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Treatment duration for acute otitis media – so many choices
Twenty years ago, the dilemma in treating acute otitis media (AOM) was which among 10-plus antibiotics to prescribe. A recent column discussed the evolving pathogen distribution in AOM and its effects on antibiotic choices.1 But here we consider treatment duration. Until the past decade, AOM treatment (except azithromycin) involved 10-day courses. But lately, 10-day antibiotic regimens for uncomplicated infections are disappearing. Shorter-course recommendations are the new norm because of the evolving clinical data showing that an appropriately chosen antibiotic (in partnership with host defenses and source control) resolves infection faster than was previously thought. Shorter courses make sense because of fewer adverse effects, less distortion of normal flora, and less likely induction of pathogen resistance. Table 4.12 in the newest 2021-2024 SOID Redbook lists three antibiotic durations for AOM, and actually there are more than that.
Why so many duration options? Clinical data show that not all AOM is alike and short courses work for subsets of AOM because, besides antibiotics, key elements in AOM resolution are host anatomy and immunity. Bacterial AOM results from a combination of refluxed pathogens in the middle ear being trapped when the eustachian tube malfunctions (infection occurs when middle ear plumbing gets stopped up). If the eustachian tube spontaneously drains and the host immune response slows/stops pathogen growth, no antibiotics are needed. Indeed, a sizable proportion of mild/moderate AOM episodes spontaneously resolve, particularly in children over 2 years old. So a high likelihood of spontaneous remission allows an initial 0-days duration option (watchful waiting) or delayed antibiotics (rescue prescriptions) for older children.
That said, when one chooses to initially prescribe antibiotics for AOM, different durations are recommended. Table 1 has my suggestions.
Data that gave me better microbiological understanding of why oral AOM trials less than 10 days were successful involved purulent AOM drainage from children who had pressure-equalizing (PE) tubes.2 The authors randomized children to either standard-dose amoxicillin-clavulanate or placebo. Of note, 95% of pathogens were susceptible to the antibiotic; 5% were pneumococcus intermediately resistant to penicillin. The authors sampled ear drainage daily for 7 days. Figure 1 shows that cultures remained positive in only around 5% of children by day 3-5 of antibiotics, but viable bacteria persisted through 7 days in over half of placebo recipients. Remember, both groups benefited from a form of source control (drainage of the middle ear via PE tubes). So, if antibiotics can do the job in 3-5 days, why continue antibiotics beyond 5 days?
Anatomy and severity. In children over 5 years old (reasonably mature eustachian tube anatomy) with nonrecurrent (no AOM in past month), nonsevere (no otalgia or high fever) AOM, 5 days is enough. But 2- to 5-year-olds (less mature anatomy) need 7 days and those <2 years old (least mature plumbing) need 10 days. Likewise, severe AOM usually warrants 10 days. Some experts recommend 10 days for bilateral AOM as well.
These age/severity differences make sense because failures are more frequent with:
1. Younger age.3 While not proven, my hypothesis is that “natural” source control (spontaneous internal draining the middle ear into the nasopharynx [NP]) is less frequent in younger children because they have less mature eustachian tube systems. Further, reflux of persisting NP organisms could restart a new AOM episode even if the original pathogen was eliminated by a short 5-day course.
2. Severe AOM. A rationale for longer courses in severe AOM (ear pain, high fever) is that high middle-ear pressures (indicated by degree of tympanic membrane bulging and ear pain) could impede antibiotic penetration, or that high initial bacterial loads (perhaps indicated by systemic fever) require more antibiotic. And finally, return to baseline eustachian tube function may take longer if severe AOM caused enhanced inflammation.
3. Recurrent AOM. (AOM within 1 prior month) – With recurrent AOM, the second “hit” to the eustachian tube may lead to more dysfunction, so a longer antibiotic course may be required to allow more complete source control and more time for more complete functional recovery after a repeated inflammatory injury.
4. Bilateral AOM. Two independent but infected sites mean twice the chance for failure. So, a longer course could allow more time for both sites to undergo “natural” source control.4
More bacteria – more antibiotic? So, is more antibiotic really needed for a higher bacterial load? In vitro this is known as the “inoculum effect,” particularly for beta-lactam drugs, for example, amoxicillin and cephalosporins. Laboratory susceptibility testing is performed with a specifically defined quantity of bacteria (105 bacteria/mL) and the minimum inhibitory concentration (MIC) is the lowest antibiotic concentration that stops bacterial growth. We know that drugs will likely fail if the MIC exceeds the achievable antibiotic concentration at the infection site. But is it as simple as just exceeding the MIC at the infection site? No, pharmacodynamics tell us that overall antibiotic exposure is also important. For example, to be successful, beta-lactam concentrations need to be above the MIC for 40%-50% of the day.
Higher MIC with higher bacterial load. Particularly for beta-lactams, testing with a quantity of bacteria >105/mL produces a higher MIC in vitro. This suggests that clinical failure could occur, even when our in vivo dosing leads to 40%-50% above the “standard” MIC that was obtained from testing the lab standard of 105/mL bacteria, when the infected site’s (middle ear) bacterial load is >105/mL (such higher bacterial loads occur in up to 30% of AOM).5 One way to negate inoculum effect is source control (drain the abscess or debridement), which reduces the bacterial load as well as allowing better antibiotic penetration– both favoring infection resolution. But with suboptimal source control, for example, the middle ear is not drained externally or internally, longer courses (more antibiotic exposure) could aid resolution. Whether the exposure can be administered as higher doses in fewer days or standard doses for more days is debatable but consider that a single parenteral dose of ceftriaxone successfully resolves AOM not attributable to penicillin-nonsusceptible pneumococcus.6Bottom line: Even though the number of potential antibiotics has contracted in the past 20 years, the need to individualize AOM treatment remains important and duration choices are more complex. Indeed, AOM comes in different flavors with patient age, clinical presentation, and episode frequency dictating the choice of duration.
Dr. Christopher J. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics in Kansas City, Mo. Email him at [email protected].
References
1. Pichichero ME. MDedge. 2022 Jan 11.
2. Ruohola A et al. Pediatrics. 2003;111(5):1061-7.
3. Hoberman A et al. N Engl J Med. 2016;375(25):2446-56.
4. Pichichero ME et al. Otolaryngol Head Neck Surg. 2001;124(4):381-7.
5. Harrison CJ et al. Pediatr Infect Dis. 1985;4(6):641-6.
6. Leibovitz E et al. Pediatr Infect Dis. 2000;19(11):1040-5.
Twenty years ago, the dilemma in treating acute otitis media (AOM) was which among 10-plus antibiotics to prescribe. A recent column discussed the evolving pathogen distribution in AOM and its effects on antibiotic choices.1 But here we consider treatment duration. Until the past decade, AOM treatment (except azithromycin) involved 10-day courses. But lately, 10-day antibiotic regimens for uncomplicated infections are disappearing. Shorter-course recommendations are the new norm because of the evolving clinical data showing that an appropriately chosen antibiotic (in partnership with host defenses and source control) resolves infection faster than was previously thought. Shorter courses make sense because of fewer adverse effects, less distortion of normal flora, and less likely induction of pathogen resistance. Table 4.12 in the newest 2021-2024 SOID Redbook lists three antibiotic durations for AOM, and actually there are more than that.
Why so many duration options? Clinical data show that not all AOM is alike and short courses work for subsets of AOM because, besides antibiotics, key elements in AOM resolution are host anatomy and immunity. Bacterial AOM results from a combination of refluxed pathogens in the middle ear being trapped when the eustachian tube malfunctions (infection occurs when middle ear plumbing gets stopped up). If the eustachian tube spontaneously drains and the host immune response slows/stops pathogen growth, no antibiotics are needed. Indeed, a sizable proportion of mild/moderate AOM episodes spontaneously resolve, particularly in children over 2 years old. So a high likelihood of spontaneous remission allows an initial 0-days duration option (watchful waiting) or delayed antibiotics (rescue prescriptions) for older children.
That said, when one chooses to initially prescribe antibiotics for AOM, different durations are recommended. Table 1 has my suggestions.
Data that gave me better microbiological understanding of why oral AOM trials less than 10 days were successful involved purulent AOM drainage from children who had pressure-equalizing (PE) tubes.2 The authors randomized children to either standard-dose amoxicillin-clavulanate or placebo. Of note, 95% of pathogens were susceptible to the antibiotic; 5% were pneumococcus intermediately resistant to penicillin. The authors sampled ear drainage daily for 7 days. Figure 1 shows that cultures remained positive in only around 5% of children by day 3-5 of antibiotics, but viable bacteria persisted through 7 days in over half of placebo recipients. Remember, both groups benefited from a form of source control (drainage of the middle ear via PE tubes). So, if antibiotics can do the job in 3-5 days, why continue antibiotics beyond 5 days?
Anatomy and severity. In children over 5 years old (reasonably mature eustachian tube anatomy) with nonrecurrent (no AOM in past month), nonsevere (no otalgia or high fever) AOM, 5 days is enough. But 2- to 5-year-olds (less mature anatomy) need 7 days and those <2 years old (least mature plumbing) need 10 days. Likewise, severe AOM usually warrants 10 days. Some experts recommend 10 days for bilateral AOM as well.
These age/severity differences make sense because failures are more frequent with:
1. Younger age.3 While not proven, my hypothesis is that “natural” source control (spontaneous internal draining the middle ear into the nasopharynx [NP]) is less frequent in younger children because they have less mature eustachian tube systems. Further, reflux of persisting NP organisms could restart a new AOM episode even if the original pathogen was eliminated by a short 5-day course.
2. Severe AOM. A rationale for longer courses in severe AOM (ear pain, high fever) is that high middle-ear pressures (indicated by degree of tympanic membrane bulging and ear pain) could impede antibiotic penetration, or that high initial bacterial loads (perhaps indicated by systemic fever) require more antibiotic. And finally, return to baseline eustachian tube function may take longer if severe AOM caused enhanced inflammation.
3. Recurrent AOM. (AOM within 1 prior month) – With recurrent AOM, the second “hit” to the eustachian tube may lead to more dysfunction, so a longer antibiotic course may be required to allow more complete source control and more time for more complete functional recovery after a repeated inflammatory injury.
4. Bilateral AOM. Two independent but infected sites mean twice the chance for failure. So, a longer course could allow more time for both sites to undergo “natural” source control.4
More bacteria – more antibiotic? So, is more antibiotic really needed for a higher bacterial load? In vitro this is known as the “inoculum effect,” particularly for beta-lactam drugs, for example, amoxicillin and cephalosporins. Laboratory susceptibility testing is performed with a specifically defined quantity of bacteria (105 bacteria/mL) and the minimum inhibitory concentration (MIC) is the lowest antibiotic concentration that stops bacterial growth. We know that drugs will likely fail if the MIC exceeds the achievable antibiotic concentration at the infection site. But is it as simple as just exceeding the MIC at the infection site? No, pharmacodynamics tell us that overall antibiotic exposure is also important. For example, to be successful, beta-lactam concentrations need to be above the MIC for 40%-50% of the day.
Higher MIC with higher bacterial load. Particularly for beta-lactams, testing with a quantity of bacteria >105/mL produces a higher MIC in vitro. This suggests that clinical failure could occur, even when our in vivo dosing leads to 40%-50% above the “standard” MIC that was obtained from testing the lab standard of 105/mL bacteria, when the infected site’s (middle ear) bacterial load is >105/mL (such higher bacterial loads occur in up to 30% of AOM).5 One way to negate inoculum effect is source control (drain the abscess or debridement), which reduces the bacterial load as well as allowing better antibiotic penetration– both favoring infection resolution. But with suboptimal source control, for example, the middle ear is not drained externally or internally, longer courses (more antibiotic exposure) could aid resolution. Whether the exposure can be administered as higher doses in fewer days or standard doses for more days is debatable but consider that a single parenteral dose of ceftriaxone successfully resolves AOM not attributable to penicillin-nonsusceptible pneumococcus.6Bottom line: Even though the number of potential antibiotics has contracted in the past 20 years, the need to individualize AOM treatment remains important and duration choices are more complex. Indeed, AOM comes in different flavors with patient age, clinical presentation, and episode frequency dictating the choice of duration.
Dr. Christopher J. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics in Kansas City, Mo. Email him at [email protected].
