The impact of the coronavirus disease of 2019 (COVID-19), which is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2,1 has been widespread, with >500 000 cases diagnosed in >170 countries since the virus was identified in January 2020.2 The preliminary data have been focused on severe respiratory manifestations, which are seen predominantly in adults, with scant initial data on the burden of COVID-19 in children.3 We, therefore, read with interest the findings of Dong et al,4 who reported in this issue of Pediatrics a series of >2000 children with suspected or confirmed COVID-19. The authors found that 4% of virologically confirmed cases had asymptomatic infection, and this rate almost certainly understates the true rate of asymptomatic infection because many children who are asymptomatic are unlikely to be tested. Among children who were symptomatic, 5% had dyspnea or hypoxemia (a substantially lower percentage than what has been reported for adults3 ), and 0.6% progressed to acute respiratory distress syndrome or multiorgan system dysfunction (a rate that is also lower than that seen in adults). Preschool-aged children and infants were more likely than older children to have severe clinical manifestations.
There are several salient points from this article. First, although children are less likely than older adults to become severely ill, there are subpopulations of children with an increased risk for more significant illness. These data on disease severity are consistent with data on non-COVID-19 coronaviruses. The authors of one viral surveillance study in a PICU in China reported that coronavirus was detected in more children with acute respiratory distress syndrome than human metapneumovirus.5 The authors of another study conducted on hospitalized Norwegian children detected coronaviruses in 10% of hospitalized children with respiratory tract infections.6 Younger age, underlying pulmonary pathology, and immunocompromising conditions have been associated with more severe outcomes with non-COVID-19 coronavirus infections in children.7
Second, the attributable risk for severe disease from COVID-19 in children is challenging to discern. Previous studies have revealed that children from whom coronaviruses are detected from the respiratory tract can have viral co-infections in up to two-thirds of cases.6 In the study by Dong et al,4 testing for other viruses was not standardized, and two-thirds of cases were clinically diagnosed, not virologically confirmed. In addition, children without virological confirmation were more likely to have severe disease than children from whom COVID-19 was detected, potentially because their symptoms were caused by other pathogens.
Third, children may play a major role in community-based viral transmission. Available data suggest that children may have more upper respiratory tract involvement (including nasopharyngeal carriage) rather than lower respiratory tract involvement.4 There is also evidence of fecal shedding in the stool for several weeks after diagnosis,8 leading to concern about fecal-oral transmission of the virus, particularly for infants and children who are not toilet trained, and viral replication in the gastrointestinal tract.9 Prolonged shedding in nasal secretions and stool has substantial implications for community spread in child care centers, in schools, and in the home. Additionally, non-COVID-19 coronaviruses are detectable in respiratory secretions in a large percentage of healthy children,6 and the extent to which this is also seen in COVID-19 is unclear. Prolonged viral shedding in individuals who are symptomatic, combined with shedding in persons who are asymptomatic, would render contact tracing and other public health measures to mitigate spread less effective.
We have learned an amazing amount about COVID-19 in a short amount of time, with copious epidemiological, virological, and clinical data being published. The severe acute respiratory syndrome coronavirus 2 sequence, now published,10 was first posted to the bioRχiv preprint server a remarkable 6 weeks after the start of the epidemic, enabling the essential work of molecular epidemiology. The transmission of data has been surpassed only by the transmission of the virus itself. However, there is still much that we need to learn about the impact of this virus on children as well as the impact of children on viral spread. Although vertical transmission has not yet been reported,11 many of the infants born to mothers infected with COVID-19 were delivered surgically and quickly separated from their mothers. Many infectious diseases affect pregnant women more severely, and respiratory disease in pregnant women may result in poor fetal outcomes. Data on the basic reproductive number of the virus (the number of persons to whom an individual who is infected transmits the virus) have varied widely,12,13 and household studies can be used to refine the data we have on viral transmission and viral shedding. Widespread availability of testing will allow for us to more accurately describe the spectrum of illness and may result in the adjustment of the apparent morbidity and mortality rate as individuals who are less ill are diagnosed. Although the focus for pandemics is often on the impact on the persons who use the highest resources or on the economically productive age groups, rigorously gauging the impact of COVID-19 on children will be important to accurately model the pandemic and to ensure that appropriate resources are allocated to children requiring care. Many infectious diseases affect children differently from adults, and understanding those differences can yield important insights into disease pathogenesis, informing management and the development of therapeutics. This will likely be true for COVID-19, just as it was for older infectious diseases.
