Kiki’s Comments                                                                                                        July 2020

                        TWiV 640: Test Often, Fast Turnaround

Key Points:

*We should endorse the use of inexpensive and less sensitive tests that, though less sensitive than PCR, will be more effective if used more consistently to prevent disease spread as they already identify more infectious individuals—we have to change the model that the federal government is using for testing. If the test isn’t as good, but we do it daily with quicker results, we will be much better off at suppressing disease spread.

*Pooled model for testing can be very helpful for determining outbreaks when the level of disease in the group population is lower; this can be useful for universities and schools

*CT values are a good predictive level for infectivity of an individual cultivated with virus; two consecutive (within 24 hours) lower sensitivity tests with similar CT values can be considered fairly accurate

Notes from Michael Mina: Harvard School of Public Health

*What is your opinion of the CDC being removed from public data? This is unfathomable—this entire pandemic from the US perspective has been terrible with misinformation and misplaced responsibilities. There is no reasonable explanation, scientifically, for this, except possibly to control the numbers being seen and to remove information from the populace.

*Testing: If done properly this can be successful in stemming the spread of the virus. High frequency testing with a low sensitivity test is better for disease control than the best test in the world that is taken by the population infrequently. FDA has to change their methodology to tell people that there are tests that exist now that are inexpensive and could be federally funded for $1 each that are not as sensitive as PCR, but that, if people took the test every morning, would tell the majority of highly infectious people that they should not go out. This will be very valuable for controlling COVID-19. It is ok if these tests are 3 or 4 points worse than the PCR tests. On aggregate, doing this would drive the R-effective way down overnight. If done widely, you would not even need to do contact tracing as people would be doing it themselves. 

n.b. if we took paper companies and had them start printing monoclonal antibodies onto the paper, we could have a good baseline daily test for individuals to determine whether they are highly infectious

*NYU Abbott ID NOW test: this is an isothermal molecular test for COVID-19 that is a 50% sensitive 10-minute test. It is important to note that the low sensitivity samples all had pretty high CT values, which is near the limit of detection, usually at the end of the course of an infection. After people are well beyond transmissibility periods are where we are seeing the lower sensitivity, which may not be as relevant to disease control (i.e. it may not be as helpful to identify individuals late in infection, passed the point when they can transmit the disease). We have created an ecosystem focused on high-end, expensive tests, which has resulted in us not testing as many people—CDC released that 9 of 10 individuals with COVID-19 are not tested. If we look at this method in our testing program in the US and we know that the virus transmits at high viral loads, then maybe we should look to using cheap tests, even if less accurate later in the infection, in order to benefit disease control. In other words, inexpensive tests that are fairly sensitive when people are peak infectivity will help most for disease control and contact tracing efforts. It is not as helpful to identify people as COVID-positive a few weeks post infection. 

n.b. CT value of 40 to 37 is a 10-fold increase. People who are really sick will have CT values 20 or lower, even as high as 13. 

*What is the window of transmission in a traditional patient: from the perspective of host kinetics, the window is probably on the order of a week. If you think of how high this virus can grow, people cannot sustain a viral load in the millions in the respiratory mucosa for long without the virus burning through most of the cells. For extended periods of contact, for example in households, the transmission window is likely much longer. If you are so sick that you are going to the hospital, that individual may be able to transmit the virus for longer. 

n.b. if someone has a CT value of 35 and a high IgG level, these people should probably be able to go back to work

*Pool testing: this may be useful in schools and universities to test for outbreaks. The pooled model can be very helpful at low levels of disease. If a pooled positive, the individual samples could then be tested to find the infectious individuals or, to not dilute the signal, the whole pooled subgroup could isolate for the day or time period. Pooling can work with high sensitivity testing or even lower sensitivity testing. Ideally testing would be every three or so days, but if that is not possible then more dispersed testing that is ramped up when outbreaks are detected could be effective. While this will likely not be ideal on the individual level, finding positives in multiple groups would be indicative of an outbreak and need for enhanced isolation or precautionary measures. 


*What can be done around pre-kindergarten and young years of school that do not allow for social distancing? This is a very difficult issue, but those close contact, shared toy places for such extended hours are rife for transmission of COVID-19, not to mention other viruses. Right now, this kind of education may be very dangerous. If we start implementing the cheap, daily, and rapid tests, even with lower sensitivity, we could help to minimize risks of spreading the disease, i.e. you test your child every morning and if they have a positive they stay home and if they have a negative they go to school (even false negatives are likely to be caught the second day, which would be better than no testing). If too many individuals are testing positive then the school should close for a period. It would also help to remove toys from the rooms because of children all sharing and touching the same items, but this may be difficult for kids of that age. As a side note, kindergarten is not universal and is relatively newer to our society (Vincent did not go to one), so if the parents can keep their children home then that would be preferable. 

*Is pooled sampling going to be helpful for tracing this virus? Yes, as long as the virus levels are low. If the virus is already widespread, many of the pooled groups will be positive and thus individual samples on mass would be tested, not saving much time or effort, but if the number of infections is smaller this will be helpful. This may be particularly helpful for identifying outbreaks.

By Kiki Warren (