Asymptomatic transmission, going back to school and immunity: The Sars-CoVid2 episode with Jena S. Griffith, RDN, IHC, part 1

I resisted doing anything CV19 related to the podcast, but I have news fatigue and just need some good research on the topic. That's why I invited my investigative journalist turned dietitian friend Jena S. Griffith back on The Less Stressed Life Podcast for a two-episode series on the CV to talk current research and common questions around asymptomatic transmission, going back to school, immunity, testing, treatment, and masks.

CHAPTER MARKERS:

• A study on infectivity of asymptomatic SARS-CoV-2 carriers [07:02]
• Rapid asymptomatic transmission of COVID-19 during the incubation period demonstrating strong infectivity in a cluster of youngsters aged 16-23 years outside Wuhan and characteristics of young patients with COVID-19: A prospective contact-tracing study [08:56]
• Children are unlikely to be the main drivers of the COVID‐19 pandemic – A systematic review [15:12]
• Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units [19:46]
• Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals [29:12]
• Four common cold Coronaviruses [30:57]

ASYMPTOMATIC TRANSMISSION:

Point:

A.  Gao M, Yang L, Chen X, et al. A study on infectivity of asymptomatic SARS-CoV-2 carriers. Respir Med. 2020;169:106026. DOI:10.1016/j.rmed.2020.106026

Material and methods: 455 contacts who were exposed to the asymptomatic COVID-19 virus carrier became the subjects of our research. They were divided into three groups: 35 patients, 196 family members, and 224 hospital staff. We extracted their epidemiological information, clinical records, auxiliary examination results, and therapeutic schedules.

Results: The median contact time for patients was four days and that for family members was five days. Cardiovascular disease accounted for 25% among original diseases of patients. Apart from hospital staff, both patients and family members were isolated medically. During the quarantine, seven patients plus one family member appeared new respiratory symptoms, where fever was the most common one. The blood counts in most contacts were within a normal range. All CT images showed no sign of COVID-19 infection. No severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were detected in 455 contacts by nucleic acid test.

Conclusion: In summary, all the 455 contacts were excluded from SARS-CoV-2 infection and we conclude that the infectivity of some asymptomatic SARS-CoV-2 carriers might be weak. 

Counterpoint: 

B. Huang L, Zhang X, Zhang X, et al.Rapid asymptomatic transmission of COVID-19 during the incubation period demonstrating strong infectivity in a cluster of youngsters aged 16-23 years outside Wuhan and characteristics of young patients with COVID-19: A prospective contact-tracing study. J Infect. 2020;80(6):e1-e13. DOI:10.1016/j.jinf.2020.03.006 

Since January 23, 2020, we enrolled a cluster of eight youngsters with COVID-19 (median age [range], 22 [16-23] years; six males) originating from Patient-Index returning from Wuhan to Hefei on January 19. Patient-Index visited his 16-year-old female cousin in the evening on his return and met 15 previous classmates in a get-together on January 21. He reported being totally asymptomatic and was described by all his contacts as healthy on January 19-21. His very first symptoms were itchy eyes and fever developed at noon and in the afternoon on January 22, respectively. Seven youngsters (his cousin and six classmates) became infected with COVID-19 after a-few-hour-contact with Patient-Index. None of the patients and contacts had visited Wuhan (except Patient-Index), or had any exposure to wet-markets, wild-animals, or medical-institutes within three months. For affected youngsters, the median incubation period was 2 days (range, 1-4). The median serial-interval was 1 day (range, 0-4). Half or more of the eight COVID-19-infected youngsters had a fever, cough, sputum production, nasal congestion, and fatigue on admission. All patients had mild conditions. Six patients developed pneumonia (all mild; one bilateral) on admission. As of February 20, four patients were discharged. 

Conclusions: SARS-CoV-2-infection presented strong infectivity during the incubation-period with rapid transmission in this cluster of youngsters outside Wuhan. COVID-19 developed in these youngsters had fast onset and various nonspecific atypical manifestations, and were much milder than in older patients as previously reported.