References
1. Pichichero ME. MDedge. 2022 Jan 11.
2. Ruohola A et al. Pediatrics. 2003;111(5):1061-7.
3. Hoberman A et al. N Engl J Med. 2016;375(25):2446-56.
4. Pichichero ME et al. Otolaryngol Head Neck Surg. 2001;124(4):381-7.
5. Harrison CJ et al. Pediatr Infect Dis. 1985;4(6):641-6.
6. Leibovitz E et al. Pediatr Infect Dis. 2000;19(11):1040-5.
Twenty years ago, the dilemma in treating acute otitis media (AOM) was which among 10-plus antibiotics to prescribe. A recent column discussed the evolving pathogen distribution in AOM and its effects on antibiotic choices.1 But here we consider treatment duration. Until the past decade, AOM treatment (except azithromycin) involved 10-day courses. But lately, 10-day antibiotic regimens for uncomplicated infections are disappearing. Shorter-course recommendations are the new norm because of the evolving clinical data showing that an appropriately chosen antibiotic (in partnership with host defenses and source control) resolves infection faster than was previously thought. Shorter courses make sense because of fewer adverse effects, less distortion of normal flora, and less likely induction of pathogen resistance. Table 4.12 in the newest 2021-2024 SOID Redbook lists three antibiotic durations for AOM, and actually there are more than that.
Why so many duration options? Clinical data show that not all AOM is alike and short courses work for subsets of AOM because, besides antibiotics, key elements in AOM resolution are host anatomy and immunity. Bacterial AOM results from a combination of refluxed pathogens in the middle ear being trapped when the eustachian tube malfunctions (infection occurs when middle ear plumbing gets stopped up). If the eustachian tube spontaneously drains and the host immune response slows/stops pathogen growth, no antibiotics are needed. Indeed, a sizable proportion of mild/moderate AOM episodes spontaneously resolve, particularly in children over 2 years old. So a high likelihood of spontaneous remission allows an initial 0-days duration option (watchful waiting) or delayed antibiotics (rescue prescriptions) for older children.
That said, when one chooses to initially prescribe antibiotics for AOM, different durations are recommended. Table 1 has my suggestions.
Data that gave me better microbiological understanding of why oral AOM trials less than 10 days were successful involved purulent AOM drainage from children who had pressure-equalizing (PE) tubes.2 The authors randomized children to either standard-dose amoxicillin-clavulanate or placebo. Of note, 95% of pathogens were susceptible to the antibiotic; 5% were pneumococcus intermediately resistant to penicillin. The authors sampled ear drainage daily for 7 days. Figure 1 shows that cultures remained positive in only around 5% of children by day 3-5 of antibiotics, but viable bacteria persisted through 7 days in over half of placebo recipients. Remember, both groups benefited from a form of source control (drainage of the middle ear via PE tubes). So, if antibiotics can do the job in 3-5 days, why continue antibiotics beyond 5 days?
Anatomy and severity. In children over 5 years old (reasonably mature eustachian tube anatomy) with nonrecurrent (no AOM in past month), nonsevere (no otalgia or high fever) AOM, 5 days is enough. But 2- to 5-year-olds (less mature anatomy) need 7 days and those <2 years old (least mature plumbing) need 10 days. Likewise, severe AOM usually warrants 10 days. Some experts recommend 10 days for bilateral AOM as well.
These age/severity differences make sense because failures are more frequent with:
1. Younger age.3 While not proven, my hypothesis is that “natural” source control (spontaneous internal draining the middle ear into the nasopharynx [NP]) is less frequent in younger children because they have less mature eustachian tube systems. Further, reflux of persisting NP organisms could restart a new AOM episode even if the original pathogen was eliminated by a short 5-day course.
2. Severe AOM. A rationale for longer courses in severe AOM (ear pain, high fever) is that high middle-ear pressures (indicated by degree of tympanic membrane bulging and ear pain) could impede antibiotic penetration, or that high initial bacterial loads (perhaps indicated by systemic fever) require more antibiotic. And finally, return to baseline eustachian tube function may take longer if severe AOM caused enhanced inflammation.
3. Recurrent AOM. (AOM within 1 prior month) – With recurrent AOM, the second “hit” to the eustachian tube may lead to more dysfunction, so a longer antibiotic course may be required to allow more complete source control and more time for more complete functional recovery after a repeated inflammatory injury.
4. Bilateral AOM. Two independent but infected sites mean twice the chance for failure. So, a longer course could allow more time for both sites to undergo “natural” source control.4
More bacteria – more antibiotic? So, is more antibiotic really needed for a higher bacterial load? In vitro this is known as the “inoculum effect,” particularly for beta-lactam drugs, for example, amoxicillin and cephalosporins. Laboratory susceptibility testing is performed with a specifically defined quantity of bacteria (105 bacteria/mL) and the minimum inhibitory concentration (MIC) is the lowest antibiotic concentration that stops bacterial growth. We know that drugs will likely fail if the MIC exceeds the achievable antibiotic concentration at the infection site. But is it as simple as just exceeding the MIC at the infection site? No, pharmacodynamics tell us that overall antibiotic exposure is also important. For example, to be successful, beta-lactam concentrations need to be above the MIC for 40%-50% of the day.
Higher MIC with higher bacterial load. Particularly for beta-lactams, testing with a quantity of bacteria >105/mL produces a higher MIC in vitro. This suggests that clinical failure could occur, even when our in vivo dosing leads to 40%-50% above the “standard” MIC that was obtained from testing the lab standard of 105/mL bacteria, when the infected site’s (middle ear) bacterial load is >105/mL (such higher bacterial loads occur in up to 30% of AOM).5 One way to negate inoculum effect is source control (drain the abscess or debridement), which reduces the bacterial load as well as allowing better antibiotic penetration– both favoring infection resolution. But with suboptimal source control, for example, the middle ear is not drained externally or internally, longer courses (more antibiotic exposure) could aid resolution. Whether the exposure can be administered as higher doses in fewer days or standard doses for more days is debatable but consider that a single parenteral dose of ceftriaxone successfully resolves AOM not attributable to penicillin-nonsusceptible pneumococcus.6Bottom line: Even though the number of potential antibiotics has contracted in the past 20 years, the need to individualize AOM treatment remains important and duration choices are more complex. Indeed, AOM comes in different flavors with patient age, clinical presentation, and episode frequency dictating the choice of duration.
Dr. Christopher J. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics in Kansas City, Mo. Email him at [email protected].
References
1. Pichichero ME. MDedge. 2022 Jan 11.
2. Ruohola A et al. Pediatrics. 2003;111(5):1061-7.
3. Hoberman A et al. N Engl J Med. 2016;375(25):2446-56.
4. Pichichero ME et al. Otolaryngol Head Neck Surg. 2001;124(4):381-7.
5. Harrison CJ et al. Pediatr Infect Dis. 1985;4(6):641-6.
6. Leibovitz E et al. Pediatr Infect Dis. 2000;19(11):1040-5.
The etiology of acute otitis media in young children in recent years
Since the COVID-19 pandemic began, pediatricians have been seeing fewer cases of all respiratory illnesses, including acute otitis media (AOM). However, as I prepare this column, an uptick has commenced and likely will continue in an upward trajectory as we emerge from the pandemic into an endemic coronavirus era. Our group in Rochester, N.Y., has continued prospective studies of AOM throughout the pandemic. We found that nasopharyngeal colonization by Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Moraxella catarrhalis remained prevalent in our study cohort of children aged 6-36 months. However, with all the precautions of masking, social distancing, hand washing, and quick exclusion from day care when illness occurred, the frequency of detecting these common otopathogens decreased, as one might expect.1
Leading up to the pandemic, we had an abundance of data to characterize AOM etiology and found that the cause of AOM continues to change following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13). Our most recent report on otopathogen distribution and antibiotic susceptibility covered the years 2015-2019.2 A total of 589 children were enrolled prospectively and we collected 495 middle ear fluid samples (MEF) from 319 AOM cases using tympanocentesis. The frequency of isolates was H. influenzae (34%), pneumococcus (24%), and M. catarrhalis (15%). Beta-lactamase–positive H. influenzae strains were identified among 49% of the isolates, rendering them resistant to amoxicillin. PCV13 serotypes were infrequently isolated. However, we did isolate vaccine types (VTs) in some children from MEF, notably serotypes 19F, 19A, and 3. Non-PCV13 pneumococcus serotypes 35B, 23B, and 15B/C emerged as the most common serotypes. Amoxicillin resistance was identified among 25% of pneumococcal strains. Out of 16 antibiotics tested, 9 (56%) showed a significant increase in nonsusceptibility among pneumococcal isolates. 100% of M. catarrhalis isolates were beta-lactamase producers and therefore resistant to amoxicillin.
PCV13 has resulted in a decline in both invasive and noninvasive pneumococcal infections caused by strains expressing the 13 capsular serotypes included in the vaccine. However, the emergence of replacement serotypes occurred after introduction of PCV73,4 and continues to occur during the PCV13 era, as shown from the results presented here. Non-PCV13 serotypes accounted for more than 90% of MEF isolates during 2015-2019, with 35B, 21 and 23B being the most commonly isolated. Other emergent serotypes of potential importance were nonvaccine serotypes 15A, 15B, 15C, 23A and 11A. This is highly relevant because forthcoming higher-valency PCVs – PCV15 (manufactured by Merck) and PCV20 (manufactured by Pfizer) will not include many of the dominant capsular serotypes of pneumococcus strains causing AOM. Consequently, the impact of higher-valency PCVs on AOM will not be as great as was observed with the introduction of PCV7 or PCV13.
Of special interest, 22% of pneumococcus isolates from MEF were serotype 35B, making it the most prevalent. Recently we reported a significant rise in antibiotic nonsusceptibility in Spn isolates, contributed mainly by serotype 35B5 and we have been studying how 35B strains transitioned from commensal to otopathogen in children.6 Because serotype 35B strains are increasingly prevalent and often antibiotic resistant, absence of this serotype from PCV15 and PCV20 is cause for concern.
The frequency of isolation of H. influenzae and M. catarrhalis has remained stable across the PCV13 era as the No. 1 and No. 3 pathogens. Similarly, the production of beta-lactamase among strains causing AOM has remained stable at close to 50% and 100%, respectively. Use of amoxicillin, either high dose or standard dose, would not be expected to kill these bacteria.
Our study design has limitations. The population is derived from a predominantly middle-class, suburban population of children in upstate New York and may not be representative of other types of populations in the United States. The children are 6-36 months old, the age when most AOM occurs. MEF samples that were culture negative for bacteria were not further tested by polymerase chain reaction methods.
Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute, at Rochester (N.Y.) General Hospital. He has no conflicts of interest to declare.
References
1. Kaur R et al. Front Pediatr. 2021;9:722483.
2. Kaur R et al. Euro J Clin Microbiol Infect Dis. 2021;41:37-44
3. Pelton SI et al. Pediatr Infect Disease J. 2004;23:1015-22.
4. Farrell DJ et al. Pediatr Infect Disease J. 2007;26:123-8..
5. Kaur R et al. Clin Infect Dis 2021;72(5):797-805.
6. Fuji N et al. Front Cell Infect Microbiol. 2021;11:744742.
Since the COVID-19 pandemic began, pediatricians have been seeing fewer cases of all respiratory illnesses, including acute otitis media (AOM). However, as I prepare this column, an uptick has commenced and likely will continue in an upward trajectory as we emerge from the pandemic into an endemic coronavirus era. Our group in Rochester, N.Y., has continued prospective studies of AOM throughout the pandemic. We found that nasopharyngeal colonization by Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Moraxella catarrhalis remained prevalent in our study cohort of children aged 6-36 months. However, with all the precautions of masking, social distancing, hand washing, and quick exclusion from day care when illness occurred, the frequency of detecting these common otopathogens decreased, as one might expect.1
Leading up to the pandemic, we had an abundance of data to characterize AOM etiology and found that the cause of AOM continues to change following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13). Our most recent report on otopathogen distribution and antibiotic susceptibility covered the years 2015-2019.2 A total of 589 children were enrolled prospectively and we collected 495 middle ear fluid samples (MEF) from 319 AOM cases using tympanocentesis. The frequency of isolates was H. influenzae (34%), pneumococcus (24%), and M. catarrhalis (15%). Beta-lactamase–positive H. influenzae strains were identified among 49% of the isolates, rendering them resistant to amoxicillin. PCV13 serotypes were infrequently isolated. However, we did isolate vaccine types (VTs) in some children from MEF, notably serotypes 19F, 19A, and 3. Non-PCV13 pneumococcus serotypes 35B, 23B, and 15B/C emerged as the most common serotypes. Amoxicillin resistance was identified among 25% of pneumococcal strains. Out of 16 antibiotics tested, 9 (56%) showed a significant increase in nonsusceptibility among pneumococcal isolates. 100% of M. catarrhalis isolates were beta-lactamase producers and therefore resistant to amoxicillin.
