multicellular microbes take up residence in the gut after birth.  These microbes are a virtual army responsible for innate immunity and the initial fighting response to pathogenic agents. Furthermore, these bacteria contribute forty times more genes in the gut than human genes in the entire body. The exact role of these genes is uncertain, but they may produce proteins that may influence the bodies fighting power.  It is believed this gut bacterial diversity and their metabolites protect us by establishing an intact mechanical barrier, facilitating the release of bacterial and human antimicrobial chemicals and competing with pathogens for nutrients. They trigger the inflammasome, a coordinated release of immune stimulating chemicals (cytokines) that arm the lymphocytes, macrophages, neutrophils, dendritic and plasma cells that produce the coordinated inflammatory response.  A delayed innate response can result in a virus that gains a foothold that cannot be stopped. Similar to friendly fire, an over exuberant immune response can injure tissue from toxic inflammatory chemicals long after the pathogen has been vanquished.

Older age, diabetes and obesity are clearly risk factors for severe adverse outcomes with COVID-19. The common metric of these risks are a dysfunctional immune response. A slow initial response or an unregulated and injurious inflammatory reaction can result in devastating consequences for the infected host.  The gut microbes and their genes, the so called microbiome, are fundamental for a proper defense to infectious agents. A healthy microbiota is still being defined, but with new molecular biological techniques, a diverse population of organisms is critical to drive down the middle lane of life–away from infectious disease and autoimmune/allergic disorders. Altered microbiota or dysbiosis, is the hallmark of obesity and diabetes. And our country is flush with these risks. Over 40% of the U.S. is obese, representating a four-fold increase in prevalence since the 1960’s.

The microbiota can be malleable and is dictated by food for good or bad. And, food choices in our country may have steered us into more fatal outcomes with COVID-19. Processed food, hydrogenated and trans fats, high fructose corn syrup, larger portion size with higher calories and antibiotic tainted meats have assaulted the beneficial microbes in us. Could this be one of the reasons we are the leading country in COVID-19 cases and deaths?

Social distancing and masks are first line defenses against the Coronavirus fight.  Food choices MAY be another volitional pathway to maintain health. Fermented foods can select for beneficial commensal bacteria that make-up one’s microbiota. Greek yogurt, sauerkraut, tempeh, kimchi, and miso can favor the growth of Lactobacilli and Bifidobacter genera, both known to be healthy members of the microbiome.  Germany, Korea and Japan have low per capita rates of disease, attributed to timely public health measures and widespread COVID-19 testing. Might these differences be partly explained by eating sauerkraut in Germany, kimchi in Korea and miso in Japan?  Do some long standing cultural food preferences select for a healthier microbiome that is protective for Coronavirus infection or helps to modulate an appropriate immune response?  It seems to this clinician that it’s worth a clinical study as we, the people of every culture and nation, come together to collectively look to each other for any possible clue to mitigate the ravages of this virus.

Uncertainty to Despair to Hope and Redemption: My Professional Life Battling an RNA Virus

I feel  like I am reliving a bad dream. The race to find a treatment and/or cure to SARS-CoV-2 is reminiscent of decades of practicing gastroenterology while hepatitis C roamed the hospital wards as a death sentence for many. I found myself recently recalling a patient whose story ends with science finding a cure.  The story begins in a community hospital’s ICU.

 As I peered around the ICU curtain, I could see the outline of a motionless ill man. I was visually greeted by a panoply of colors not usually seen in human health. Yellow skin and eyes, violaceous bumps on his extremities and blue hued fingertips. As I entered the room, I recognized him as the car salesman I had spoken to several months ago discussing the pros and cons of  an SUV versus a minivan. His labs and physical exam delivered the bad news that his liver and kidneys were not working and he had vasculitis, an inflammation of the blood vessels. While he had a case that medical students study intently, private doctors rarely see in decades of practice: essential mixed cryoglobulinemia secondary to Hepatitis C. In an attempt to curtail the virus, antibodies bind to viral proteins. Excess antibody-protein complexes, instead of being  cleared from the blood circulation, get deposited in the blood vessel walls causing inflammation and sometimes closure of the vessel. He was in danger of losing his kidneys, his liver and his life. A National Institute of Health study had shown a few years earlier that the immune stimulating natural agent interferon could have a beneficial effect on Hepatitis C. Interferon was started and miraculously the bumps disappeared, the kidneys started to make urine, dialysis was stopped and the jaundice receded. He left the hospital and completed 12 months of interferon, combating fatigue, low white blood counts and depression due to drug side effects. He had been cured of Hepatitis C and had dodged a fatal complication of the virus using a toxic biologic agent.  

