Coronavirus news & views

What We Learned From Sweden’s Response To COVID

“Sometimes I wonder whether the world is being run by smart people who are putting us on or by imbeciles who really mean it.”
― Laurence J. Peter, The Peter Principle

Many people have asked why we didn't let the virus hit us like a big wave and get it over with. The Great Barrington Declaration (GBD), a letter penned by three physicians, favored such an approach and called it “focused protection.” It recommended quarantining the highly vulnerable, i.e., the elderly and those with high risk factors like diabetes, heart and lung disease, etc., and letting the virus run amok through the rest of the population to quickly build natural herd immunity across the country. They said we should do away with non-pharmaceutical interventions that prevent infections, such as masks, sanitation, personal distancing, quarantines, closings, etc. The recommendation was published as a letter on October 5, 2020 because no medical journal would accept it as an article. Vaccines were still considered to be months away at that time, but actually began to roll out in mid-December of that year. Admittedly, the letter’s authors did not have a crystal ball.

We didn’t accept that recommendation, but Sweden did something very similar on their own and kept their country open and had considerably less morbidity and mortality than the US. Armchair health experts who learned their subjects at Google and Facebook Universities have been clucking their tongues and scolding the CDC and public health professionals ever since. Should we have responded like Sweden did? Would it have been better if we had followed the recommendations made in the GBD?

When the declaration came out, it was widely panned as being ridiculous by health experts and organizations around the world. A Yale epidemiologist pointed out that almost half the US population would be considered to have an underlying risk factor for COVID meaning that half the population would have to be quarantined from the other half, not much different from the protective measures already underway at that point. It also would have meant that people at less risk would be exposed to a rather nasty virus. They essentially would be sacrificed to a disease more lethal than any flu we have encountered since 1918. And then there is the problem with long COVID and other morbidities such as an uptick in new onset diabetes in many COVID survivors. Even though kids have a very low level of mortality from COVID, the disease was still much worse than any flu for them and too many of them were hospitalized in serious shape with a malady called multisystem inflammatory syndrome or MIS. This was the sacrifice the folks who proposed the GBD were willing to impose on half the population.

Anyway, this post is supposed to be about Sweden, not the US. Did Sweden’s experiment turn out as positive as many people believe? It depends on which countries you compare it to. Comparing the Swedish experience to that of the US, it seems they did pretty well. They did not shut down and had much less mortality than we did. But is that an accurate apples-to-apples comparison? Sweden is a country of just over 10 million people. Its demographic is much more homogenous than that in the US and it has much less poverty. In the US, COVID hit impoverished and minority populations especially hard. They have fewer medical resources to deal with the disease. In contrast, Sweden does not have such a large minority or poor population and it has cradle to grave social welfare for everyone, including medical care. It does not at all resemble the US.

It is more accurate to compare Sweden to its neighboring Nordic countries with similar populations, demographics, and social welfare, but that also enacted more stringent social controls in response to the pandemic like the US did.

It turns out that compared to other Nordic countries, Sweden fared quite poorly with the highest mortality rate. Sweden had four times the number of COVID deaths compared to many of its neighbors. In particular, it had ten times the COVID death rate of Norway.

What about the economy? Of course the Nordic countries that enforced public and commercial shutdowns suffered significant economic hits like the rest of the world. Importantly, so did Sweden, which kept its economy open. Nevertheless, the country suffered as much economic downturn as its neighboring countries that enforced stricter shutdowns. In fact, the Organization for Economic Cooperation and Development and Development (OECD), of which Sweden is a member, reported that the country actually did markedly worse than Denmark, Norway and Finland. It seems that economic health is not only related to open commerce, but also to the public health of the country. Sick people do not work or venture out to buy things. It seems that public health affects economic health. That was not considered in the GBD, which was concerned about the economic impact of closing down commerce via fiat. They did not consider the economic impact of closing down commerce by hospitalizing so many people.

As these effects of its open policies became clear, Sweden eventually began to enforce greater social restrictions later in the pandemic, but the damage had already been done. The architect behind its initial open policies eventually admitted that things did not work out as planned. And in December 2020, Sweden’s King Gustav publically declared that the government’s approach had failed.

The real lesson from Sweden is that if you keep things open and people get sick, the economy still suffers in a pandemic. As far as the economy goes, it is a case of “damned if you do and damned if you don’t” enforce public restrictions.

And if you don’t, people still get sick and die and dead people stop buying things.

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Politics: A Risk Factor For Death From COVID?

What are you gonna believe, medical science or dubious talking heads?

In 2021 former Green Bay Packers quarterback, Aaron Rodgers, said he was “immunized” against COVID. He wasn’t. He claimed to have done “research” and learned how to get an infusion of antibodies and take some unproven ‘medicine.’ His ‘research’ was talking to radio pundit and hot-air purveyor, Joe Rogan. How many more people like Rodgers listen to the wisdom of the likes of Rogan or Tucker Carlson and think they know more than medical professionals and then rationalize their avoidance of COVID vaccines? And to what effect?

The Kaiser Family Foundation estimates that from June 2021 through March 2022 about 234,000 COVID deaths could have been prevented had the decedents been vaccinated against the SARS-CoV-2 virus. That protection was especially important during the more deadly Delta virus wave during the earlier stage of the pandemic, but it still extends into the Omicron era, which fortunately is not as deadly as Delta was, but still is not to be taken lightly. People are still dying from the virus.

How does politics come into this?

A 2022 study published in the journal, Lancet Regional Health-Americas, found higher COVID mortality rates in more conservative congressional districts across the US. And in another 2022 study using 2020 presidential election returns, researchers at the University of Maryland and the University of California at Irvine found that, through October 2021, Republican-majority counties across the US experienced nearly 73 additional COVID deaths per 100,000 people relative to majority Democratic counties.

These are correlations looking for a cause. A good causal candidate could be differences in vaccination rates between people who tend toward conservatism vs liberalism. The former are much less likely to get vaccinated than their left leaning neighbors. But, that connection needs to be made.

Sure enough, a July 2023 report by Yale researchers in the journal, JAMA Internal Medicine, compared COVID death rates in counties in Florida and Ohio that voted for Trump vs Biden before and after the vaccines came out. The bottom line was that after the vaccines rolled out, Trump voting counties saw 40% higher fatality rates per million residents. Before the vaccines, the COVID death rates were the same for all counties. Viral infection rates were similar for both types of counties throughout the period of analysis. Importantly, counties and individuals that went for Trump had lower vax rates than those that went for Biden.

That pretty much closes the circle on the causation. The greater reluctance of more conservative people to get vaccinated and boosted likely killed them at a greater rate.

Karma?

Now, don’t get me started on the conservative vs liberal attitudes on face masks and social distancing. Conservatives are wrong on these matters. I say this as a conservative myself. But, I also am a data driven scientist who believes data trumps partisanship.

How do you think SARS and MERS were stopped without a vaccine or anti-viral drugs? How do you think society stopped any epidemic such as small pox, influenza, bubonic plague, etc. throughout its history before modern medicine and effective vaccines? How do you think today we are handling Ebola for which there is no vaccine or drug? Non-pharmaceutical physical measures, like masks, gloves, sanitation, social distancing, etc. are effective ways to halt infectious diseases in lieu of vaccine and drug preventive measures.

Conservative resistance to these non-pharmaceutical physical protective measures also probably contributed to their higher death rates observed in the studies mentioned above.

Karma.