C. Asymptomatic spread: main report Fauci used was a letter in the NEJM reporting an incident of a woman traveling in Germany. Researchers did not speak to her but reported that she did not have symptoms. Health authorities in Germany directly questioned her, and she was in fact, symptomatic. https://www.nejm.org/doi/full/10.1056/NEJMc2001468

https://www.sciencemag.org/news/2020/02/paper-non-symptomatic-patient-transmitting-coronavirus-wrong

D. The death rate was actually lowest since the end of March on June 21st....271. The daily death rate can be found for all countries and states (scroll to end) at http://www.worldometers.info

GOING BACK TO SCHOOL:

Point:

A. Ludvigsson JF. Children are unlikely to be the main drivers of the COVID-19 pandemic - A systematic review [published online ahead of print, 2020 May 19]. Acta Paediatr. 2020;10.1111/apa.15371. DOI:10.1111/apa.15371

Results: We identified 700 scientific papers and letters and 47 full texts were studied in detail. Children accounted for a small fraction of COVID‐19 cases and mostly had social contacts with peers or parents, rather than older people at risk of severe disease. Data on viral loads were scarce but indicated that children may have lower levels than adults, partly because they often have fewer symptoms, and this should decrease the transmission risk. Household transmission studies showed that children were rarely the index case and case studies suggested that children with COVID‐19 seldom caused outbreaks. However, it is highly likely that children can transmit the SARS‐COV‐2 virus, which causes COVID‐19, and even asymptomatic children can have viral loads.

Conclusion: Children are unlikely to be the main drivers of the pandemic. Opening up schools and kindergartens is unlikely to impact COVID‐19 mortality rates in older people.

B. Shekerdemian LS, Mahmood NR, Wolfe KK, et al. Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units [published online ahead of print, 2020 May 11]. JAMA Pediatr. 2020;10.1001/jamapediatrics.2020.1948. 

Results  Of the 48 children with COVID-19 admitted to participating PICUs, 25 (52%) were male, and the median (range) age was 13 (4.2-16.6) years. Forty patients (83%) had significant preexisting comorbidities; 35 (73%) presented with respiratory symptoms and 18 (38%) required invasive ventilation. Eleven patients (23%) had failure of 2 or more organ systems. Extracorporeal membrane oxygenation was required for 1 patient (2%). Targeted therapies were used in 28 patients (61%), with hydroxychloroquine being the most commonly used agent either alone (11 patients) or in combination (10 patients). At the completion of the follow-up period, 2 patients (4%) had died and 15 (31%) were still hospitalized, with 3 still requiring ventilatory support and 1 receiving extracorporeal membrane oxygenation. The median (range) PICU and hospital lengths of stay for those who had been discharged were 5 (3-9) days and 7 (4-13) days, respectively.

Conclusions and Relevance:  This early report describes the burden of COVID-19 infection in North American PICUs and confirms that severe illness in children is significant but far less frequent than in adults. Prehospital comorbidities appear to be an important factor in children. These preliminary observations provide an important platform for larger and more extensive studies of children with COVID-19 infection.

Flu deaths in 2019-20: 81 children under 14 years old, 122 under 24 years. (In 2018-19, there were 477 children under 17 years old)

C. Heavey L, Casey G, Kelly C, Kelly D, McDarby G. No evidence of secondary transmission of COVID-19 from children attending school in Ireland, 2020. Euro Surveill. 2020;25(21):2000903. doi:10.2807/1560-7917.ES.2020.25.21.2000903

As many countries begin to lift some of the restrictions to contain COVID-19 spread, lack of evidence of transmission in the school setting remains. We examined Irish notifications of SARS-CoV2 in the school setting before school closures on 12 March 2020 and identified no pediatric transmission. This adds to current evidence that children do not appear to be drivers of transmission, and we argue that reopening schools should be considered safe accompanied by certain measures.

D. AAP Statement
(Not mentioned in the podcast) https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/covid-19-planning-considerations-return-to-in-person-education-in-schools/ 

The AAP strongly advocates that all policy considerations for the coming school year should start with the goal of having students physically present in school.