PCV13 has resulted in a decline in both invasive and noninvasive pneumococcal infections caused by strains expressing the 13 capsular serotypes included in the vaccine. However, the emergence of replacement serotypes occurred after introduction of PCV73,4 and continues to occur during the PCV13 era, as shown from the results presented here. Non-PCV13 serotypes accounted for more than 90% of MEF isolates during 2015-2019, with 35B, 21 and 23B being the most commonly isolated. Other emergent serotypes of potential importance were nonvaccine serotypes 15A, 15B, 15C, 23A and 11A. This is highly relevant because forthcoming higher-valency PCVs – PCV15 (manufactured by Merck) and PCV20 (manufactured by Pfizer) will not include many of the dominant capsular serotypes of pneumococcus strains causing AOM. Consequently, the impact of higher-valency PCVs on AOM will not be as great as was observed with the introduction of PCV7 or PCV13.
Of special interest, 22% of pneumococcus isolates from MEF were serotype 35B, making it the most prevalent. Recently we reported a significant rise in antibiotic nonsusceptibility in Spn isolates, contributed mainly by serotype 35B5 and we have been studying how 35B strains transitioned from commensal to otopathogen in children.6 Because serotype 35B strains are increasingly prevalent and often antibiotic resistant, absence of this serotype from PCV15 and PCV20 is cause for concern.
The frequency of isolation of H. influenzae and M. catarrhalis has remained stable across the PCV13 era as the No. 1 and No. 3 pathogens. Similarly, the production of beta-lactamase among strains causing AOM has remained stable at close to 50% and 100%, respectively. Use of amoxicillin, either high dose or standard dose, would not be expected to kill these bacteria.
Our study design has limitations. The population is derived from a predominantly middle-class, suburban population of children in upstate New York and may not be representative of other types of populations in the United States. The children are 6-36 months old, the age when most AOM occurs. MEF samples that were culture negative for bacteria were not further tested by polymerase chain reaction methods.
Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute, at Rochester (N.Y.) General Hospital. He has no conflicts of interest to declare.
References
1. Kaur R et al. Front Pediatr. 2021;9:722483.
2. Kaur R et al. Euro J Clin Microbiol Infect Dis. 2021;41:37-44
3. Pelton SI et al. Pediatr Infect Disease J. 2004;23:1015-22.
4. Farrell DJ et al. Pediatr Infect Disease J. 2007;26:123-8..
5. Kaur R et al. Clin Infect Dis 2021;72(5):797-805.
6. Fuji N et al. Front Cell Infect Microbiol. 2021;11:744742.
Since the COVID-19 pandemic began, pediatricians have been seeing fewer cases of all respiratory illnesses, including acute otitis media (AOM). However, as I prepare this column, an uptick has commenced and likely will continue in an upward trajectory as we emerge from the pandemic into an endemic coronavirus era. Our group in Rochester, N.Y., has continued prospective studies of AOM throughout the pandemic. We found that nasopharyngeal colonization by Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Moraxella catarrhalis remained prevalent in our study cohort of children aged 6-36 months. However, with all the precautions of masking, social distancing, hand washing, and quick exclusion from day care when illness occurred, the frequency of detecting these common otopathogens decreased, as one might expect.1
Leading up to the pandemic, we had an abundance of data to characterize AOM etiology and found that the cause of AOM continues to change following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13). Our most recent report on otopathogen distribution and antibiotic susceptibility covered the years 2015-2019.2 A total of 589 children were enrolled prospectively and we collected 495 middle ear fluid samples (MEF) from 319 AOM cases using tympanocentesis. The frequency of isolates was H. influenzae (34%), pneumococcus (24%), and M. catarrhalis (15%). Beta-lactamase–positive H. influenzae strains were identified among 49% of the isolates, rendering them resistant to amoxicillin. PCV13 serotypes were infrequently isolated. However, we did isolate vaccine types (VTs) in some children from MEF, notably serotypes 19F, 19A, and 3. Non-PCV13 pneumococcus serotypes 35B, 23B, and 15B/C emerged as the most common serotypes. Amoxicillin resistance was identified among 25% of pneumococcal strains. Out of 16 antibiotics tested, 9 (56%) showed a significant increase in nonsusceptibility among pneumococcal isolates. 100% of M. catarrhalis isolates were beta-lactamase producers and therefore resistant to amoxicillin.
PCV13 has resulted in a decline in both invasive and noninvasive pneumococcal infections caused by strains expressing the 13 capsular serotypes included in the vaccine. However, the emergence of replacement serotypes occurred after introduction of PCV73,4 and continues to occur during the PCV13 era, as shown from the results presented here. Non-PCV13 serotypes accounted for more than 90% of MEF isolates during 2015-2019, with 35B, 21 and 23B being the most commonly isolated. Other emergent serotypes of potential importance were nonvaccine serotypes 15A, 15B, 15C, 23A and 11A. This is highly relevant because forthcoming higher-valency PCVs – PCV15 (manufactured by Merck) and PCV20 (manufactured by Pfizer) will not include many of the dominant capsular serotypes of pneumococcus strains causing AOM. Consequently, the impact of higher-valency PCVs on AOM will not be as great as was observed with the introduction of PCV7 or PCV13.
Of special interest, 22% of pneumococcus isolates from MEF were serotype 35B, making it the most prevalent. Recently we reported a significant rise in antibiotic nonsusceptibility in Spn isolates, contributed mainly by serotype 35B5 and we have been studying how 35B strains transitioned from commensal to otopathogen in children.6 Because serotype 35B strains are increasingly prevalent and often antibiotic resistant, absence of this serotype from PCV15 and PCV20 is cause for concern.
The frequency of isolation of H. influenzae and M. catarrhalis has remained stable across the PCV13 era as the No. 1 and No. 3 pathogens. Similarly, the production of beta-lactamase among strains causing AOM has remained stable at close to 50% and 100%, respectively. Use of amoxicillin, either high dose or standard dose, would not be expected to kill these bacteria.
Our study design has limitations. The population is derived from a predominantly middle-class, suburban population of children in upstate New York and may not be representative of other types of populations in the United States. The children are 6-36 months old, the age when most AOM occurs. MEF samples that were culture negative for bacteria were not further tested by polymerase chain reaction methods.
Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute, at Rochester (N.Y.) General Hospital. He has no conflicts of interest to declare.
References
1. Kaur R et al. Front Pediatr. 2021;9:722483.
2. Kaur R et al. Euro J Clin Microbiol Infect Dis. 2021;41:37-44
3. Pelton SI et al. Pediatr Infect Disease J. 2004;23:1015-22.
4. Farrell DJ et al. Pediatr Infect Disease J. 2007;26:123-8..
5. Kaur R et al. Clin Infect Dis 2021;72(5):797-805.
6. Fuji N et al. Front Cell Infect Microbiol. 2021;11:744742.
Mumps: Sometimes forgotten but not gone
The 7-year-old boy sat at the edge of a stretcher in the emergency department, looking miserable, as his mother recounted his symptoms to a senior resident physician on duty. Low-grade fever, fatigue, and myalgias prompted rapid SARS-CoV-2 testing at his school. That test, as well as a repeat test at the pediatrician’s office, were negative. A triage protocol in the emergency department prompted a third test, which was also negative.
“Everyone has told me that it’s likely just a different virus,” the mother said. “But then his cheek started to swell. Have you ever seen anything like this?”
The boy turned his head, revealing a diffuse swelling that extended down his right cheek to the angle of his jaw.
“Only in textbooks,” the resident physician responded.
It is a credit to our national immunization program that most practicing clinicians have never actually seen a case of mumps. Before vaccination was introduced in 1967, infection in childhood was nearly universal. Unilateral or bilateral tender swelling of the parotid gland is the typical clinical finding. Low-grade fever, myalgias, decreased appetite, malaise, and headache may precede parotid swelling in some patients. Other patients infected with mumps may have only respiratory symptoms, and some may have no symptoms at all.
Two doses of measles-mumps-rubella vaccine have been recommended for children in the United States since 1989, with the first dose administered at 12-15 months of age. According to data collected through the National Immunization Survey, more than 92% of children in the United States receive at least one dose of measles-mumps-rubella vaccine by 24 months of age. The vaccine is immunogenic, with 94% of recipients developing measurable mumps antibody (range, 89%-97%). The vaccine has been a public health success: Overall, mumps cases declined more than 99% between 1967 and 2005.
But in the mid-2000s, mumps cases started to rise again, with more than 28,000 reported between 2007 and 2019. Annual cases ranged from 229 to 6,369 and while large, localized outbreaks have contributed to peak years, mumps has been reported from all 50 states and the District of Columbia. According to a recently published paper in Pediatrics, nearly a third of these cases occurred in children <18 years of age and most had been appropriately immunized for age.
Of the 9,172 cases reported in children, 5,461 or 60% occurred between 2015 and 2019. Of these, 55% were in boys. While cases occurred in children of all ages, 54% were in children 11-17 years of age, and 33% were in children 5-10 years of age. Non-Hispanic Asian and/or Pacific Islander children accounted for 38% of cases. Only 2% of cases were associated with international travel and were presumed to have been acquired outside the United States
The reason for the increase in mumps cases in recent years is not well understood. Outbreaks in fully immunized college students have prompted concern about poor B-cell memory after vaccination resulting in waning immunity over time. In the past, antibodies against mumps were boosted by exposure to wild-type mumps virus but such exposures have become fortunately rare for most of us. Cases in recently immunized children suggest there is more to the story. Notably, there is a mismatch between the genotype A mumps virus contained in the current MMR and MMRV vaccines and the genotype G virus currently circulating in the United States.
With the onset of the pandemic and implementation of mitigation measures to prevent the spread of COVID-19, circulation of some common respiratory viruses, including respiratory syncytial virus and influenza, was sharply curtailed. Mumps continued to circulate, albeit at reduced levels, with 616 cases reported in 2020. In 2021, 30 states and jurisdictions reported 139 cases through Dec. 1.
Clinicians should suspect mumps in all cases of parotitis, regardless of an individual’s age, vaccination status, or travel history. Laboratory testing is required to distinguish mumps from other infectious and noninfectious causes of parotitis. Infectious causes include gram-positive and gram-negative bacterial infection, as well as other viral infections, including Epstein-Barr virus, coxsackie viruses, parainfluenza, and rarely, influenza. Case reports also describe parotitis coincident with SARS-CoV-2 infection.
When parotitis has been present for 3 days or less, a buccal swab for RT-PCR should be obtained, massaging the parotid gland for 30 seconds before specimen collection. When parotitis has been present for >3 days, a mumps Immunoglobulin M serum antibody should be collected in addition to the buccal swab PCR. A negative IgM does not exclude the possibility of infection, especially in immunized individuals. Mumps is a nationally notifiable disease, and all confirmed and suspect cases should be reported to the state or local health department.
Back in the emergency department, the mother was counseled about the potential diagnosis of mumps and the need for her son to isolate at home for 5 days after the onset of the parotid swelling. She was also educated about potential complications of mumps, including orchitis, aseptic meningitis and encephalitis, and hearing loss. Fortunately, complications are less common in individuals who have been immunized, and orchitis rarely occurs in prepubertal boys.
The resident physician also confirmed that other members of the household had been appropriately immunized for age. While the MMR vaccine does not prevent illness in those already infected with mumps and is not indicated as postexposure prophylaxis, providing vaccine to those not already immunized can protect against future exposures. A third dose of MMR vaccine is only indicated in the setting of an outbreak and when specifically recommended by public health authorities for those deemed to be in a high-risk group. Additional information about mumps is available at www.cdc.gov/mumps/hcp.html#report.
Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].
The 7-year-old boy sat at the edge of a stretcher in the emergency department, looking miserable, as his mother recounted his symptoms to a senior resident physician on duty. Low-grade fever, fatigue, and myalgias prompted rapid SARS-CoV-2 testing at his school. That test, as well as a repeat test at the pediatrician’s office, were negative. A triage protocol in the emergency department prompted a third test, which was also negative.
“Everyone has told me that it’s likely just a different virus,” the mother said. “But then his cheek started to swell. Have you ever seen anything like this?”
