COVID-19 Q&A from the Pediatric Hospital Medicine ListServ
Answers provided by Drs. Lindsay Cameron, Ankhi Dutta, Katherine King, and Jill Weatherhead
from the Section of Pediatric Infectious Diseases, Baylor College of Medicine Texas Children’s Hospital
Answers provided by Drs. Lindsay Cameron, Ankhi Dutta, Katherine King, and Jill Weatherhead
from the Section of Pediatric Infectious Diseases, Baylor College of Medicine Texas Children’s Hospital
1. What are your thoughts on universal screening of pediatric patients since it seems that they are less symptomatic?
Ankhi Dutta MD MPH: Based on our knowledge of the extensive public health measures implemented in the SARS epidemic in 2003 and with SARs-CoV2 experience in South Korea and Singapore, active case detection, isolation, contact tracing and quarantine practices were crucial in slowing the spread of the disease and flattening the curve. So ideally, universal screening of pediatric patients would be helpful in determining the extent of infection in this population to reduce the chain of human-human transmission and implement the public health measured needed to reduce the spread.
2. What might be the biologic basis for relative immunity of children against COVID 19 and other beta coronaviruses (MERS CoV, SARS CoV)? For those that are requiring admission, what is the disease course/severity? Does the disease differ in newborns?
Katherine King MD PhD: Children have the receptor for the SARS CoV2 virus and can be infected. However, the severity and mortality suffered by children is significantly lower than adults, with most studies reporting only 2% or less of cases in the pediatric age group. No one yet knows why this is the case, but there are many plausible biological explanations. For example, immunity, especially adaptive immunity wanes with age. Furthermore, adults are more likely to have underlying medical conditions such as hypertension, obesity, and diabetes that have been reported to drive up disease severity with COVID-19. The disease is extremely uncommon in infants – even infants born to COVID-19 affected mothers have mostly had no signs of infection. There is a case report of a newborn with early onset sepsis due to COVID-19, in which the child presented with hypoxemia and RUL pneumonia but recovered after several days of supportive care (NEJM April 2020). Among children, about 12-16% of patients have been reported to be asymptomatic (Dong Pediatrics, Choi Clin Exp Pediatr). Among those with symptoms, they are typically mild but most often present with fever (median duration less than 3 days) and cough, although rhinorrhea, headache, myalgia, sore throat, chills, abdominal pain, nausea, vomiting, and diarrhea have also been reported.
3. In contrast to the last question, HealthDay (4/22/20) reports that “while children seem to have been largely spared from the worst of the coronavirus pandemic, a new study suggests it’s possible that up to 50,000 U.S. children might end up hospitalized with COVID-19 by the end of 2020.” Moreover, “if around 25% of the U.S. population has been infected with COVID-19 by the end of this year, it’s likely that more than 5,000 children and teens would be critically ill and require mechanical ventilation, the researchers estimated.” (JPHMP 4/16/20) What are your thoughts on this study and is this realistic?
Ankhi Dutta MD MPH: This is yet to be seen and probably an overestimation. A systematic literature review that was recently published looked at 45 studies related to SARS-CoV2 in children around the world, which showed children accounting for 1-5% of the diagnosed cases, mostly with less severe disease than adults. In a study published by the Chinese Center for Disease Control, 2% of the 44672 patients with confirmed COVID19 were children between 0-19 years of age. The largest pediatric series from China (n=2143), shows over 90% of their pediatric population had asymptomatic, mild-moderate disease. Of the remaining children only 5.2% had severe disease and 0.6% had critical disease. There was one mortality in this study, in a child aged 14 years but no details were provided in this study.
An Italian study published March 18th, showed only 1.2% of 22512 confirmed COVID19 cases in Italy to occur in children, with mostly with mild-moderate illness and no reported deaths.
