28 July 2022 Blog Post: Do As I Say, Not As I Do and the CDC “5 Day” Rule

28 July 2022 Blog Post: Do As I Say, Not As I Do and the CDC "5 Day" Rule

After a week of robust work in his home President Biden has now tested negative for SARS-CoV-2 and is returning to his regular schedule. In addition to reinforcing this ridiculous notion that Americans should continue to work while sick, the White House stated from the outset of his infection that they would go “above and beyond ” the CDC 5 day guidance in managing his isolation.

To review the current CDC guidelines on isolation (which occurs when an individual is sick and tests positive as distinct from quarantine), the recommended protocol is as follows:

  1. Stay home for 5 days and isolate from others in the home. Wear a well-fitting mask if you must be around others in your home. Do not travel.
  2. End isolation after 5 full days if you are fever-free for 24 hours (no Ibuprofen or Tylenol!) and symptoms are improving (not necessarily gone). If you never had symptoms, end after 5 days from your first positive test. If you were “very sick” end isolation at 10 days and consult your doctor.
  3. Take precautions until 10 days – namely wearing a well fitting mask in the home or in public. Do not travel until the full 10 days have passed

President Biden first tested positive for the virus on Thursday July 21st, one week after traveling to the Middle East. After his working isolation, he subsequently tested negative on the evening of July 26th and again the morning of July 27th, at which time he returned to his usual routine.

In reality, the ‘above and beyond’ protocol followed by President Biden’s medical team is precisely the one we should be following and is the same advice I offer my patients. Rapid antigen tests offer a reasonably precise guide to infectiousness (88% sensitivity when compared to viral culture), as they detect proteins produced by actively replicating virus. There is not a role for PCR in this effort, as PCR testing can remain positive long after an infectious period had passed (this is what got us into trouble about surface spread of the virus, when PCR methodology could detect SARS-CoV-2 on bedside tables in the Diamond Princess back in 2020).

A better summary of the importance of rapid antigen testing in defining isolation duration you will not find than that offered by Dr. Emily Bruce, a microbiologist and molecular geneticist at the University of Vermont:

“If I had to sum it up in one very concise message, it would be that if you’re antigen positive, you shouldn’t go out and interact closely with people who you don’t want to be infected.”

In my clinical experience most patients test negative between Day #7 and Day #10 after their first positive test. We do have rare cases of continued positive antigen tests to Day #11, #12 and even #13 but this is a <1% occurance. The addition of Paxlovid as a treatment tool further complicates matters as a rebound phenomenon can lead to positive tests at Day #14 or as far out as Day #23 (the longest I have seen). Antivirals change the dynamics of symptoms (people feel better faster), the immune response and transmissibility. So awareness of the potential a Paxolvid rebound should be on the forefront of President Biden’s medical team – presumably he is tested daily so if such occurs, they would have immediate insight into such and again resume his isolation.

A recent study by Boucau et al has shown that a significant percentage (25%) of those infected with the Omicron variant remain infectious after 8 days. In the study, patients with newly diagnosed COVID-19 underwent serial nasal swabs correlating antigen testing (BinaxNow assay was used) to viral load and viral culture (the latter two are gold standards of infectiousness, but not viable tests to be deployed at the population level due to the cost and technical expertise required).

Paper Link: https://www.medrxiv.org/content/10.1101/2022.03.01.22271582v1 

The authors found that the duration of shedding viable virus lasted for an average of 6 days with an interquartile range of 4 to 8 days. In other words, 25% of those studied had no transmissible virus at Day 4, 50% had none at Day 6 but 25% remained infectious at Day 8. The longest observed infectious periods were 16 days for a Delta variant and 14 days for an Omicron variant. Interestingly there was no difference in infectiousness duration by vaccination status (unvaccinated versus vaccinated versus boosted).

Or, as Dr. Amy Barczak, an infectious disease specialist at Massachusetts General Hospital summarized:

“The facts of how long people are infectious for have not really changed.  There is not data to support five days or anything shorter than ten days of isolation.”

That is, unless, you employ once or twice daily rapid antigen testing after Day #5, which is exactly what President Biden’s team did. As we should all be doing, in fact.