The boy turned his head, revealing a diffuse swelling that extended down his right cheek to the angle of his jaw.
“Only in textbooks,” the resident physician responded.
It is a credit to our national immunization program that most practicing clinicians have never actually seen a case of mumps. Before vaccination was introduced in 1967, infection in childhood was nearly universal. Unilateral or bilateral tender swelling of the parotid gland is the typical clinical finding. Low-grade fever, myalgias, decreased appetite, malaise, and headache may precede parotid swelling in some patients. Other patients infected with mumps may have only respiratory symptoms, and some may have no symptoms at all.
Two doses of measles-mumps-rubella vaccine have been recommended for children in the United States since 1989, with the first dose administered at 12-15 months of age. According to data collected through the National Immunization Survey, more than 92% of children in the United States receive at least one dose of measles-mumps-rubella vaccine by 24 months of age. The vaccine is immunogenic, with 94% of recipients developing measurable mumps antibody (range, 89%-97%). The vaccine has been a public health success: Overall, mumps cases declined more than 99% between 1967 and 2005.
But in the mid-2000s, mumps cases started to rise again, with more than 28,000 reported between 2007 and 2019. Annual cases ranged from 229 to 6,369 and while large, localized outbreaks have contributed to peak years, mumps has been reported from all 50 states and the District of Columbia. According to a recently published paper in Pediatrics, nearly a third of these cases occurred in children <18 years of age and most had been appropriately immunized for age.
Of the 9,172 cases reported in children, 5,461 or 60% occurred between 2015 and 2019. Of these, 55% were in boys. While cases occurred in children of all ages, 54% were in children 11-17 years of age, and 33% were in children 5-10 years of age. Non-Hispanic Asian and/or Pacific Islander children accounted for 38% of cases. Only 2% of cases were associated with international travel and were presumed to have been acquired outside the United States
The reason for the increase in mumps cases in recent years is not well understood. Outbreaks in fully immunized college students have prompted concern about poor B-cell memory after vaccination resulting in waning immunity over time. In the past, antibodies against mumps were boosted by exposure to wild-type mumps virus but such exposures have become fortunately rare for most of us. Cases in recently immunized children suggest there is more to the story. Notably, there is a mismatch between the genotype A mumps virus contained in the current MMR and MMRV vaccines and the genotype G virus currently circulating in the United States.
With the onset of the pandemic and implementation of mitigation measures to prevent the spread of COVID-19, circulation of some common respiratory viruses, including respiratory syncytial virus and influenza, was sharply curtailed. Mumps continued to circulate, albeit at reduced levels, with 616 cases reported in 2020. In 2021, 30 states and jurisdictions reported 139 cases through Dec. 1.
Clinicians should suspect mumps in all cases of parotitis, regardless of an individual’s age, vaccination status, or travel history. Laboratory testing is required to distinguish mumps from other infectious and noninfectious causes of parotitis. Infectious causes include gram-positive and gram-negative bacterial infection, as well as other viral infections, including Epstein-Barr virus, coxsackie viruses, parainfluenza, and rarely, influenza. Case reports also describe parotitis coincident with SARS-CoV-2 infection.
When parotitis has been present for 3 days or less, a buccal swab for RT-PCR should be obtained, massaging the parotid gland for 30 seconds before specimen collection. When parotitis has been present for >3 days, a mumps Immunoglobulin M serum antibody should be collected in addition to the buccal swab PCR. A negative IgM does not exclude the possibility of infection, especially in immunized individuals. Mumps is a nationally notifiable disease, and all confirmed and suspect cases should be reported to the state or local health department.
Back in the emergency department, the mother was counseled about the potential diagnosis of mumps and the need for her son to isolate at home for 5 days after the onset of the parotid swelling. She was also educated about potential complications of mumps, including orchitis, aseptic meningitis and encephalitis, and hearing loss. Fortunately, complications are less common in individuals who have been immunized, and orchitis rarely occurs in prepubertal boys.
The resident physician also confirmed that other members of the household had been appropriately immunized for age. While the MMR vaccine does not prevent illness in those already infected with mumps and is not indicated as postexposure prophylaxis, providing vaccine to those not already immunized can protect against future exposures. A third dose of MMR vaccine is only indicated in the setting of an outbreak and when specifically recommended by public health authorities for those deemed to be in a high-risk group. Additional information about mumps is available at www.cdc.gov/mumps/hcp.html#report.
Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].
The 7-year-old boy sat at the edge of a stretcher in the emergency department, looking miserable, as his mother recounted his symptoms to a senior resident physician on duty. Low-grade fever, fatigue, and myalgias prompted rapid SARS-CoV-2 testing at his school. That test, as well as a repeat test at the pediatrician’s office, were negative. A triage protocol in the emergency department prompted a third test, which was also negative.
“Everyone has told me that it’s likely just a different virus,” the mother said. “But then his cheek started to swell. Have you ever seen anything like this?”
The boy turned his head, revealing a diffuse swelling that extended down his right cheek to the angle of his jaw.
“Only in textbooks,” the resident physician responded.
It is a credit to our national immunization program that most practicing clinicians have never actually seen a case of mumps. Before vaccination was introduced in 1967, infection in childhood was nearly universal. Unilateral or bilateral tender swelling of the parotid gland is the typical clinical finding. Low-grade fever, myalgias, decreased appetite, malaise, and headache may precede parotid swelling in some patients. Other patients infected with mumps may have only respiratory symptoms, and some may have no symptoms at all.
Two doses of measles-mumps-rubella vaccine have been recommended for children in the United States since 1989, with the first dose administered at 12-15 months of age. According to data collected through the National Immunization Survey, more than 92% of children in the United States receive at least one dose of measles-mumps-rubella vaccine by 24 months of age. The vaccine is immunogenic, with 94% of recipients developing measurable mumps antibody (range, 89%-97%). The vaccine has been a public health success: Overall, mumps cases declined more than 99% between 1967 and 2005.
But in the mid-2000s, mumps cases started to rise again, with more than 28,000 reported between 2007 and 2019. Annual cases ranged from 229 to 6,369 and while large, localized outbreaks have contributed to peak years, mumps has been reported from all 50 states and the District of Columbia. According to a recently published paper in Pediatrics, nearly a third of these cases occurred in children <18 years of age and most had been appropriately immunized for age.
Of the 9,172 cases reported in children, 5,461 or 60% occurred between 2015 and 2019. Of these, 55% were in boys. While cases occurred in children of all ages, 54% were in children 11-17 years of age, and 33% were in children 5-10 years of age. Non-Hispanic Asian and/or Pacific Islander children accounted for 38% of cases. Only 2% of cases were associated with international travel and were presumed to have been acquired outside the United States
The reason for the increase in mumps cases in recent years is not well understood. Outbreaks in fully immunized college students have prompted concern about poor B-cell memory after vaccination resulting in waning immunity over time. In the past, antibodies against mumps were boosted by exposure to wild-type mumps virus but such exposures have become fortunately rare for most of us. Cases in recently immunized children suggest there is more to the story. Notably, there is a mismatch between the genotype A mumps virus contained in the current MMR and MMRV vaccines and the genotype G virus currently circulating in the United States.
With the onset of the pandemic and implementation of mitigation measures to prevent the spread of COVID-19, circulation of some common respiratory viruses, including respiratory syncytial virus and influenza, was sharply curtailed. Mumps continued to circulate, albeit at reduced levels, with 616 cases reported in 2020. In 2021, 30 states and jurisdictions reported 139 cases through Dec. 1.
Clinicians should suspect mumps in all cases of parotitis, regardless of an individual’s age, vaccination status, or travel history. Laboratory testing is required to distinguish mumps from other infectious and noninfectious causes of parotitis. Infectious causes include gram-positive and gram-negative bacterial infection, as well as other viral infections, including Epstein-Barr virus, coxsackie viruses, parainfluenza, and rarely, influenza. Case reports also describe parotitis coincident with SARS-CoV-2 infection.
When parotitis has been present for 3 days or less, a buccal swab for RT-PCR should be obtained, massaging the parotid gland for 30 seconds before specimen collection. When parotitis has been present for >3 days, a mumps Immunoglobulin M serum antibody should be collected in addition to the buccal swab PCR. A negative IgM does not exclude the possibility of infection, especially in immunized individuals. Mumps is a nationally notifiable disease, and all confirmed and suspect cases should be reported to the state or local health department.
Back in the emergency department, the mother was counseled about the potential diagnosis of mumps and the need for her son to isolate at home for 5 days after the onset of the parotid swelling. She was also educated about potential complications of mumps, including orchitis, aseptic meningitis and encephalitis, and hearing loss. Fortunately, complications are less common in individuals who have been immunized, and orchitis rarely occurs in prepubertal boys.
The resident physician also confirmed that other members of the household had been appropriately immunized for age. While the MMR vaccine does not prevent illness in those already infected with mumps and is not indicated as postexposure prophylaxis, providing vaccine to those not already immunized can protect against future exposures. A third dose of MMR vaccine is only indicated in the setting of an outbreak and when specifically recommended by public health authorities for those deemed to be in a high-risk group. Additional information about mumps is available at www.cdc.gov/mumps/hcp.html#report.
Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].
More tools for the COVID toolbox
I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m2) seen in the pediatric emergency department with tachycardia, O2 saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.1
She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.
Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”
The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.2
Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?
Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.
Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.3
Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.
What adverse events were observed? Monoclonal antibody infusions are in general safe but anaphylaxis has been reported. Other infusion-related adverse events include urticaria, pruritis, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting, and rash. Nearly all events were grade 1, mild, or grade 2, moderate. For nonsevere infusion-related reactions, consider slowing the infusion; if necessary, the infusion should be stopped.
Implementation challenges
The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.
Summary
Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.4 Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.
Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].
References
1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.
2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.
3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.
4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.
I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m2) seen in the pediatric emergency department with tachycardia, O2 saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.1
She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.
Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”
The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.2
Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?
Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.
Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.3
Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.
What adverse events were observed? Monoclonal antibody infusions are in general safe but anaphylaxis has been reported. Other infusion-related adverse events include urticaria, pruritis, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting, and rash. Nearly all events were grade 1, mild, or grade 2, moderate. For nonsevere infusion-related reactions, consider slowing the infusion; if necessary, the infusion should be stopped.
Implementation challenges
The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.
Summary
Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.4 Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.
Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].
References
1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.
2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.
3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.
4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.
I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m2) seen in the pediatric emergency department with tachycardia, O2 saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.1
She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.
Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”
The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.2
Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?
Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.
Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.3
Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.
What adverse events were observed? Monoclonal antibody infusions are in general safe but anaphylaxis has been reported. Other infusion-related adverse events include urticaria, pruritis, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting, and rash. Nearly all events were grade 1, mild, or grade 2, moderate. For nonsevere infusion-related reactions, consider slowing the infusion; if necessary, the infusion should be stopped.
Implementation challenges
The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.
Summary
Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.4 Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.
Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].
References
1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.
2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.
3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.
4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.
Effect of COVID-19 pandemic on respiratory infectious diseases in primary care practice
A secondary consequence of public health measures to prevent the spread of SARS-CoV-2 included a concurrent reduction in risk for children to acquire and spread other respiratory viral infectious diseases. In the Rochester, N.Y., area, we had an ongoing prospective study in primary care pediatric practices that afforded an opportunity to assess the effect of the pandemic control measures on all infectious disease illness visits in young children. Specifically, in children aged 6-36 months old, our study was in place when the pandemic began with a primary objective to evaluate the changing epidemiology of acute otitis media (AOM) and nasopharyngeal colonization by potential bacterial respiratory pathogens in community-based primary care pediatric practices. As the public health measures mandated by New York State Department of Health were implemented, we prospectively quantified their effect on physician-diagnosed infectious disease illness visits. The incidence of infectious disease visits by a cohort of young children during the COVID-19 pandemic period March 15, 2020, through Dec. 31, 2020, was compared with the same time frame in the preceding year, 2019.1
Recommendations of the New York State Department of Health for public health, changes in school and day care attendance, and clinical practice during the study time frame
On March 7, 2020, a state of emergency was declared in New York because of the COVID-19 pandemic. All schools were required to close. A mandated order for public use of masks in adults and children more than 2 years of age was enacted. In the Finger Lakes region of Upstate New York, where the two primary care pediatric practices reside, complete lockdown was partially lifted on May 15, 2020, and further lifted on June 26, 2020. Almost all regional school districts opened to at least hybrid learning models for all students starting Sept. 8, 2020. On March 6, 2020, video telehealth and telephone call visits were introduced as routine practice. Well-child visits were limited to those less than 2 years of age, then gradually expanded to all ages by late May 2020. During the “stay at home” phase of the New York State lockdown, day care services were considered an essential business. Day care child density was limited. All children less than 2 years old were required to wear a mask while in the facility. Upon arrival, children with any respiratory symptoms or fever were excluded. For the school year commencing September 2020, almost all regional school districts opened to virtual, hybrid, or in-person learning models. Exclusion occurred similar to that of the day care facilities.