Opinions expressed in these commentaries are those of the authors and not necessarily those of the American Academy of Pediatrics or its Committees.
FUNDING: No external funding.
COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2020-0702.
- COVID-19
coronavirus disease of 2019
References
Competing Interests
POTENTIAL CONFLICT OF INTEREST: The University of Virginia has filed patent applications related to new technologies for the rapid production of vaccines, and Dr Zeichner is an inventor on those patent applications; and Dr Cruz has indicated she has no potential conflicts of interest to disclose.
FINANCIAL DISCLOSURE: Drs Cruz and Zeichner are associate editors for Pediatrics.
Comments
SARS-COV-2: DIFFERENT AGE, DIFFERENT VIRION
One of the most intriguing questions raised during these frantic months of pandemics is: why are elder people more affected by SARS-Cov-2? Why do they suffer from severe COVID-19 symptoms, compared with the relatively spared pediatric population (see, e.g., Parri et al., 2020; Qiu et al., 2020)? Attempts at explanations are focusing on the role of ACE2 receptors (Bunyavanich et al., 2020), immunity (Wang et al., 2020), mandatory vaccinations (Tozzi 2020a), viral structural proteins, and so on. Nonetheless, an underrated virionic element could provide useful insights to tackle our crucial question. SARS-Cov-2 particles are made not just of RNA and the four main viral structural proteins - spike, membrane, envelope, and nucleocapsid proteins (Fehr and Perlman, 2016; Chen et al., 2020) -, but also of a “foreign” component, entirely provided by the host. The SARS-Cov-2 lipid wall is stolen from the human endoplasmic reticulum-Golgi intermediate compartment (ERGIC), i.e., the vesicular-tubular cluster which mediates trafficking between endoplasmic reticulum (ER) and Golgi complex (Appenzeller-Herzog and Hauri, 2006; Tozzi, 2020b). It is no coincidence that coronaviruses display markers for the endoplasmic reticulum and Golgi (Brian and Baric, 2005). Like other enveloped viruses characterized by intracellular assembly, coronaviruses make use of the ERGIC membranes as a physical support for different steps of their vital cycle, such as replication and assembly by budding (Risco et al., 2002). Following replication and subgenomic RNA synthesis, viral structural proteins are translated. The ensuing proteins move along the secretory pathway and anchor to the physical support of the hosts’ ERGIC membranes (Krijnse-Locker et al., 1994). After the assembly, the virions - including viral proteins, viral RNA and host ERGIC membranes - are transported to the cell surface in vesicles and released by exocytosis (Risco et al., 2002).
In sum we may state that SARS-Cov-2 changes “skin” when jumping from a host to another.
ERGIC membranes and ageing. Once established that SARS-Cov-2 particles incorporate human ERGIC membranes, the next step it to examine whether such membranes are modified during senescence. Going through the literature, several clues point towards variations in human ERGIC membranes at different ages. It is well documented that biochemical, morphological and functional modifications of endoplasmic reticulum (REL) and Golgi membranes take place during ageing. From a long time ago, morphological studies in animals and humans revealed disorganization of the normally well-laminated pattern of REL and Golgi vescicles during senescence (Brizzee et al., 1975). Brouwer and Knook (1983) described the changes of cellular composition, morphology, function, physiology occurring in the reticuloendothelial system (RES) during aging. The interplay between RES and the immune system leads to increased susceptibility to infectious diseases and tumorogenesis during senescence. Back to the present, Desperes et al. (2019) identified ageing biomarkers associated with the Golgi apparatus. In contrast to the small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Further, the expression of numerous genes related to Golgi structural integrity and function was significantly altered. Cho et al. (2011) reported that the structure of the Golgi complex is dispersed in senescent cells. In particular, the upregulation of the G protein γ subunit γ11, which helps translocation from the plasma membrane to the Golgi complex, increases with ageing. Udono et al. (2015) showed that impaired expression of the senescence-associated gene ATP6V0A2 scatters the Golgi structure. Significantly different glycosylation structures in presenescent (young) and senescent (old) TIG-1 fibroblast cell lines were found.
