#Pediatric #COVID19 discussion thread - why is severity in children less than adults? Do other coronavirus infections in childhood play a role? Are there other protective factors in children? Let's dive in. 1/n
SARS-CoV-2, referred to as COVID-19. Since being identified in late 2019, there have been over 1 million infections worldwide with case fatality rate reported to be around 5.7% as of April 7, 2020 according to @JohnsHopkins 2/n coronavirus.jhu.edu/map.html
Numerous theories have been postulated on why children are not being affected by coronavirus at a severity level that is equal to their adult counterparts.
The idea of prior immunity or a more robust immune response to new illnesses have been some ideas discussed. 3/n
The idea of prior immunity or a more robust immune response to new illnesses have been some ideas discussed. 3/n
data recently presented at the 2020 @FAUMedSchool research day, it was found that children in an outpatient peds setting were found to have a high diversity of pathogens found via respiratory pathogen PCR panel. 4/n 
Interestingly, as children got older, the diversity found on their swabs were lower. This has also been found in prior studies looking at organism biodiversity as people age. *article* 5/n ncbi.nlm.nih.gov/pmc/articles/P… ncbi.nlm.nih.gov/pmc/articles/P…
Lower diversity of viruses and bacteria has been associated with more frequent upper respiratory infections, particularly in infants up to 12 months old msphere.asm.org/content/1/6/e0… 6/n
There is also a potential interplay between bacterial & viral pathogens that can be found in the nasal passageways of ASx individuals. Studies have found Rhinovirus, M. Catarrhalis, S. pneumoniae, Adenovirus, among others in the nares of ASx people. 7/n who.int/immunization/r…
Additionally, we know that children have more febrile infections per year compared to adults & this number decreases as pts age. Human coronavirus has been a cause of the common cold with four subtypes identified as causing common cold Sx - 229E, NL63, OC43, and HKU1 8/n
Specifically, human coronavirus (CoV) sub-type NL63 is known to attach to the same ACE-2 receptor as the novel SARS-CoV-2 coronavirus. This is where things can get interesting! Keep reading! 9/n ncbi.nlm.nih.gov/pmc/articles/P…
In the outpt peds PCR study, human CoV was found as one of the most common viral infections. This resp PCR panel was also more inclusive than most, detecting M. Catarrhalis, S. pneumoniae, & non-typeable H. flu in addition to the standard 20+ virus + atypical bacteria. 10/n
When multiple +'s are found on resp PCR it is hard to determine which pathogen(s) may be causing the Sx vs. found incidentally as carrier state. The symbiotic relationship between the viruses & bacteria can also play a role in allowing one to potentiate into URI Sx. 11/n
hypothesis: kids may have a lesser risk of illness with the novel coronavirus because they may have a common CoV (NL63) living in their nasal passages which is essentially blocking the adherence of SARS-CoV-2 from some of the ACE2 receptors. 12/n
Beyond the physical blockade of the receptor by another virus, there is another component to infection from SARS-CoV-2 that must occur prior to viral entry into the host cell. 13/n
SARS-CoV-2 has a spike ‘S’ protein. In addition to the S protein, there are three other structural base proteins: the envelope, membrane, and nucleocapsid. S protein has two distinct functional domains, termed S1 & S2, both of which are necessary for CoV to enter a cell 14/n
In order for fusion to take place, the S2 protein needs to be cleaved by proteases found in the cell. This allows for the fusion sequences to be exposed. This cleavage is generally mediated by furin, a protein convertase. 15/n assaygenie.com/how-furin-and-… ncbi.nlm.nih.gov/gene?Db=gene&C…
Furin is found in most tissues in our body, with some areas having more than others. Furin plays a vital role in many infections (and cancers). 16/n ncbi.nlm.nih.gov/pmc/articles/P…
Elevated furin levels in human cystic fibrosis cells result in hypersusceptibility to exotoxin A–induced cytotoxicity 17/n ncbi.nlm.nih.gov/pmc/articles/P…
Elevated furin levels are also found in patients with diabetes and is associated with increased mortality. Diabetics are at higher risk for poor outcomes with SARS-CoV-2 18/n ncbi.nlm.nih.gov/pubmed/29888466
Furin for thought: do children express less furin than adults resulting in decreased cleavage of SARS-CoV-2 and reduced cell entry? Does it take furin longer to accomplish this in kids? 19/n
There is a range of time that it takes for SARS-CoV-2 to attach to the ACE-2 receptor(s) and then begin the process of having its S2 protein cleaved by furin. Can the virus be killed or knocked off the receptor during that time prior to cell entry? 20/n
Additional thoughts: Does the diversity of organisms found in kids make them less susceptible to SARS-CoV-2? As we age, the immune system undergoes decline, predisposing older adults to a higher risk of acute viral & bacterial infections. 21/n ncbi.nlm.nih.gov/pmc/articles/P…
Somewhat counter-intuitive, the innate immune response declines with age and "older" innate immune systems also leads increase in pro-inflammatory cytokines IL-1β, IL-6, IL-18 and TNFα 22/n ncbi.nlm.nih.gov/pmc/articles/P…
This has been a long rabbit hole of #medschool basic science review and SARS-CoV-2 #pediatric theory. Hopefully you have more questions after reading through and can help to complete further studies on cases in kids. Thanks for reading! 23/23
It’s not a classic @tony_breu style #tweetorial — more like part tutorial and part hypothesis. We’ll go with a #Tweepothesis @PedPrac12
@VirusesImmunity - would appreciate your take on the COVID19 & pediatric vs adult infx risk #tweepothesis above
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