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September 2020

Will A COVID-19 Vaccine Be Effective?

In an earlier post made in late May, your humble blogger predicted that the major hurdle in controlling the CoV-2 pandemic was not in developing an effective vaccine, but in getting enough people to be vaccinated. A recent poll from the Kaiser Family Foundation supports that notion. 54% of respondents said they would not get the vaccine if it was available for free before the November 3 presidential election. I also posited that that time frame for developing a vaccine is untenable. I would like to see a poll on how many people would refuse a vaccine that was approved and released, say in April next year, which is a more tenable timeframe. Given the absurd anti-vaccination sentiment in the US, I am not optimistic that the response would be much better.

A population needs about 70% of its people to carry protective immunity in order for herd immunity to be effective. It is unreasonable and unethical to reach that 70% threshold via natural infection with a novel pathogen like CoV-2 that causes debilitating disease that we currently do not know how to effectively treat. Therefore, a vaccine that confers a similar level of immunity, but without the risks associated with the disease, is the only way to ethically attempt to achieve a population-wide protective herd immunity. But, if too few Americans get a Covid-19 vaccine when it becomes available, it won't help reduce the spread of the virus making the whole vaccine development effort largely moot, at least for the next two or three years.

In any infectious disease outbreak, the critical factor for controlling it is the “R naught” or R0 number, which is a measure of how contagious the pathogen is. For seasonal flu, R0 = 2, meaning that on average, an infected person will infect two others, thereby increasing the viral spread. For CoV-2, R0 = 4, which means that on average, an infected person will infect four others, twice the infection rate of flu. During an infectious disease outbreak, the goal of public health officials is to get the R0 value to <1, which signifies that the infection is petering out. The only ways to achieve this are to 1) wait for seasonal viruses to run out of their season, 2) via quarantine to limit exposure and spread, 3) vaccination to confer herd immunity, 4) natural infection to achieve herd immunity, or 5) using anti-pathogen medicines such as antibiotics. For a pathogen like CoV-2, for which there are no good medicines, or a vaccine to reduce the R0 value, or for which there does not seem to be a seasonal limit, and for which natural infection is not ethical, #2, or isolation, is the only way to reduce disease spread. Facemasks are an effective way to isolate and prevent spread of respiratory pathogens. In fact, researchers in the UK predict that if just 50% of people wore face masks, the CoV-2 R0 would drop to <1, buying us time until we can develop an effective vaccine with which to achieve a more permanent herd immunity. But, that can only happen if enough people get vaccinated. That will be the great impediment.

We will see.

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Timeline Of Early COVID-19 Events

Late 2019: In November 2019, analyses of wire and computer intercepts, coupled with satellite images leads the US National Center for Medical Intelligence to suspect that a contagion was emerging in China’s Hubei Province, specifically in Wuhan, China's 10th largest city with a population of ~11 million (for comparison, NYC has a population of just over 8 million). This intelligence is shared with the US Defense Intelligence Agency, the Pentagon’s Joint Chiefs, and the White House. Around Thanksgiving, analysts report that China’s leadership is aware of a growing epidemic, but decided to keep the details secret from the world.

Dec 31, 2019: Chinese officials inform the WHO about a cluster of 41 patients with a mysterious pneumonia.

In the middle of the night on the 31st, Wuhan officials quietly begin disinfecting its wet market.

Jan 1, 2020: A Chinese CDC team from Beijing arrived in Wuhan and collected 585 “environment” samples from a garbage truck, drains and sewers in the market. They report that 33 of samples test positive for the virus. 14 of the positive samples are from the area of the market where wildlife was traded.

The Wuhan market closes.

The Chinese government prohibits genome sequencing of new coronavirus samples and orders existing viral samples destroyed.

Jan 1-3: Wuhan police silence eight medical doctors they call “rumor mongers,” warning them against talking about the novel disease. One of them, Dr. Li Wenliang, an ophthalmologist, contracts the virus on Jan 8 and dies Feb 7.

Jan 2: The Central Hospital of Wuhan prohibits staff from publicly discussing the disease.

Jan 6: The US CDC issues a Level 1 travel watch with recommendations on washing hands, avoiding animals, animal markets, and contact with unwell people if travelling to Wuhan.

Jan 7: Chinese scientists report that the cause of the Wuhan flu is a novel coronavirus.

Jan 11: China records it first death linked to the new virus.

Jan 12: The Shanghai Public Health Clinical Center, the facility that published the first genome sequence of the virus, closes without reason.