The importance of in-person learning is well-documented, and there is already evidence of the negative impacts on children because of school closures in the spring of 2020. Lengthy-time away from school and associated interruption of supportive services often result in social isolation, making it difficult for schools to identify and address important learning deficits as well as child and adolescent physical or sexual abuse, substance use, depression, and suicidal ideation.

E. (not mentioned in the podcast episode)

Munro APS, Faust SN Children are not COVID-19 super spreaders: time to go back to school Archives of Disease in Childhood 2020;105:618-619.

At the current time, children do not appear to be super spreaders. Sero-surveillance data will not be available to confirm or refute these findings prior to the urgent policy decisions that need to be taken in the next few weeks such as how and when to re-open schools. Policies for non-pharmacological interventions involving children are going to have to be made on a risk-benefit basis with current evidence available.

Governments worldwide should allow all children back to school regardless of comorbidities. Detailed surveillance will be needed to confirm the safety of this approach, despite recent analysis demonstrating the ineffectiveness of school closures in the recent past.18 The media highlight of a possible rare new Kawasaki-like vasculitis that may or may not be due to SARS-CoV2 does not change the fact that severe COVID-19 is as rare as many other serious infection syndromes in children that do not cause schools to be closed. Individualized risk assessment and decision-making by clinicians should occur for those considered at exceptional risk (such as in immediately after bone marrow transplant) or where there are other older family members at significant risk.

F. (Not mentioned in this episode)

Sheikh A, Sheikh A, Sheikh Z, Dhami S. Reopening schools after the COVID-19 lockdown. J Glob Health. 2020;10(1):010376. DOI:10.7189/jogh.10.010376

 
G. (Not mentioned in the podcast)

Kuttiatt VS, Menon RP, Abraham PR, Sharma S. Should Schools Reopen Early or Late? - Transmission Dynamics of COVID-19 in Children [published online ahead of print, 2020 Jun 16]. Indian J Pediatr. 2020;1-2. DOI:10.1007/s12098-020-03401-0

The prolonged closure of schools during the COVID-19 pandemic is likely to have a negative psychosocial effect on children besides secondary economic effects. Societal learning and grooming of children that happen in the school environment cannot be supplanted by a virtual learning platform. In the current scenario, there is uncertainty regarding the timeline of school reopening. In our opinion, the unique disease characteristics and the transmission dynamics of COVID-19 in children favor calibrated early reopening.

A notable feature of the COVID-19 pandemic is that children account for only less than 2% of total COVID-19 cases and most develop only mild illness [1, 2]. Even when children with co-morbidities are being reported at risk of severe disease, mortality was very rare. Many asymptomatic infections were noted. Most acquired infection from close contact with adults in family clusters. However, transmission from children to others was rare. In a recent report, the mother of a two-year-old SARS-CoV-2 infected child was found to be uninfected despite having prolonged close contact [3]. Also, WHO-China Joint Commission did not find a single instance of children transmitting the infection to adults [4]. An infected child linked to the cluster of COVID-19 in the French Alps, attended three schools while symptomatic but did not transmit the virus to any of the close contacts [5]. This is in sharp contrast to the reports of a few adults acting as ‘super-spreaders’ [6]. Experience from Sweden, which has not implemented strict lockdown and allowed schools to function, and Spain where schools were re-opened early, present a favourable picture.

In the light of above observations, it might be prudent to anticipate an optimistic scenario when schools open. However, caution is necessary; the role of asymptomatic carriers in transmission dynamics in children should be prospectively reviewed. One study reported few children shedding virus for up to one month in stools [7]. Another concern is the practical difficulty in adherence to social distancing, wearing mask etc. in young children.

Weighing the pros and cons, high transmission of COVID-19 in school settings is unlikely to happen. However, strict adherence to preventive measures is desirable; “at-risk” individuals (children/adults with co-morbid conditions and the elderly) should avoid contact with school-going children. Studies on asymptomatic infection and possible protection by heterologous immunity by vaccines in universal immunization program in school settings are desirable.