𝗦𝗶𝗴𝗻 𝗨𝗽 𝗳𝗼𝗿 𝗢𝘂𝗿 𝗡𝗲𝘄𝘀𝗹𝗲𝘁𝘁𝗲𝗿

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27 July 2022 Blog Post: Population Prevalence and the ‘Luck’ of COVID Acquisition

27 July 2022 Blog Post: Population Prevalence and the 'Luck' of COVID Acquisition

For those interested in a contrarian COVID-19 approach, I recommend following Dr. Vinay Prasad of UCSF on Twitter (@VPrasadMDMPH). While his snap opinions seem to be written, at times, with the sole intention of being inflammatory, he does offer a competing perspective as a researcher in an academic setting.

Readers will be interested to know that despite his opinion that SARS-CoV-2 infection is ‘inevitable’ and unavoidable, Dr. Prasad himself has never had COVID-19. Something he attributes to ‘luck.’ In fact, the biggest predictor of acquiring SARS-CoV-2 its frequency in the population and Dr. Prasad has the good fortune of working in a city that has aggressively limited the spread of the virus, perhaps more.so than any other US metropolitan area.

Now forgive a slight aside, we will return to the dynamics of SARS-CoV-2 transmission. Luck is a very unsatisfying (and unscientific) explanation for any phenomenon. Imagine if Darwin upon observing the finches in the Galapagos simply decided that their unique evolutionary patterns was just ‘luck’. Or, if physicians rather than discussing preventive measures simply chalked heart disease risk up to luck.  

In reality, the acquisition of any illness is multifactorial in nature. Take, for instance, breast cancer – the risk factors of which have been elucidated over decades of research. Approximately half of breast cancers can be explained by known risk factors, like reproductive factors. An additional 10 percent are associated with family history and genetics.

Delving deeper into these risk factors shows that breast cancer likelihood is influenced by age (older age groups are at higher risk), gender (women are at higher risk although there is male breast cancer), tall stature (increased height associated with increased risk), and estrogen levels (higher levels, higher risk).  Now are these absolutes?  Of course not. But they do all come together to inform risk.

A similar effect can be seen when it comes to the risk of acquiring a SARS-CoV-2 infection with the biggest predictor of risk being population prevalence. Prevalence is defined as the proportion of a population who have a specific characteristic (in this case SARS-CoV-2 infection) in a given time period. While it can be expressed as rate, in the graphs below we express prevalence as a proportion of 100 individuals (technically this is a ‘point prevalence’ for those keeping track at home).

The frequency of COVID-19 in LA County has varied tremendously throughout the pandemic (Figure 1 below), with two very obvious spikes in the Winters of 2020/2021 and 2021/2022 (Omicron). The small blip seen in August of 2021 is the Delta wave, tiny by comparison. But look at the right side of the graph, you see a rising prevalence beginning in May of this year.

If we focus in on the right side of the graph (Figure 2 below), we see that Omicron faded out by the end of February and the prevalence was very low until mid May. Rates have risen slowly but steadily and now we stand at about an 8% population prevalence – or, in other words, 8 of every 100 people have an active SARS-CoV-2 infection in the County.

In the same way that multiple factors can modify one’s likelihood of developing cancer, so is it true for SARS-CoV-2 infection. Occupation (healthcare workers, essential workers early on), mask usage, time and proximity to a known case all modify risk. Individuals with wider social circles (people who are more popular or have more friends) are also at higher risk. It makes sense in this context that Tom Hanks and two US Presidents have had the infection as stated simply, they interact with more people. Population prevalence itself may be the strongest predictor – and therein lies the ‘luck’ of Dr. Prasad. He works in San Francisco which has had the lowest COVID-19 case rates in the country.  To date, 167,931 cases  have been reported in San Francisco (population: 883,305 – a rate of 19011 cases per 100,000) as compared to 3,153,690 in Los Angeles (population: 10,004,000 – a rate of 31524 cases per 100,000). So simply working in a city which has aggressively sought to contain the spread of the virus might be sufficient to explain his ‘luck.’

 

𝗦𝗶𝗴𝗻 𝗨𝗽 𝗳𝗼𝗿 𝗢𝘂𝗿 𝗡𝗲𝘄𝘀𝗹𝗲𝘁𝘁𝗲𝗿

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25 July 2022 Blog Post: On The Return of Masking, Summer 2022 Edition

25 July 2022 Blog Post: On The Return of Masking, Summer 2022 Edition

Headlines this weekend across print and television media in Los Angeles essentially had the same message – COVID cases in the County while plateauing are high enough to bring back a mask mandate.  The current threshold on mask mandate return has been set to an average daily rate of COVID-19 related hospital admissions exceeding 10 per 100,000 population. Measurements last week were 10.5 and 11.4 per the County Health Department.