The Next Pandemic Is Here

Who ya gonna call?  --“Ghostbusters”

We seem to have mostly weathered two-plus years of a pandemic like the world has not seen in our lifetimes. It raced across the globe killing and maiming people, and overwhelming health care capabilities. Sure, we have read the history about the black plague, small pox, and the Spanish flu pandemics, but vicarious experience through books and film is no substitute for first-hand experience. We now have that experience. It was sobering to see the novel SARS-CoV-2 virus ravage country after country while medical experts played a desperate game of catch-up to learn how to retard the spread of a brand new virus and how to treat the brand new COVID-19 disease it spawned. It was sobering seeing and hearing about people we know get very ill and sometimes die, and sobering reading the statistics of millions of deaths that occurred worldwide.

While most of us today have not seen such a pandemic wild-fire before, we have seen other, more smoldering pandemics that do not spread as fast. HIV is a good example. It too is a world-wide disease that, for many years was a death sentence for those who were infected. Now it is a well-managed chronic disease, thanks to medical science.

The world was not as frantic over HIV and AIDS as we were over CoV-2 and COVID. The reasons for this are probably two-fold: First, it was quickly recognized that AIDS was largely limited to homosexual men and IV drug users and, therefore, was not an eminent threat to most of us. It was not necessary to quarantine, mask up, and shut down businesses and schools in order to prevent catching the “gay disease.” Second, despite the world-wide spread of AIDS, it is not easy to catch. You must be in very intimate contact with an infected person to catch it—it is not caught by simply breathing the same air as an infected person like COVID is. Clearly, not all pandemics are created equal. Some smolder like AIDS, others fulminate like COVID. What will our next pandemic be like?

As the global population grows, as the climate changes, as humans push into spaces occupied by wild animals, and as we continue enjoying our ever increasing global connectedness, future pandemics become more likely. We are not guaranteed the luxury of facing just one a century, or even one at a time. As greatly encouraging, even exciting as it was to watch the post-molecular BioX science, as I have called it, roar into life to produce several effective and novel anti-CoV-2 vaccines in record time, there is no guarantee BioX can save us next time.

Well, the “next pandemic” already is upon us and BioX is struggling to deal with it. This pandemic is not as volatile as COVID or the Spanish flu. In fact, compared to COVID, it is a “slow mo’” pandemic, more like AIDS. But, it promises to be more difficult than COVID, even for BioX, to mitigate. It currently kills about 700,000 people annually around the world, but threatens to kill 10 million people a year by 2050 (in contrast, COVID killed ~6 million around the world in 2.5 years).

The problem

 In March 1942, Anne Miller of New Haven, Connecticut, was near death. A bacterial infection had made its way into her bloodstream, which was a death sentence at that time. Desperate to save her, doctors administered an experimental drug called penicillin, which Alexander Fleming accidentally discovered 14 years earlier. In just hours, she recovered, becoming the first person to ever be saved by an antibiotic. Rather than dying in her thirties, Mrs. Miller lived to be 90 years old and Fleming went on to win the Nobel Prize for his inadvertent discovery.

Today, decades later, germs like the one that infected Mrs. Miller, but easily eradicated with antibiotics, are increasingly becoming resistant to penicillin and the many other antibiotics that have since been developed. There is a very good chance that right now, you have such a “superbug” in or on your body—a resistant germ that, given the opportunity could enthusiastically sicken you leaving medical people at a loss on how to treat you. You would be at the mercy of the bug just as all patients with a microbial infection were before Mrs. Miller.

We are not talking about a new, exotic germ like CoV-2 suddenly appearing and ravishing the world. The antimicrobial resistance crisis stems from the simple fact that new antibiotic development cannot keep pace with the rate that common microbes become resistant to antibiotics. This very slowly growing pandemic we are now in involves run-of-the-mill pathogens, bacteria and fungi that have caused disease since humans first dragged their knuckles on the earth. These are bugs which we had well controlled with antibacterial and antifungal drugs, but there is a very definite trend toward these germs becoming resistant to ALL known antimicrobial medicines we have. Infection with multidrug resistant pathogens is the slow moving pandemic that already is among us but that is growing at a logarithmic rate.

Since multi-drug-resistant infections do not respond to our antibiotics, treatment increasingly involves surgically removing an infected organ. For example, in the case of drug-resistant Clostridioides difficile (aka, “C-diff”) colitis, an emergency colectomy is performed when patients no longer respond to antibiotic therapy. CDC data show C-diff infections occur in half a million patients each year, and at least 29,000 die within one month of initial diagnosis. Up to 30% of patients with severe C-diff colitis develop sepsis require emergency surgery, and still their mortality remains high.

As of 2019, about 18 drug resistant pathogens affected >3 million people in the US, causing 48,000 deaths. These bugs cause pneumonia, septic shock, various GI problems, STDs, urinary tract infections, typhoid fever, TB, and infection with the so-called “flesh eating bacteria.” Compared to COVID, this has received relatively little attention in the popular press, but has been a frequent topic in medical lectures and conferences for the last 20 or more years. These infectious disease lectures tend to scare the bejeebers out my colleagues and me. This smoldering pandemic is that serious.

And it is not just antibiotic-resistant bacteria we have to worry about. Certain fungi, especially of the Candida genus, cause various serious ailments in people. Recently, for the first time, the CDC reported five unrelated cases (two in DC and three in Texas) of people infected with fungi that showed “de novo” resistance to all drugs. Usually, drug resistant fungi only appear after infected patients have been treated with antifungals. But, the patients in these five de novo cases had no prior exposure to antifungal drugs. The fungi were already drug-resistant when they infected the patients; they were picked up from the environment already resistant to our medicines.

Antibiotic resistance is now one of the biggest threats to global health. It occurs naturally in naturally occurring pathogens, but is accelerated by overuse of antibiotics in humans and animals, especially farm animals. What happens is that upon treatment with an antibiotic, a single infectious bug out of a population of millions or billions fortuitously mutates and becomes resistant to the antibiotic. The antibiotic then kills off all the non-resistant population, including beneficial bacteria, opening the door for the drug-resistant pathogen to take over. This resistance can occur via many different mechanisms. The bacteria or fungal cell can stop taking up the drug, it can spit out the drug if it is taken up, it can neutralize the drug once it takes it up, or it can change its internal machinery so that it no longer responds to the drug. This problem can be further exacerbated since bacteria and fungi can pass along their mutations by sharing mobile genetic material with their progeny and even with other bugs in their immediate environment that have never been exposed to the antibiotic. They can even pass along this DNA to microbes of different species. Bacteria can also pick up DNA remnants left over from dead germs. Thus, DNA that confers resistance to anti-microbial drugs can spread to the environment even in treated human and animal waste contaminating lakes and streams and ground water.

Currently, the major problem with drug resistant infections occurs in in-patient clinical settings—perhaps you have seen the heightened infection control efforts (gowns, gloves, masks, and isolation) in hospitals designed to prevent the spread of untreatable pathogens. People receiving health care, especially those with weakened immune systems, are at higher risk for getting an infection. Routine procedures, such as bladder catheterization or kidney dialysis are common ways to introduce drug resistant germs into clinical patients. But, infection can happen in any surgical or invasive procedure. Treatment of diabetes, cancer, and organ transplantation can weaken a person’s immune system making them even more susceptible for infections that either are, or that can become drug resistant.

But, antibiotic infections can also occur in the community outside of clinical settings. There is the case of Mike who needed a month long hospital stay for kidney failure after bringing home a new puppy from which he caught a multidrug-resistant Campylobacter infection. He was one of 113 people across 17 states who was part of an outbreak linked to pet store puppies. He recovered after surgery to remove a dead section of his stomach.