H. Starr M. Back to school: Safe for children with underlying medical conditions [published online ahead of print, 2020 May 19]. Aust J Gen Pract. 2020;49:10.31128/AJGP-COVID-21. DOI:10.31128/AJGP-COVID-21

Children account for only 1–5% of diagnosed COVID-19 cases,3,4 and at least 90% have asymptomatic or mild disease. Children who appear to be at highest risk for more severe disease are infants <1 year of age and those with underlying medical conditions. Among 2572 pediatric COVID-19 cases reported recently by the US Centers for Disease Control and Prevention, the most common underlying conditions were chronic lung disease, cardiovascular disease, and immunosuppression. 4 Importantly, only three deaths were reported.

Older staff and those with underlying medical conditions should seek medical advice regarding the risk of returning to school. Although there is limited evidence, it does not appear that pregnant women are at increased risk of acquiring COVID-19 or of developing more severe disease.

Given that children do not appear likely to infect teachers with SARS-CoV-2, the greatest risk of transmission in the school environment will be between adults. Thus, teachers and parents should maintain physical distancing between themselves and each other at school. Staff and students should practice good hygiene to prevent the spread of COVID-19.

I. An article that cites fatality rate for those younger than 19 is essentially 0%: https://www.bloomberg.com/opinion/articles/2020-06-10/coronavirus-are-schools-reopening-this-fall?fbclid=IwAR1h0yo3JO0B8e3SMBUScmBd18YareIfIMlSLvB8uCSuv1clSp8XWfeSg5Q

Direct CDC link within the article above: https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm

J. Re-opening of schools in 22 European countries, no increase in infections: https://www.theguardian.com/world/2020/may/18/french-minister-tells-of-risks-of-missing-school-as-more-pupils-return-covid-19

IMMUNITY

A. Grifoni A, Weiskopf D, Ramirez SI, et al. Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals' Cell. 2020;181(7):1489-1501.e15. DOI:10.1016/j.cell.2020.05.015

This May 2020 paper made two important discoveries that would indicate herd immunity is imminent.

1. 100% of those that recovered from CV-19 had active CD4 and T cells, conferring classic immunity, as was expected.
2. 50% of the patients that NEVER had CV-19 also had immunity. How could that be? Turns out that infection with the common cold c-viruses has protective effects!

40-50% on average NEVER had it already had immunity; really important point. If you have or have been infected with common cold Coronaviruses. 

4 main Coronaviruses cold coronavirus: OC43, NL63, 229E, HKU1

B. Walach H, Hockertz S. Wuhan Covid19 data - more questions than answers. Toxicology. 2020;440:152486. DOI:10.1016/j.tox.2020.152486 

This data signature seems to suggest that the Covid-19 infection runs its course undetected for quite some time and when it is detected it is already in a recessive mode. Might this be due to a rapid mutation (Tang, Wu et al. 2020), or due to the fact that a large number of infections are subclinical with no major symptoms, or due to a molecular switch that switches off the virulence once certain conditions are reached? (Harris, Moran, et al. 2018)

Guest bio: 

Jena received her Bachelor of Science and completed her dietetic internship with a nutrition education concentration at the University of Northern Colorado. Before that, she earned certifications from the Institute of the Psychology of Eating and the Institute of Integrative Nutrition that enabled her to practice as an Integrative Health Coach. Jena has maintained a private nutrition practice and serves as the lead nutrition instructor for Albemarle county’s community education program. Currently, she is the nutrition director for Culpeper Wellness Foundation and Powell Wellness Center, the top-ranking medical wellness center in Virginia. Jena also has a journalism degree from New York University and is the Editor of the Integrative RDN, a newsletter for Dietitians in Integrative & Functional Medicine.

For more than 15 years, Jena has immersed herself in research and education in the fields of health, wellness, nutrition, and fitness. Her mission is to compassionately support, educate and inspire people to lead energetic, healthy, and joyful lives.

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