Jan 13: Thailand reports the first coronavirus infection outside China.

Jan 14: The first confirmed case of COVID-19 in the US appears in the Seattle area in a 35 year old man who had recently arrived from Wuhan. However, a recent UCLA examination of its hospital records shows that there was an unexpected 50% spike in patients with respiratory illness beginning Dec. 22 and continuing through the end of February. This raises the possibility that COVID-19 might have been in the US at least a month before this patient was diagnosed with it.

The WHO states that there is no evidence of person-to-person transmission of the virus.

Jan 17: The US CDC sends 100 people to three US airports to screen travelers from Wuhan.

Jan 20: Since health care workers have come down with COVID-19, the WHO announces that there is person-to-person transmission of the virus.

Jan 21: Anthony Fauci, head of the National Institute for Allergy and Infectious Disease says that “this is not a major threat for the people of the United States, and this is not something that the citizens….should be worried about.”

China reports COVID-19 cases across several major cities including Beijing and Shanghai.

Jan 22: Countries begin closing borders and restricting travel. This includes North Korea, Singapore, Vietnam, Russia, Hong Kong, Mongolia, Pakistan, Malaysia, Mexico, Philippines, Sri Lanka, Thailand, UK, Papua New Guinea, Palau, Vanuatu, Kazakhstan, Nepal, Tibet, Canada, Italy, Trinidad, Tobago, Jamaica, Poland, Iraq, and Turkey.

The US State Department issues a Level 4 travel advisory to not travel to China. It also advises that Americans in China should consider departing, and authorizes American diplomatic staff and their families to evacuate China.

Jan 23: China completely isolates Wuhan—no traffic, including planes, and trains, is allowed in or out of the city, and all public transportation within the city is suspended. A few days later the entire Hubei province is shut down. The day before the Wuhan travel ban, 100,000 people leave the city on trains. An estimated 5 million people travel out the area in the days prior to the quarantine.

The WHO declares that the virus is not a Public Health Emergency of International Concern.

Jan 24: Chinese doctors publish in the medical journal, Lancet, the first report on “Clinical Features of Patients Infected With 2019 Novel Coronavirus in Wuhan, China.” It includes the first description of symptom-free infected people. It also reports that 13 of the original 41 cases had no link to the Wuhan wet market, indicating probable human transmission of the virus.

Another report in the same issue of Lancet describes person-to-person of the virus within a family and the WHO documents another case of person-to-person transmission in Vietnam.

The WHO changes its mind and warns the world of a possible pandemic.

Jan 25: The beginning of the Chinese New Year (the year of the Rat). Nancy Pelosi and NYC mayor de Blasio encourage Californians and New Yorkers to participate in Chinese New Year Parades and to visit China Towns in NYC and San Francisco.

Jan 26: Fauci advises, “The American people should not be worried or frightened by this. It’s a very low risk to the United States, but it’s something that we, as public health officials, need to take very seriously.”

China bans all wildlife trade and the Chinese CDC begins developing vaccines against the novel coronavirus.

Chinese police drop their case against eight people accused on January first of spreading false rumors about a new SARS-like virus.

Jan 30: WHO reverses its decision from one week earlier to declare the coronavirus outbreak a Public Health Emergency of International Concern and advises "all countries should be prepared for containment, including active surveillance, early detection, isolation and case management, contact tracing,…”

US health experts agree that a ban on travel from epidemic hot areas is needed.

Jan 31: Trump announces a travel ban from China and declares a Public Health Emergency. US borders close to all foreign nationals who pose a threat of transmitting the virus. U.S. citizens returning from Hubei province in China are quarantined for two weeks.

Feb 1: Joe Biden and Nancy Pelosi accuse Trump of fearmongering and xenophobia for the travel ban.

Feb 3: Fauci predicts that because of travel restrictions, the danger to Americans was “just minuscule.” He also warns against “outlandish extrapolations of fear” and advises that “…there is no reason whatsoever to wear a mask.”

Feb 4: Italians embark on a campaign to hug Chinese to encourage them in the coronavirus fight and as an anti-prejudice statement.

Feb 12: COVID-19 cases begin to spike in S. Korea.

Feb 19: COVID-19 cases begin to spike in Iran.

Feb 21: COVID-19 begins to spike in Italy.

Feb 25: The US CDC warns that clusters of outbreaks are likely to arise in the US and that hospitals, businesses, and schools should begin preparing for social distancing. The US has 57 confirmed COVID-19 cases, 40 of whom are connected to the Diamond Princess cruise ship. While there are no signs of sustained transmission in the US, the warning is based on the rising infections in Iran, Korea and Italy.