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The NIH Hospital Experience. About 10 years ago, the NIH Clinical Center in Bethesda was hit with an epidemic of drug resistant infections that killed a number of patients in just a few months. It was such an intractable problem that NIH finally had to gas rooms with a disinfectant, rip out plumbing, and build a wall to isolate infected patients. Still, over a period of six months it reached 17 patients, 11 of whom died. In this case, the bug was Klebsiella pneumoniae, which arrived in June 2011 with a 43-year-old female lung transplant patient who had just transferred from New York City. NIH nurses noted something startling in her chart: She was carrying an antibiotic-resistant infection.

Desperately trying to contain the superbug before it could spread, the NIH staff quickly isolated the woman in the ICU. Staff members donned disposable gowns and gloves before entering her room and her nurses cared for no other patients. After a month, the patient was discharged and the staff believed that their containment measures had worked. There were no signs that the bacteria had spread. But a few weeks later, they were shocked when a second patient tested positive for resistant Klebsiella. A third and fourth soon followed and all these patients died.

This pattern was baffling since, if the bug had not been cleared, it should have reappeared sooner. Even though it was the same type of bacteria, K. pneumoniae, perhaps it had spontaneously arisen anew in the other three patients. But by reading the genomes of the bacteria isolated from each patient, including the NYC transfer, scientists at NIH’s National Human Genome Research Institute saw that the bacteria in the subsequent patients came from the New York patient.

That meant two unsettling things: The bacteria lingered for weeks unnoticed in the hospital environment; and the hospital’s infection control measures for the New York patient failed. A further search for the bacteria found it on a ventilator that had been bleached twice. They also found it in a sink drain in a patient’s room, so they tore out all the plumbing. Yet, it began popping up it in more patients, at a rate of about one per week.

As hospital staff desperately raced to stanch the outbreak, they also struggled to treat the infected patients. Out of desperation, doctors battling the deadly, drug-resistant superbug turned to colistin, an antibiotic of last resort. It is not a new drug, having been discovered in 1949 in a beaker of fermenting bacteria in Japan. It had quickly fallen out of favor then since it causes significant kidney damage. The fact that the doctors resorted to such an old, dangerous drug highlights the lack of new antibiotics coming out of the pharmaceutical pipeline even in the face of a global epidemic of hospital-acquired bugs that quickly grow resistant to our toughest drugs.

While colistin defeated the superbug in a few patients, in at least four, the bacteria evolved so rapidly it outran colistin, too. Those four died. This was when the wall was built and all new Klebsiella-positive patients were moved into a new isolation unit behind the wall. Blood pressure cuffs and other normally reusable gear were tossed after one use. Clinical monitors were hired to follow doctors and nurses around to ensure that they were donning gowns, gloves and masks, and scrubbing their hands after seeing each patient.

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Among the most concerning mutating bacteria are carbapenem-resistant Enterobacteriaceae (CRE). Enterobacteriaceae are a large family of more than 70 bacteria that includes the common E. coli, that normally live in the digestive system and help digest food. But, if conditions allow the bacteria to leave the digestive system, they can cause serious disease that needs to be treated with antibiotics. They too can quickly develop resistance to front-line drugs and become a serious problem.  Carbapenem is an antibiotic "drug of last resort" used to treat disease caused by bacteria resistant to other front line antibiotics. Therefore, CRE are resistant to all or nearly all antibiotics and kill up to half the >13,000 patients who get bloodstream infections from them. The CDC first detected this type of antibiotic-resistant bacteria in 2000. Since then, it has been reported in 41 states. In the 10 years between 2001 and 2011, the percentage of Enterobacteriaceae resistant to antibiotics increased almost fourfold according to the CDC. Recently, the CDC tracked one type of CRE from a single health-care facility to facilities in at least 42 states.

The cause

The antimicrobial resistance crisis stems from the simple fact that new antibiotic development cannot keep pace with the rate that bacteria become resistant to antibiotics. Between 1945 and 1968, drug companies invented 13 new categories of antibiotics. Between 1968 and today, just two new categories of antibiotics have arrived. In 1980, the FDA approved 4-5 new antibiotics a year, but now only about 1-2 new drugs are submitted annually for approval. Hence, the solution appears quite simple: Develop more novel antibiotics. However, this is quite complicated since BioX science, which led to the rapid development of the novel mRNA anti-COVID vaccines, has not quite caught up to novel antibiotic development. There are two general reasons for this. First, finding a drug that disrupts the metabolism of bacteria or fungi, but that does not interfere with mammalian biochemical pathways is a difficult and narrow path. Second, so far, the market for novel antibiotics has been comparatively small, meaning that the profit incentive for pharma companies has not been large compared to that for so-called lifestyle medications. While a new antibiotic may bring in a billion dollars over its lifetime, a drug for heart disease may net $10 billion. Drugs to treat depression and erectile dysfunction are typically taken for years making them much more profitable than antibiotics that are used short-term.

Even if we could develop new antibiotics faster, their overuse is the primary driver of antibiotic resistance. According to the CDC, in 2018 seven antibiotic prescriptions were written for every 10 Americans. Of these, one-third were unnecessary, and very often were prescribed for viral illnesses that do not respond to antibiotics. Clinicians writing these prescriptions argue that the antibiotic can help prevent the primary viral infection from leading to a secondary bacterial infection. In other words, many antibiotics are prescribed for prophylaxis rather than treatment.

The number of new antibiotics that the FDA approves annually has slowed to a trickle, while the rate of bacterial mutation has grown exponentially. It used to take 21 years on average for bacteria to become resistant when antibiotics were first used. Now it takes just 1 year for bacteria to develop drug resistance because antibiotics are so readily prescribed and used. Today, the CDC lists 18 different types of antibiotic-resistant bacteria, five of which are classified as urgent threats to human health.

Physician-prescribed antibiotics, however, are not the only, or even main, source of our antibiotic resistance crisis. In the U.S., 70%-80% of all antibiotics are given to animals, especially farm animals destined for human consumption.  Drug-resistant pathogens from farm animals can spread to the environment providing a gateway through which drug resistant germs can quickly spread across our communities, food supply, and even our soil and water around the world.

Surprisingly, antibiotic use is even rampant in salmon and other fish farms, which is especially concerning, considering that 90% of fresh salmon eaten in the U.S. comes from such farms. Antibiotic-resistant infections also affect petting zoo animals, which can then transfer the germs to people.

The solution

Antibiotics clearly have been miracle medicines, saving countless lives; however, anytime they are used, they drive the development of antibiotic resistant pathogens that ultimately defeat their purpose.  Developing new antimicrobial drugs to counter the growing resistance to current drugs is not working; it is not keeping pace with the appearance of new antibiotic resistant germs. Without drastic changes in the science and economics behind antibiotic development and business, this will only be a partial solution to the growing pandemic. However, what we can do now is resort to low-tech, less expensive, and more innovative mitigation measures. These include alternative prevention steps such as more judicious use of antibiotics and increased use of isolation and sanitation measures (where have we heard this before?). Isolation and sanitation defenses against infectious diseases have been part of our disease fighting repertoire since the earliest awareness that contagions can spread through communities. It is an ancient remedy, but still the most effective way to protect ourselves against contagious diseases worldwide. Between 2013-2019, these mitigation measures led to an 18% reduction in US deaths from drug resistant infections. It always is better to prevent than treat.