Liu et al. (2018) described how the Serum Golgi protein 73 (GP73), a promising marker for liver fibrosis in adults, decreases with age in healthy controls. A hyperactive state of the protein secretory pathway mediates factors secretion and the fate of senescent cells. Su et al. (2018) investigated during cellular senescence the protein kinase D1 (PKD1)-mediated protein secretory pathway from the trans-Golgi network (TGN) to the cell surface. They found that components of this pathway, including PKD1, ADP-ribosylation factor 1 and phosphatidylinositol 4-kinase IIIβ, are increased at the TGN in senescent cells. The inhibition of this pathway reduces IL-6/IL-8 secretion during Ras oncogene-induced senescence (OIS), retards Ras OIS and alleviates the associated ER stress and autophagy. Janikiewicz et al. (2018) argued that mitochondrial and ER membranes’ composition plays a role in longevity, via modifications in lipid biosynthesis and trafficking, calcium homeostasis, reactive oxygen species production and autophagy. Calvo-Rodríguez et al. (2016) suggested that neuronal aging is associated to increased ER-mitochondrial cross talking and subcellular Ca2+ remodeling. Acute murine γ-herpesvirus 68 infection, that causes apoptosis of type II lung epithelial cells in aging mice, up-regulates endoplasmic reticulum stress markers (Torres-González et al., 2012). Brown and Naidoo (2012) and Chadwick and Lajoie (2019) described the role of ER stress response pathways in aging and age-related diseases, occurring via pathways such as unfolded protein responses.
In sum, we may state that SARS-Cov-2 displays different “skins” when jumping from older to young hosts, and vice versa.
Phenotypical differences between SARS-Cov-2 emerging from young and old human cells. We can state that human ERGIC membranes change with time passing. This means that the SARS-Cov-2 particles produced in the tissues of children are phenotypically different from the SARS-Cov-2 particles produced in the tissues of elder people. Whether SARS-Cov-2 infects children, adults or elder people, the released virions will display different arrangement and composition of ERGIC membranes. We hypothesize that the virus particles emerging from the younger cells might be characterized by “favourable” features that either decrease particle stability and viral load, or reduce SARS-Cov-2 infectivity, or enhance host ‘s immunological responses. It has been observed that children are infected as adults, but do not display the more severe, life-threatening symptoms of COVID-19 seen in elder people. According to our framework, the explanation is straightforward: invasive SARS-Cov-2 particles emerged from an adult (say, a the severely-ill grandfather) are able to infect a child (say, his nephew); nevertheless, during the replication in the young tissues, the emerging SARS-Cov-2 novel particles become less dangerous and invasive, because they acquire the ERGIC membranes of the kid. If our hypothesis holds true, children are less infective than adults, even if their viral load might be the same as adults.
In sum, we may state that the different “skins” of SARS-Cov-2 lead to changes in COVID-19 severity.