This early success had been a rare gold nugget amidst multiple disappointing and tragic events in my experience with the RNA virus, hepatitis C. The lessons learned from this virus are worth retelling as this is a story that parallels our current ordeal with another RNA virus, SARS-CoV-2. 

The biologic veil of Hepatitis C was heavy and was only lifted in fits and starts. In the alphabet soup of hepatitis viruses, A and B were discovered early but “C” was undetectable and given the placeholder non-A-non-B for years until special techniques were devised to recognize its presence. Infection was through blood transmission, usually through blood transfusion, sharing of needles or instruments that were contaminated with the virus and inadvertently inoculated through the skin. In contrast to SARS-CoV-2, which has a presymptomatic stage of a few days, Hepatitis C’s silent period was years or decades before disaster would take hold. Cirrhosis, or significant scar tissue in the liver could impair the sieve like blood circulation within the liver shunting blood to places it normally wouldn’t go resulting in gastrointestinal bleeding, ascites and encephalopathy. Years of infection can lead to liver cancer with a dismal prognosis. 

My early encounters with hepatitis C felt like bailing water from the Titanic while it was taking on water. I could band bleeding blood vessels, start water pills and limit salt in those with fluid overload and give antibiotics to reduce the toxin burden and reduce hepatic coma risks. But without specific treatment for the virus, we were on a slowly sinking ship. Then the drug interferon came along. It was a mixed blessing. It was toxic, causing fatigue in most and depression in a significant minority. It could lower white blood counts and damage the nervous system. It worked in only 10% of patients with the most common genotype of the virus. Most diabolically, those who needed it most were cirrhotics, and for patients with this condition, it was the most toxic and had the lowest response rate. I saw harsh drug side effects that included suicidal thoughts, absenteeism from work on the drug and plummeting white blood counts in countless patients. I questioned whether it was worth the one in ten chance that the drug would work. Slow progress (too slow for patients on the liver transplant waiting list) was the rule of the day. Ribavirin, an oral drug, used with interferon, raised the response rate to over 40% at the expense of the new side effects of anemia and potential birth defects. Most of my discussions with afflicted patients were often discouraging treatment, waiting for “some breakthrough in the future.”

The initial breakthrough came: direct acting antiviral drugs were available in 2011. They were protease inhibitors, drugs that blocked the assembly of viral proteins within the cell. The first generation protease inhibitors had novel side effects including disabling rash, headaches and mouth sores.

I came to dread the newly diagnosed hepatitis C consult. It felt like a “pick your poison” option.  I could offer an imperfect and potentially toxic mix of therapy, not unlike the oncologist administering chemotherapy to a cancer victim. 

This all changed with the synthesis of the drug sofosbuvir, an RNA polymerase inhibitor not unlike Remdesivir, an encouraging agent for SARS-CoV-2. Sofosbuvir, coupled with new protease inhibitors was the miracle I had not witnessed in my four decades rendering care to my patients. It’s side effect profile was no different than placebo and amazingly the cure rate would climb to over 98%. It worked equally well in patients with cirrhosis and the course of therapy was “weeks” rather than “years.” And, it was a cure! Patients who would have been candidates for liver transplantation saw improvement and were removed from the transplant lists. Liver cancer risks were reduced. Other non-liver conditions like heart disease, immune function and cognitive function improved with eradication of the virus. I felt my office was the equivalent of a Lourdes destination for the hepatitis C patient.

