Chronicles of Ellery Ivan MD

Currently, no SARS-COV2 test gives a 100% accurate result. Ideally, these tests need to be evaluated to determine their sensitivity and specificity, by comparison with a “gold standard.” The absence of a gold standard for the disease makes the evaluation of test accuracy challenging.

Diagnostic tests (typically involving a nasopharyngeal swab) can be inaccurate in two ways. A false positive result erroneously labels a person infected, with consequences including unnecessary quarantine and contact tracing. False negative results are more consequential, because infected persons — who might be asymptomatic — may not be isolated and can infect others. [1]

Previously, test availability has been a concern here in the Philippines especially on RT-PCR, but test accuracy may prove a larger long-term problem. Another concern is the high number of rapid IgM IgG test available in the market yet it's sensitivity and specificity of COVID-19 remains problematic.

Interpreting the result of a test for COVID-19 depends on two things: the accuracy of the test, and the pre-test probability or estimated risk of disease before testing. [2]

To understand accuracy of the exam, concepts on sensitivity and specificity must be first understood. Sensitivity is the proportion of patients with disease who have a positive test, or the true positive rate. Specificity is the proportion of patients without disease who have a negative test, or true negative rate. These terms describe the operating characteristics of a test and can be used to gauge the credibility of a test result.[2]

Two studies from Wuhan, China, arouse concern about false negative RT-PCR tests in patients with apparent Covid-19 illness. The studies suggest that 70% is probably a reasonable estimate for sensitivity of the nasal swab of RT-PCR. At this sensitivity level, with a pretest probability of 50%, the post-test probability with a negative test would be 23% — far too high to safely assume someone is uninfected. [2]

In summary, a positive RT-PCR test for covid-19 test has more weight than a negative test because of the test’s high specificity but moderate sensitivity. A single negative covid-19 test should not be used as a rule-out in patients with strongly suggestive symptoms. What this highlights is that we are still on our infancy stage in detecting SARS-COV2 and diagnosing COVID-19.

In a perfect world, designing a reference standard for measuring the sensitivity of SARS-CoV-2 tests in asymptomatic people is optimal. Simply following people for the subsequent development of symptoms may be inadequate, tiresome and dangerous as they may remain asymptomatic yet be infectious.

References:

[1] Watson Jessica, Whiting Penny F, Brush John E. Interpreting a covid-19 test result. https://www.bmj.com/content/369/bmj.m1808.long

[2] Steven Woloshin, Neeraj Patel, Aaron S Kesselheim. False Negative Tests for SARS-CoV-2 Infection — Challenges and Implications. https://www.nejm.org/doi/abs/10.1056/NEJMp2015897

Day 5 of #100DaysToOffload. Find out more about it here.

A came across an article in the New York Times and it was about updates on the development of a SAR-COV2 vaccine. I was thus inspired to share a thing or two about vaccine development.

For starters, vaccine development typically require years of research and testing before reaching the clinic or health centers. And even after that, market surveillance is also done to check for presence of adverse events or any unexpected effects of vaccines. And if need be, regulatory controls will withdraw the vaccine from the market.

The US CDC has general stages for the development cycle of a vaccine and these are:

• Exploratory stage
• Pre-clinical stage
• Clinical development
• Regulatory review and approval
• Manufacturing
• Quality control

According to the article mentioned, there are at least 135 vaccines in development in various stages. The vaccines in development are diverse and use different methods to invoke the immune response in our body.

Please do visit the article to learn more on the various potential vaccines in development.

One last note, although the US Government has endorsed and selected 5 vaccine trials to receive federal support. And it's aptly named, “Operation Warpspeed”. I'm sensing a Star Trek vibe. We can be hopeful in 2021 there's going to be an available vaccine out in the market. But maybe, I won't bet on it yet.

Reference:

1. Coronavirus Vaccine Tracker. Jonathan Corum and Carl Zimmer. https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html Accessed: June 11, 2020

2. Vaccine Testing and the Approval Process https://www.cdc.gov/vaccines/basics/test-approve.html Accessed: June 11, 2020

3. Trump Administration Selects Five Coronavirus Vaccine Candidates as Finalists. Noah Weiland and David E. Sanger. https://www.nytimes.com/2020/06/03/us/politics/coronavirus-vaccine-trump-moderna.html Accessed: June 11, 2020

Day 4 of #100daystooffload

HAPPY 122nd INDEPENDENCE DAY REPUBLIC OF THE PHILIPPINES!

Last night, I had a nightmare. I was doing my routine in the hospital and my daily activities in the hospital, when for now apparent reason I was given a copy of my chest xray result. The image was typical of a COVID-19 patient. At this point, my mind raced (I didn't know that it was a dream, it felt real).

“Was I ready to die?”, I thought to myself. Then I woke up.