New Orleans goes ahead with its Mardi Gras parade and celebration.

Feb 28 and 29: Fauci changes his tune and acknowledges that “It could be really bad,” but also adds, “I don’t think it’s gonna be, because I think we’d be able to do the kind of mitigation (sic). It could be mild.” And, “Right now…there is no need to change anything that you’re doing on a day-by-day basis. Right now the risk is still low, but this could change….I mean this could be a major outbreak.”

March 1: The first confirmed COVID-19 case appears in NYC. More cases rapidly appear in following days and viral sequence analyses traces the source of the virus back to China but via Europe. The travel ban from China seems to have worked, but viral entry from Europe was not expected.

March 8: The entire country of Italy goes into complete lockdown.

March 10: Fauci again advises that “…the risk is relatively low,” but also cknowledges that “there are parts of the country right now that are having community spread in which the risk there is clearly a bit more than that.” He cautions, “…we should like the country to realize that as a nation, we can’t be doing the kinds of things we were doing a few months ago.”

A choir practice in Skagit County Washington is attended by 61 people, including one who had developed a “cold” three days prior. In the days following the 2.5 hour practice, 52 COVID-19 cases occur (an infection rate of 87%). Three are hospitalized and two die from the disease.

March 11: WHO declares a pandemic.

Trump bans all travel from 26 European countries.

March 12: Biden rejects all travel bans saying that viruses do not respect borders.

March 13: Trump declares a national emergency.

March 16: Trump urges Americans to avoid restaurants, bars, unnecessary travel, and groups of more than 10 people.

States begin ordering “shelter in place” restrictions.

March 18: Trump signs the Defense Protection Act that allows the military to provide States with PPE and ventilators from the US strategic reserves. He also announces that the US Navy hospital ships, Comfort and Mercy, will be deployed to the East and West Coasts in case hospitals are overwhelmed by COVID-19 cases.

March 23: NYC confirms 21,000 COVID-19 cases making it the epicenter of the US outbreak.

March 31: More than 1/3 of the world population is under some form of lockdown.

April 3: For the first time, Biden supports travel bans to slow spread of CoV-2.

Summary: No one knew we were facing a once-in-a-generation pandemic. The important question is: “Why did it take so long for the health professionals around the world to recognize the extent of the threat and advise the world to act more forcefully? The answer partly is because this virus did not behave as expected based on recent experience with SARS, MERS, avian flu, swine flu, Zika and Ebola outbreaks. Those viruses did not come with “stealth” vectors, or asymptomatic virus spreaders, which led to much faster and unexpected transmission of Cov-2. Also, the constellation of COVID-19 symptoms were confusing and not as straightforward as, say Ebola, where it is unambiguous how the virus affects people. Finally, this range of often unrelated symptoms associated with COVID-19 is further confounded by the long-lasting adverse health sequelae in many patients that are rare in most other viral infections.

In other words, health professionals had a very steep learning curve with this virus that they did not have with other significant pathogens we have encountered in recent decades.  The professionals had to learn on the fly and are still learning. This timeline reflects that learning curve and shows how professional opinions changed over a matter of weeks, or even days, as new information emerged.

This will happen again.

Note on sources: This timeline was assembled from numerous sources including the Washington Post, The Wall Street Journal, The New York Times, The Guardian, Summit News, CNN online, Real Clear Politics, Yahoo News, Business Insider, Forbes, Wikipedia, ABC News, and several medical journals.


Disinfectant Treatment Redux

Remember when, at a press conference, Trump turned to some doctors and asked the inelegant question of whether they could use “disinfectants” to treat COVID-19? “Disinfectant” was a poor word choice made by a non-medical expert, and the press did what it does best and over-interpreted that malapropism to claim that he was asking whether Clorox or Lysol could be injected to treat the disease. That was a rhetorical overreach on their part.

What if, instead of “disinfectant,” he used the word “antiseptic?” Antiseptics are biocidal chemicals that stop or slow the growth of microorganisms and are frequently used in hospitals and clinics to sterilize skin and mucous membranes to reduce the risk of infection during medical procedures. Disinfectants also are biocidal chemicals that kill and slow microorganism growth and also are often used in hospitals and clinics to sterilize surfaces and instruments to prevent the spread of pathogens. Many people use the terms interchangeably. For example, antiseptics used to sterilize skin before surgery and are sometimes called skin disinfectants.

