Daily COVID-19 Briefing: Tuesday

Top news, reports and insights for today:

  1. Daily headline summaries for Tuesday:
  • Maryland reports largest rise yet in COVID-19 cases 4 days after reopening. The most recent test positivity rate is 25% suggesting testing is still selective; cases no doubt under-estimated (NPR)
  • Tracking SARS-CoV-2 using genetic analysis: The virus jumped from animals to humans, then spread through human-to-human contact; circulation started in China as early as October 9, 2019; the virus mutated minimally before March 1; multiple “seeding” events occurred in the U.S. but most infections in Washington State likely came from one individual (Scientific American)
  • Wildcat strikes, walkouts and protests erupt across U.S. “essential” industries over low pay, lack of safety and protections for workers (The Guardian)
Image captured from the Guardian website: https://www.theguardian.com/world/2020/may/19/strikes-erupt-us-essential-workers-demand-better-protection-amid-pandemic
  1. U.S. COVID-19 cases remain flat, deaths dip
     On Monday, the U.S. reported 21,287 new cases, a rise of 1.4%. The 7-day moving average has been declining generally, but flattening in recent days. Last week, 159,270 cases were reported nationwide, a 12% rise. The 1-week growth factor was <1 (0.96) as there were 166,000 new cases the week before. The U.S. is poised to pass 1.5 million cases tomorrow, and continues to have the most cases of any nation, with more than 1 million more cases than Russia (now at #2) and Spain (at #3). States with more than 25% case growth in the last week include Arizona (+25%), Minnesota (+39%), North Dakota (+27%), North Carolina (26%) and Maine (+29%).
     On Monday, there were 792 COVID-19 deaths reported, a rise of less than 1% and the second day of fewer than 800 reported fatalities. Last week, 9,484 Americans died of COVID-19, a rise of 13%, compared to 12,125 the week before (growth factor=0.78). The declining trend in deaths is a positive development, remembering that we would anticipate a rebound in reported deaths tomorrow given the weekend reporting lag. States reporting 25% or more increase in total deaths include Arizona (+28%), New Mexico (30%), Iowa (+31%), Nebraska (+25%), South Dakota (+29%), Delaware (+32%), and New Hampshire (+29%).
    What this means? Because deaths lag behind cases, and cases lag behind infections, it is plausible that the dip in deaths will be temporary. In my opinion, we are now waiting for signs of the conveyor-belt of infections to become visible over the next few weeks as the impact of reopening moves like a ‘pig in a python’.
  1. From anosmia to ‘COVID toes’: What to do with the strange mix of COVID-19 symptoms
     Yesterday, there was a nice article in Scientific American summarizing the challenges we face in understanding the often baffling array of symptoms that have popped up during this pandemic. I have been yelling at anyone who would listen since the beginning about the importance of getting the case definition right. Until we have tens of millions more tests, we should be using clinical check-lists to screen everyone. That requires doing a lot of important work to determine how symptoms cluster together and how they map to test results. That itself is a big discussion for another time. In the meantime, lets consider why this has been such a challenge for us disease detectives.
     Any attempt to characterize the symptoms and signs of disease requires balancing two key features of any case definition: sensitivity and specificity. It’s a balancing act because we have competing needs: define the disease broadly enough that it captures all true positive cases, but narrowly enough that it captures all true negative cases. The first part is intuitive (what set of symptoms, when endorsed, identifies everyone who really has COVID-19). The second part is trickier and less intuitive (which symptoms, when endorsed, avoid identifying people with a similar respiratory infection as having COVID-19 when they don’t). The former is the essence of sensitivity, the latter is specificity. The balancing act gets especially tricky when the most common symptoms (fever, cough, fatigue, headache) are also signs of other diseases (ergo low specificity). That’s why my ears always perk up when a rare and mysterious symptom comes onto the radar. Examples include anosmia (loss of sense of smell) or chilblains (sore, red, swollen toes). From a measurement point of view, these symptoms are as good as gold because while they are rare, they are they can be used to differentiate COVID-19 infection from other illnesses. Problem is that requiring rare symptoms lowers our sensitivity and we miss true positives. We know a great deal about how to handle these measurement challenges, its simply a matter of gathering the right data and doing the leg work. To my knowledge, this hasn’t been done yet and is sorely needed.
     Another challenge is that the symptom profiles are clouded by the shear scale of the pandemic. With 5 million cases of a disease nobody had heard of 6 months ago, it is hard to separate the diagnostic wheat from the chaff. When huge numbers of people get a new disease, super rare symptoms will occur and get noticed. Some of these will be noise and some will be signal. There is an art to telling the difference.
     Another challenge is that there are symptoms that occur because of the pathogen itself, and those that occur as a result of host characteristics related to individual differences in immune response. For example, some of the sickest people end up in respiratory failure due to cytokine storm, an exaggerated out-of-control response by the body to a novel viral invader. Separating indicators of differential host susceptibility and symptoms of infection is a key challenge – and its often not a clear line of separation.
     A final challenge is more sociological than scientific. During a fast moving and scary epidemic, facts and opinions go viral, become memes and persist in the collective mindset, even when they no longer serve a purpose. Both the WHO and the CDC were stuck on an initial case definition from a single brief report from China based on a just 41 very sick ICU patients (Huang, Lancet). Long after we had learned that up to 30% of COVID patients don’t present with a fever, that fatigue and malaise were more common than shortness of breath, and that gastrointestinal complaints were important additions to the mix, it took weeks or months before officials moved past the “big 3” (fever, cough and SOB).
    Bottom line: A more complete and nuanced understanding of the diverse symptom profiles of this novel disease are emerging. It’s a fundamental task of the disease detective to gather the right clues and examine them through the right lens. That work still lies ahead. How can I help?