Incidence of respiratory infectious disease illnesses
Clinical diagnoses and healthy visits of 144 children from March 15 to Dec. 31, 2020 (beginning of the pandemic) were compared to 215 children during the same months in 2019 (prepandemic). Pediatric SARS-CoV-2 positivity rates trended up alongside community spread. Pediatric practice positivity rates rose from 1.9% in October 2020 to 19% in December 2020.
The table shows the incidence of significantly different infectious disease illness visits in the two study cohorts.
During the pandemic, 258 infection visits occurred among 144 pandemic cohort children, compared with 687 visits among 215 prepandemic cohort children, a 1.8-fold decrease (P < .0001). The proportion of children with visits for AOM (3.7-fold; P < .0001), bronchiolitis (7.4-fold; P = .036), croup (27.5-fold; P < .0001), and viral upper respiratory infection (3.8-fold; P < .0001) decreased significantly. Fever without a source (1.4-fold decrease; P = .009) and skin/soft tissue infection (2.1-fold decrease; P = .042) represented a higher proportion of visits during the pandemic.
Prescription of antibiotics significantly decreased (P < .001) during the pandemic.
Change in care practices
In the prepandemic period, virtual visits, leading to a diagnosis and treatment and referring children to an urgent care or hospital emergency department during regular office hours were rare. During the pandemic, this changed. Significantly increased use of telemedicine visits (P < .0001) and significantly decreased office and urgent care visits (P < .0001) occurred during the pandemic. Telehealth visits peaked the week of April 12, 2020, at 45% of all pediatric visits. In-person illness visits gradually returned to year-to-year volumes in August-September 2020 with school opening. Early in the pandemic, both pediatric offices limited patient encounters to well-child visits in the first 2 years of life to not miss opportunities for childhood vaccinations. However, some parents were reluctant to bring their children to those visits. There was no significant change in frequency of healthy child visits during the pandemic.
To our knowledge, this was the first study from primary care pediatric practices in the United States to analyze the effect on infectious diseases during the first 9 months of the pandemic, including the 6-month time period after the reopening from the first 3 months of lockdown. One prior study from a primary care network in Massachusetts reported significant decreases in respiratory infectious diseases for children aged 0-17 years during the first months of the pandemic during lockdown.2 A study in Tennessee that included hospital emergency department, urgent care, primary care, and retail health clinics also reported respiratory infection diagnoses as well as antibiotic prescription were reduced in the early months of the pandemic.3
Our study shows an overall reduction in frequency of respiratory illness visits in children 6-36 months old during the first 9 months of the COVID-19 pandemic. We learned the value of using technology in the form of virtual visits to render care. Perhaps as the pandemic subsides, many of the hand-washing and sanitizing practices will remain in place and lead to less frequent illness in children in the future. However, there may be temporary negative consequences from the “immune debt” that has occurred from a prolonged time span when children were not becoming infected with respiratory pathogens.4 We will see what unfolds in the future.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. Dr. Schulz is pediatric medical director at Rochester (N.Y.) Regional Health. Dr. Pichichero and Dr. Schulz have no conflicts of interest to disclose. This study was funded in part by the Centers for Disease Control and Prevention.
References
1. Kaur R et al. Front Pediatr. 2021;(9)722483:1-8.
2. Hatoun J et al. Pediatrics. 2020;146(4):e2020006460.
3. Katz SE et al. J Pediatric Infect Dis Soc. 2021;10(1):62-4.
4. Cohen R et al. Infect. Dis Now. 2021; 51(5)418-23.
A secondary consequence of public health measures to prevent the spread of SARS-CoV-2 included a concurrent reduction in risk for children to acquire and spread other respiratory viral infectious diseases. In the Rochester, N.Y., area, we had an ongoing prospective study in primary care pediatric practices that afforded an opportunity to assess the effect of the pandemic control measures on all infectious disease illness visits in young children. Specifically, in children aged 6-36 months old, our study was in place when the pandemic began with a primary objective to evaluate the changing epidemiology of acute otitis media (AOM) and nasopharyngeal colonization by potential bacterial respiratory pathogens in community-based primary care pediatric practices. As the public health measures mandated by New York State Department of Health were implemented, we prospectively quantified their effect on physician-diagnosed infectious disease illness visits. The incidence of infectious disease visits by a cohort of young children during the COVID-19 pandemic period March 15, 2020, through Dec. 31, 2020, was compared with the same time frame in the preceding year, 2019.1
Recommendations of the New York State Department of Health for public health, changes in school and day care attendance, and clinical practice during the study time frame
On March 7, 2020, a state of emergency was declared in New York because of the COVID-19 pandemic. All schools were required to close. A mandated order for public use of masks in adults and children more than 2 years of age was enacted. In the Finger Lakes region of Upstate New York, where the two primary care pediatric practices reside, complete lockdown was partially lifted on May 15, 2020, and further lifted on June 26, 2020. Almost all regional school districts opened to at least hybrid learning models for all students starting Sept. 8, 2020. On March 6, 2020, video telehealth and telephone call visits were introduced as routine practice. Well-child visits were limited to those less than 2 years of age, then gradually expanded to all ages by late May 2020. During the “stay at home” phase of the New York State lockdown, day care services were considered an essential business. Day care child density was limited. All children less than 2 years old were required to wear a mask while in the facility. Upon arrival, children with any respiratory symptoms or fever were excluded. For the school year commencing September 2020, almost all regional school districts opened to virtual, hybrid, or in-person learning models. Exclusion occurred similar to that of the day care facilities.
Incidence of respiratory infectious disease illnesses
Clinical diagnoses and healthy visits of 144 children from March 15 to Dec. 31, 2020 (beginning of the pandemic) were compared to 215 children during the same months in 2019 (prepandemic). Pediatric SARS-CoV-2 positivity rates trended up alongside community spread. Pediatric practice positivity rates rose from 1.9% in October 2020 to 19% in December 2020.
The table shows the incidence of significantly different infectious disease illness visits in the two study cohorts.
During the pandemic, 258 infection visits occurred among 144 pandemic cohort children, compared with 687 visits among 215 prepandemic cohort children, a 1.8-fold decrease (P < .0001). The proportion of children with visits for AOM (3.7-fold; P < .0001), bronchiolitis (7.4-fold; P = .036), croup (27.5-fold; P < .0001), and viral upper respiratory infection (3.8-fold; P < .0001) decreased significantly. Fever without a source (1.4-fold decrease; P = .009) and skin/soft tissue infection (2.1-fold decrease; P = .042) represented a higher proportion of visits during the pandemic.
Prescription of antibiotics significantly decreased (P < .001) during the pandemic.
Change in care practices
In the prepandemic period, virtual visits, leading to a diagnosis and treatment and referring children to an urgent care or hospital emergency department during regular office hours were rare. During the pandemic, this changed. Significantly increased use of telemedicine visits (P < .0001) and significantly decreased office and urgent care visits (P < .0001) occurred during the pandemic. Telehealth visits peaked the week of April 12, 2020, at 45% of all pediatric visits. In-person illness visits gradually returned to year-to-year volumes in August-September 2020 with school opening. Early in the pandemic, both pediatric offices limited patient encounters to well-child visits in the first 2 years of life to not miss opportunities for childhood vaccinations. However, some parents were reluctant to bring their children to those visits. There was no significant change in frequency of healthy child visits during the pandemic.
To our knowledge, this was the first study from primary care pediatric practices in the United States to analyze the effect on infectious diseases during the first 9 months of the pandemic, including the 6-month time period after the reopening from the first 3 months of lockdown. One prior study from a primary care network in Massachusetts reported significant decreases in respiratory infectious diseases for children aged 0-17 years during the first months of the pandemic during lockdown.2 A study in Tennessee that included hospital emergency department, urgent care, primary care, and retail health clinics also reported respiratory infection diagnoses as well as antibiotic prescription were reduced in the early months of the pandemic.3
Our study shows an overall reduction in frequency of respiratory illness visits in children 6-36 months old during the first 9 months of the COVID-19 pandemic. We learned the value of using technology in the form of virtual visits to render care. Perhaps as the pandemic subsides, many of the hand-washing and sanitizing practices will remain in place and lead to less frequent illness in children in the future. However, there may be temporary negative consequences from the “immune debt” that has occurred from a prolonged time span when children were not becoming infected with respiratory pathogens.4 We will see what unfolds in the future.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. Dr. Schulz is pediatric medical director at Rochester (N.Y.) Regional Health. Dr. Pichichero and Dr. Schulz have no conflicts of interest to disclose. This study was funded in part by the Centers for Disease Control and Prevention.
References
1. Kaur R et al. Front Pediatr. 2021;(9)722483:1-8.
2. Hatoun J et al. Pediatrics. 2020;146(4):e2020006460.
3. Katz SE et al. J Pediatric Infect Dis Soc. 2021;10(1):62-4.
4. Cohen R et al. Infect. Dis Now. 2021; 51(5)418-23.
A secondary consequence of public health measures to prevent the spread of SARS-CoV-2 included a concurrent reduction in risk for children to acquire and spread other respiratory viral infectious diseases. In the Rochester, N.Y., area, we had an ongoing prospective study in primary care pediatric practices that afforded an opportunity to assess the effect of the pandemic control measures on all infectious disease illness visits in young children. Specifically, in children aged 6-36 months old, our study was in place when the pandemic began with a primary objective to evaluate the changing epidemiology of acute otitis media (AOM) and nasopharyngeal colonization by potential bacterial respiratory pathogens in community-based primary care pediatric practices. As the public health measures mandated by New York State Department of Health were implemented, we prospectively quantified their effect on physician-diagnosed infectious disease illness visits. The incidence of infectious disease visits by a cohort of young children during the COVID-19 pandemic period March 15, 2020, through Dec. 31, 2020, was compared with the same time frame in the preceding year, 2019.1
Recommendations of the New York State Department of Health for public health, changes in school and day care attendance, and clinical practice during the study time frame
On March 7, 2020, a state of emergency was declared in New York because of the COVID-19 pandemic. All schools were required to close. A mandated order for public use of masks in adults and children more than 2 years of age was enacted. In the Finger Lakes region of Upstate New York, where the two primary care pediatric practices reside, complete lockdown was partially lifted on May 15, 2020, and further lifted on June 26, 2020. Almost all regional school districts opened to at least hybrid learning models for all students starting Sept. 8, 2020. On March 6, 2020, video telehealth and telephone call visits were introduced as routine practice. Well-child visits were limited to those less than 2 years of age, then gradually expanded to all ages by late May 2020. During the “stay at home” phase of the New York State lockdown, day care services were considered an essential business. Day care child density was limited. All children less than 2 years old were required to wear a mask while in the facility. Upon arrival, children with any respiratory symptoms or fever were excluded. For the school year commencing September 2020, almost all regional school districts opened to virtual, hybrid, or in-person learning models. Exclusion occurred similar to that of the day care facilities.
Incidence of respiratory infectious disease illnesses
Clinical diagnoses and healthy visits of 144 children from March 15 to Dec. 31, 2020 (beginning of the pandemic) were compared to 215 children during the same months in 2019 (prepandemic). Pediatric SARS-CoV-2 positivity rates trended up alongside community spread. Pediatric practice positivity rates rose from 1.9% in October 2020 to 19% in December 2020.
The table shows the incidence of significantly different infectious disease illness visits in the two study cohorts.
During the pandemic, 258 infection visits occurred among 144 pandemic cohort children, compared with 687 visits among 215 prepandemic cohort children, a 1.8-fold decrease (P < .0001). The proportion of children with visits for AOM (3.7-fold; P < .0001), bronchiolitis (7.4-fold; P = .036), croup (27.5-fold; P < .0001), and viral upper respiratory infection (3.8-fold; P < .0001) decreased significantly. Fever without a source (1.4-fold decrease; P = .009) and skin/soft tissue infection (2.1-fold decrease; P = .042) represented a higher proportion of visits during the pandemic.