The Center for Disease Control released their report on pediatric illness recently (Feb 12th- April 2nd) which showed 1.7% of the confirmed COVID19 cases were children (2572 of 149,760). 5.7% of these pediatric patients were hospitalized. Children less than one year of age seems to have had the highest hospitalization rates (59/95, 62%). Five of these children were admitted to an ICU. Hospitalization rates among those aged 1–17 years was actually lower (4.1%–14%). Among 345 pediatric cases with information on underlying conditions, 80 (23%) had at least one underlying condition. Only three deaths has been reported so far, all with underlying medical conditions.
Given this data, it is unlikely that a large number of children and teens would be critically ill requiring ICU care. However, we need to be continue to be vigilant about the situation especially in children less than 1 year and those with co-morbidities.
4. There was a recent report on universal screening in pregnant women in the NEJM. What are your thoughts on this report and how screening should be happening in this population? If a mother is COVID positive and there is no one else to care for the baby, does separation in the first 2-3 days in the hospital have any benefit?
Jill Weatherhead MD MSc: The recent study in the NEJM, evaluated 215 pregnant women who were universally screened upon entrance into labor and delivery for SARS-CoV-2 using PCR. The study found 13.7% positive tests in asymptomatic women. More data has demonstrated the evidence of pre-symptomatic and asymptomatic shedding of SARS-CoV-2 thus it is possible that universal screening would uncover COVID-19 cases prior to symptom onset. This could be potentially critical knowledge in terms of infection prevention in the hospital as well as prevention of maternal-infant transmission. However, this particular study was completed in a geographic location with widespread community transmission and may not have extensive external validity to other locations. ACOG recommends additional testing strategies (ie universal testing) is appropriate for asymptomatic patients presenting to labor and delivery units in high prevalence areas.
Postnatal transmission of SARS-CoV-2 from mother to infant has been described although robust maternal-infant transmission data is still limited. In situations of a COVID-19 positive mother in labor and delivery, ACOG currently recommends a patient-healthcare provider discussion on temporary separation of mother from infant driven by the limited data on mother-infant transmission. Likewise, the initial guidance by the APP (April 2nd, 2020) suggests separation may be the best way to prevent maternal-infant spread during the post-natal period. The concern is focused around limited infant immune response to viral pathogens early in life and evidence of severe outcomes to other viral pathogens in newborns. This is particularly relevant in the absence of knowledge regarding the immune response required for control and eradication of SARS-CoV-2. Mothers who are COVID-19 positive who are not temporarily separated from their infant at birth, should understand the potential risk and follow strict hygiene practices including washing hands before touching the baby, keep six feet distance when feasible, wear a face mask and washings hands before touching any breast pump or bottle parts.
5. Is someone without symptoms likely to be as contagious as someone who is sick? For example, does the viral load level impact contagiousness? Are the PPE recommendations the same for symptomatic and asymptomatic patients?
Lindsay Cameron MD MPH: SARS-COV-2 is transmitted via respiratory droplets. Those who are symptomatic are more likely to transmit the virus through respiratory droplets (through sneeze, cough, etc) than asymptomatic individuals. Studies that have tracked the level of viremia in infected persons revealed a gradual decrease in the viral load over time. While viremic, persons with SARS-COV-2 infection can transmit the virus to others. At some point, as the person recovers, he or she will be less symptomatic, but can remain viremic. Therefore, viral transmission can occur from an asymptomatic individual and the recommendations on isolation and quarantine of contacts is the same. Persons with confirmed SARS-COV-2 should be isolated for a 14-day time period, irrespective of symptoms. The PPE recommendations are also the same for those who are symptomatic and those who are asymptomatic. In some, viral spread may occur beyond 14 days. Viral testing can be re-performed at the end of a 14-day period of isolation to confirm the individual is no longer viremic. Many hospitals are using this method of screening (serial testing until negative) to guide lifting work restrictions.
6. Why is the pandemic in New York so radically different from the rest of the US? Data appears to show higher attack rate, death rate, and hospitalization rate. Can this be explained by public transit and population density alone? Was it due to a delay in shutting things down?