Science rendered a disease that afflicted 3.5 million Americans and killed up to 20,000 people a year to an affliction that most likely will be eradicated from the planet in our lifetime. The success of the treatment for hepatitis C can be looked upon as a template for our next RNA viral battle: SARS-CoV-2.  Hopefully, we can build from the success of the hepatitis C RNA polymerase inhibitor and extrapolate to a drug combination that can treat the disease as we wait for a definitive cure and vaccine.  Covid-19’s fate must be one that someday, when I reminisce about this time, I write another science driven medical success story.

The Art and Science of Barriers

“Good Fences make good neighbors” is a memorable and salient line from Robert Frost’s poem, “Mending Walls.”  While the context of its meaning is a plea for the importance of privacy, it is a useful phrase for the COVID-19 pandemic as we all try social distancing as our physical defense and protective barrier from the Coronavirus. Six feet away from one another and swathed with a nose and face covering mask seems to be the barrier du jour. It has been that throughout life we must deal with barriers that represent either obstacles, as in the poetic verse of Robert Frost, or provide succor to our existence. In our current COVID-19 world, our imposed barrier, a protective mask, will be critical to manage our “new normal” prior to a transformative drug or vaccine. In essence, we need a science driven mask that is effective, comfortable and re-wearable.

Biologic barriers are present from conception. Surrounded by the amniotic membrane, we are protected from most pathogens. Upon its rupture and our ride down the birth canal we start the self versus society struggle.  Hepatitis B, polio, rotavirus, diphtheria, tetanus and pneumococcal vaccinations are our initial immune barrier. Child proofing mechanical barriers (plug locks, stair locks, edge protectors) are present during our formative years. Car seats and later seat belts protect us from motor vehicle morbidity. Science has driven these medical protections and public health measures have orchestrated their distribution to the public and their acceptances as standards of care.

Societal barriers have protected humans for eons from human aggression, accidents and microbes. The Caves of Lascaux  protected Paleolithic man, The Great Wall of China retarded invasion by the Mongols. The Roman emperor Hadrian built his namesake “wall” in Northern England to keep out the “barbarians.” Ramparts and moats around European castles in the Middle Ages slowed the devastation wrought by the Vikings. In our lifetime we put up with anti-terrorist barriers at TSA checkpoints at all U.S. airports. Physical barriers and screening techniques have been shown over time to decrease disease and death from outside threats to our well-being.

Our protection from COVID-19 now demands a barrier to our nasopharynx. We are now safely surrounded by our homes’ four walls and limited “world” contact through our UPS and Amazon delivery services. In order to integrate into society we need extra protection from the virus. A mask or “facial condom” could provide us with the protection and turn human interaction into an acceptable risk. We are now familiar with the N95, surgical, and home-made masks. We have YouTube videos of media celebrities constructing masks. Now,  “mask science” is the next logical step to assure that our efforts are working to prevent Covid-19 transmission. What we really need is some evidence based guidelines developed from a controlled study.

 The geometry is well known: N95 keeps out 95% of particles that are as small as 0.3 microns; droplets containing COVID-19 are 50 microns or less. Droplet spread is 6 feet, more if sneezing or aerosol transmission is involved from the contact. What we don’t know is what materials and layering are most effective against virus spread when used in a real world scenario.

Compliance and comfort are inextricably linked. When I donned a mask in the OR, my face felt like I was in the microclimate of Miami during the summer and my eyeglasses fogged up like winter in London. We have designers and aerosol engineers that can overcome “wearability” issues that could lead to improved compliance. We have industry and universities that have the capability of testing combinations of fabric under simulated and actual environmental conditions.  Distribution capabilities are available to send masks to every household in the United States utilizing the Postal Service.

Americans have internalized the use of seatbelts and TSA screenings in my lifetime. Introducing and complying with  a “new fence” is easier when the alternative may be a painful respiratory death. Wearing a fashionable, comfortable and effective face mask should become the “new normal.”  The design, efficacy and distribution is simply just one more barrier for science to overcome.