ERGIC antibodies in COVID-19? We suggest to investigate the possible occurrence of Golgi and endoplasmic reticulum antibodies in the serum and bronchoalveolar liquid of patients affected by COVID-19. When intracellular structures like the Golgi complex and endoplasmic reticulum are extruded from a dying cell, their extracellular location may be the source of autoimmune reactions and production of specific monoclonal antibodies (Ma et al., 2019; Grossmann et al, 1989; Nozawa et al., 2002; Hong et al., 2004; Borradaile et al., 2006; Weber et al., 2010). This phenomenon, well described during cellular apoptosis and necrosis, might occur when new SARS-Cov-2 particles emerge in the respiratory airways from the infected cells too. The huge amount of ERGIC membranes’ extracellular release during SARS-Cov-2 infection might be one of the factors that contribute to the lethal cytokine storm seen in COVID-19 (Fu et al., 2020). Antibodies against ER and ERGIC have been reported in human autoimmune diseases (Hong et al., 2004). For example, Bizzarro et al. (1999) detected anti-Golgi complex IgG antibodies in the sera of five patients during routine investigation for suspected systemic autoimmune disease. The phenomenon was transient in three patients with a probable viral infection, while it was persistent in the other two who developed an autoimmune disease a few years later. The anti-Golgi antibodies target the golgins, i.e., coiled-coil proteins anchored to the Golgi membrane that project into the surrounding cytoplasm (Witkos et al., 2015; Cheung and Pfeffer, 2016). This arrangement allows the tethering of nearby membranes or cytoskeletal elements (Satoh et al., 2019). The ability of golgins to aggregate different membranes might be responsible of the recently reported finding that SARS-COV-2 particles tend to aggregate and cluster together (Tozzi et al., 2020): in touch with this observation, it might be speculated that a different composition of golgins between children and elders might modify the ability of SARS-COV-2 to gather in larger structures that increase its fitness. The anti-Endoplasmic Reticulum antibodies target several resident proteins, e.g., calreticulin (Kotian et al., 2019). Calreticulin controls gene expression, calcium homeostasis regulation, molecular chaperoning and in particular, cellular adhesiveness: we speculate that this latter function might contribute to the different virulence of SARS-Cov-2 at distinct ages.
In sum, we may state that the different “skins” of SARS-Cov-2 produce different amounts of autoantibodies.
In conclusion, the different “skin features” of SARS-Cov-2 emerging from old and young cells might contribute to variations in clinical severity, viral load, infectivity.
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Arturo Tozzi
Center for Nonlinear Science, Department of Physics, University of North Texas, Denton, Texas, USA
1155 Union Circle, #311427Denton, TX 76203-5017 USA
tozziarturo@libero.it
Arturo.Tozzi@unt.edu
RE: Child Daycare Exposure to COVID-19 Positive Teacher In Los Angeles
As several states weigh the risks of reopening in the midst of the SARS-CoV-2, COVID-19 pandemic, we must pay more attention to the best guidance for viral prevention in early childhood education facilities in the community setting. Because limited research exists about COVID-19 in children (Cruz AT and Zeichner SL. COVID-19 in Children: Initial Characterization of the Pediatric Disease. Pediatrics. 2020;145(6):e20200834), the exposure of seven children ages 1 to 4 years to a COVID-19 positive teacher at a child daycare facility without evidence of either adult-to-child or child-to-adult transmission may provide insight regarding the application of mitigation strategies to slow viral transmission in these settings.
Recognizing that asymptomatic persons may also play a role in the spread of COVID-19, screening children and workers upon arrival by itself may not be sufficient in detecting all viral infections. In this case, screening was not adequately practiced as the teacher delayed reporting of respiratory symptoms for 48 hours and continued to work. This resulted in prolonged period of viral exposure among child contacts that wore no face coverings.
With a combination of strategies including screening of children and workers upon arrival, dismissal of symptomatic persons for isolation, reduced student-to-teacher ratio, staggered schedules, 6-foot spacing between persons, restricted parent drop-offs, face covering usage, hand hygiene practices, and regular disinfection of toys and high-touch surfaces, the investigated facility continued to operate without evidence of transmission to children or their family contacts throughout the 14-day and 28-day surveillance.
In the wake of political debate over the end of social distancing, face coverings, and stay-at-home orders, the lack of evident viral transmission among daycare children exposed for several hours to a COVID-19 positive teacher points to the benefit of continued mitigation strategies applied in the real world at schools and child daycares for the foreseeable future.
Authors
Clarence Monteclaro, MD, MBA, Department of Public Health, Los Angeles County
Maxine Liggins, MD, MPH, Department of Public Health, Los Angeles County
Rachel Civen, MD, MPH, Department of Public Health, Los Angeles County
Corresponding Author.
