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  1. Sledge, George W. Jr. MD

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We're exhausted, dismayed, and angered over the way our lives have gone off track these past 2 years. COVID-19 never seems to end, and the new normal is distinctly abnormal. Leaving aside the minor inconveniences, the effects on society have been ample. To name a few: economic disruption (job losses due to shutdowns, supply chain issues, stock market flip-flops), social disruption (increased murder rates, increased crimes against women and people of Asian descent), political polarization piled on existing political polarization to the detriment of basic public health measures, schools closed and 6-year-olds trapped at home with working parents whose interplay with their co-workers is by Zoom conferences. But more than anything else, a nagging sense that nothing is safe and predictable anymore has led many to live in a permanent state of unease.

  
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All of us in the health care professions know the human toll, the lives lost, the exhausted ICU nurses and ED physicians, the noisy ventilators, and the sad family conferences. And all this followed by the long COVID symptoms that we are just beginning to understand and will wrestle with for years. We all have stories we could share, but we are too tired to care anymore.

 

Already 2019 seems like a different era, some facsimile of an old Jetsons Saturday morning children's cartoon, when life was dominated by technologic advances and Mother Nature was just one minor special interest group, recognized but usually ignored by a populace enamored by the latest shiny new gadgets. An era where one could go online and get a ticket to Bangkok or Paris, stand in line at a crowded airport, sit next to someone with a mild cough, fly overseas for 12 hours and think nothing about it.

 

That was BC: Before COVID. In the After Covid (AC) universe, a trip to the local grocery store can seem fraught with hazard. Fly overseas to a medical conference? Forget it. Get on a cruise ship, those floating coronavirus hot boxes? Are you nuts? We no longer have the freedoms we took for granted, and many of the limitations are the self-imposed ones derived as much from our own psyches as from public health departments or the CDC.

 

What's worse, we no longer trust our fellow citizens. Is the woman standing behind me at the checkout line, her homemade cloth mask covering only her chin, vaccinated and boosted? Is her child's cough some mild rhinovirus or the latest highly transmissible variant? Will I get in an argument over mask wearing at my child's school? I never used to worry about someone's flu vaccine status-perhaps foolishly-but now I ask every patient I see in clinic about their COVID shots.

 

And underling everything else, this question: when will it all end? A once-in-a-century pandemic leaves us with few relevant historical comparisons. The last great pandemic was the 1918-1920 Great Influenza, which killed somewhere in the range of 50-100 million people in a world less populated than today. That pandemic came in four waves: a mild one with characteristics of a regular flu season, followed by the major killing fields of late 1918, followed by another significant outbreak that killed tens of thousands in the U.S. in 1919, followed by a 1920 series of localized but lesser outbreaks. So roughly 3 years of fear and deaths, and then back to normal.

 

Of course, that flu never actually went away. It mutated into something less dangerous, its progeny continuing until today. It still kills in the thousands per year, though fewer in the era of COVID: masks work. Perhaps influenza's slide from pandemic to the endemic is our fate with COVID-19. Or perhaps, and this is devoutly to be yearned for, deliverance will come in the form of a universal COVID vaccine, as some have suggested.

 

Either of those two outcomes would be welcome. But history offers other, more dismal scenarios. Imagine, if you will, that you are miraculously transported to Stratford-upon-Avon in 1564. If you attend Holy Trinity church on April 26, you will see the baptism of William Shakespeare. The parish register for that date, probably a few days after his birth, lists him as Gulielmus filius Johannes Shakspere."

 

But don't linger there. On July 11, the same parish register informs us "Here begins the plague." After that there is a steady drumbeat of plague-related deaths lasting through the end of the year, including many young children. Shakespeare was lucky.

 

Follow him as he moves to London, sometime in the late 1580s, and the plague is waiting there as well. In 1592, the plague killed roughly one Londoner in twelve. The city authorities had strict rules shutting down the playhouses and other public spectacles once plague deaths reached 30 per week, so young Shakespeare uses his down time to write his poem Venus and Adonis, which earns him the patronage of an Earl of Southampton. The poem includes these lovely lines: "Long may they kiss each other, for this cure/...To drive infection from the dangerous year/That the star-gazers having writ on death/May say, the plague is banish'd by thy breath." Or, as in the case of COVID, "spread by thy breath."

