bookmark_borderConversation with Tom Frieden on Coronavirus

On April 13, 2020, Helen Branswell, senior infectious diseases and global health reporter for STAT, hosted a chat with Tom Frieden, current president and CEO of the global public health initiative Resolve to Save Lives. Dr. Frieden is a former director of the CDC and commissioner of the NYC Department of Health.

I highly recommend watching this chat including the Q&A session at the end. It is about a 40 minute investment of your time. Notable takeaways:

  • We need to continue working together around the world and learn best practices from each other
  • The time we have been sheltering in place was buying us time to prepare to continue fighting it so we can BOX IT IN* – widespread testing, isolate the infected, find the exposed, quarantine the exposed
  • Current state of testing for disease – tests are pretty good although difficult to get a good sample, but still need to ramp up testing
  • Current state of antibody testing – most of the tests out there are “junk” – we need reliable tests and also, we don’t know whether everyone gets antibodies nor whether or how long they confer immunity – however, it would give us good epidemiologic information on how much it has spread in the population
  • MASKS – outside of healthcare front line or anyone taking care of the sick, more important for actively sick to use to prevent spread (but they should be staying home anyway)
  • MASKS for general public is a judgment call – but important to ensure that they aren’t being taken from healthcare workers, they don’t give undue increased confidence of protection – still more important to WASH YOUR HANDS AND NOT TOUCH YOUR FACE
  • Don’t ask “when can we reopen” – this is about data, not dates – we have to maximize public health protection while minimizing economic dislocation.
  • This virus is here to stay – we need to learn how to live with it. There will be waves of outbreaks, we need to keep them small and contained clusters so we don’t have to come back to this type of lockdown.

*BOX IT INclick here for the briefing document (downloaded April 19, 2020) for more detailed information.

bookmark_borderCOVID-19 Expert Panel Highlights

This article was published on March 15, 2020, five days after Harvard University announced (on March 10th) that their students had five days to vacate campus. When this announcement was made, 99% of the general public was in shock and disbelief about what was coming.

Highlights of Expert Panel on COVID-19 from Harvard, MIT, Mass General Hospital

The following is reprinted from the article, accessed on April 24, 2020.

by Melissa Bender, MD MPH, March 15, 2020

Experts from one of the country’s premier medical research centers, Massachusetts General Hospital, took to their computer screens on Thursday for the first-ever “virtual Grand Rounds.” Their goal: to take stock of what’s currently known about the COVID-19 global pandemic and share information with the medical community. But the key insights are also important for policymakers, reporters, and the general public to know. 

Sometimes a rather banal weekly gathering in a dark, mid-sized auditorium, this time the event took on the atmosphere of a public health “situation room.” Presenters spoke with urgent calmness like pilots in a storm, with frequent and insistent requests for “next slide,” each one packed with fresh data and assessments of where things stand in this crisis that has gripped the world.

The idea for such a format was sparked a week earlier, when about 80 scientists convened at Harvard Medical School, representing elite research institutes, academic medical centers, and the public health department. Experts who are veterans of the 2003 SARS epidemic in Guanzhou, China phoned in via live video link. At the conclusion of that meeting, participants formed an umbrella organization called the Greater Boston Consortium for Pathogen Readiness, establishing working groups for COVID-19 response. Just one week later, the leaders of each working group presented this virtual update to the Boston medical community as to where things stand, in the form of the video Grand Rounds moderated by Bruce D. Walker, founding Director of the Ragon Institute of Harvard, MIT, and Mass General Hospital.

I break down some of the key findings presented by the speakers. But it’s important to note that many of these data-driven assessments are preliminary.  The COVID-19 situation remains quite fluid, and researchers will continually update what they know and the confidence they have in knowing it.

1. The Behavior of COVID-19

How contagious is COVID-19?

COVID-19 appears to be spread by droplets when an infected person sneezes, coughs, or speaks. These droplets fall onto surfaces or people’s hands, where the virus can remain active and transmit infection to others. Scientists are still determining how long the virus can survive on various types of substances and under different environmental conditions. There is some, not-yet-peer-reviewed data produced by a team of governmental and non-governmental scientists that the COVID-19 virus can survive in the air, but professor of medicine at Harvard Medical School, Dr. Galit Alter explained in her presentation that spread has not been demonstrated at a biological level. In other words, it has not been proven that individuals become infected by way of airborne viral transmission. 