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Alternative medical treatment and prevention options.  Besides the obvious masks, gloves, sanitation, and quarantine measures, there are other alternative medical (i.e., non-antibiotic) options that can be used to prevent and control drug resistant infection. In fact, these methods are often preferable to using antibiotics, which also deplete the microbiome of “good bacteria” that are critical for good health. These options include vaccines, therapeutic antibodies, and bacteriophages.

From 2000 to 2016, members of the WHO increased the use of the pneumococcal vaccine around the world, thereby decreasing antibiotic use which slowed the development of antibiotic resistant S. pneumoniae saving ~250,000 children from death. Pneumonia caused by secondary infection with other bacteria is a leading cause of complications and death in patients who get the flu. Therefore, the influenza vaccines also are effective tools to decrease the risk of drug-resistant bacterial pneumonias by preventing viral influenza. Since patients with COVID can also develop secondary complications from bacterial pneumonia, COVID vaccination now is another important weapon in the arsenal to prevent the development of antibiotic resistant bacterial lung infection.  

In recent years, healthcare providers also have been increasingly using therapeutic antibodies to treat viral and bacterial infection. For example, antibody therapy is often used to treat recurrent C-diff GI infections, and antibodies to prevent and treat bacterial associated pneumonia also are being developed. So far, we have not seen bacteria develop resistance to antibodies.

Finally, a different and very novel approach to dealing with untreatable bacterial infection has recently taken advantage of bacteriophages, which are viruses that can specifically infect and kill bacteria. There are a few cases in which phage therapy has been used to cure people dying of multidrug-resistant bacterial infections.  According to Pew Charitable Trusts, as of June 2019, 29 non-antibiotic products like therapeutic antibodies and phages were in clinical development and seven were in Phase 3 clinical trials. 

Perhaps BioX is indeed coming to rescue us from the growing pandemic of drug-resistant pathogens.

Notes: 1) By way of disclaimer, your correspondent has consulted for a biotech company that engages in “big genome” research to search for novel antibiotic molecules produced by everyday bacteria and fungi that grow in the soil under your feet. Something like this could be part of the future of novel antibiotic development. 2) In order to have blog updates delivered to your email, see the simple Subscription Instructions here. Remember, you can easily unsubscribe when you want. But, you can’t beat the price.

What Happened To The Flu And Other Respiratory Diseases?

A NYC based travel blogger who travels a lot used to get a respiratory infection whenever she flew. That stopped when the airline mask mandates went into effect. The mandates, of course, were designed to hinder the spread of the CoV-2 virus that causes COVID, but it makes sense that if masks and other physical (that is, non-medical) mandates worked to mitigate COVID, then we would see a decrease in other contagious respiratory diseases after the mandates were, well…mandated.

We did.

The mandates worked, despite persistent claims of some to the contrary. This particular blog subject was stimulated by a radio talk show where a couple of nonscientist talking heads announced that there was no scientific proof that the masks or other mandates prevented disease. I previously posted in these pages evidence that masks, in particular, do indeed work to retard the spread of disease (see here, here, here, and here). In this post, I present further data on how the mandates significantly reduced the incidence of other infectious respiratory diseases around the world. If the measures can reduce flu, then you can bet that they also reduced COVID-19.

Note, however, that this is not necessarily an endorsement for returning to the measures. Your humble scribe didn’t much like his glasses fogging up, or having to make two trips from the car to the store because he forgot his mask. But, let’s argue the issue based on its merits and not from false premises based on incorrect claims.

After South Korea implemented various hygiene and social distancing measures in response to COVID, they saw the 2019-20 flu season end an astounding 12 weeks earlier than the previous year. Epidemiological surveillance data bolstered by clinical diagnostic testing showed that infection from several different pathogenic respiratory viruses (including adenovirus, bocavirus, metapneumovirus, rhinovirus, flu, parainfluenza, and respiratory syncytial virus) dropped to nearly 0% just five weeks into 2020!

In the United States, the incidence of infection by influenza, respiratory adenovirus, rhinovirus, enterovirus, RSV, non-COVID coronaviruses, metapneumovirus, and parainfluenza viruses all decreased in March 2020, soon after implementation of mandates. Similar results were seen in Japan.

More dramatically, since pandemic mitigation measures were put in place, there has been a 99% global reduction of infections from both influenza types A and B compared to prior years. In particular, one of two flu B substrains has not been isolated in the world since August 2021 suggesting that this variant is now extinct. The overall genetic diversity of influenza viruses has also dramatically diminished indicating that other flu sub-types (or clades) have disappeared around the world since the pandemic mandates were put in place.

And this reduction of respiratory infectious disease does not only hold for those caused by viruses. Another study looked at surveillance data from 26 countries across 6 continents for several bacterial diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for disease due to Streptococcus agalactiae, a non-respiratory pathogen, were also collected from nine laboratories for comparison. All countries experienced a significant and sustained reduction in respiratory bacterial diseases in early 2020 (Jan 1 to May 31), coinciding with the introduction of non-medical COVID containment measures in each country. By contrast, the incidence of disease due to S agalactiae (which is not transmitted by the respiratory route) did not differ significantly from the 2 previous years.

Clearly, the mandates significantly reduced the incidence of respiratory infections by non-COVID viruses and bacteria. They worked. So, why did we still have COVID infections after the mandates went into place? The mandates reduced, not eliminated these diseases, so infections still happened. Since we did not have historical COVID infection data from previous years to compare with, the effects of the current mandates on the incidence of COVID are not as clear cut as they are with other diseases for which we do have historical data for comparison. But, as I wrote before (see above), it is clear that places in the US and around the world that used masks and other protective measures saw reduced incidence of COVID compared to similar places that did not.

Bottom line: The studies mentioned here regarding non-COVID infectious diseases fully support data previously posted in these pages that the mandates, including masks, are effective non-medical tools for controlling infectious respiratory diseases.

Don’t let anyone tell you differently.

Lions And Tigers And…Deer? Oh My!

First it was bats and humans, then domestic cats and dogs, farmed mink, and big zoo cats; now gorillas, hippos, and wild deer that have been infected by the SARS-CoV-2 (CoV-2 for short) virus. Many of these animals have become ill and several have died of COVID-19, most recently three snow leopards in South Dakota and Nebraska zoos. This is quite a wanton virus.

Of course, before CoV-2 and COVID-19 were known to the world, we knew that bats, humans and a few other animals, notably civets and even camels, were ready hosts of several different strains of “‘rona” viruses. We also knew that domesticated animals are also susceptible to their own coronavirus diseases—in fact veterinary coronavirus vaccines have been in use for years. Humans are known hosts for several coronaviruses, including those that cause the common cold, as well as the viruses that cause SARS, MERS, and now COVID-19. And we know that humans often catch these germs from bats and other intermediate hosts as diverse as civets and camels. After we genetically identified CoV-2 and were able to follow its spread, we quickly noticed that domestic pets also could be infected. This was closely followed with news that seven big cats at the Bronx zoo had become infected, and that mink farms across Europe were hotbeds for CoV-2 spread between humans and the animals and back. In fact, mink farms became such a hotbed of CoV-2 zoonotic spread that a couple of European countries completely shut down mink farming and culled all their animals. Several US states have also sharply curtailed mink farming. PETA probably applauds.