Prescription of antibiotics significantly decreased (P < .001) during the pandemic.
Change in care practices
In the prepandemic period, virtual visits, leading to a diagnosis and treatment and referring children to an urgent care or hospital emergency department during regular office hours were rare. During the pandemic, this changed. Significantly increased use of telemedicine visits (P < .0001) and significantly decreased office and urgent care visits (P < .0001) occurred during the pandemic. Telehealth visits peaked the week of April 12, 2020, at 45% of all pediatric visits. In-person illness visits gradually returned to year-to-year volumes in August-September 2020 with school opening. Early in the pandemic, both pediatric offices limited patient encounters to well-child visits in the first 2 years of life to not miss opportunities for childhood vaccinations. However, some parents were reluctant to bring their children to those visits. There was no significant change in frequency of healthy child visits during the pandemic.
To our knowledge, this was the first study from primary care pediatric practices in the United States to analyze the effect on infectious diseases during the first 9 months of the pandemic, including the 6-month time period after the reopening from the first 3 months of lockdown. One prior study from a primary care network in Massachusetts reported significant decreases in respiratory infectious diseases for children aged 0-17 years during the first months of the pandemic during lockdown.2 A study in Tennessee that included hospital emergency department, urgent care, primary care, and retail health clinics also reported respiratory infection diagnoses as well as antibiotic prescription were reduced in the early months of the pandemic.3
Our study shows an overall reduction in frequency of respiratory illness visits in children 6-36 months old during the first 9 months of the COVID-19 pandemic. We learned the value of using technology in the form of virtual visits to render care. Perhaps as the pandemic subsides, many of the hand-washing and sanitizing practices will remain in place and lead to less frequent illness in children in the future. However, there may be temporary negative consequences from the “immune debt” that has occurred from a prolonged time span when children were not becoming infected with respiratory pathogens.4 We will see what unfolds in the future.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. Dr. Schulz is pediatric medical director at Rochester (N.Y.) Regional Health. Dr. Pichichero and Dr. Schulz have no conflicts of interest to disclose. This study was funded in part by the Centers for Disease Control and Prevention.
References
1. Kaur R et al. Front Pediatr. 2021;(9)722483:1-8.
2. Hatoun J et al. Pediatrics. 2020;146(4):e2020006460.
3. Katz SE et al. J Pediatric Infect Dis Soc. 2021;10(1):62-4.
4. Cohen R et al. Infect. Dis Now. 2021; 51(5)418-23.
Adolescent immunizations and protecting our children from COVID-19
I began thinking of a topic for this column weeks ago determined to discuss anything except COVID-19. Yet, news reports from all sources blasted daily reminders of rising COVID-19 cases overall and specifically in children.
In August, school resumed for many of our patients and the battle over mandating masks for school attendance was in full swing. The fact that it is a Centers for Disease Control and Prevention recommendation supported by both the American Academy of Pediatrics and the Pediatric Infectious Disease Society fell on deaf ears. One day, I heard a report that over 25,000 students attending Texas public schools were diagnosed with COVID-19 between Aug. 23 and Aug. 29. This peak in activity occurred just 2 weeks after the start of school and led to the closure of 45 school districts. Texas does not have a monopoly on these rising cases. Delta, a more contagious variant, began circulating in June 2021 and by July it was the most predominant. Emergency department visits and hospitalizations have increased nationwide. During the latter 2 weeks of August 2021, COVID-19–related ED visits and hospitalizations for persons aged 0-17 years were 3.4 and 3.7 times higher in states with the lowest vaccination coverage, compared with states with high vaccination coverage (MMWR Morb Mortal Wkly Rep. 2021;70:1249-54). Specifically, the rates of hospitalization the week ending Aug. 14, 2021, were nearly 5 times the rates for the week ending June 26, 2021, for 0- to 17-year-olds and nearly 10 times the rates for children 0-4 years of age. Hospitalization rates were 10.1 times higher for unimmunized adolescents than for fully vaccinated ones (MMWR Morb Mortal Wkly Rep. 2021;70:1255-60).
Multiple elected state leaders have opposed interventions such as mandating masks in school, and our children are paying for it. These leaders have relinquished their responsibility to local school boards. Several have reinforced the no-mask mandate while others have had the courage and insight to ignore state government leaders and have established mask mandates.
How is this lack of enforcement of national recommendations affecting our patients? Let’s look at two neighboring school districts in Texas. School districts have COVID-19 dashboards that are updated daily and accessible to the general public. School District A requires masks for school entry. It serves 196,171 students and has 27,195 teachers and staff. Since school opened in August, 1,606 cumulative cases of COVID-19 in students (0.8%) and 282 in staff (1%) have been reported. Fifty-five percent of the student cases occurred in elementary schools. In contrast, School District B located in the adjacent county serves 64,517 students and has 3,906 teachers and staff with no mask mandate. Since August, there have been 4,506 cumulative COVID-19 cases in students (6.9%) and 578 (14.7%) in staff. Information regarding the specific school type was not provided; however, the dashboard indicates that 2,924 cases (64.8%) occurred in children younger than 11 years of age. County data indicate 62% of those older than 12 years of age were fully vaccinated in District A, compared with 54% of persons older than 12 years in District B. The county COVID-19 positivity rate in District A is 17.6% and in District B it is 20%. Both counties are experiencing increased COVID-19 activity yet have had strikingly different outcomes in the student/staff population. While supporting the case for wearing masks to prevent disease transmission, one can’t ignore the adolescents who were infected and vaccine eligible (District A: 706; District B: 1,582). Their vaccination status could not be determined.
As pediatricians we have played an integral part in the elimination of diseases through educating and administering vaccinations. Adolescents are relatively healthy, thus limiting the number of encounters with them. The majority complete the 11-year visit; however, many fail to return for the 16- to 18-year visit.
So how are we doing? CDC data from 10 U.S. jurisdictions demonstrated a substantial decrease in vaccine administration between March and May of 2020, compared with the same period in 2018 and 2019. A decline was anticipated because of the nationwide lockdown. Doses of HPV administered declined almost 64% and 71% for 9- to 12-year-olds and 13- to 17-year-olds, respectively. Tdap administration declined 66% and 61% for the same respective age groups. Although administered doses increased between June and September of 2020, it was not sufficient to achieve catch-up coverage. Compared to the same period in 2018-2019, administration of the HPV vaccine declined 12.8% and 28% (ages 9-12 and ages 13-17) and for Tdap it was 21% and 30% lower (ages 9-12 and ages 13-17) (MMWR Morb Mortal Wkly Rep. 2021;70:840-5).
Now, we have another adolescent vaccine to discuss and encourage our patients to receive. We also need to address their concerns and/or to at least direct them to a reliable source to obtain accurate information. For the first time, a recommended vaccine may not be available at their medical home. Many don’t know where to go to receive it (http://www.vaccines.gov). Results of a Kaiser Family Foundation COVID-19 survey (August 2021) indicated that parents trusted their pediatricians most often (78%) for vaccine advice. The respondents voiced concern about trusting the location where the child would be immunized and long-term effects especially related to fertility. Parents who received communications regarding the benefits of vaccination were twice as likely to have their adolescents immunized. Finally, remember: Like parent, like child. An immunized parent is more likely to immunize the adolescent. (See Fig. 1.)
It is beyond the scope of this column to discuss the psychosocial aspects of this disease: children experiencing the death of teachers, classmates, family members, and those viewing the vitriol between pro- and antimask proponents often exhibited on school premises. And let’s not forget the child who wants to wear a mask but may be ostracized or bullied for doing so.
Our job is to do our very best to advocate for and to protect our patients by promoting mandatory masks at schools and encouraging vaccination of adolescents as we patiently wait for vaccines to become available for all of our children.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures.
I began thinking of a topic for this column weeks ago determined to discuss anything except COVID-19. Yet, news reports from all sources blasted daily reminders of rising COVID-19 cases overall and specifically in children.
In August, school resumed for many of our patients and the battle over mandating masks for school attendance was in full swing. The fact that it is a Centers for Disease Control and Prevention recommendation supported by both the American Academy of Pediatrics and the Pediatric Infectious Disease Society fell on deaf ears. One day, I heard a report that over 25,000 students attending Texas public schools were diagnosed with COVID-19 between Aug. 23 and Aug. 29. This peak in activity occurred just 2 weeks after the start of school and led to the closure of 45 school districts. Texas does not have a monopoly on these rising cases. Delta, a more contagious variant, began circulating in June 2021 and by July it was the most predominant. Emergency department visits and hospitalizations have increased nationwide. During the latter 2 weeks of August 2021, COVID-19–related ED visits and hospitalizations for persons aged 0-17 years were 3.4 and 3.7 times higher in states with the lowest vaccination coverage, compared with states with high vaccination coverage (MMWR Morb Mortal Wkly Rep. 2021;70:1249-54). Specifically, the rates of hospitalization the week ending Aug. 14, 2021, were nearly 5 times the rates for the week ending June 26, 2021, for 0- to 17-year-olds and nearly 10 times the rates for children 0-4 years of age. Hospitalization rates were 10.1 times higher for unimmunized adolescents than for fully vaccinated ones (MMWR Morb Mortal Wkly Rep. 2021;70:1255-60).
Multiple elected state leaders have opposed interventions such as mandating masks in school, and our children are paying for it. These leaders have relinquished their responsibility to local school boards. Several have reinforced the no-mask mandate while others have had the courage and insight to ignore state government leaders and have established mask mandates.
How is this lack of enforcement of national recommendations affecting our patients? Let’s look at two neighboring school districts in Texas. School districts have COVID-19 dashboards that are updated daily and accessible to the general public. School District A requires masks for school entry. It serves 196,171 students and has 27,195 teachers and staff. Since school opened in August, 1,606 cumulative cases of COVID-19 in students (0.8%) and 282 in staff (1%) have been reported. Fifty-five percent of the student cases occurred in elementary schools. In contrast, School District B located in the adjacent county serves 64,517 students and has 3,906 teachers and staff with no mask mandate. Since August, there have been 4,506 cumulative COVID-19 cases in students (6.9%) and 578 (14.7%) in staff. Information regarding the specific school type was not provided; however, the dashboard indicates that 2,924 cases (64.8%) occurred in children younger than 11 years of age. County data indicate 62% of those older than 12 years of age were fully vaccinated in District A, compared with 54% of persons older than 12 years in District B. The county COVID-19 positivity rate in District A is 17.6% and in District B it is 20%. Both counties are experiencing increased COVID-19 activity yet have had strikingly different outcomes in the student/staff population. While supporting the case for wearing masks to prevent disease transmission, one can’t ignore the adolescents who were infected and vaccine eligible (District A: 706; District B: 1,582). Their vaccination status could not be determined.
As pediatricians we have played an integral part in the elimination of diseases through educating and administering vaccinations. Adolescents are relatively healthy, thus limiting the number of encounters with them. The majority complete the 11-year visit; however, many fail to return for the 16- to 18-year visit.
So how are we doing? CDC data from 10 U.S. jurisdictions demonstrated a substantial decrease in vaccine administration between March and May of 2020, compared with the same period in 2018 and 2019. A decline was anticipated because of the nationwide lockdown. Doses of HPV administered declined almost 64% and 71% for 9- to 12-year-olds and 13- to 17-year-olds, respectively. Tdap administration declined 66% and 61% for the same respective age groups. Although administered doses increased between June and September of 2020, it was not sufficient to achieve catch-up coverage. Compared to the same period in 2018-2019, administration of the HPV vaccine declined 12.8% and 28% (ages 9-12 and ages 13-17) and for Tdap it was 21% and 30% lower (ages 9-12 and ages 13-17) (MMWR Morb Mortal Wkly Rep. 2021;70:840-5).
Now, we have another adolescent vaccine to discuss and encourage our patients to receive. We also need to address their concerns and/or to at least direct them to a reliable source to obtain accurate information. For the first time, a recommended vaccine may not be available at their medical home. Many don’t know where to go to receive it (http://www.vaccines.gov). Results of a Kaiser Family Foundation COVID-19 survey (August 2021) indicated that parents trusted their pediatricians most often (78%) for vaccine advice. The respondents voiced concern about trusting the location where the child would be immunized and long-term effects especially related to fertility. Parents who received communications regarding the benefits of vaccination were twice as likely to have their adolescents immunized. Finally, remember: Like parent, like child. An immunized parent is more likely to immunize the adolescent. (See Fig. 1.)