Epidemiologists talk about the “basic reproductive number,” which is the average number of secondary cases caused by each infected person in an unmitigated epidemic. Dr. Marc Lipsitch, a professor of epidemiology and Director of the Center for Communicable Disease Dynamics at Harvard’s school of public health, summarized available data for COVID-19, which currently suggests that the reproductive number is around 2  – similar to the infectiousness of pandemic flu of 1918. If this is the case, models of disease spread predict that around 50 percent of the population will need to become immune — either by way of infection or vaccine — before the disease will die out. Dr. Lipsitch cited data that about 1-2% of those who become symptomatic will die, with the bulk of the mortality risk occurring in the elderly and people with cancer, heart disease, or other chronic health conditions. Children, for the most part, appear to be spared by this disease.

How bad is COVID-19?

This is a brand new pathogen, but this much is clear: COVID-19 is, as should be obvious by now, much worse than the flu. The World Health Organization estimates a mortality risk of 3.4% based on early data. There are varying levels of the risk faced by people in different groups. While many infected people remain asymptomatic or experience a mild illness, especially young children, others become severely ill or die. People over the age of 60 and those with chronic medical conditions are the hardest hit, but they are not the only ones. Some young, healthy people with no known medical conditions are dying from this disease. On a grand scale, this virus could result in a great loss of life among Americans of all ages. 

We currently do not have a full understanding of the spectrum of illness from COVID-19, meaning we don’t know how often the disease will manifest as a mild, severe, or fatal disease. Since we haven’t yet been able to do surveillance testing in American communities or even of some patients in hospitals, mild and moderate cases are being missed. Even so, Dr. Anthony S. Fauci, head of the National Institute of Allergy and Infectious Diseases, recently suggested the COVID-19 may be 10 times as lethal as the flu, even for young, healthy individuals. 

In her presentation, Dr. Alter emphasized that for reasons not yet understood, infection in certain patients, particularly the elderly and those with chronic medical conditions, can result rapidly and unpredictably in a severe lung inflammation called Acute Respiratory Distress Syndrome (ARDS), which can cause a cascade of organ and system failures. 

How bad will things get? 

Chairing the Epidemiology and Modelling working group, Dr. Lipsitch sounded a clarion alarm that fits with what other experts have also been saying. He said: 

 We are very badly underreporting the number of cases in the United States, including in Boston…because of limitations on testing, and that’s an ongoing problem. And it really makes it hard to figure out what stage of the epidemic we are in, in the United States, and regionally.

He and many others have also warned that the United States is on track to have some health care systems overwhelmed as they have been in Northern Italy, and the curves demonstrate that we are perhaps only 10 days behind Italy in the course of our epidemic.

2. What are the Main Clinical Challenges?

Transmission before symptoms

Patients can transmit COVID-19 before they have any symptoms at all. In one study, even among patients who required hospital admission for treatment of COVID-19, fewer than half (44%) had fevers at the time of presentation. This makes it difficult to identify patients in the community by way of routine screening measures. It is also different from some other viruses like SARS in which the majority if not all cases present with fever as an initial symptom. 

There are many significant implications of this study’s finding. It suggests, for example, that some screening mechanisms–for example, protecting the president by monitoring whether White House reporters have a fever–may be welcome but inadequate precautions. Fever screening would have been much more effective for SARS, in contrast. The finding also suggests that many people may not realize they need to get tested or self isolate if they mistakenly believe a fever is necessarily or generally associated with COVID-19.   

Biphasic illness

Some patients remain asymptomatic or develop only mild symptoms, but according to Dr. Lindsey Baden’s presentation others may experience a “biphasic illness.” Baden, Director of Clinical Research in the Division of Infectious Diseases at the Brigham and Women’s Hospital, explained that this means an individual could become mildly ill for a period of time, and then worsen suddenly and dramatically at a later stage. 