I remember before I slept I had a discussion about COVID-19 with the family about the risk of getting it is high for healthcare workers, among other things.

I realized that going to the hospital every single day has a tax on your physical and mental health. And then we have an add-on. We hear numerous negative comments from people ranging from the uselessness of medical workers to government quack conspiracies. Personally, I think the medical workers mind can't process those information at this point in time when faced with a clear and present danger in front of them.

A simple thank you, a simple prayer will definitely go a long way. If you can't utter it, then do us a favor and just shut your mouth.

Day 3 of #100daystooffload

Today is a milestone as we breached the 10,000 cases of COVID-19. Certainly not a cause for celebration but rather a time for reflection on how far we are or how far we have gone forward. It's been 97 days since the first covid-19 case was detected in the Philippines. Let's see what the charts convey and probably think or opine on where we are right now.

Let's try to dissect this chart.

It seems that we have an average of 300 diagnosed cases per day and as the news of new testing centers opening up in the coming weeks. I think we can see more diagnosed cases. I am not privy or I am unable to locate the number of tests done on a daily basis in the laboratories. This information can elucidate new insights on our fight against covid-19.

Recoveries since last month have steadily increased and more recoveries are good news indeed.

The target is always zero deaths. And we hope and pray for that eventuality in the coming days or weeks.

Some few things that leave me pondering, are the recoveries and deaths of healthcare workers (doctors, nurses, midwives, medtechs, IWs and just anybody working in a hospital) tracked on a daily or weekly basis? I've seen reports that tell us we are experiencing deaths of HCW in high proportions. And this information just adds more stress in my daily rounds

Day 2 of #100DaysToOffload

#100DaysToOffload is a simple concept that Kev Quirk thought of one day. The rationale behind the whole thing is to challenge people to write on their personal blog every day for 100 days.

Since I'm trying to make writing / blogging a habit and a chance to diffuse the stress during the time of Covid-19, I thought this would be a great way to challenge myself even in my busy schedule.

Of course, my 100 days won't be consecutive. I won't be able to finish the challenge for sure.

Start of #100DaysToOffload.

It has been 94 days since the first case of Covid-19 was diagnosed in the Philippines and 47 days since quarantine in one form or another was instituted in the Philippines.

The graph above shows variability in our diagnosis of Covid-19. We have an average of 94 case diagnosis per day since January 30. But if we start on March 6, 2020 where the sudden surge of diagnosis occurred, we have 154 cases on a given day. On rough estimates therefore, I believe if we are to expect a flattening of a curve we should have numbers below this number for at least two weeks.

As mentioned in a previous post, the daily confirmations show great variability and thus a 5 day moving average can better illustrate our curve. As of the moment, it looks like three mountain peaks roughly of the same height and this means we see the same number of diagnosis on average for the last 4-5 weeks. On a good note, this may also illustrate that our mitigation procedures are working, thus there is no continuous upward trend. I certainly hope so. Therefore, once we let go of our mitigation procedure, we can expect a sudden rise of the curve after two weeks or so.

Another way to illustrate the effect of Covid-19 in our society is through the numbers of recoveries and deaths. In other words, how deadly is the Covid-19 here in the Philippines? The actual case fatality rate of Covid is determined as the proportion of reported cases which are fatal within a specified time. It is a measure of the severity of the disease and is expressed in percentage.

The above graph is a simple representation of the impact of covid-19 to people on a daily basis. How many survive and how many die in a given day. Initially, more deaths were reported until April 15, 2020 when more recoveries of patients were observed than deaths. A total of 353 people recovered from COVID, outnumbering for the first time the total deaths (349) from the disease.

The best number is no more new deaths representing 100% recovery for the new cases. We can hope that as much. Keep us medical workers in your prayers!

#100DaysToOffload

It has been 87 days since the first COVID-19 Filipino was diagnosed in the Philippines. Since then we have accumulated a total of 7294 confirmed cases. And it seems there is no end or deceleration. I've tried to monitor the cases on my own and create my own charts to understand the gravity of the situation.

This chart uses a 5-day moving average to visualize the number of new COVID-19 cases and calculate the rate of change. This is calculated for each day by averaging the values of that day, the two days before, and the two next days. This approach helps prevent major events (such as a change in reporting methods) from skewing the data.

The chart above on the other hand presents a more comprehensive view on our situation. The daily confirmed cases of COVID-19 has not let up since March 12 and continues to accumulate at almost the same intensity daily. The 5 day moving average seems to be on a plateau since March 20. It could be of two possibilities, first, we have reached our maximum testing capabilities and thus can only “maximally” confirmed a certain number of cases. Or, second, that this is our actual or real cases of COVID-19 in the Philippines. Unfortunately, due to my limited access to information. I can only infer for now.

In conclusion, I think the curve is not flattening, if anything else we are merely in the beginning of the tunnel and the light at the end feels like a wisp.