 

So how do we evaluate this news? LA County Health makes it exceedingly difficult to double check their numbers as they do not actually publish raw data on hospitalization. Further, there is the very reasonable critique regarding classification of hospitalizations – are those patients admitted for COVID primarily or was the virus isolated as part of standard hospital screening protocol as is tangential to their admission diagnosis?

Before delving into that, let’s try to piece together what is actually happening in the community. First, whatever we can look at is about 2 weeks behind as, inexplicably, LA County Health has only published case data until 7/12/2022.

Cases are clearly increasing and are now at a rate almost double of what was seen in the Summer of 2020 and five times what we saw in Summer 2021 (Figure 1). This upwards trend began in May and clear separation from prior years was achieved by mid May (this would have been the time for mask mandates, if the Health Department was seriously concerned). I find it helpful to plot year over year as it provides some context both numerically and historically. In Summer 2020 we were all in our homes and not permitted to go to the beach. During Summer 2021, Delta began its slow breakout.

Many will argue (with some rationale), that with widespread vaccination and treatment that case rates no longer matter. And, to some extent, that is true. But what vaccination and treatment allow is a rise of the threshold of protection at the community level against mortality. For those that are unvaccinated, undervaccinated, immunocompromised or lack access to health care, mortality remains a risk. This is demonstrated in the Figure below which shows the mortality rate in 2022 which achieved a near historic low at the end of April (0.03 daily deaths per 100,000) beginning a steady rise, crossing over 2021’s rates (note that at the end of 2021’s graph we are just beginning to see the higher mortality rate associated the Delta variant beginning to creep in).  The daily mortality rate is now 0.07 deaths per 100,000 (Figure 2 below). We are nowhere near pre-vaccination mortality rates however.

So clearly, more cases do lead to more deaths. Prevalence rate – which is a function of the number of tests and positivity rate is an attempt by me to account for home testing – is also clearly rising although is still dwarfed by the Omicron surge of December/January (Figure 3 below).

Now to the crux of the issue here – given that more cases in the community is now leading to more deaths in the community, can we identify those individuals among whom this is occurring?  Of course we can and the answer isn’t terribly surprising – those that are older and unvaccinated (Figure 4 below, taken directly from the LA County Health website).

To what extent will community wide masking modify this risk?  Not as much as one might think. In December of 2021, Abaluck et al. published in Science their results on community masking in Bangladesh showing an 11.9% decrease in COVID-19 symptoms and a 9.5% reduction in symptomatic seropositivity (those with COVID-like symptoms who also had antibody evidence of infection).

At this point in time, we are looking at a community-wide prevalence of at least 8%, so a decrease to 7.2% makes little impact. Far more effective from an interventional aspect would have been employing this mandate when prevalence rates were lower. At this point in time, a mask mandate is too little, too late. To say nothing of adherence, enforcement and pandemic fatigue amongst all of us.

Instead of a community-wide effort, I would advocate for situational masking (with an N95 or KN95) particularly among those who are unvaccinated or did not garner an immune response to a vaccination series (although Evushield, a long acting monoclonal antibody is a reasonable choice here and among those patients of mine who received such and subsequently contracted COVID-19, their symptoms were very mild). We continue to wear masks in our medical office with the assumption that patients coming in are, by definition, at higher risk than those in the general population. We also have an adult practice with a higher proportion of patients over the age 65 than most general practices. For this reason, you will see us with masks on in the office at all times. 

In the future, Dr. Ferrar and the County Health Department need to be more aware of community case rates. Relying on hospitalization rates to determine policy is inherently flawed, as hospitalizations are a lagging marker and may be confounded by access to care and mis-assignment (hospitalized due to COVID versus hospitalized with COVID). This current increase in cases began in May and to have a discussion in late July about how to intervene is significantly flawed.

𝗦𝗶𝗴𝗻 𝗨𝗽 𝗳𝗼𝗿 𝗢𝘂𝗿 𝗡𝗲𝘄𝘀𝗹𝗲𝘁𝘁𝗲𝗿

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