Soup Saviors: Chicken and Matzo Ball Soup Stories

Chicken soup has long been an off-label medicinal treatment for the common cold and flu as long as most of us can remember. So, it seems in these troubled times of COVID-19, we are hearing of its use in both healthy and coronavirus inflicted patients. An elixir from antiquity, chicken soup and its Passover-inspired cousin, matzo ball soup, are the “magic potions” from yesteryear that have been a proven adjuvant to analgesics and cough suppressants. However an Amazon search for chicken soup brings up a dizzying array of “out of stock” and “delayed delivery” for dozens of pre-made poultry influenced self-prescribed potions.  Chicken noodle, chicken and stars, old-fashioned chicken noodle, low sodium, healthy request, chunky, cream of chicken and every conceivable form of soup on a grocery shelf is starkly absent. In fact, chicken soup is one of two most requested items on Amazon. When I took a moment to ponder why, my memory was flooded with memories of my grandmother, aunt and mother serving up large bowls of chicken soup for every childhood illness that befell me. And, to be quite frank, I almost instantly felt better after its consumption.

My maternal grandmother, Nan, unveiled her divine Matzo Ball Soup at the start of each Passover Seder. Even a “soup skeptic” like my father, devoured the contents of the bowl. I can still hear the clanking of his soup spoon on the bottom of the porcelain dish. My nuclear family had matzo ball soup anticipation throughout the year, and not unlike McDonald’s McRibs strategy, Nan would bring it out during random Erev Shabbat gatherings. While there were many proponents of Nan’s soup credentials there was not unanimous agreement. Aunt Rose’s Matzo Ball Soup was touted as the gold standard by my relatives north of the Bronx. The debate on the best soup went on for decades.

Chickens can incubate avian influenza but they can provide sustenance through their soup derivatives. The 12th century Jewish physician and rabbi, Maimonides declared the medicinal properties of chicken soup back in the 12th century. Modern science has weighed in on its medicinal values. Chicken soup can slow  the entry of white cells into the nasal cavity, explaining the improvement in airflow. Medical researchers at Mt. Sinai in Miami Beach ascertaned chicken soup challenge in humans showed an improvement in nasal mucus flow, a marker of viral clearance. Chicken soup can also improve cilia function, the hair-like projections on naso-respiratory cells that “clean up” the nasal and respiratory passages, The soup additives, onions and garlic can have antiviral effects.

As Jews celebrate Passover and recall the 10 plagues of antiquity while living through a 21st Century pandemic, let us remember the benefits and memories that our loved ones provided: the humble Matzo ball/chicken soup miracle.

COVID-19: Musings of a Baby Boomer: The Human Challenge

I was quite young but I could sense the unease in my mother when she first sent me off to elementary school amidst an uncertain risk of paralytic polio in the 1950’s era. She maintained her frightened countenance until 1960 when the Sabin vaccine miraculously appeared.  Many years later, my wife, a pediatrician, had intubated a young patient with measles who needed ventilatory support. A few days later, she staggered into my office, ashen and lightheaded. Her blood pressure was 70 and her sclerae were icteric. She had contracted rubeola and measles hepatitis. Looking up from her hospital bed she uttered, “if I don’t make it, you’ll need to find someone to help raise our (1 year old) son.  My nurse is wonderful and I give you permission to date her if I die.” My wife recovered and is my social distance partner 35 years later. These are but a few of my anecdotal “high anxiety” moments of contagious disease in my “baby boomer” memory. And that’s the point. These events are distant memories, rarely surface and are almost never mentioned. We move on and forget the lessons they taught until the next infectious insult makes us scramble for direction and hopefully solutions. In fact, throughout history this repetition is startling.