Lindsay Cameron MD MPH: The impact on the number of cases in New York City was likely impacted by a number of factors: 1) New York is a major travel center for International flights and business travel into and out of the East Coast. This likely lead to a large number of imported cases early on in the pandemic. 2) New York City has a very high population density compared to other U.S. cities. This makes it very hard to social distance and lead to widespread transmission of the virus over a short time period. 3) Many New York City residents depend on public transportation for inner city and intracity transportation. Staying 6 feet apart, as recommended by the CDC to decrease transmission, is very difficult in public transport vehicles. 4) Testing delays across the U.S. and in New York City likely led to a delay in isolation and quarantine of impacted persons likely also played a role in the transmission of the virus.
The impact of viral spread was not influenced by a delay in “shutting things down.” New York City implemented social gathering restrictions, school closures and closure of non-essential businesses at nearly the same time as other states who were affected in the U.S. early in the pandemic (Washington, California, etc.). These dates and the epidemiologic modeling curves are provided here: https://covid19.healthdata.org/united-states-of-america/new-york
7. Nationally, there has been talk of the risk/benefit analysis of shutting down the country/economy. For example, stay-at-home orders have resulted in a spike in unemployment, which we know leads to poverty issues, increased abuse rates, health issues, and huge economic impacts. Many individuals have raised the concept of a controlled return to work/school in order to prevent complete economic demise. Is that feasible to do this? Are we expecting waves of infections? What is our endpoint for quarantining?
Katherine King MD PhD: Quarantine refers to the physical separation of an individual with a known exposure to prevent transmission of an infection in the presymptomatic phase. Isolating infected individuals, quarantining exposed individuals, and practicing hand hygiene and social distancing should be expected to continue until there is herd immunity in the population (generally thought to be 60-80% of the population for COVID-19). In other words, we should expect these measures to become part of our normal lives for the next year or two until most of the population has been infected or vaccinated.
Stay-at-home orders are a more extreme response to prevent a surge of infections that would overwhelm our hospitals as has been seen in Italy and New York City. Without a doubt, these measures are extremely costly both in economic and human terms, and these costs must be weighed heavily. Many epidemiologists suggest that a cautious reopening of society may occur safely two weeks after the initial surge has been controlled (i.e. zero new cases per day). Currently many states are considering or proceeding with reopening two weeks after the peak of cases, or even before a peak of cases has occurred. Such premature reopening is likely to create the conditions for repeated waves of infection. Ultimately, the success of relaxation of stay-at-home orders will depend on the efficiency with which counties, cities, and communities can identify and isolate new cases, trace and quarantine contacts, and maintain good social distancing, masking, and hand hygiene practices.
8. With regard to those who have had COVID or have evidence of a past infection, what are the thoughts about degree/length of protection? Do we have any data or can we extrapolate from other coronaviruses? South Korea has some reports of COVID positive patients testing positive, then negative, then positive again. Does this just represent dead virus being detected or is there other evidence that reinfection is possible for immune competent individuals?
Katherine King MD PhD: The degree of protection conferred by prior COVID-19 infection is currently not known. It is unknown whether individuals with asymptomatic or mild cases develop a protective antibody response, and it is unknown what degree of a neutralizing antibody response is sufficient to confer protection against future infection. Currently available serologic tests do not distinguish between total antibody and neutralizing antibody and therefore cannot be taken as an indication of immunity. It remains unknown if short term reinfection is possible.
Based on prior vaccine and immunologic studies of other coronaviruses that cause the common cold (HKU1, NL63, OC43, 229E) and on SARS-CoV and MERS, immunity to these viruses after infection or vaccination tends to last 1-2 years.
9. What is a realistic timeline for a vaccine?
Jill Weatherhead MD MSc: Vaccines typically take years to develop, up to 10-15 years in some cases. Vaccine development requires several stages including pre-clinical animal models, three stages of vaccine clinical trials followed by approval, licensure, scaling up production and monitoring. The quickest development of a vaccine to date was the Mumps vaccine in which the viral strain was isolated in 1963 and a vaccine was introduced to the market by Merck in 1967. More recently an Ebola vaccine was developed in 5 years. However, never in history has there been so much time and capital placed into vaccine development of a single pathogen. There are currently over 90 SARS-CoV-2 vaccines being developed globally by academic institutions, drug companies and technology corporations. Given the amount of new technology, significant funding, past experience with other coronavirus vaccines (SARS-1 and MERS), and processes that allow overlapping of steps in the vaccine development process, the NIH estimates of an 18 month timeline to develop a SARS-CoV-2 vaccine is unprecedented but may be possible.