More recently two snow leopards at the Lincoln, NE children’s zoo and one in a zoo in South Dakota died from COVID. The Lincoln zoo also had two infected Sumatran tigers who recovered after being treated with steroids and antibiotics to prevent secondary infections and pneumonia. How the animals were infected is uncertain, but the most likely scenario is that they caught the virus from a caretaker. The problem is, none of the caretakers tested positive for the virus. Bats? Something else?

Since April 2020, when a tiger tested positive at the Bronx Zoo, dozens of other animals in zoos around the world have caught COVID. This month, the Denver Zoo reported the first coronavirus cases in hyenas, and the St. Louis Zoo found eight positive cases among its big cats, including two snow leopards. Abroad, the virus has killed a lion in India and two tiger cubs in Pakistan. Big cats seem especially susceptible since three other snow leopards at the Louisville Zoo were infected last December, and another snow leopard tested positive at the San Diego Zoo in July. The virus doesn’t just infect our fuzzy friends either; two hippos, named Imani and Hermien, at a zoo in Antwerp recently tested positive for COVID-19. Zoo keepers were first alerted to a potential problem when they noticed that the colossi had “runny noses.”  One reckons that a runny nose for a hippo is a big deal. One also wonders who gets to dab that nasal maw in order to test for the virus.

In fact, zoo and domestic animal infections have become so prevalent that an animal COVID vaccine developed by Zoetis, a NJ-based veterinary pharma company and former Pfizer subsidiary, has been authorized by the USDA for experimental use. The Cincinnati Zoo, for one, has vaccinated  80 animals, from giraffes to apes, against COVID.

Deer too. Oh my! It is one thing for zoo animals to acquire COVID—their captivity makes it easy to limit their interaction with other animals and humans to prevent spread of contagions, and they seldom complain that their rights are being infringed when they are quarantined. However, COVID in wild animals is a different story, as we have seen with bats and how easily they transmit the virus to humans. Scientists now have evidence that CoV-2 also readily propagates in white-tailed deer. In fact, the virus is already widespread in cervids across the US, which likely has significant implications for the long-term course of this pandemic.

In September of last year, genetic analysis of the gene that encodes the ACE2 protein (i.e., the viral receptors expressed on many cells in the body) in many different animal species suggested that CoV-2 could easily infect deer (and several other animals too). A survey of white-tailed deer in the Northeast and Midwest found that 40% had antibodies against the CoV-2 virus, indicating prior exposure. Between April and December 2020, veterinarians at Penn State found active CoV-2 infections in ~30% of deer tested across Iowa. Then during the winter COVID surge in humans from Nov. 23, 2020, to Jan. 10 of this year, ~80% of the tested deer were infected. The prevalence of the virus in deer was 50 to 100 times greater than in Iowa residents at the time (and the deer reportedly did not wear face masks). The study, published about two months ago, indicates that white-tailed deer have become a permanent reservoir for CoV-2. While it is not fully understood how the virus entered the deer population, genetic sequence analysis of nearly 100 viral samples found that the variants circulating in deer matched the variants circulating in people. This suggests that deer caught the virus from people multiple times in Iowa alone. How that happens is not known since people usually do not have close contact with live deer. More concerning is whether viral variants arising in deer readily pass back to people.

Bottom line. Clearly, a lot of different animal species can catch Cov-2 and spread it. It is clear that people can spread coronaviruses to pets and other animals, but the FDA says that the reverse, animal-to-human virus transmission, is not common. But, it clearly happens as we have seen with this pandemic, and with many other viruses that cause SARS, MERS, AIDS, Ebola, flu, etc., that spread from animals to humans. The prevalence of CoV-2 infection in so many species of mammals, especially in animals that have close contact with humans, suggests that several animal species, not just bats, can serve as permanent reservoirs for the virus and the jump to humans is something that can happen over and over. This is not unprecedented. It is what we see with influenza, which is carried back and forth between the Northern and Southern hemispheres with migratory birds, in which different flu viruses shuffle their genomes to create the new strains of flu for which we have to vaccinate against each year. This animal reservoir for flu makes it next to impossible to eliminate influenza, and similar animal hosts for CoV-2 likely would make it nigh impossible to eliminate COVID too. I raised this specter some months ago in these pages when reporting that pet dogs and cats can carry the virus. Our furry friends represent a viral reservoir that is in even closer contact with people than bats, deer, and fortunately, hippos and leopards.

We also have to be worried about the CoV-2 virus mutating in the different animal species that harbor and spread it. We know that happens in bats, which makes it almost certain that new strains of the virus will arise in deer and dogs too. We have already seen this on mink farms in the Netherlands and Poland. Farmworkers passed the virus to captive animals where it spread, mutated, and then spilled back into humans. In fact, zoonotic transmission from animals to humans probably happens thousands of times a year. Researchers from the EcoHealth Alliance and from Duke-NUS Medical School in Singapore, estimate that each year many people are newly infected with SARS-related coronaviruses. Many may get sick, but there are many reasons why most of these infections never grow into noticeable outbreaks (for example see my earlier blog post about unusual respiratory infection clusters in China and Los Angeles just before COVID). The researchers also created a detailed map of Asian habitats of 23 bat species known to harbor SARS-related coronaviruses then overlaid it with data on where humans live to create a map of potential infection hot spots. They found that close to 500 million people live in areas where bat-to-human transfer is likely, and this risk is highest in southern China, Vietnam, Cambodia, and Indonesia. Other surveys done before COVID-19 showed that many people in Southeast Asia harbor antibodies against other SARS-related coronaviruses. Blending these data with data on how often people encounter bats and how long antibodies remain in the blood, the researchers calculated that ~400,000 undetected human infections with these viruses occur each year across the region.

That is just for bat-to-human transfer in Southern Asia. It now looks like we will have to also concern ourselves with zoonotic coronavirus transfer from Buddy and Bambi too.

For this reason, researchers are working to develop a universal coronavirus vaccine that will be effective against most viral strains and variants. I will write about this soon. Stay tuned.

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The History Of Vaccine Mandates In The US

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As employers and the President are pushing vaccine mandates because too many have refused them, voices are crying out for their perceived rights saying “my body my choice.” They do not like their bosses or the government telling them to get vaccinated. This is a clash between individual rights and public health measures designed to save lives and to protect the larger community. Who gets to make the key decisions? How far can the government and employers go? Do individual rights trump community safety?

On Sept. 9, Biden announced the most sweeping vaccine requirements in American history, ordering that businesses with 100 or more employees ensure that all their workers are either vaccinated or get tested weekly for the coronavirus. The new rules also require vaccinations for federal workers and for federal contractors, as well as for workers at healthcare facilities that receive funding from Medicare and Medicaid. This will affect about 100 million people.

The authority for these government mandates, claims Biden, is a 1970 federal statute that gives the Secretary of Labor authority to issue a six month Emergency Temporary Standard (ETS) to protect workers from “grave danger from exposure to substances or agents determined to be toxic or physically harmful.” His move has triggered a political and legal battle, with many Republican governors vowing to fight the mandates in court. The mandates raise several new questions regarding this vague statute: Is a virus a “…toxic or physically harmful substance?” Does COVID-19 present a “grave danger?” Has the executive branch exceeded its authority in offering a solution to a problem previously reserved to the states? Do these mandates violate the 14th Amendment by depriving workers of their personal liberties? It is important to note that Biden’s mandates do not actually make vaccines compulsory: The government may levy a fine or forbid a child from attending school, but no American will be forced to get an unwanted jab. This has not always been the case.

There are historical precedents for vaccine mandates and even for forced vaccination.