Clarence Monteclaro, MD, MBA, Department of Public Health, Los Angeles County
11833 Washington Ave., Los Angeles, CA 90059
cmonteclaro@ph.lacounty.gov
323-568-8704
Financial Disclosure
The authors have no financial relationships relevant to this article to disclose.
Funding Source
Project as part of routine outbreak contact investigation was done with no specific support. The Los Angeles County Department of Public Health Institutional Board Review approved this investigation.
Potential Conflicts of Interest
The authors have no conflicts of interest relevant to this article to disclose.
RE: Child Daycare Exposure to COVID-19 Positive Teacher In Los Angeles
As several states weigh the risks of reopening in the midst of the SARS-CoV-2, COVID-19 pandemic, we must pay more attention to the best guidance for viral prevention in early childhood education facilities in the community setting. Because limited research exists about COVID-19 in children (Cruz AT and Zeichner SL. COVID-19 in Children: Initial Characterization of the Pediatric Disease. Pediatrics. 2020;145(6):e20200834), the exposure of seven children ages 1 to 4 years to a COVID-19 positive teacher at a child daycare facility without evidence of either adult-to-child or child-to-adult transmission may provide insight regarding the application of mitigation strategies to slow viral transmission in these settings.
Recognizing that asymptomatic persons may also play a role in the spread of COVID-19, screening children and workers upon arrival by itself may not be sufficient in detecting all viral infections. In this case, screening was not adequately practiced as the teacher delayed reporting of respiratory symptoms for 48 hours and continued to work. This resulted in prolonged period of viral exposure among child contacts that wore no face coverings.
With a combination of strategies including screening of children and workers upon arrival, dismissal of symptomatic persons for isolation, reduced student-to-teacher ratio, staggered schedules, 6-foot spacing between persons, restricted parent drop-offs, face covering usage, hand hygiene practices, and regular disinfection of toys and high-touch surfaces, the investigated facility continued to operate without evidence of transmission to children or their family contacts throughout the 14-day and 28-day surveillance.
In the wake of political debate over the end of social distancing, face coverings, and stay-at-home orders, the lack of evident viral transmission among daycare children exposed for several hours to a COVID-19 positive teacher points to the benefit of continued mitigation strategies applied in the real world at schools and child daycares for the foreseeable future.
Authors
Clarence Monteclaro, MD, MBA, Department of Public Health, Los Angeles County
Maxine Liggins, MD, MPH, Department of Public Health, Los Angeles County
Rachel Civen, MD, MPH, Department of Public Health, Los Angeles County
Laurene Mascola, MD, Department of Public Health, Los Angeles County
Corresponding Author.
Clarence Monteclaro, MD, MBA, Department of Public Health, Los Angeles County
11833 Washington Ave., Los Angeles, CA 90059
cmonteclaro@ph.lacounty.gov
323-568-8704
Short title
Child Daycare Exposure to COVID-19 Positive Teacher in Los Angeles
Financial Disclosure
The authors have no financial relationships relevant to this article to disclose.
Funding Source
Project as part of routine outbreak contact investigation was done with no specific support. The Los Angeles County Department of Public Health Institutional Board Review approved this investigation.
Potential Conflicts of Interest
The authors have no conflicts of interest relevant to this article to disclose.
Abbreviations: none
Table of Contents Summary
This report presents the lack of viral transmission among daycare children exposed to a COVID-19 positive teacher and points to mitigation strategies in these settings.
What’s Known on This Subject
Because limited research exists about COVID-19 in children (Cruz AT and Zeichner SL. COVID-19 in Children: Initial Characterization of the Pediatric Disease. Pediatrics. 2020;145(6):e20200834), little is known about the best guidance for viral prevention in early childhood education facilities in the community setting.
What This Study Adds
The exposure of seven children ages 1 to 4 years to a COVID-19 positive teacher at a child daycare facility with no evidence of adult-to-child or child-to-parent transmission may provide insight regarding the application of mitigation strategies to slow viral transmission in these settings.
RE: Low Dehydroepiandrosterone (DHEA), a known, natural antiviral agent, is Directly Involved in COV-19 Infection and Pathology.