Ankhi Dutta MD MPH: Based on our knowledge of the extensive public health measures implemented in the SARS epidemic in 2003 and with SARs-CoV2 experience in South Korea and Singapore, active case detection, isolation, contact tracing and quarantine practices were crucial in slowing the spread of the disease and flattening the curve. So ideally, universal screening of pediatric patients would be helpful in determining the extent of infection in this population to reduce the chain of human-human transmission and implement the public health measured needed to reduce the spread.
2. What might be the biologic basis for relative immunity of children against COVID 19 and other beta coronaviruses (MERS CoV, SARS CoV)? For those that are requiring admission, what is the disease course/severity? Does the disease differ in newborns?
Katherine King MD PhD: Children have the receptor for the SARS CoV2 virus and can be infected. However, the severity and mortality suffered by children is significantly lower than adults, with most studies reporting only 2% or less of cases in the pediatric age group. No one yet knows why this is the case, but there are many plausible biological explanations. For example, immunity, especially adaptive immunity wanes with age. Furthermore, adults are more likely to have underlying medical conditions such as hypertension, obesity, and diabetes that have been reported to drive up disease severity with COVID-19. The disease is extremely uncommon in infants – even infants born to COVID-19 affected mothers have mostly had no signs of infection. There is a case report of a newborn with early onset sepsis due to COVID-19, in which the child presented with hypoxemia and RUL pneumonia but recovered after several days of supportive care (NEJM April 2020). Among children, about 12-16% of patients have been reported to be asymptomatic (Dong Pediatrics, Choi Clin Exp Pediatr). Among those with symptoms, they are typically mild but most often present with fever (median duration less than 3 days) and cough, although rhinorrhea, headache, myalgia, sore throat, chills, abdominal pain, nausea, vomiting, and diarrhea have also been reported.
3. In contrast to the last question, HealthDay (4/22/20) reports that “while children seem to have been largely spared from the worst of the coronavirus pandemic, a new study suggests it’s possible that up to 50,000 U.S. children might end up hospitalized with COVID-19 by the end of 2020.” Moreover, “if around 25% of the U.S. population has been infected with COVID-19 by the end of this year, it’s likely that more than 5,000 children and teens would be critically ill and require mechanical ventilation, the researchers estimated.” (JPHMP 4/16/20) What are your thoughts on this study and is this realistic?
Ankhi Dutta MD MPH: This is yet to be seen and probably an overestimation. A systematic literature review that was recently published looked at 45 studies related to SARS-CoV2 in children around the world, which showed children accounting for 1-5% of the diagnosed cases, mostly with less severe disease than adults. In a study published by the Chinese Center for Disease Control, 2% of the 44672 patients with confirmed COVID19 were children between 0-19 years of age. The largest pediatric series from China (n=2143), shows over 90% of their pediatric population had asymptomatic, mild-moderate disease. Of the remaining children only 5.2% had severe disease and 0.6% had critical disease. There was one mortality in this study, in a child aged 14 years but no details were provided in this study.
An Italian study published March 18th, showed only 1.2% of 22512 confirmed COVID19 cases in Italy to occur in children, with mostly with mild-moderate illness and no reported deaths.
The Center for Disease Control released their report on pediatric illness recently (Feb 12th- April 2nd) which showed 1.7% of the confirmed COVID19 cases were children (2572 of 149,760). 5.7% of these pediatric patients were hospitalized. Children less than one year of age seems to have had the highest hospitalization rates (59/95, 62%). Five of these children were admitted to an ICU. Hospitalization rates among those aged 1–17 years was actually lower (4.1%–14%). Among 345 pediatric cases with information on underlying conditions, 80 (23%) had at least one underlying condition. Only three deaths has been reported so far, all with underlying medical conditions.