It is beyond the scope of this column to discuss the psychosocial aspects of this disease: children experiencing the death of teachers, classmates, family members, and those viewing the vitriol between pro- and antimask proponents often exhibited on school premises. And let’s not forget the child who wants to wear a mask but may be ostracized or bullied for doing so.
Our job is to do our very best to advocate for and to protect our patients by promoting mandatory masks at schools and encouraging vaccination of adolescents as we patiently wait for vaccines to become available for all of our children.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures.
I began thinking of a topic for this column weeks ago determined to discuss anything except COVID-19. Yet, news reports from all sources blasted daily reminders of rising COVID-19 cases overall and specifically in children.
In August, school resumed for many of our patients and the battle over mandating masks for school attendance was in full swing. The fact that it is a Centers for Disease Control and Prevention recommendation supported by both the American Academy of Pediatrics and the Pediatric Infectious Disease Society fell on deaf ears. One day, I heard a report that over 25,000 students attending Texas public schools were diagnosed with COVID-19 between Aug. 23 and Aug. 29. This peak in activity occurred just 2 weeks after the start of school and led to the closure of 45 school districts. Texas does not have a monopoly on these rising cases. Delta, a more contagious variant, began circulating in June 2021 and by July it was the most predominant. Emergency department visits and hospitalizations have increased nationwide. During the latter 2 weeks of August 2021, COVID-19–related ED visits and hospitalizations for persons aged 0-17 years were 3.4 and 3.7 times higher in states with the lowest vaccination coverage, compared with states with high vaccination coverage (MMWR Morb Mortal Wkly Rep. 2021;70:1249-54). Specifically, the rates of hospitalization the week ending Aug. 14, 2021, were nearly 5 times the rates for the week ending June 26, 2021, for 0- to 17-year-olds and nearly 10 times the rates for children 0-4 years of age. Hospitalization rates were 10.1 times higher for unimmunized adolescents than for fully vaccinated ones (MMWR Morb Mortal Wkly Rep. 2021;70:1255-60).
Multiple elected state leaders have opposed interventions such as mandating masks in school, and our children are paying for it. These leaders have relinquished their responsibility to local school boards. Several have reinforced the no-mask mandate while others have had the courage and insight to ignore state government leaders and have established mask mandates.
How is this lack of enforcement of national recommendations affecting our patients? Let’s look at two neighboring school districts in Texas. School districts have COVID-19 dashboards that are updated daily and accessible to the general public. School District A requires masks for school entry. It serves 196,171 students and has 27,195 teachers and staff. Since school opened in August, 1,606 cumulative cases of COVID-19 in students (0.8%) and 282 in staff (1%) have been reported. Fifty-five percent of the student cases occurred in elementary schools. In contrast, School District B located in the adjacent county serves 64,517 students and has 3,906 teachers and staff with no mask mandate. Since August, there have been 4,506 cumulative COVID-19 cases in students (6.9%) and 578 (14.7%) in staff. Information regarding the specific school type was not provided; however, the dashboard indicates that 2,924 cases (64.8%) occurred in children younger than 11 years of age. County data indicate 62% of those older than 12 years of age were fully vaccinated in District A, compared with 54% of persons older than 12 years in District B. The county COVID-19 positivity rate in District A is 17.6% and in District B it is 20%. Both counties are experiencing increased COVID-19 activity yet have had strikingly different outcomes in the student/staff population. While supporting the case for wearing masks to prevent disease transmission, one can’t ignore the adolescents who were infected and vaccine eligible (District A: 706; District B: 1,582). Their vaccination status could not be determined.
As pediatricians we have played an integral part in the elimination of diseases through educating and administering vaccinations. Adolescents are relatively healthy, thus limiting the number of encounters with them. The majority complete the 11-year visit; however, many fail to return for the 16- to 18-year visit.
So how are we doing? CDC data from 10 U.S. jurisdictions demonstrated a substantial decrease in vaccine administration between March and May of 2020, compared with the same period in 2018 and 2019. A decline was anticipated because of the nationwide lockdown. Doses of HPV administered declined almost 64% and 71% for 9- to 12-year-olds and 13- to 17-year-olds, respectively. Tdap administration declined 66% and 61% for the same respective age groups. Although administered doses increased between June and September of 2020, it was not sufficient to achieve catch-up coverage. Compared to the same period in 2018-2019, administration of the HPV vaccine declined 12.8% and 28% (ages 9-12 and ages 13-17) and for Tdap it was 21% and 30% lower (ages 9-12 and ages 13-17) (MMWR Morb Mortal Wkly Rep. 2021;70:840-5).
Now, we have another adolescent vaccine to discuss and encourage our patients to receive. We also need to address their concerns and/or to at least direct them to a reliable source to obtain accurate information. For the first time, a recommended vaccine may not be available at their medical home. Many don’t know where to go to receive it (http://www.vaccines.gov). Results of a Kaiser Family Foundation COVID-19 survey (August 2021) indicated that parents trusted their pediatricians most often (78%) for vaccine advice. The respondents voiced concern about trusting the location where the child would be immunized and long-term effects especially related to fertility. Parents who received communications regarding the benefits of vaccination were twice as likely to have their adolescents immunized. Finally, remember: Like parent, like child. An immunized parent is more likely to immunize the adolescent. (See Fig. 1.)
It is beyond the scope of this column to discuss the psychosocial aspects of this disease: children experiencing the death of teachers, classmates, family members, and those viewing the vitriol between pro- and antimask proponents often exhibited on school premises. And let’s not forget the child who wants to wear a mask but may be ostracized or bullied for doing so.
Our job is to do our very best to advocate for and to protect our patients by promoting mandatory masks at schools and encouraging vaccination of adolescents as we patiently wait for vaccines to become available for all of our children.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures.
Universal masking is the key to safe school attendance
“I want my child to go back to school,” the mother said to me. “I just want you to tell me it will be safe.”
As the summer break winds down for children across the United States, pediatric COVID-19 cases are rising. According to the American Academy of Pediatrics, nearly 94,000 cases were reported for the week ending Aug. 5, more than double the case count from 2 weeks earlier.1
Anecdotally, some children’s hospitals are reporting an increase in pediatric COVID-19 admissions. In the hospital in which I practice, we are seeing numbers similar to those we saw in December and January: a typical daily census of 10 kids admitted with COVID-19, with 4 of them in the intensive care unit. It is a stark contrast to June when, most days, we had no patients with COVID-19 in the hospital. About half of our hospitalized patients are too young to be vaccinated against COVID-19, while the rest are unvaccinated children 12 years and older.
Vaccination of eligible children and teachers is an essential strategy for preventing the spread of COVID-19 in schools, but as children head back to school, immunization rates of educators are largely unknown and are suboptimal among students in most states. As of Aug. 11, 10.7 million U.S. children had received at least one dose of COVID-19 vaccine, representing 43% of 12- to 15-year-olds and 53% of 16- to 17-year-olds.2 Rates vary substantially by state, with more than 70% of kids in Vermont receiving at least one dose of vaccine, compared with less than 25% in Wyoming and Alabama.
Still, in the absence of robust immunization rates, we have data that schools can still reopen successfully. We need to follow the science and implement universal masking, a safe, effective, and practical mitigation strategy.
It worked in Wisconsin. Seventeen K-12 schools in rural Wisconsin opened last fall for in-person instruction.3 Reported compliance with masking was high, ranging from 92.1% to 97.4%, and in-school transmission of COVID-19 was low, with seven cases among 4,876 students.
It worked in Salt Lake City.4 In 20 elementary schools open for in-person instruction Dec. 3, 2020, to Jan. 31, 2021, compliance with mask-wearing was high and in-school transmission was very low, despite a high community incidence of COVID-19. Notably, students’ classroom seats were less than 6 feet apart, suggesting that consistent mask-wearing works even when physical distancing is challenging.
One of the best examples of successful school reopening happened in North Carolina, where pediatricians, pediatric infectious disease specialists, and other experts affiliated with Duke University formed the ABC Science Collaborative to support school districts that requested scientific input to help guide return-to-school policies during the COVID-19 pandemic. From Oct. 26, 2020, to Feb. 28, 2021, the ABC Science Collaborative worked with 13 school districts that were open for in-person instruction using basic mitigation strategies, including universal masking.5 During this time period, there were 4,969 community-acquired SARS-CoV-2 infections in the more than 100,000 students and staff present in schools. Transmission to school contacts was identified in only 209 individuals for a secondary attack rate of less than 1%.
Duke investigator Kanecia Zimmerman, MD, told Duke Today, “We know that, if our goal is to reduce transmission of COVID-19 in schools, there are two effective ways to do that: 1. vaccination, 2. masking. In the setting of schools ... the science suggests masking can be extremely effective, particularly for those who can’t get vaccinated while COVID-19 is still circulating.”
Both the AAP6 and the Pediatric Infectious Diseases Society7 have emphasized the importance of in-person instruction and endorsed universal masking in school. Mask-optional policies or “mask-if-you-are-unvaccinated” policies don’t work, as we have seen in society at large. They are likely to be especially challenging in school settings. Given an option, many, if not most kids, will take off their masks. Kids who leave them on run the risk of stigmatization or bullying.
On Aug. 4, the Centers for Disease Control and Prevention updated its guidance to recommend universal indoor masking for all students, staff, teachers, and visitors to K-12 schools, regardless of vaccination status. Now we’ll have to wait and see if school districts, elected officials, and parents will get on board with masks. ... and we’ll be left to count the number of rising COVID-19 cases that occur until they do.
Case in point: Kids in Greater Clark County, Ind., headed back to school on July 28. Masks were not required on school property, although unvaccinated students and teachers were “strongly encouraged” to wear them.8
Over the first 8 days of in-person instruction, schools in Greater Clark County identified 70 cases of COVID-19 in students and quarantined more than 1,100 of the district’s 10,300 students. Only the unvaccinated were required to quarantine. The district began requiring masks in all school buildings on Aug. 9.9
The worried mother had one last question for me. “What’s the best mask for a child to wear?” For most kids, a simple, well-fitting cloth mask is fine. The best mask is ultimately the mask a child will wear. A toolkit with practical tips for helping children successfully wear a mask is available on the ABC Science Collaborative website.
Dr. Bryant, president of the Pediatric Infectious Diseases Society, is a pediatrician at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].
References
1. American Academy of Pediatrics. “Children and COVID-19: State-level data report.”
2. American Academy of Pediatrics. “Children and COVID-19 vaccination trends.”
3. Falk A et al. MMWR Morb Mortal Wkly Rep. 2021;70:136-40.
4. Hershow RB et al. MMWR Morb Mortal Wkly Rep 2021;70:442-8.
5. Zimmerman KO et al. Pediatrics. 2021 Jul;e2021052686. doi: 10.1542/peds.2021-052686.
6. American Academy of Pediatrics. “American Academy of Pediatrics updates recommendations for opening schools in fall 2021.”
7. Pediatric Infectious Diseases Society. “PIDS supports universal masking for students, school staff.”
8. Courtney Hayden. WHAS11. “Greater Clark County Schools return to class July 28.”
9. Dustin Vogt. WAVE3 News. “Greater Clark Country Schools to require masks amid 70 positive cases.”
“I want my child to go back to school,” the mother said to me. “I just want you to tell me it will be safe.”
As the summer break winds down for children across the United States, pediatric COVID-19 cases are rising. According to the American Academy of Pediatrics, nearly 94,000 cases were reported for the week ending Aug. 5, more than double the case count from 2 weeks earlier.1
Anecdotally, some children’s hospitals are reporting an increase in pediatric COVID-19 admissions. In the hospital in which I practice, we are seeing numbers similar to those we saw in December and January: a typical daily census of 10 kids admitted with COVID-19, with 4 of them in the intensive care unit. It is a stark contrast to June when, most days, we had no patients with COVID-19 in the hospital. About half of our hospitalized patients are too young to be vaccinated against COVID-19, while the rest are unvaccinated children 12 years and older.
Vaccination of eligible children and teachers is an essential strategy for preventing the spread of COVID-19 in schools, but as children head back to school, immunization rates of educators are largely unknown and are suboptimal among students in most states. As of Aug. 11, 10.7 million U.S. children had received at least one dose of COVID-19 vaccine, representing 43% of 12- to 15-year-olds and 53% of 16- to 17-year-olds.2 Rates vary substantially by state, with more than 70% of kids in Vermont receiving at least one dose of vaccine, compared with less than 25% in Wyoming and Alabama.