Top pick of the day

These are the 6 new possible symptoms of the coronavirus the CDC added to its list

USA Today article by Susan Miller, posted April 26, 2020.

For months we have known that a larger list of symptoms should be considered when characterizing this new infection. The CDC has however been slow to move past the original three symptoms: fever, dry cough and shortness of breath. Finally, an additional 6 symptoms have been added. All have been on my symptom checklist since early March. This change comes on the heals of a major JAMA report showing that only a third of patients hospitalized for COVID-19 had a fever on admission.

Today’s bite-sized, handpicked selection of important news, information or science for all who want to know where this epidemic is going and what we should do.

Daily COVID-19 Briefing: 4/4/20

Top news, reports and insights for today:

  1. U.S. Cases rise by just just 13%, so where are the next hot spots?
    On Friday, just over 32,000 cases were added, a 1-day rise of just 13%. Cases are now doubling every 5 days. I don’t know yet whether this is a slow down in the actual epidemic or whether we have hit the limits of how fast we are testing. California still has 60,000 samples waiting to be tested and 45 states aren’t reporting “pending” tests. While New York continues to lead the nation with over 113,000 confirmed COVID-19 cases, the overall fraction of U.S. cases there continues to fall, sitting currently at 38%. New York logged an 11% rise in cases on Friday. Other states recording big jumps were New Mexico (+23%), Alabama (+20%), Connecticut (+29%), and Pennsylvania (+20%). The graph below shows the total accumulated cases by state. There are 7 states at or near 10,000 cases including California, Michigan, Florida, Louisiana, Massachussetts, New Jersey and New York. These are the states that are already on our radar screens. But, remembering that we are usually a few days behind in this epidemic, these numbers don’t tell us where the next hot spots are likely to be. For that, take a look at the next graph, which shows growth in new cases over the past 3 days as a percentage of total cases. This graph shows a different story. There are 21 states that have seen 50% growth or more in the last three days. Five states have seen 70% growth including Pennsylvania, Louisiana, South Dakota, Oklahoma, and Idaho.
    What does this mean? As all eyes focus on coastal states like California, New York and New Jersey, the next hot spots are likely going to be in the Midwest and South, where 13 of 26 states have seen recent rises of 50% or more. Idaho and Louisiana are top contenders for the next epicenters of the outbreak. Other states to watch include Michigan, Nebraska, Oklahoma, South Dakota, Alabama and Texas.
  1. The CDC continues to get it wrong on symptoms
    A friend of mine just texted to say she was feeling badly and had a tele-visit with her doctor. She said her symptoms were not “COVID related”. When I asked her why, she said she didn’t have the “classic” symptoms, no fever and no respiratory symptoms. She did have a loss of appetite, chills, fatigue and body aches. The epidemiologist in me wants to scream when I hear this. As the Top-pick-of-the-day article points out, the messaging around the symptoms of COVID-19 remains confused and problematic. In my opinion, the CDC has done some things well and other things have been mishandled. That is to be expected when tackling a new disease. One area that is particularly worth discussing is case definition based on symptoms. At this moment, the CDC website still lists the same three symptoms: fever, cough and shortness of breath. This is a big problem. That was based on a study of just 44 patients in China very early in the outbreak. That list should have been ditched long ago. We now have plenty of better data that shows that there are more than a dozen symptoms that should be considered. Take a look at version 6 of my own COVID-19 Symptom Checklist. The SARS-CoV-2 virus impacts different people in different ways depending on age, time since infection, risk factors, genetics and a host of things we are just learning about. As many of 1-in-5 infected persons don’t have a fever. One-third of patients have gastrointestinal symptoms rather than respiratory ones. Fatigue is much more common than shortness of breath (especially early on). Some less common symptoms may be especially useful for identifying COVID-19, like pink eye, loss of sense of smell or taste, and stomach problems. Other symptoms may be especially good for predicting who is going to have very severe disease (like sudden confusion or chest pains).
    Why this matters? There are probably tens of thousands of Americans who have COVID-19 but think they don’t because they don’t have fever, cough and shortness of breath. Those people are not considering themselves infected and are probably infecting others for that reason. We can and must do better on case definition.