June 2020 COVID-19 Update
By Scott Field, MD, FCP
We continue to learn about the second coronavirus (CoV) to cause severe adult respiratory syndrome (SARS), named SARS-CoV-2, which is responsible for the present pandemic of the coronavirus disease that started in 2019 in China (COVID-19). The following referenced information is meant to supplement the 3/16/20, 4/1/20, and 5/1/20 ACPeds articles.
An important recent revelation has been that the gene for the angiotensin-converting enzyme 2 (ACE2) receptor that allows cells to get infected with SARS-CoV-2 is actually highly enriched in the surface cells of the tongue.1 That has major implications regarding transmission and testing. Saliva or tongue scrapings may be superior diagnostic specimens, short of coughed up sputum, in the first week of symptoms, and an antigen test (rather than the RNA test widely used) may be cheaper yet reliable for detecting the virus.2 Talking, singing, and certainly kissing, could spread the virus to close contacts in days prior to developing any symptoms. Mean ACE2 gene expression in epithelial cells of the tongue is almost 7 [log2 counts per million]1 compared to levels of less than 3.5 in nasal mucosa.3 Infection in the mouth may not cause symptoms, other than potential taste dysfunction, while allowing for spread of the virus by saliva droplets. Nasal mucosa being the initial infection site would likely be associated with more nasal symptoms, as is the case with most other respiratory viruses. Although anosmia (loss of smell) was seen in up to 47% of COVID-19 adults, and more (57%) of those patients also had rhinorrhea, anosmia is rarely seen as a first symptom.4 Thus, I think that it is likely that most SARS-CoV-2 infections start on the tongue before spreading to the nasopharynx, lungs, and/or gastrointestinal tract. That could also explain the long incubation period of COVID-19 compared to other respiratory viral infections.
After the first week of symptoms, antibody testing (serology) may be as effective if not more so in diagnosing COVID-19.5 Serology will probably be a more cost-effective way of identifying infected asymptomatic contacts of known cases, as the IgG antibodies rise within 1 to 3 weeks of infection.6,7 Interestingly, the IgM antibodies that usually rise first with new infections, often rise no earlier than IgG,7 and have been undetectable in patients with mild symptoms but prolonged viral shedding.8-10 Rises in IgM may be important in clearing of the virus.8 Up to 6% of SARS-CoV-2-infected individuals fail to develop detectable IgG or IgM antibodies.9,11,12
For children, the latest concerns have been the recently identified multisystem inflammatory syndrome of childhood (MIS-C) and the challenges of school and daycare. MIS-C has recently come to light as a rare but serious Kawasaki-like disease of children, mostly older than 4 years of age, who experienced or were exposed to COVID-19 within recent weeks.13,14 See our recent posting about MIS-C.
The concerns for reopening daycares and schools is that they are prime environments for spreading infectious diseases, and face coverings as well as social distancing may prove difficult if not impossible in those settings. Some experts have suggested that children may not transmit SARS-CoV-2 as well as adults, and that they may also not be as susceptible.15 Yet children can have viral loads as high or higher than adults.16,17 Possible explanations for the lesser morbidity from COVID-19 in children include the idea that they might have less ACE2 receptors in their lungs (having less expression of ACE2 has been found in nasal mucosa of young children compared to older children and adults),3 they might have cross-protection from circulating cold-causing human coronaviruses, and that they might have a better immune response with less cytokine release than adults.18 Facial barriers (masks or shields) as well as hand and surface sanitation are believed to be helpful in preventing transmission,18 so reliance on those measures may be necessary for children who are able to comply when social distancing is not achievable. Studies are needed to evaluate different mitigation strategies to better guide public policy. Viral as well as serologic testing is needed to help answer questions about the effect of children returning to group environments like daycares and schools.
Xu H, Zhong L, Deng J, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Science. Online 24 Feb 2020 https://doi.org/10.1038/s41368-020-0074-x
Covilinguality: Rapid Test for COVID-19 Clinical Trial Results. Is the Tongue a Superior Site for Testing COVID-19? (a VuMedi presentation from Sarah Hagarty on 14 May 2020)
Bunyavanich S. Nasal gene expression of angiotensin-converting enzyme 2 in children and adults. JAMA. Online 20 May 2020.doi:10:1001/jama.2020.8707
Klopfenstein T, Kadiane-Oussou NJ, Toko L, et al. Features of anosmia in COVID-19. Med Mal Infect. Online 17 Apr 2020 https://doi.org/10.1016/j.medmal.2020.04.006
Zhao J, Yuan Q, Wang H, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis. Online 28 Mar 2020. Doi: 10.1093/cid/ciaa344 https://doi.org/10.1101/2020.03.02.20030189
Guo L, Ren L, Yang s, et al. Profiling early humoral response to diagnose novel coronavirus disease (COVID-19). Clin Infect Dis. Online 21 Mar 2020 doi: 10.1093/cid/ciaa310
Long Q-L, Liu BZ, Deng H-J, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. Online Apr 29, 2020. https://doi.org/10.1038/s41591-020-0897-1
Lee Y-L, Liao C-H, Liu P-Y, et al. Dynamics of anti-SARS-CoV-2 IgM and IgG antibodies among COVID-19 patients. J Infect. Online 23 Apr 2020. Doi: 10.1016/j.jinf.2020.04.019
Wang B, Wang L, Kong X, et al. Long-term coexistence of SARS-CoV-2 with antibody response in COVID-19 patients. J Med Virol. Online 28 Apr 2020. Doi: 10.1002/jmv.25946
Wolfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2109. Nature. Online 1 Apr 2020 https://doi.org/10.1038/s4186-020-2196-x
Jin Y, Wang M, Zuo Z, et al. Diagnostic value and dynamic variance of serum antibody in coronavirus disease 2019. Int J Infect Dis. 2020 https://doi.org/10.1016/j.ijid.2020.03.065
Zhang G, Nie S, Zhang Z, Zhang Z. Longitudinal change of severe acute respiratory syndrome coronavirus 2 antibodies in patients with coronavirus disease 2019. J Infect Dis. Online 2 May 2020. Doi: 10.1093/infdis/jiaa229
Belhadjer Z, Meot M, Bajolle F, et al. Acute heat failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic. Circulation. Online 17 May 2020. doi: 10.1161/CIRCULATIONAHA.120.048360
Centers for Disease Control (CDC) Health Alert Network. Multisystem Inflammatory Syndrome in Children (MIS-C) associated with coronavirus disease 2019 (COVID-19) Online 14 May 2020. https://emergency.cdc.gov/han/2020/han00432.asp
Mallapaty S. How do children spread the coronavirus? The science still isn’t clear. Nature. 2020:581:127-128.
Han MS, Seong M-W, Heo Y, et al. Sequential analysis of viral load in a neonate and her mother infected with severe acute respiratory syndrome coronavirus 2. Clin Infect Dis. Online 16 Apr 2020. Doi: 10.1093/cid/ciaa477
Schwierzeck V, King JC, Kuhn J, et al. First reported nosocomial outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric dialysis unit. Clin Infect Dis. Online 27 Apr 2020. doi: 10.1093/cid/ciaa491
Esposito S, Principi N. To mask or not to mask children to overcome COVID-19. European J Pediatrics. On line 9 May 2020. https://doi.org/10.1007/s00431-020-03674-9