Prolonged viral “shedding”

Patients can continue to “shed” (produce) the virus for weeks after they have first been diagnosed, meaning that the virus is still actively replicating. It is not yet clear from early clinical studies whether this prolonged period of detectable virus can result in the further spread of disease. In one case reported in the New England Journal of Medicine, a young healthy man spread the virus during its incubation period, prior to the onset of symptoms. 

Hospital transmissions

COVID-19 has been spreading in communities but also in hospitals. In one report from Wuhan, China, more than 40% of hospitalized patients with COVID-19 were thought to have been infected in the hospital itself. These data represent a first report from one single hospital site, where many healthcare staff themselves were hospitalized. Before drawing conclusions about the risk of hospital-acquired COVID-19 in the United States, one would also want to know data from American hospitals regarding infection transmission rates in healthcare settings, which may differ from those in Wuhan.  Yet the specter of hospital transmission of COVID-19 is another source of concern for healthcare systems that may soon become overwhelmed by this new pathogen. 

Expand and deploy testing

Diagnostic capability (testing) for COVID-19 remains extremely limited in the United States, far behind South Korea, China, and other nations. Dr. Pardis Sabeti, a computational geneticist and professor at Harvard’s biology department and school of public health, emphasized that diagnostic testing, particularly of hospital workers and other first responders, remains essential.

Medical staff are already under stress. They are working extra shifts for long hours and being placed on emergency call lists. Personal protective equipment is in short supply. Many are themselves over the age of 60 or have a chronic medical condition that could place them at greater risk. An exposure to COVID-19 causes substantial emotional strain and could result in self-quarantines, further stressing the healthcare workforce. Access to testing is essential to diagnose those who become infected and to reassure those who are healthy that they can stay on the job. For more on this topic, see this reporting in Wired (“[H]ealth care workers are being sent home because the CDC’s strict testing guidelines and the low availability of the kits themselves mean they also can’t be tested.”)

Although not part of the presentation, it seems reasonable to conclude that the CDC criteria for testing should be loosened for healthcare workers with known exposures, or flu-like symptoms, or even concerns about possible exposures given the limited availability of testing for the patients they care for. 

A finer point that was touched on in the discussion: there are two types of tests urgently needed. One is to determine whether a patient has an active, ongoing infection with COVID-19. A second is to determine whether a person has ever been exposed to the disease, even if they no longer have an active infection. Both types of tests will be critical to controlling this virus. If a person has recovered from an asymptomatic infection and potentially immune to new COVID-19 infection, this information could be vitally important. Healthcare workers with known immunity could potentially avoid emotional stress and quarantines in the event of future exposures to patients with active COVID-19 disease; patients presenting to hospitals could be tested for immunity to COVID-19, which would help doctors to exclude the virus as a concern. And other benefits — such as determining the pace toward herd immunity — can accrue from such testing. 

Hospital beds and ventilators: Critical shortages and rationing ahead

When experts speak of health systems possibly being overwhelmed, the very concept may seem too abstract to imagine. But the concern comes down to numbers that are concrete and profoundly sobering. The United States has a limited  number of hospital beds, ventilators, doctors and nurses throughout the nation, far fewer than would be necessary even if the COVID-19 outbreak were less severe than past epidemics of the 20th century. An article in Saturday’s Washington Post makes it terrifyingly plain: “A planning study run by the federal government in 2005 estimated that if the United States were struck with a moderate pandemic like the 1957 influenza, the country would need more than 64,000 ventilators. If we were struck with a severe pandemic like the 1918 Spanish flu, we would need more than 740,000 ventilators — many times more than are available.”

3. What Can Be Done?

Flatten the Curve!

By now it’s become a well-known term, even a trending hashtag on social media: “flatten the curve.” Every epidemic, if allowed to progress in a non-immune population, follows a typical curve. 

Flatten the Curve from Markiewicz Dental on Vimeo.