Given this data, it is unlikely that a large number of children and teens would be critically ill requiring ICU care. However, we need to be continue to be vigilant about the situation especially in children less than 1 year and those with co-morbidities.
4. There was a recent report on universal screening in pregnant women in the NEJM. What are your thoughts on this report and how screening should be happening in this population? If a mother is COVID positive and there is no one else to care for the baby, does separation in the first 2-3 days in the hospital have any benefit?
Jill Weatherhead MD MSc: The recent study in the NEJM, evaluated 215 pregnant women who were universally screened upon entrance into labor and delivery for SARS-CoV-2 using PCR. The study found 13.7% positive tests in asymptomatic women. More data has demonstrated the evidence of pre-symptomatic and asymptomatic shedding of SARS-CoV-2 thus it is possible that universal screening would uncover COVID-19 cases prior to symptom onset. This could be potentially critical knowledge in terms of infection prevention in the hospital as well as prevention of maternal-infant transmission. However, this particular study was completed in a geographic location with widespread community transmission and may not have extensive external validity to other locations. ACOG recommends additional testing strategies (ie universal testing) is appropriate for asymptomatic patients presenting to labor and delivery units in high prevalence areas.
Postnatal transmission of SARS-CoV-2 from mother to infant has been described although robust maternal-infant transmission data is still limited. In situations of a COVID-19 positive mother in labor and delivery, ACOG currently recommends a patient-healthcare provider discussion on temporary separation of mother from infant driven by the limited data on mother-infant transmission. Likewise, the initial guidance by the APP (April 2nd, 2020) suggests separation may be the best way to prevent maternal-infant spread during the post-natal period. The concern is focused around limited infant immune response to viral pathogens early in life and evidence of severe outcomes to other viral pathogens in newborns. This is particularly relevant in the absence of knowledge regarding the immune response required for control and eradication of SARS-CoV-2. Mothers who are COVID-19 positive who are not temporarily separated from their infant at birth, should understand the potential risk and follow strict hygiene practices including washing hands before touching the baby, keep six feet distance when feasible, wear a face mask and washings hands before touching any breast pump or bottle parts.
5. Is someone without symptoms likely to be as contagious as someone who is sick? For example, does the viral load level impact contagiousness? Are the PPE recommendations the same for symptomatic and asymptomatic patients?
Lindsay Cameron MD MPH: SARS-COV-2 is transmitted via respiratory droplets. Those who are symptomatic are more likely to transmit the virus through respiratory droplets (through sneeze, cough, etc) than asymptomatic individuals. Studies that have tracked the level of viremia in infected persons revealed a gradual decrease in the viral load over time. While viremic, persons with SARS-COV-2 infection can transmit the virus to others. At some point, as the person recovers, he or she will be less symptomatic, but can remain viremic. Therefore, viral transmission can occur from an asymptomatic individual and the recommendations on isolation and quarantine of contacts is the same. Persons with confirmed SARS-COV-2 should be isolated for a 14-day time period, irrespective of symptoms. The PPE recommendations are also the same for those who are symptomatic and those who are asymptomatic. In some, viral spread may occur beyond 14 days. Viral testing can be re-performed at the end of a 14-day period of isolation to confirm the individual is no longer viremic. Many hospitals are using this method of screening (serial testing until negative) to guide lifting work restrictions.
6. Why is the pandemic in New York so radically different from the rest of the US? Data appears to show higher attack rate, death rate, and hospitalization rate. Can this be explained by public transit and population density alone? Was it due to a delay in shutting things down?
Lindsay Cameron MD MPH: The impact on the number of cases in New York City was likely impacted by a number of factors: 1) New York is a major travel center for International flights and business travel into and out of the East Coast. This likely lead to a large number of imported cases early on in the pandemic. 2) New York City has a very high population density compared to other U.S. cities. This makes it very hard to social distance and lead to widespread transmission of the virus over a short time period. 3) Many New York City residents depend on public transportation for inner city and intracity transportation. Staying 6 feet apart, as recommended by the CDC to decrease transmission, is very difficult in public transport vehicles. 4) Testing delays across the U.S. and in New York City likely led to a delay in isolation and quarantine of impacted persons likely also played a role in the transmission of the virus.
