Kiki’s Comments                                                                                                        May 2020

                        TWiV 617: Coronavirus Times

            Key Points:

*test, trace, and isolate will be critical to a successful reopening—this will be particularly important once the number of cases are lower to prevent the next outbreak

*some patients are PCR positive for CoV-2 two months post infection; we do not know if these individuals are actively shedding viable virus

*some PCR tests are sensitive to all coronaviruses, including the common cold coronaviruses, so may present as coronavirus positive while the patient is COVID-19 negative

*we do not know what percentage of people with positive serologies will have some, if any, immunity to future infections with CoV-2

*late stage clinical features being noticed such as joint pains, pains in joint of the fingers, and a thick mucus issue

            Clinical Update with Daniel:

*Testing: there are certain PCR primers that will pick up the common coronaviruses (non-SARS coronaviruses that typically cause the common cold) and test positive for pan-coronaviruses in a PCR test, but will be CoV-2 negative—this means that with some tests a patient can tests positive for a coronavirus, but does not have SARS-CoV-2. PCR tests may be positive for CoV-2 before the onset of symptoms. We are seeing people who are PCR positive even two months after the first positive PCR—we do not know if these individuals are still shedding viable virus, but err on the side of caution. Currently two negative PCR tests within 24 hours is the metric for assuming the individual is no longer positively infected.

*Negative and positive predictive values of sensitivity and positivity: the relevance of predictive values can be dependent on the prevalence—when there is a high prevalence of the disease, like in NYC, issues of sensitivity become a bigger issue because the number of incorrectly characterized individuals is much larger.

*Positive versus negative serology: we do not know what percentage of people with positive serologies will have some, if any, immunity to future infections with CoV-2. We will not know more about this until the next wave, likely in the Fall, when we can use this information to see if there is a predictive value. The Roche test is currently the superior test for serology, but we do not yet know what this superior value will mean when it comes to re-exposure to the virus. This is an ELISA test that has very low cross-reactivity and high specificity and sensitivity.

*Summer camp, schools, and sports: we are starting to see people returning to some sports like tennis with restrictions. The testing issue will come up when it comes to schools and summer camps. We are waiting for guidance from the governments still, as this will vary State-by-State.

*Late stage symptoms: we are seeing joint pains, pains in joint of the fingers, and a thick mucus issue. We are looking to see whether there will be a post-inflammatory issue. This is primarily being handled through Telehealth visits, where we recommend short weekly check-ins. Viral shedding may occur for a very long period post infection (some evidence of 60 days), but we do not know if this is capable of continued transmission.

*Vaccines and Therapeutics for the next wave: we should be looking towards early therapeutics trials and large-number vaccine trials. Clinicians need to be looking at the next wave and seeing what we are going to do.

*Vitamin D: there is a huge push to believe that certain vitamins, supplements, and non-prescription therapeutics can play a role in recovery from COVID-19, but we do not yet have evidence yet for whether these could be helpful. Until we do have that evidence, be aware that many things could in fact be harmful.  

*HIV: we do not know if people with no viral load from HIV are at higher risk of developing severe COVID-19. We saw a very low admissions rate of the collective HIV patients who were being properly treated and following protocols. We will know more about the impact as more information becomes available, particularly from places with higher HIV prevalence. 

            General Discussion:

*Kowasaki-like syndromes: currently being treated by administering IgG from general populace that is aimed at convincing the body that there in no need for immune action

*Sweden: there are many opinions currently being shared about the pros and cons of the implementation of the Swedish system and the statistics being produced. 


*Norm: what is the feasibility of contain, trace, and control with a disease that is already prevalent and with a populace that may not be amenable to isolation? This is possible with large manpower when the case number is high, but this will be more openly feasible when the case numbers go down as we reenter society. In those cases we can use this to stop the larger future outbreaks.

*Matt: does CoV-2 enter the brain, i.e. is it neuroinvasive? Many of the neurological symptoms mentioned can be due to cytokines rather than neuroinvasion. We do not have any paper evidence about this yet that would point towards neuroinvasion. It is possible that CoV-2 can be associated with encephalitis, but we do not have evidence for this yet. 

*Michael: does the increase in ACE2 in response to cigarette smoke also apply to other types of smoke (eg wildfire)? We think that this would make sense for increase in ACE2. The papers previously discussed about how cigarette smoke increases ACE2 expression from chronic exposure. We do not have data that indicates that this increase in ACE2 causes severe COVID-19.

*Phillip: is there a protective effect given by the BCG vaccination? The BCG effect may be a transient effect (which would add to short-term, but not long-term protection), which would make this be unlikely to be the main cause of differences in COVID-19 severity in elderly populations that received or did not receive the vaccine as children. It is difficult to compare the effect of the BCG vaccine on the epidemic until we have much more information, particularly as there are many confounding factors. There are studies currently being done to test this theory, so we will see.

By Kiki Warren (