After an initial sharp increase in cases, the number of susceptible individuals begins to diminish as some become immune and others die. Eventually, the epidemic “peaks” and then begins to fade out. This peak itself presents substantial challenges for cities and towns, since the total number of cases may exceed the capacity of local health systems — not enough health care workers, hospital beds, ventilators, gloves, and so on. The idea of “flattening the curve”  is to institute a variety of measures including social distancing — including changes in behavior by people of all ages, not just those over 60 or with chronic medical conditions — to lower this peak number of cases and soften the maximum blow of the pandemic, avoiding severe stresses on the overall health care system. Other measures include improving building ventilation, paid sick leave, possible school closings.

There are other benefits to flattening the curve. First, these same measures would result in a lower total number of cases over the course of the pandemic. As an example, Dr. Lipsitch cited differences in the way that Philadelphia vs. St. Louis managed the 1918 influenza epidemic. St. Louis implemented social distancing measures earlier and over a longer period, with great effect. In contrast, Philadelphia held a large parade, and its epidemic grew much more rapidly, with a much higher peak, and more people infected overall. Second, another advantage of flattening the curve is extending the period of time in which people become infected. The later an individual’s infection, the more time clinicians and researchers will have to understand the disease and possibly develop effective interventions to treat it. 

Treatment

Mark Namchuk, the executive director of therapeutics translation at Harvard Medical School, described emerging data around the use of existing pharmaceuticals and possibly repurposing them for COVID-19. Currently there are no approved drugs to treat COVID-19. Drugs under consideration for repurposing include those previously developed to treat infections such as SARS, Ebola, and Marburg fever, as well as possibly some of the drugs used to treat HIV, influenza, malaria, and other diseases.

The prospect of an eventual vaccine

Vaccines play an essential role in limiting the number of people susceptible to an infection, but they take time to develop. Dr. Dan Barouch, professor of medicine at Harvard and Director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center, cautioned that the timeline for the first phase of clinical trials is quite different than the even longer timeline before 300 million doses could be deployed. He estimated, consistent with other experts, that an effective and deployable vaccine is likely more than a year away. 

Dr. Barouch outlined three reasons for optimism that a vaccine may be developed: 

1) Patients who recover seem to develop a natural immunity. 

2) There isn’t a great deal of diversity between different strains of the virus, a fact which could simplify the task of targeting all strains of the virus. 

3) The most promising protein target for a future vaccine has already been identified.

There are two dozen vaccine candidates under parallel development across the world, using a variety of mechanisms.

Challenges exist, including the time required for vaccine development may be too long to mitigate the spread of this fast-moving global pandemic. Vaccine development has been proceeding at an extremely rapid pace, faster than for any other disease in human history, but the development and deployment of one is not within reach in 2020.

In the meantime, stay home, don’t touch your face, support others in your community, and go wash your hands one more time.

bookmark_borderLily Pad Metaphor

An opinion piece from March 10, 2020 by Megan McArdle entitled “When a danger is growing exponentially, everything looks fine until it doesn’t” in the Washington Post began with a simple metaphor to illustrate exponential growth and how SARS-CoV-2 was projected to grow without efforts to mitigate spread.

She gave four simple points to which I had added a fifth: we will need a plan to get back to “normal” life and prepare for and, hopefully, prevent a second wave.

https://www.washingtonpost.com/opinions/2020/03/10/coronavirus-what-matters-isnt-what-you-can-see-what-you-cant/

The following is reprinted from the opinion piece, accessed on April 24, 2020.

There’s an old brain teaser that goes like this: You have a pond of a certain size, and upon that pond, a single lilypad. This particular species of lily pad reproduces once a day, so that on day two, you have two lily pads. On day three, you have four, and so on.

Now the teaser. “If it takes the lily pads 48 days to cover the pond completely, how long will it take for the pond to be covered halfway?”

The answer is 47 days. Moreover, at day 40, you’ll barely know the lily pads are there.

That grim math explains why so many people — including me — are worried about the novel coronavirus, which causes a disease known as covid-19. And why so many other people think we are panicking over nothing.

During the current flu season, they point out, more than 250,000 people have been hospitalized in the United States, and 14,000 have died, including more than 100 children. As of this writing, the coronavirus has killed 29 people, and our caseload is in the hundreds. Why are we freaking out about the tiny threat while ignoring the big one?