But for the hairsplitters, medical professionals admit to a bit of difference between antiseptics and disinfectants. Generally, antiseptics are applied to the body, while disinfectants usually are applied to surfaces, such as countertops and handrails. However, a surface disinfectant, such as alcohol, is also often used as an antiseptic to sterilize skin. Your arm often is swabbed with alcohol before an injection, and alcohol is a common antiseptic ingredient in hand cleanser. Chlorhexidine is a disinfectant used to sterilize surgical instruments, but it also is used as an oral antiseptic. Hydrogen peroxide is another chemical that is used both as a disinfectant and antiseptic. Clearly, there is much similarity and overlap in the use of and terminology between antiseptic and disinfectant agents, which can collectively be called biocides.

Even if Trump had used the word “antiseptic” instead of his unpolished choice, “disinfectant,” one suspects that the press still would have chided him for suggesting that we inject Mercurochrome to treat COVID-19. However, he also might have been vindicated since an antiseptic and a surgical instrument disinfectant are now being tested at the University of Wisconsin-Madison for their ability to prevent CoV-2 virus infection.

The new study will test a common antiseptic, Povidone-iodine, for swabbing the nose, and the common instrument disinfectant, Chlorhexidine, for rinsing the mouth. The idea is that the agents will coat the nose and mouth and kill any virus that comes in contact with the biocidal agents, preventing the virus from gaining entry into mucosal cells from where they grow and spread throughout the body. The trial is now enrolling up to 500 participants. For a six week period, participants will swab their nose twice a day and rinse four times a day, after which they will be tested for CoV-2 infection and compared to a control group that did not “disinfect.”  If effective, this regimen could be useful for protecting healthcare workers, teachers, nursing homes, and other people routinely in high contact with others. Researchers hope to announce their findings by early to mid-fall.

Words are important, but sometimes flubbed; that is excusable, especially when it is a non-expert who did the flubbing. What is less tolerable is jumping to unwarranted and extreme rhetorical conclusions about why a flubbed word was said. If one is honest, one must admit that Trump never suggested “injecting Clorox” to treat COVID-19. Now, it seems that Trump’s poor choice of the word “disinfectant” was not so crazy after all. One day, we all might be gargling with a surgical instrument disinfectant.

Bottom line: When setting up this blog last April, I said it would not be political, and it hasn’t been. What I wrote above is not about politics, it is about science and facts, both of which can transcend politics. Sometimes when a scientist makes statements based on facts and evidence that conflict with certain political positions, people assume that the scientist is being political. That is not necessarily true.

It is not true here.

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COVID Kids

Recently, as school districts, teachers, parents, pundits and politicos across the country have debated about re-opening schools for in-person instruction vs going to virtual classrooms, many people, including Dr. Scott Atlas, a new Whitehouse medical advisor and coronavirus contrarian,  have claimed that school kids don’t often catch COVID-19, and when they do, rarely die from it, and they don’t spread it to other kids or adults in their families. Therefore, they argue for fully opening the schools where kids do not need face masks, or to worry about personal distancing measures.

There are, of course, other issues in this debate, such teacher safety, and how keeping kids at home would hinder the ability of parents to go to work, etc. I don’t intend to lobby here for restarting schools or not. The only issues I will address are whether kids can get COVID-19, be significantly affected by the disease, and spread it to others. In brief, the science informing these three issues says “yes, yes, and yes.”

Kids do catch and spread COVID-19. The science showing that children can readily be infected by CoV-2 is unequivocal. Nevertheless, some people point to other observational data showing that kids do not often get infected and, from that, conclude that children somehow are resistant to the virus. However, these people fail to consider other reasons why children are infected at a low rate. The answer, as I discuss in more detail below, is not due to some intrinsic biological factor that better protects kids than adults from the virus. Rather, the lower rate of infection in kids is due to the early school, playground, and activity closures that have limited their exposure to the CoV-2 virus. In other words, mitigation efforts were effective in preventing virus spread among school kids. And as these social restrictions gradually have been lifted, CoV-2 infections and hospitalizations have increased in children.

According to the latest data from the Centers for Disease Control and Prevention COVID-19 data tracker, about 245,000 US youth from birth to 17 years old have tested positive for the virus. Pediatric cases of COVID-19 increased by 21% in the two weeks between August 6 and August 20 (>70,000 new cases of the disease). Between July 9 and Aug 9, the number of pediatric COVID-19 cases in Florida jumped 137%, while hospitalizations increased 105%. This upward trend in infections and hospitalizations is seen across the US as recently reported by the CDC. One reason for rising infection rates in kids is increased testing, but increased testing does not account for increased COVID-19 diagnoses or hospitalizations. An increase in infection and disease is expected as children are also increasingly being less isolated than they were when schools first closed and playgrounds locked. Relaxation of quarantine measures, along with the persistent and rising CoV-2 infection rate in the US, means that it is expected that more children are being exposed to the virus and coming down with COVID-19.