In February 1991, five Philadelphia children died from measles, a disease that was mostly eradicated in the US, due to vaccination. Measles once sickened millions of kids, each year hospitalizing ~50,000 and killing close to 500 before a successful vaccine was developed in 1963. After that, cases dropped dramatically as all states mandated measles shots for school children. Vaccine hesitancy and resistance were rare because people saw the tangible success of the measles vaccine.

But, in Philadelphia that winter of 1991, the serious cases of measles came from a single source, a church cult that rejected “…all means of healing apart from God’s way.” Church members took no medicines, owned no thermometers, and saw no doctors. Rejecting all birth control, they raised large families in close quarters, a recipe for the measles epidemic, which they cooked. Trying to contain the threat to the rest of the city, officials worked through the courts to gain access to the homes of the congregants and received the authority to vaccinate the children against the wishes of their parents. In this public health emergency, defending the parents’ anti-vax actions was close to impossible. Even the ACLU took a pass.

Vaccine mandates even appeared during the Revolutionary War. George Washington mandated that all his troops be immunized against smallpox, even against their will. He described smallpox to Virginia’s Governor Patrick Henry as “more destructive to an Army in a Natural Way, than the Enemy’s Sword.” As I wrote earlier in these pages, smallpox had doomed the Colonial Army’s assault on Quebec in 1775, and it threatened Washington’s main force. Washington’s mandate proved a brilliant gambit and smallpox largely disappeared from the ranks. Some historians point to the mandate as a major factor in winning the war against the Brits.

During that war, smallpox vaccination entailed a primitive vaccination procedure known as variolation. That involved opening a lesion from an infected person and scraping its contents into the arm of a recipient. It was effective, but the vaccinated person became quite ill for a couple of weeks, and about 3% of them died from the pox. Later, in 1796, the English scientist Edward Jenner discovered a much safer method of immunization using cowpox, a virus similar to smallpox that did not cause significant disease in people. But the new smallpox vaccine got a mixed reception in the US as some resisted it for reasons of personal safety based on the variolation experience. They rationalized, “what good could possibly come from polluting the body with dangerous foreign matter?” Or, “Why challenge the plans of the Creator?” Still, Jenner’s vaccine was a clear improvement over variolation and drove a steady decline in smallpox outbreaks throughout the 19th century. States began passing laws mandating smallpox vaccinations for school children, and some forcibly vaccinated prisoners, paupers, and orphans.

In 1905, the issue of vaccine mandates reached the Supreme Court in the seminal case of Jacobson v. Massachusetts. Henning Jacobson, a Lutheran pastor in Cambridge had defied a city ordinance requiring smallpox vaccinations during an outbreak. He refused to pay a $5 fine so he was arrested. Jacobson posited that “healthy and law-abiding” people like himself (even though he was disobeying the law at the time) posed a minimal danger to the community. He argued that even if his refusal to be vaccinated led to him spreading the smallpox virus, the only victims would be others “who failed or refused to be vaccinated.” In other words, he reasoned that it would be ok to not get the vax because the vaxed would be safe, but wholly ignored the rights to safety of those who were not vaxed. 

It is an argument that is repeated today about the CoV-2 vax. Using modern science that was not available in the early 20^th century, experts have repeatedly refuted this argument, explaining that many people who want the vax cannot be fully vaccinated because they are immunocompromised, or allergic to the vaccine’s contents, or do not have access to the vaccine. Also, we now know that the more RNA viruses, like the coronavirus, are allowed to spread, the greater the chance more deadly variants can appear. Jacobson’s contention that the decision to vaccinate solely belongs to the individual, not to the state, employers, or to medical authorities remains a central tenant of today's anti-vaxers.

The Supreme Court disagreed with Jacobson. The majority opinion, written by Justice John Marshall Harlan, asserted that “the liberty secured by the Constitution does not import an absolute right in each person to be at all times, and in all circumstances, wholly freed from restraint.” Rather, he argued, the Constitution rests upon “the fundamental principle of the social compact…that all shall be governed by certain laws for the protection, safety, prosperity and happiness of the people, and not for the profit, honor or private interests of any one man, family or class of men.” Jacobson had not only broken the law, the court suggested he also had violated the principle upon which a well-ordered society depends. We are not wholly independent the court ruled. The greater good of the community can trump individual rights.

Using Jacobson as precedent, the Supreme Court in 1922, upheld a local ordinance in San Antonio requiring proof of smallpox vaccination for people entering “public schools or other places of education.”  

Later, during World War II, the US military made vaccines mandatory for a host of diseases, such as typhoid, yellow fever and tetanus, and it still mandates certain vaccines for troops in certain deployments. Soon after the war very successful vaccines were developed against several childhood diseases like polio, measles, mumps and chickenpox. Guided by the Supreme Court’s ruling in Jacobson, all 50 states put laws on the books mandating many of these vaccinations for school children. Even today, many school districts and colleges mandate certain vaccines for students and staff. Hospitals, too, often mandate certain vaccines for their staff. Until lately, vaccine mandates have not generated much angst and anger.

Why is this? Perhaps vaccines have done their job too well: Many of them have erased the tragic evidence of why they were needed in the first place. The world no longer deals with small pox, thanks to the vaccine. Almost no one in this country has seen someone ravaged by polio, or a child hospitalized with measles, or who lost his hearing due to chicken pox, all thanks to vaccines. Yet, now with COVID-19, anti-vaccine anxieties have found their way into the political mainstream, especially among conservatives. An estimated 80 million American adults remain unvaccinated against COVID and represent potential factories for producing the next deadly coronavirus variant, which is very preventable.

As I have addressed before in these pages, many factors fuel resistance to the life-saving shots, including doubts about their quick development and their possible long-term effects. But a growing distrust of professional expertise, including medical science, has also played a role, which is unwarranted. Who are you going to believe, a medical scientist like me with nothing to gain in the debate (except the safety of my friends, family, and self), or someone who read a web post from folks who are selling nostrums they claim will protect you, like Dr. Steve Hotze, or from one of America’s Frontline Doctors whose web site claimed that gynecological problems were caused by having sex with demons? Do you jump on the side of those who tout that their individual freedoms have been abridged, but who do not consider the freedoms from disease of the greater community, and whom the courts already have decided against?

Almost 300 years ago, Benjamin Franklin struggled over whether to have his sons variolated against smallpox. In his “Autobiography,” he worried that well-meaning people were tragically misjudging the calculus between the risks and benefits of the procedure, as he had once done, with a tragic result. He wrote, “In 1736, I lost one of my sons, a fine boy of four years old, by the smallpox….I long regretted bitterly and still regret that I had not given it to him by inoculation. This I mention for the sake of the parents who omit that operation, on the supposition that they should never forgive themselves if a child died under it; my example showing that the regret may be the same either way, and that, therefore, the safer should be chosen.”

What Caused India’s Devastating Second Wave?

Understanding what contributed to a second, more intense COVID-19 surge in India can inform the rest of the world on how to avoid a similar surge for this and future pathogens. This outbreak threatens to extend the pandemic itself and drive world-wide infections to new highs, creating an enormous a breeding ground for new and potentially more dangerous viral variants. If variants emerge that are not touched by the current vaccines, the world will be at square one with the pandemic. What a depressing thought.

It appears that the second wave arose due to a combination of three things: 1) India’s relaxing quarantine measures back in January, 2) the emergence of more rapidly spreading viral variants, including one that first appeared in India, and 3) a very poor rollout of vaccines to protect India’s population from spread of the virus. These are further discussed below.