The impact of viral spread was not influenced by a delay in “shutting things down.” New York City implemented social gathering restrictions, school closures and closure of non-essential businesses at nearly the same time as other states who were affected in the U.S. early in the pandemic (Washington, California, etc.). These dates and the epidemiologic modeling curves are provided here: https://covid19.healthdata.org/united-states-of-america/new-york
7. Nationally, there has been talk of the risk/benefit analysis of shutting down the country/economy. For example, stay-at-home orders have resulted in a spike in unemployment, which we know leads to poverty issues, increased abuse rates, health issues, and huge economic impacts. Many individuals have raised the concept of a controlled return to work/school in order to prevent complete economic demise. Is that feasible to do this? Are we expecting waves of infections? What is our endpoint for quarantining?
Katherine King MD PhD: Quarantine refers to the physical separation of an individual with a known exposure to prevent transmission of an infection in the presymptomatic phase. Isolating infected individuals, quarantining exposed individuals, and practicing hand hygiene and social distancing should be expected to continue until there is herd immunity in the population (generally thought to be 60-80% of the population for COVID-19). In other words, we should expect these measures to become part of our normal lives for the next year or two until most of the population has been infected or vaccinated.
Stay-at-home orders are a more extreme response to prevent a surge of infections that would overwhelm our hospitals as has been seen in Italy and New York City. Without a doubt, these measures are extremely costly both in economic and human terms, and these costs must be weighed heavily. Many epidemiologists suggest that a cautious reopening of society may occur safely two weeks after the initial surge has been controlled (i.e. zero new cases per day). Currently many states are considering or proceeding with reopening two weeks after the peak of cases, or even before a peak of cases has occurred. Such premature reopening is likely to create the conditions for repeated waves of infection. Ultimately, the success of relaxation of stay-at-home orders will depend on the efficiency with which counties, cities, and communities can identify and isolate new cases, trace and quarantine contacts, and maintain good social distancing, masking, and hand hygiene practices.
8. With regard to those who have had COVID or have evidence of a past infection, what are the thoughts about degree/length of protection? Do we have any data or can we extrapolate from other coronaviruses? South Korea has some reports of COVID positive patients testing positive, then negative, then positive again. Does this just represent dead virus being detected or is there other evidence that reinfection is possible for immune competent individuals?
Katherine King MD PhD: The degree of protection conferred by prior COVID-19 infection is currently not known. It is unknown whether individuals with asymptomatic or mild cases develop a protective antibody response, and it is unknown what degree of a neutralizing antibody response is sufficient to confer protection against future infection. Currently available serologic tests do not distinguish between total antibody and neutralizing antibody and therefore cannot be taken as an indication of immunity. It remains unknown if short term reinfection is possible.
Based on prior vaccine and immunologic studies of other coronaviruses that cause the common cold (HKU1, NL63, OC43, 229E) and on SARS-CoV and MERS, immunity to these viruses after infection or vaccination tends to last 1-2 years.
9. What is a realistic timeline for a vaccine?
Jill Weatherhead MD MSc: Vaccines typically take years to develop, up to 10-15 years in some cases. Vaccine development requires several stages including pre-clinical animal models, three stages of vaccine clinical trials followed by approval, licensure, scaling up production and monitoring. The quickest development of a vaccine to date was the Mumps vaccine in which the viral strain was isolated in 1963 and a vaccine was introduced to the market by Merck in 1967. More recently an Ebola vaccine was developed in 5 years. However, never in history has there been so much time and capital placed into vaccine development of a single pathogen. There are currently over 90 SARS-CoV-2 vaccines being developed globally by academic institutions, drug companies and technology corporations. Given the amount of new technology, significant funding, past experience with other coronavirus vaccines (SARS-1 and MERS), and processes that allow overlapping of steps in the vaccine development process, the NIH estimates of an 18 month timeline to develop a SARS-CoV-2 vaccine is unprecedented but may be possible.