Humans have constructed great civilizations in only 10,000 years, surmounting  challenges and establishing the supply chains that provide food, clothing and shelter for the billions that inhabit this planet.  Yet we are impeded by one major human foible: selective long term memory loss in order to cope with the next medical task at hand. What do I mean?  Take human memory and the history of contagious disease in society. We learn, at an early age, that American and international history were shaped by infectious disease. Early settlements in Virginia in the 16th century failed due to malaria outbreaks. In 18th century Philadelphia, an outbreak of yellow fever forced our founding fathers to flee the city.  Bubonic plague outbreaks in Europe in the 6th and 14th centuries killed 50% of the inhabitants and changed Roman and Medieval society. The medieval citizens fled the crowded cities for pastoral domiciles sensing that social distancing would prevent the deadly illness. Great armies were felled by typhus and cholera during the Napoleonic Wars and World War II.  We don’t have to go back very far to see a world where our parents and grandparents had a stark recollection of epidemic infectious disease. Diphtheria, polio and measles, to name a few childhood illnesses were part of their daily reality. Parents banned their children from community swimming pools, recognizing that distancing them from the source was paramount.  I, born in 1953, recall fellow students in my class with leg braces from polio following summers spent hospitalized. As I entered medicine in the 1970’s, there were reminders of past epidemics on the wards. I rounded in iron lung wards in Rancho Los Amigos Hospital in Downey, California. I ambulated the pediatric wards at L.A. County-USC Medical Center, puzzled by the prominent parapets outside the patient rooms. “They were there so that physicians could round and quarantine themselves during polio outbreaks,” my attending noted.  Again, in the early 1980s a mystery illness with a severely immunocompromised picture in the patient appeared in daunting numbers. The AIDS epidemic was upon us as we scrambled for its cause and cure. As time passed, the memories of these debilitating epidemics receded whereupon complacency and the rise of the anti-vaccination movement became the cause celebré of the 1980’s and beyond. The resurgence of the measles due to lack of sufficient vaccination in the 1980’s did little to discourage the anti-science crowd. Perhaps a lack of firsthand experience with the measles contributed in part to their anti-vaccine stance.  As I gazed into the mouth of a patient during the measles outbreak and saw a Koplik spot, a physical finding that indicates measles, I realized that the outdated knowledge of this physical finding I learned 10 years prior was not so archaic. Actually, I had simply forgotten about this pathognomonic signal of impending rubeola. “Out of sight,out of mind,” I said to myself.

Now, the COVID-19 pandemic has arrived and upended our lives as did the many infectious diseases of bygone years.  Initial roll-out efforts for mass testing, tracking and isolating has been less than adequate. We have finally resorted to social distancing, an ancient form of infection avoidance.  Clearly, the same weapons seen in the great mortality known as the Bubonic Plague during the 14th century. Ultimately, a vaccine will rescue us along with medical mitigation via drugs and antibody rich plasma from those who have recovered. Let us take the lessons of this catastrophic time and the stories from our heroes: the first responders, the healthcare team and informed public servants with us for centuries to come.  Otherwise, we sentence ourselves to repeat the same mistakes.

Society of Acquired Pathogens (S.O.A.P.)


The following is an edited transcript of infectious agents seminar against human health, October, 2019:

Moderator: Thank you for taking the time out from afflicting disease to attend this seminar and welcome our latest pathogen in training, SARS-CoV-2. Viral agents and Rickettsia should take the first few rows that contain cell cultures. It is my pleasure to introduce our guest speaker,  inflicting misery on Homo sapiens for centuries, our President, Yersinia pestis.

Yersinia pestis: Thank you. For those of you who are unfamiliar with my resumé, I am responsible for bubonic, pneumonic and septic plague. Partnering with the black rat and rat flea, I have inflicted death rates of 50-80% for generations. I helped take down the Roman Empire in the 6th century by killing thousands of farmers.  Since the farmers were now not available to pay their Roman taxes to support the military, this led to the collapse of the Roman armies. My greatest hit was 1346-1353 where I took out half of the population of Europe. I started out in China, traveled with traders overland and with the shipping trade and went west, south and northwest, tightening the noose of misery on millions. I took on one of the greatest city-states at the time, Florence, and annihilated hundreds of thousands. For those Florentines that had a false sense of security and fled to the countryside, my coterie of fleas and bacilli followed them and finished them off. I rushed into Avignon, then the seat of the papacy, and inflicted so much suffering that the Pope blessed the Rhône River as a burial site. As the centuries passed and I lost some of my virulence, I came back every few generations of humans to remind them of my sordid deeds.