1. Relaxed safety measures. India’s second surge came after loosening restrictions, which let public complacency set in, which, in turn, was exacerbated by government officials like Prime Minister Modi and Health Minister Harsh Vardhan declaring that the pandemic was defeated. Life returned to normal. Masks went away, as did social-distancing. Weddings and parties resumed, which usually are large events in India. A new season of state-level elections ushered in big political rallies and street parades. A massive religious festival known as the Kumbh Mela took place, bringing an estimated 5 million Hindu pilgrims to the banks of the river Ganges in April. By mid-March, cases started gradually climbing again—then suddenly accelerated, becoming a vertical line rather than an upward sloping curve. The government was slow to respond. It was not until late April that Modi finally acknowledged the urgency of the situation. Local containment measures are beginning to be enacted, including shutting down the capitol of Dehli, and a few Indian states. However, Modi remains reluctant to enact country-wide restrictions like he did during the first wave. Without a more aggressive vaccine campaign, that could be a bad decision.

The more the virus spreads throughout India, and even into its neighboring countries of Nepal, Pakistan, and Bangladesh, the greater the risk that it will generate more infectious and dangerous viral variants that will not be affected by the current vaccines. If that happens, well vaccinated countries will have to start over. That is not a pleasant prospect, and is further discussed below.

2. More infectious viral variants. India’s more deadly second wave of the CoV-2 virus can also be attributed to more infectious and more persistent viral variants. In this second wave, India, like many other countries, has been inundated with viral variants first identified in the UK and South Africa that were recently discussed in these pages. The UK variant has a mutation in its spike protein that makes it more infectious than its parent virus. The South African variant has a different mutation in its spike protein that makes the virus more resistant to some vaccines.
   

India’s second surge also has introduced the world to a unique viral variant dubbed the "double mutant," which was first identified in October. It is now the dominant strain in the state of Maharashtra, home to India’s financial center, Mumbai.

“Double mutant” is actually a misnomer for this variant since it has 13 mutations throughout its genome. However, it acquired that sobriquet because it has joined the UK and South African spike protein mutations in the same virus. It is a double whammy.

While scientists are still learning about the double mutant variant, India is seeing people who were previously infected become re-infected with this new variant. Also, younger and healthier people are being hospitalized in greater numbers. These observations are concerning. Similar observations of re-infection have also been seen in Brazil with yet another viral variant that was first identified there (more about Brazil in a future post). The ability of viral variants to re-infect people can be an important driver of future pandemic waves even in countries where the population is well vaccinated, but where isolation measures have been lifted or ignored.

For the country overall, the double mutant virus made up 70.4% of the samples collected during the week ending March 25, and that is compared with 16.1% just three weeks earlier, according to Covid CG, a tracking tool from the Broad Institute of MIT and Harvard. The tool mines data from the GISAID Initiative, a global database for coronavirus genomes. These data also show that the double mutant virus has already hopped to at least 21 countries including the US. In Australia viral genome sequencing showed that the double mutant made up 40% of the samples collected over the week ending April 15, compared with 16.7% a month earlier. It accounted for 66.7% of samples from New Zealand for the week that ended April 8, up from 20% a month ago. It also has been detected in California, according to Dr. Benjamin Pinsky, director of the Clinical Virology Laboratory at Stanford University. Clearly, where the double mutant virus appears, it quickly achieves dominance.

3. Poor vaccine distribution. As of 4/30, India had only administered 15 million vaccinations, a tiny proportion of its population of 1.4 billion people. The country is the primary producer of the AstraZeneca vaccine that has run into supply chain problems causing delays in vaccine delivery. In February, Biden signed the Defense Production Act to boost U.S. COVID-19 vaccine production but that decision cut off US exports of raw materials that India needs in order to maintain its vaccine production capabilities. Thus, vaccine makers around the world, including the Serum Institute of India (SII), the largest vaccine manufacturer in the world, face a shortage of materials to make COVID-19 vaccines. The ban has garnered much criticism as resource hoarding that threatens global vaccine production. On April 16, SII appealed directly to Biden to lift the embargo of raw material exports so that vaccine production could continue. Several days later, the White House announced it would partially lift the ban for materials the Indian company needed to manufacture the AstraZeneca vaccine, specifically.

The US also inexplicably has a large stockpile of millions of doses of the AstraZeneca vaccine, that were made here, even though it is not approved for use in the US. If we are not using it, why not release the stores to the world? The Biden administration also has faced criticism for hoarding these doses that could help India and other countries around the world that also are experiencing a new surge in infections. On Friday, April 30^th, the U.S. Chamber of Commerce called on Biden release the AstraZeneca vaccines to India and other hard-hit countries.

There is some irony in all of this since India is a huge manufacturer of vaccines and pharmaceuticals for the world, and likes to bill itself as the “pharmacy of the world.” India produces 60 percent of the world’s vaccines, but cannot supply its own country, partly because of reduced production due to the supply chain problems, but also because it failed to order sufficient vaccine doses. India almost completely halted vaccine exports last month in order to divert supplies to its domestic population, which is affecting supply in the rest of the world. Rather than rely on its own manufacturers for vaccines, India approved Russia’s Sputnik vaccine, and has fast-tracked the approval process for other vaccines manufactured in foreign countries. That means that while the industrialized world was being vaccinated with vaccines produced in India, the country was still looking at approving foreign-made vaccines for use in its country.

Bottom line. The combination of relaxed safety protocols, the appearance of deadlier viral variants, and poor distribution of vaccines to its people has left the country as the world’s epicenter for the pandemic. As the virus races through its huge population, all of this provides an enormous breeding ground for new variants to arise, which is worrisome even for countries that have had successful vaccine rollouts and have begun to see reduced viral spread. Let us hope this is not a perfect storm for restarting the pandemic with vaccine-resistant variants.

And India is not the only problem. In Africa, vaccination is also off to a slow start. Just 6m doses have been administered in sub-Saharan Africa, fewer than in New Jersey. Just 1% of African adults have received a first jab, versus a global average of 13%. Prepare for Africa to become the next hot-spot and breeding ground for troublesome variants, if Brazil and South America do not beat them to the punch.

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What Is Going On In India?

The situation. India is in the throes of a second major Covid-19 surge that has hit faster and harder than the first wave did. That is often how viral pandemics behave. This catastrophic second wave came after a strict lockdown of the country in early 2020 following the first wave. In January 2021 India’s Prime Minister Modi declared that the lockdown had succeeded and that they had defeated the virus, and he re-opened the country. Until March, India was recording barely 13,000 new COVID-19 cases a day, fewer than Germany or France, and a drop in the bucket for a nation of 1.4 billion people. A few weeks after Modi’s victory declaration, however, daily cases began slowly climbing, then in late March they exploded, becoming a vertical line rather than an upward sloping curve. By mid-April India reported 315,000 new cases in one day, setting a world record. Yesterday (May 5) India set yet another record with 3700 daily deaths, according to the Johns Hopkins University tracker. The case and death rates are still climbing. Today, almost 50% of the world’s new cases come from India, according to the WHO.

India has reported 2,000-4,000 COVID-19 deaths a day for several weeks now. Since the country’s health infrastructure is poor, this likely represents a significant undercount of the mortality. As of April 30, the official total death count was around 200,000. However, the official tallies do not reflect the thousands in poor and rural areas who cannot get medical care and die at home and are not counted. For example, in just one day at one crematorium in Bhopal, workers cremated 110 COVID-19 victims, but the official total death toll for the city was just 10. Experts suspect that the total death toll in India is 1-2 million.