Quite a number of people have suggested that it’s because the media just wants President Trump to look bad. Trump seems particularly fond of this suggestion.

But go back to those lily pads: When something dangerous is growing exponentially, everything looks fine until it doesn’t. In the early days of the Wuhan epidemic, when no one was taking precautions, the number of cases appears to have doubled every four to five days.

The crisis in northern Italy is what happens when a fast doubling rate meets a “threshold effect,” where the character of an event can massively change once its size hits a certain threshold.

In this case, the threshold is things such as ICU beds. If the epidemic is small enough, doctors can provide respiratory support to the significant fraction of patients who develop complications, and relatively few will die. But once the number of critical patients exceeds the number of ventilators and ICU beds and other critical-care facilities, mortality rates spike.

Daniele Macchini, a doctor in Bergamo, Italy, recently posted a heart-stopping account to Facebook of what he and his colleagues have endured: the hospital emptying out, the wards eerily silent as they waited for the patients they couldn’t quite believe would come … and then, the “tsunami.”

“One after the other the departments that had been emptied fill up at an impressive pace. … The boards with the names of the patients, of different colors depending on the operating unit, are now all red and instead of surgery you see the diagnosis, which is always the damned same: bilateral interstitial pneumonia.”

A British health-care worker shared a message from a doctor in Italy, who alleged that covid-19 patients in their hospital who are over 65, or have complicating conditions, aren’t even being considered for the most intensive forms of supportive treatment.

The experts are telling us that here in the United States, we can avoid hitting that threshold where sizable regions of the country will suddenly step into hell. We still have time to #flattenthecurve, as a popular infographic put it, slowing the spread so that the number of cases never exceeds what our health system can handle. The United States has an unusually high number of ICU beds, which gives us a head start. But we mustn’t squander that advantage through complacency.

So everyone needs to understand a few things.

First, the virus is here, and it is spreading quickly, even though everything looks normal. Right now, the United States has more reported cases than Italy had in late February. What matters isn’t what you can see but what you can’t: the patients who will need ICU care in two to six weeks.

Second, this is not “a bad flu.” It kills more of its hosts, and it will spread farther unless we take aggressive steps to slow it down, because no one is yet immune to this disease. It will be quite some time before the virus runs out of new patients.

Third, we can fight it. Despite early exposure, Singapore and Hong Kong have kept their caseloads low, not by completely shutting down large swaths of their economies as China did but through aggressive personal hygiene and “social distancing.” South Korea seems to be getting its initial outbreak under control using similar measures. If we do the same, we can not only keep our hospitals from overloading but also buy researchers time to develop vaccines and therapies.

Fourth, and most important: We are all in this together. It is your responsibility to keep America safe by following the CDC guidelines, just as much as it is House Speaker Nancy Pelosi’s or President Trump’s responsibility to lead us to safety. And until this virus is beaten, we all need to act like it.

bookmark_borderHold the Line

Back on March 20, 2020, Johnathan Smith, an infectious disease epidemiologist at Yale University, published “Hold the Line” on Medium. Short, simple, and accurate, he brought home the importance of social distancing in fighting the spread of this coronavirus.

Takeaways (emphasis mine):

  • “First, we are in the very infancy of this epidemic’s trajectory.”
  • “Seemingly small social chains get large and complex with alarming speed. If your son visits his girlfriend, and you later sneak over for coffee with a neighbor, your neighbor is now connected to the infected office worker that your son’s girlfriend’s mother shook hands with. This sounds silly, it’s not.”
  • “In contrast to hand-washing and other personal measures, social distancing measures are not about individuals, they are about societies working in unison. These measures also take a long time to see the results. It is hard (even for me) to conceptualize how on a population level ‘one quick little get together’ can undermine the entire framework of a public health intervention, but it does. I promise you it does. I promise. I promise. I promise. You can’t cheat it.”
  • “People are already itching to cheat on the social distancing precautions just a “little” — a playdate, a haircut, or picking up a needless item at the store, etc. From a transmission dynamics standpoint, this very quickly recreates a highly connected social network that undermines all of the work the community has done so far.”