 Of course, I couldn’t do it alone so I’d like to introduce my fellow “partners in crime.”

Bacillus anthracis: Thank you, Yersinia. Some may say I take a backseat to the Plague but others recognize me as a formidable foe. I cause Anthrax. I received some kudos from human terrorists who used my spores to infect others through the U.S. mail in 2001. I am crafty and can infect humans through the skin, lungs and gut. Proudly,  I can kill 85% of victims within hours or days. What about those deaths in England in 1348-1349? Yes, I chipped in with Yersinia by killing cattle, transmitting my disease through eating meat and leaving my spores in burial graves. My spores can stay viable in soil for over 40 years! Now, THAT is staying power.

Moderator: We acknowledge the lesser known genera, Rickettsia and their contribution to human suffering.

Rickettsia prowazekii: I’ll be brief as I cannot stay long outside my cell culture medium. I may be intracellular but even humans acknowledge my clout: my disease is called EPIDEMIC typhus. My ride is the human louse, pediculus humanus corporis. I thrive with poverty, war and overcrowding and feel at home in endothelium, the cell that lines blood vessels. I cause rash, headache, cough, muscle pain and then progress to shock and delirium and then death. I have caused more deaths than all the wars combined. I was there during the Peloponnesian War in ancient Greece, the Thirty Years’ War and the Napoleonic Wars. In fact, I killed more of Napoleon’s troops than did the Russians. I caused misery and death during the Great Irish Potato Famine in 1846 and spread to England. The English called it the “Irish fever,” blaming the Irish instead of giving me full credit for the disease. While poverty and hygiene has improved recently and the human louse is in short supply, I jumped to the flying squirrel to cause intermittent disease in modern humans. Please be assured, I am still in the game and doing my part.

Moderator: My thanks to all of the innovative microbes that have stricken so many for so many centuries. Now, we welcome our latest entry to the world of human virulence,  an RNA virus from an unheralded family. Let’s give a warm welcome and a round of applause for SARS-CoV-2.

SARS-CoV-2:  I am humbled to take my place among the greats of infectious disease. I want to express my gratitude to our “think tank” and mammalian assistant, the bat, who has unselfishly provided incubation over the centuries to improve our infectivity.  I proudly come from the family of Coronaviruses. We have been in the human disease business for over 800 years, but have been underwhelming as we have only succeeded in causing the common cold with our first 4 family members. We showed promise in 2003 with the release of my brother, SARS-1, and a later cousin, MERS. SARS-1 had an encouraging mortality of 50% and we were packing the ICU’s in Asia. We did not plan for high transmission rates and with public health measures we were stymied early in the game. I inherited 85% of the genome and fine tuned my transmission rates. In contrast to my ancestor SARS-1, who was most infectious during severe illness, I made sure I could jump to another human even before they were experiencing my infective presence. This was the magic bullet for my success and I am honored to be nominated for rookie pathogen of the year.

Yersinia pestis: I want to thank all in participating in this important update. Let me remind you that Homo sapiens are adaptable and we must be vigilant. In Florence, after several generations of plague, they formed isolation hospitals, board of health administrators and invoked quarantining measures to restrict my spread. They finally got the tools to see some of us in 1683 (early microscope, van Leeuwenhoek). Our fellow microbes have been betraying us starting in the 20th century with penicillin (the mold Penicillium notatum), streptomycin (the bacteria Streptomyces griseus), and tetracycline (Streptomyces aureofaciens). Our machinery has been co-opted  (DNA polymerase) and our bacterial tools to prevent viral infections in us have been discovered (CRISPR technology). We can take solace in that humans have short memories and often make irrational choices and blame others that have nothing to do with their plight. But we must stay vigilant: It is never too late to mutate! Let me call this meeting adjourned and we all look forward to next year’s gathering.