Low Dehydroepiandrosterone (DHEA), a known, natural antiviral agent, is Directly Involved in COV-19 Infection and Pathology.
© Copyright 2020, James Michael Howard, Fayetteville, Arkansas, U.S.A.
The epidemiology of COV-19 follows DHEA levels in humans. In this chart of DHEA from birth to death, levels of DHEA are high at birth and for a short time thereafter (newborns) (Period A). DHEA then declines to low levels (Period B), then increases (Period C and D) until it begins to decline Periods D, E, and F) reaching very low levels in old age. COV-19 pathology is highest during periods of low DHEA (Periods B, somewhere in Period D, depending upon one’s personal production, Period E, and Period F); early childhood, early decline of adulthood and old age. This is why infancy exerts protective effects while early childhood does not.
“Cases of coronavirus disease 2019 (COVID-19) among children in China have been less severe than those in adults, according to a new study.
However, being in a young age group wasn’t entirely protective. Infants had higher rates of severe illness than older children. Experts also say more testing and research will be needed to understand children’s role in spreading the virus in their communities.”
( https://www.aappublications.org/news/2020/03/16/coronavirus031620 )
I suggest a case may be made that DHEA), a known antiviral agent, levels are directly involved in protection from the COV-19 in infants. T
"A novel viral respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for an epidemic of the coronavirus disease 2019 (COVID-19) in cases in China and worldwide. Four full-term, singleton infants were born to pregnant women who tested positive for COVID-19 in the city of Wuhan, the capital of Hubei province, China, where the disease was first identified. Of the three infants, for who consent to be diagnostically tested was provided, none tested positive for the virus. None of the infants developed serious clinical symptoms such as fever, cough, diarrhea, or abnormal radiologic or hematologic evidence, and all four infants were alive at the time of hospital discharge." (Frontiers Pediatrics, 16 March 2020 | https://doi.org/10.3389/fped.2020.00104 )
It has been determined that "Preliminary evidence suggests children are just as likely as adults to become infected with SARS-CoV-2 but are less likely to be symptomatic or develop severe symptoms." "Preliminary evidence suggests children are just as likely as adults to become infected with SARS-CoV-2 but are less likely to be symptomatic or develop severe symptoms." (The Pediatric Infectious Disease Journal: March 12, 2020 - Volume Online First - Issue -
doi: 10.1097/INF.0000000000002660 ). (I have notified the authors of this possible explanation.)
"I suggest the basis of these findings is higher dehydroepiandrosterone (DHEA) in children compared to adults. DHEA is known to reduce virulence of many infections, including viral infections. DHEA is the active molecule which is made from the inactive, DHEA sulfate (DHEAS). Testosterone is known to reduce sulfatase which reduces DHEA availability from DHEAS. I suggest this is the reason that children exhibit less effects from coronavirus infections compared to adults, that is, individuals post pubertal. Furthermore, DHEA naturally begins to decline around ages of 20-25, reaching very low levels in old age. This would explain the increased virulence in adults, especially in old age.
It is my hypothesis that human evolution is driven by increases in testosterone. This would explain why infectious agents are entering the human population from other animals as our testosterone increases. (Human testosterone is much higher and DHEA much lower than in chimpanzees and other great apes. Currently, it is thought that "simian immunodeficiency virus or SIV" mutation gave rise to the HIV, which increased because of monkey meat consumption. As testosterone increases in humans, DHEAS increases. So, like the HIV, coronavirus enters our population as we increase testosterone and reduce DHEA. Human testosterone testosterone begins to increase in the fall and winter, and influenza activity often increases in October.
Again, I suggest the basis of these findings that children exhibit reduced COVID19 virulence is higher DHEA in children. This immediately suggests that treatment with DHEA should be available to aging adults as their DHEA naturally declines with age.