 

In 1603, the plague came again in a big way, killing 30,000 people in a city of 200,000, and the playhouses were shut down to prevent spread of the infection. And in 1606 the plague returned, and again Shakespeare and his company faced government-enforced shutdown and loss of income.

 

Shakespeare's company, originally the Lord Chamberlain's Men during Queen Elizabeth's time, then the King's Men (for they were favorites of King James) left London and toured the provinces when the playhouses were shut down. But if one stayed in London, and the Black Death was known to have afflicted a family member, one's house was boarded up for a month and the house's occupants forbidden to leave. In James Shapiro's wonderful book The Year of Lear, subtitled Shakespeare in 1606, the author makes the case that the playwright's landlady may have died of the plague at the age of 40. If so, as in 1564, Pasteurella pestis may have come too close for comfort.

 

Shakespeare mentions the words "plague" and "pestilence" in his plays, though usually not as the centerpiece of the works. Perhaps the memories are too painful for the citizens of London. But the plague is frequently there in the background, as in real life. Take Romeo and Juliet, for instance. When Romeo's friend Mercutio is stabbed and lays dying, he says "a plague a' both your houses." To modern ears, this is just a witty metaphor, but if you were attending the Globe Theatre then, how would it have sounded? You've seen friends die in days, purulent painful buboes turning lymph nodes into torture chambers. You are scared for your life just thinking about it. Perhaps the phrase would be the equivalent of saying something like, "I hope you both die of cancer." If you lived through 1603, where 15 percent of the population perished in a matter of months, this was no innocent metaphor. It was a curse.

 

Later in the play, in what will have tragic consequences for the young lovers, a letter is not delivered to Romeo in time. The reason is the plague: "the searchers of the town, /Suspecting that we were both in a house/Where the infectious pestilence did reign, /Sealed up the doors, and would not let us out." Quarantine is a very old idea, and for Shakespeare's audience, a living presence.

 

The plague would not disappear from London until after 1666, when the Great Fire of London, and the subsequent rebuilding of much of the city in brick rather than in thatched roofs, made it less friendly to the fleas and rats that transmitted the plague.

 

Here's the thing that amazes me: the Black Death first arrived in England in 1348. 1603 was 255 years after that, and the bubonic plague has another half century or more to torment the citizens of England. Two hundred fifty-five years ago was 1767; imagine COVID arriving then and coming back every few years, killing only a few in "good" years and 15 percent in the bad years. And having a half century more to go before disappearing for good. What an intensely depressing thought. But that was the world in which Will Shakespeare lived.

 

If there is any cheer to be derived from the infectious disease history of Shakespeare's times, those long-ago plague years, let it be this: in 1606, when the Globe Theatre shut down for most of a year, Will Shakespeare didn't goof off. Shakespeare scholars believe that he penned Macbeth, Antony and Cleopatra, and King Lear, all within a 12-month period. Has any writer ever had a better year?

 

Or, perhaps, consider late 1665. This is the last time that the plague will visit England, but its spread has temporarily shut down Cambridge University. The students are sent home until things cool down in 1666 and classes resume. One of the students, young Isaac Newton, goes home to Woolsthorpe Manor. In 1726, near the end of a not-too-shabby scientific career, he shares this anecdote with his biographer: "After dinner, the weather being warm, we went into the garden & drank tea under the shade of some apple trees... he told me, he was just in the same situation, as when formerly, the notion of gravitation came into his mind...occasioned by the fall of an apple, as he sat in a contemplative mood."

 

Somewhere, in some lab, or perhaps in a crowded apartment, some grad student or postdoc, who's life has been put on hold by the pandemic, is sitting in a contemplative mood. Newton's apple, I want to believe, has fallen out of the sky and plunked this smart kid on the head and we just haven't heard about it yet. Perhaps finding the cure for cancer or working out the development of the universal vaccine that will end COVID-19 once and for all, but in any event creating something that will transform the world. There is, after all, precedent; the greatest playwright in human history and the human race's greatest physicist both allow us to hope that something good will come out of all this pain and suffering.

 

GEORGE W. SLEDGE, JR., MD, is Professor of Medicine at Stanford University. He also is Oncology Times' Editorial Board Chair. In his column, Musings of a Cancer Doctor, Sledge shares his personal thoughts on cancer research, patient care, and health care trends. Comment on this article and previous postings on his OT blog at bit.ly/OT-Sledge.

  
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