The second wave of the pandemic also has overwhelmed hospitals across India. Securing a hospital bed, even for the critically ill, is nearly impossible. Hospitals put up signs declaring they have no beds, and families in large cities have to search for days to find beds, often hundreds of miles away. Sick people die on the roads outside hospitals and in traffic jams created by ambulances ferrying critically ill patients in search of a bed. There are images of patients gasping for oxygen while waiting to see a doctor.

Because getting admitted to a hospital is so difficult now, patients who are admitted are much sicker than in India’s first wave. The average temperature readings of second wave patients are 2 to 3 degrees higher than they were during the first wave when temperatures averaged 100-101 degrees Fahrenheit. Blood oxygen levels of recently admitted patients run lower than they did last year meaning the patients are more critical and in greater need of oxygen. The patients are also younger this time around, between the ages of 35 and 45, and often without other pre-existing conditions.

Critical healthcare necessities are in short supply in India, from intensive care beds, medicine, oxygen, and ventilators. Delhi hospitals have tweeted messages appealing for oxygen. At one Delhi hospital, 20 critically ill patients died after the hospital’s oxygen delivery was delayed seven hours. Families are often told that they have to provide their own oxygen for hospitalized family members or take them home. In a video post, the director of a hospital said they had 60 patients in need of oxygen with only two hours of supply left.

Help for India has been offered by several countries, including the US, UK, Germany and even from India’s archrival Pakistan, which offered ventilators, oxygen supply kits, digital X-ray machines, PPE, and related items.

Bottom line. This is a snapshot of what things look like in India now, almost a year and a half after the virus first introduced itself to the world. In January, India believed that its strict lockdown measures had defeated the virus. They did not. How the more deadly second wave of the virus and disease appeared, almost overnight, will be the topic of the next blog post. It should concern all of us, because it could also happen here.

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Paying The Piper

In the face of a pandemic caused by a new and deadly virus, states and local governments enact social-distancing measures, bans on crowds, closure orders, and mask mandates in an effort to flatten the curve and prevent health care systems from being overwhelmed with critically infected people. Initially, people are fairly compliant with the order, but, as the days of restriction turn into weeks, then months, compliance wanes. Theater owners complain about financial losses. Clergy bemoan church closures. People argue whether children are safer in classrooms or at home, and many rebel at having to wear face masks in public, complaining that the government has no right to infringe on their civil liberties. Sound familiar?

But this is not about the 2020-21 coronavirus pandemic; these are descriptions of the US response to the deadly Spanish flu pandemic between 1918 and 1920. In many ways our current pandemic mirrors the one that occurred a century ago, and that is presciently described in the book, The Great Influenza, by John M. Barry. Like CoV-2, the H1N1 “Spanish” flu killed less than 1% of the people it infected, but during a third wave of infection with a more virulent strain, that flu killed more people around the world in just 24 weeks than were killed in the 10 years of WWI and WWII combined! In remote areas with little access to health care, the flu wiped out entire villages.

Like COVID-19, the Spanish flu pandemic hit hard and fast, going from a handful of reported cases in a few cities to a nationwide outbreak within a few weeks, then with increased mobility due to WWI, it quickly spread around the world, from America to Europe and back. Many communities, responding to the ebbs and flows of the epidemic waves, issued several rounds of closure in an attempt to keep the disease in check. These social-distancing orders worked to reduce cases and deaths. However, just as today, they often proved difficult to maintain. By the late autumn of 1918, just weeks after wide-spread social-distancing orders went into effect, the pandemic seemed to be coming to an end as the number of new infections declined. People clamored to return to their normal lives. Businesses pressed officials to be allowed to reopen. Believing the pandemic was waning, some state and local authorities began rescinding public health edicts. Sound familiar?

Americans hurried to return to their pre-pandemic routines. In some cities, they packed into movie theaters and dance halls, crowded into stores and shops, and gathered with friends and family for holidays and celebrations. Meanwhile, officials warned the nation that cases and deaths likely would continue for months to come, but the warnings fell on increasingly deaf ears, as people enjoyed a return to normalcy. The nation carried on, inured to the toll the pandemic was taking. But as health officials warned, the pandemic wore on, stretching into a third deadly wave that lasted through the spring of 1919, with a fourth wave hitting in the winter of 1920. Some blamed those world-wide resurgences on careless Americans.

The different responses and experiences of two large American cities are noteworthy here. In Denver, local business interests lobbied heavily to get rid of the quarantine measures that had shut down schools, churches, libraries, pool halls, businesses, and theaters. The city capitulated. The city opened up and was hammered by the deadly third wave of the flu. On Armistice Day, November 11, 1918, residents poured out of their homes to celebrate the end of World War I. A few days later, many were dead, victims of the pandemic flu. Two weeks later, a headline in the Denver Post captured the devastation: “All Flu Records Smashed in Denver in Last 24 Hours.”  An editorial in the Denver Monthly Magazine said, “For some reason, even the most enlightened citizens will not take the influenza epidemic seriously. They know that it is the most widespread epidemic that has ever visited America. They know the disease is a deadly menace and snuffs out life almost before the victim realizes he is ill. Yet when health officers try to impress upon people the necessity of following essential rules and regulations, the average citizen simply refuses to heed these admonitions.”

In contrast to Denver, St. Louis enacted and maintained strong social distancing measures, including in-home quarantines for infected people. They experienced a fraction of the deaths that Denver saw. The quarantine measures worked there.

The similarities in our responses to the 1919-20 flu and 2020-? coronavirus pandemics are noteworthy. But, there is one big, hopefully defining difference between the two pandemics that might make the outcomes quite different. Vaccines. There were no flu vaccines to rescue the world from the ravages of the Spanish flu. In fact, the influenza virus would not even be discovered for another 15 years, and a vaccine was not available until 1945. For the first 12 or so months of the current coronavirus pandemic, we were in the same boat—we faced a novel virus with no vaccine or effective medicine. When there is no available medical response to a pathogen, we must rely on protective public health measures to provide a buffer against the pathogen while we learn how to respond to it.

Today, we have significant advantages with a much better understanding of virology and epidemiology then we did in 1918. We know that both social distancing and masking work to help save lives. Most critically, we now have multiple safe and effective anti-CoV-2 vaccines that are being deployed, with the pace of vaccinations increasingly weekly.

Still, the deadly third wave of influenza shows what can happen when people prematurely relax their guard against viruses that can mutate and become more deadly. That is why we must remain vigilant while the coronavirus vaccines roll out. We are still learning about this virus and are only beginning to learn about the variants spawned by the virus. We still need a public health buffer from the virus to keep us safe until we better understand its full capabilities and can vaccinate more people.

Be smart. Stay safe. Get the vaccine.

More Than Half CoV-2 Transmission Comes From People Without COVID-19 Symptoms

The Journal of the American Medical Association just reported that 59% of new CoV-2 infections are likely caused by infected people who do not show COVID-19 symptoms. This conclusion is based on the results of a decision analytical model that assessed the spread from pre-symptomatic, never-symptomatic and symptomatic people infected with CoV-2. 35% of viral transmission came from pre-symptomatic people, and 24% from people who never develop symptoms.  

This means that until the vaccines are widely disseminated, identifying and isolating people with COVID-19 will be much less effective at controlling the spread of the virus than previously thought. Effective control of the disease still requires social isolation measures such as wearing face masks indoors, distancing from others, hand hygiene, and limiting indoor contact with other people.