Note: It is known that DHEA protects against West Nile Virus (J Med Virol. 1992 Nov;38(3):159-66. In fact, “A significant protective effect of a native adrenal steroid, dehydroepiandrosterone (DHEA), was demonstrated in studies of two lethal viral infection models in mice: systemic coxsackievirus B4 and herpes simplex type 2 encephalitis. … While the molecular basis for DHEA's effect on the immune system is not known, studies by others suggest that it may counteract the stress related immunosuppressive effects of glucocorticoids stimulated by viral infection. … Because DHEA is a native steroid that has been used clinically with minimal side effects, the utility of DHEA in the therapeutic modulation of acute and chronic viral infections including the acquired immune deficiency syndrome deserves intensive study.” (Journal of Medical Virology Volume26, Issue3 November 1988 Pages 301-314 https://doi.org/10.1002/jmv.189026031)
(Note: It is my hypothesis that DHEA evolved to work with testosterone because it stimulates androgen receptors through which intracellular DHEA is stimulated. Therefore, the natural decline of testosterone of aging combines to increases the reduction of intracellular DHEA with aging. These two androgens work together. This is why treatment of older individuals with either DHEA or testosterone alone, often do not produce significantly positive results. This is partly derived from ("Androgens in Human Evolution," Rivista di Biologia / Biology Forum 2001; 94: 345-362. If your library does not subscribe to "Rivista ... ," you may find this at: http://anthropogeny.com/Androgens%20in%20Human%20Evolution.htm where you may also see a chart of testosterone in humans and great apes which directly supports my hypothesis and was reported in the literature 2 years later.)"
Contesting interpretation of COVID-19 in infants and preschool-aged children
The study by Dong et al (1) presents a large case series of COVID-19 pediatric patients in China. Because relatively little is known about infection in children, this is a very important paper. The authors are to be celebrated. They are doing heroic work under extraordinary stress.
The team identified n=731 lab-confirmed cases and n=1412 suspected* cases <18 years old diagnosed between Jan 20, 2020 and Feb 8, 2020. (*This suspected group will be important later.) As seen in other work, SARSCoV19 has much less severe effects on children than adults: most children were asymptomatic or had mild illness. The one child in the <2,000 who died was one of the older children, a 14 year old. And the study did not investigate whether children were capable of spreading SARS-CoV-2 to others.
I do think there is a worrying misinterpretation in the associated commentary (2): "Preschool-aged children and infants were more likely to have severe clinical manifestations than older children." I don't believe that the data support these conclusions.
Thinking back to the 1412 suspected* versus confirmed cases I mentioned above.
1) The confirmed cases were significantly less sick than the suspected cases (see Table 1). In fact, ALL the asymptomatic kids were lab-confirmed #SARSCoV2.
2) The preschool-aged children and infants were much more likely to be suspected cases (they were sick with something & lived in a high-risk area or had contact with a COVID-19 case) than the older children were.
In other words, the infants and preschool-aged were more likely to be sick but not necessarily with COVID-19. Dong et al. say as much in the Discussion of their paper: "...more severe and critical cases in the suspected than confirmed group..., which suggests that some suspected cases might be caused by other respiratory infections (e.g., RSV)." (1)
In other words, a lot of these sick babies and preschool-aged kids were probably sick from RSV or other illnesses that are known to have bad effects in young kids. They were presumed to have COVID-19 because they were in an area with an active outbreak. But it’s plausible that these children just had other respiratory infections that are very common to children this age.
I'm writing this Comment because I was on the phone last night with a sister-colleague who says that a friend who's 38 weeks pregnant is scared because she heard of a new study that says that #COVID19 is especially bad in infants. I am fairly sure that her additional fear is based on this commentary and the news reports about it. Being pregnant during this outbreak is already stressful enough without added (I believe, unfounded) worries that your baby has increased susceptibility to COVID-19.
I would like to see a presentation of the age-specific outcomes restricted to confirmed cases or stratified by confirmed versus presumed status. These data would provide much-needed clarity about the outcomes that infants and preschool-aged children are facing.
1. Dong Y, Mo X, Hu Y, et al. Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics. 2020; doi: 10.1542/peds.2020-0702
2. Cruz A, Zeichner S. COVID-19 in children: initial characterization of the pediatric disease. Pediatrics. 2020; doi: 10.1542/peds.2020-0834