In March, childhood COVID-19 cases were just 2% of the total, now they are 9% according to a recent weekly report from the Children’s Hospital Association and the American Academy of Pediatrics. Pediatric COVID-19 cases in the US rose 90% between mid-July to mid-August. Also, examples of superspreader events among children are becoming more common around the world (these events are the major drivers of viral spread). There are several reports of such outbreaks among children at foreign schools. A superspreader event also was recently reported at a summer camp in Georgia where one young staffer initiated the spread of the virus to 76% of campers. A total of 260 kids (median age 12), and staffers (median age 17) were infected in just a couple of days—clearly kids can catch and spread the virus. This confirms results reported earlier by the Korea Centers for Disease Control and Prevention, which  examined >59,000 contacts from ~6000 pediatric COVID-19 patients and found that infected children between ages 10-19 spread the virus as readily as adults do. Yet another study published in late July in JAMA Pediatrics, reported that kids in this age range carried similar upper respiratory viral levels as adults. Surprisingly, kids five and younger carried 10-100 times the viral genetic material as adults and older kids. The reason for this unexpectedly high viral load in very young children is not clear, but it could be due to the immature immune system children have in their early years that might be less effective in controlling the virus. This finding raises concern that very young infected children could be highly efficient vectors for viral spread, which would fit the pattern seen with other respiratory viruses.

COVID-19 morbidity in children: As I wrote this blog post, a radio talking head in the background announced that since the CDC reports that kids seldom die from COVID-19, there is no reason to keep schools from opening. However, the pundit, like so many others, only considered COVID-19 risk in terms of mortality and failed to take into account the significant morbidity of the disease. While it is true that, compared to adults, fewer kids die or get seriously ill with COVID-19, many children, even those with mild or asymptomatic forms of the disease, develop a post-infection condition called multisystem inflammatory syndrome in children (MIS-C) that can lead to organ failure and possibly long-term health problems. This is a condition reminiscent of toxic shock syndrome where different organs including the heart, brain, lungs, kidneys, skin, eyes and GI system become inflamed. As early as last May, the CDC issued a health advisory to pediatric doctors alerting them to this new complication of COVID-19, which was first reported in April by doctors in the UK. More than half the MIS-C cases are under nine years old with the median age being eight. As of August 20, A CDC tracker reports that the US has seen almost 700 serious cases of MIS-C, and about 5000 children were reported with a less severe form of MIS-C. Because the disease is so new, the long term consequences of this systemic inflammatory response is not known. For that reason alone, caution is warranted as we try to get a handle on this novel complication and understand  its long-term consequences.

Most children with MIS-C require ICU hospitalization and can experience symptoms that last for weeks. It is often accompanied by subtle changes in myocardial function where the heart’s left ventricle, or main pumping chamber, is impaired. This is the chamber that pumps oxygenated blood arriving from the from the lungs to the rest of the body. At the Children’s Hospital of Philadelphia, 17 of 28 MIS-C patients showed this myocardial injury as reported in the Journal of the American College of Cardiology. Over a brief followup period, affected patients tended to recover systolic (pumping) function, but diastolic (resting) dysfunction persisted.

A recent report in Nature Medicine, indicates that MIS-C isn’t a direct result of the virus, but is likely due to an intense autoimmune response, akin to a cytokine storm, to the infection. This very unexpected consequence of the disease represents one of the several novel aspects of COVID-19 that we have had to very quickly recognize and just as quickly learn how to deal with. The good news is that we are steadily learning more about the disease and making headway in knowing how to treat it. The bad news is that it will be years before we can fully understand what all this means for the long-term health of these pediatric patients.

Biomedicine is wonderfully interesting for those who have patience.

Bottom line: As of July 24, the CDC recommended that K-12 schools reopen this year. On the other hand, a study published last month in The Journal of the American Medical Association estimated that by closing schools in March, we  reduced the rate of new COVID-19 cases by 66%. If the JAMA report is accurate, it means that about 1.4 million fewer people became ill and about 40,600 fewer people died, which argues against re-opening schools for in-person instruction.

What would you do?