Still, in the absence of robust immunization rates, we have data that schools can still reopen successfully. We need to follow the science and implement universal masking, a safe, effective, and practical mitigation strategy.
It worked in Wisconsin. Seventeen K-12 schools in rural Wisconsin opened last fall for in-person instruction.3 Reported compliance with masking was high, ranging from 92.1% to 97.4%, and in-school transmission of COVID-19 was low, with seven cases among 4,876 students.
It worked in Salt Lake City.4 In 20 elementary schools open for in-person instruction Dec. 3, 2020, to Jan. 31, 2021, compliance with mask-wearing was high and in-school transmission was very low, despite a high community incidence of COVID-19. Notably, students’ classroom seats were less than 6 feet apart, suggesting that consistent mask-wearing works even when physical distancing is challenging.
One of the best examples of successful school reopening happened in North Carolina, where pediatricians, pediatric infectious disease specialists, and other experts affiliated with Duke University formed the ABC Science Collaborative to support school districts that requested scientific input to help guide return-to-school policies during the COVID-19 pandemic. From Oct. 26, 2020, to Feb. 28, 2021, the ABC Science Collaborative worked with 13 school districts that were open for in-person instruction using basic mitigation strategies, including universal masking.5 During this time period, there were 4,969 community-acquired SARS-CoV-2 infections in the more than 100,000 students and staff present in schools. Transmission to school contacts was identified in only 209 individuals for a secondary attack rate of less than 1%.
Duke investigator Kanecia Zimmerman, MD, told Duke Today, “We know that, if our goal is to reduce transmission of COVID-19 in schools, there are two effective ways to do that: 1. vaccination, 2. masking. In the setting of schools ... the science suggests masking can be extremely effective, particularly for those who can’t get vaccinated while COVID-19 is still circulating.”
Both the AAP6 and the Pediatric Infectious Diseases Society7 have emphasized the importance of in-person instruction and endorsed universal masking in school. Mask-optional policies or “mask-if-you-are-unvaccinated” policies don’t work, as we have seen in society at large. They are likely to be especially challenging in school settings. Given an option, many, if not most kids, will take off their masks. Kids who leave them on run the risk of stigmatization or bullying.
On Aug. 4, the Centers for Disease Control and Prevention updated its guidance to recommend universal indoor masking for all students, staff, teachers, and visitors to K-12 schools, regardless of vaccination status. Now we’ll have to wait and see if school districts, elected officials, and parents will get on board with masks. ... and we’ll be left to count the number of rising COVID-19 cases that occur until they do.
Case in point: Kids in Greater Clark County, Ind., headed back to school on July 28. Masks were not required on school property, although unvaccinated students and teachers were “strongly encouraged” to wear them.8
Over the first 8 days of in-person instruction, schools in Greater Clark County identified 70 cases of COVID-19 in students and quarantined more than 1,100 of the district’s 10,300 students. Only the unvaccinated were required to quarantine. The district began requiring masks in all school buildings on Aug. 9.9
The worried mother had one last question for me. “What’s the best mask for a child to wear?” For most kids, a simple, well-fitting cloth mask is fine. The best mask is ultimately the mask a child will wear. A toolkit with practical tips for helping children successfully wear a mask is available on the ABC Science Collaborative website.
Dr. Bryant, president of the Pediatric Infectious Diseases Society, is a pediatrician at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].
References
1. American Academy of Pediatrics. “Children and COVID-19: State-level data report.”
2. American Academy of Pediatrics. “Children and COVID-19 vaccination trends.”
3. Falk A et al. MMWR Morb Mortal Wkly Rep. 2021;70:136-40.
4. Hershow RB et al. MMWR Morb Mortal Wkly Rep 2021;70:442-8.
5. Zimmerman KO et al. Pediatrics. 2021 Jul;e2021052686. doi: 10.1542/peds.2021-052686.
6. American Academy of Pediatrics. “American Academy of Pediatrics updates recommendations for opening schools in fall 2021.”
7. Pediatric Infectious Diseases Society. “PIDS supports universal masking for students, school staff.”
8. Courtney Hayden. WHAS11. “Greater Clark County Schools return to class July 28.”
9. Dustin Vogt. WAVE3 News. “Greater Clark Country Schools to require masks amid 70 positive cases.”
“I want my child to go back to school,” the mother said to me. “I just want you to tell me it will be safe.”
As the summer break winds down for children across the United States, pediatric COVID-19 cases are rising. According to the American Academy of Pediatrics, nearly 94,000 cases were reported for the week ending Aug. 5, more than double the case count from 2 weeks earlier.1
Anecdotally, some children’s hospitals are reporting an increase in pediatric COVID-19 admissions. In the hospital in which I practice, we are seeing numbers similar to those we saw in December and January: a typical daily census of 10 kids admitted with COVID-19, with 4 of them in the intensive care unit. It is a stark contrast to June when, most days, we had no patients with COVID-19 in the hospital. About half of our hospitalized patients are too young to be vaccinated against COVID-19, while the rest are unvaccinated children 12 years and older.
Vaccination of eligible children and teachers is an essential strategy for preventing the spread of COVID-19 in schools, but as children head back to school, immunization rates of educators are largely unknown and are suboptimal among students in most states. As of Aug. 11, 10.7 million U.S. children had received at least one dose of COVID-19 vaccine, representing 43% of 12- to 15-year-olds and 53% of 16- to 17-year-olds.2 Rates vary substantially by state, with more than 70% of kids in Vermont receiving at least one dose of vaccine, compared with less than 25% in Wyoming and Alabama.
Still, in the absence of robust immunization rates, we have data that schools can still reopen successfully. We need to follow the science and implement universal masking, a safe, effective, and practical mitigation strategy.
It worked in Wisconsin. Seventeen K-12 schools in rural Wisconsin opened last fall for in-person instruction.3 Reported compliance with masking was high, ranging from 92.1% to 97.4%, and in-school transmission of COVID-19 was low, with seven cases among 4,876 students.
It worked in Salt Lake City.4 In 20 elementary schools open for in-person instruction Dec. 3, 2020, to Jan. 31, 2021, compliance with mask-wearing was high and in-school transmission was very low, despite a high community incidence of COVID-19. Notably, students’ classroom seats were less than 6 feet apart, suggesting that consistent mask-wearing works even when physical distancing is challenging.
One of the best examples of successful school reopening happened in North Carolina, where pediatricians, pediatric infectious disease specialists, and other experts affiliated with Duke University formed the ABC Science Collaborative to support school districts that requested scientific input to help guide return-to-school policies during the COVID-19 pandemic. From Oct. 26, 2020, to Feb. 28, 2021, the ABC Science Collaborative worked with 13 school districts that were open for in-person instruction using basic mitigation strategies, including universal masking.5 During this time period, there were 4,969 community-acquired SARS-CoV-2 infections in the more than 100,000 students and staff present in schools. Transmission to school contacts was identified in only 209 individuals for a secondary attack rate of less than 1%.
Duke investigator Kanecia Zimmerman, MD, told Duke Today, “We know that, if our goal is to reduce transmission of COVID-19 in schools, there are two effective ways to do that: 1. vaccination, 2. masking. In the setting of schools ... the science suggests masking can be extremely effective, particularly for those who can’t get vaccinated while COVID-19 is still circulating.”
Both the AAP6 and the Pediatric Infectious Diseases Society7 have emphasized the importance of in-person instruction and endorsed universal masking in school. Mask-optional policies or “mask-if-you-are-unvaccinated” policies don’t work, as we have seen in society at large. They are likely to be especially challenging in school settings. Given an option, many, if not most kids, will take off their masks. Kids who leave them on run the risk of stigmatization or bullying.
On Aug. 4, the Centers for Disease Control and Prevention updated its guidance to recommend universal indoor masking for all students, staff, teachers, and visitors to K-12 schools, regardless of vaccination status. Now we’ll have to wait and see if school districts, elected officials, and parents will get on board with masks. ... and we’ll be left to count the number of rising COVID-19 cases that occur until they do.
Case in point: Kids in Greater Clark County, Ind., headed back to school on July 28. Masks were not required on school property, although unvaccinated students and teachers were “strongly encouraged” to wear them.8
Over the first 8 days of in-person instruction, schools in Greater Clark County identified 70 cases of COVID-19 in students and quarantined more than 1,100 of the district’s 10,300 students. Only the unvaccinated were required to quarantine. The district began requiring masks in all school buildings on Aug. 9.9
The worried mother had one last question for me. “What’s the best mask for a child to wear?” For most kids, a simple, well-fitting cloth mask is fine. The best mask is ultimately the mask a child will wear. A toolkit with practical tips for helping children successfully wear a mask is available on the ABC Science Collaborative website.
Dr. Bryant, president of the Pediatric Infectious Diseases Society, is a pediatrician at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].
References
1. American Academy of Pediatrics. “Children and COVID-19: State-level data report.”
2. American Academy of Pediatrics. “Children and COVID-19 vaccination trends.”
3. Falk A et al. MMWR Morb Mortal Wkly Rep. 2021;70:136-40.
4. Hershow RB et al. MMWR Morb Mortal Wkly Rep 2021;70:442-8.
5. Zimmerman KO et al. Pediatrics. 2021 Jul;e2021052686. doi: 10.1542/peds.2021-052686.
6. American Academy of Pediatrics. “American Academy of Pediatrics updates recommendations for opening schools in fall 2021.”
7. Pediatric Infectious Diseases Society. “PIDS supports universal masking for students, school staff.”
8. Courtney Hayden. WHAS11. “Greater Clark County Schools return to class July 28.”
9. Dustin Vogt. WAVE3 News. “Greater Clark Country Schools to require masks amid 70 positive cases.”
Respiratory infection– and asthma-prone children
Some children are more susceptible to viral and bacterial respiratory infections in the first few years of life than others. However, the factors contributing to this susceptibility are incompletely understood. The pathogenesis, development, severity, and clinical outcomes of respiratory infections are largely dependent on the resident composition of the nasopharyngeal microbiome and immune defense.1
Respiratory infections caused by bacteria and/or viruses are a leading cause of death in children in the United States and worldwide. The well-recognized, predominant causative bacteria are Streptococcus pneumoniae (pneumococcus), nontypeable Haemophilus influenzae (Hflu), and Moraxella catarrhalis (Mcat). Respiratory infections caused by these pathogens result in considerable morbidity, mortality, and account for high health care costs. The clinical and laboratory group that I lead in Rochester, N.Y., has been studying acute otitis media (AOM) etiology, epidemiology, pathogenesis, prevention, and treatment for over 3 decades. Our research findings are likely applicable and generalizable to understanding the pathogenesis and immune response to other infectious diseases induced by pneumococcus, Hflu, and Mcat since they are also key pathogens causing sinusitis and lung infections.
Previous immunologic analysis of children with AOM by our group provided clarity in differences between infection-prone children manifest as otitis prone (OP; often referred to in our publications as stringently defined OP because of the stringent diagnostic requirement of tympanocentesis-proven etiology of infection) and non-OP children. We showed that about 90% of OP children have deficient immune responses following nasopharyngeal colonization and AOM, demonstrated by inadequate innate responses and adaptive immune responses.2 Many of these children also showed an increased propensity to viral upper respiratory infection and 30% fail to produce protective antibody responses after injection of routine pediatric vaccines.3,4
In this column, I want to share new information regarding differences in the nasopharyngeal microbiome of children who are respiratory infection prone versus those who are non–respiratory infection prone and children with asthma versus those who do not exhibit that clinical phenotype. We performed a retrospective analysis of clinical samples collected from 358 children, aged 6 months to 5 years, from our prospectively enrolled cohort in Rochester, N.Y., to determine associations between AOM and other childhood respiratory illnesses and nasopharyngeal microbiota. In order to define subgroups of children within the cohort, we used a statistical method called unsupervised clustering analysis to see if relatively unique groups of children could be discerned. The overall cohort successfully clustered into two groups, showing marked differences in the prevalence of respiratory infections and asthma.5 We termed the two clinical phenotypes infection and asthma prone (n = 99, 28% of the children) and non–infection and asthma prone (n = 259, 72% of the children). Infection- and asthma-prone children were significantly more likely to experience recurrent AOM, influenza, sinusitis, pneumonia, asthma, and allergic rhinitis, compared with non–infection- and asthma-prone children (Figure).
The two groups did not experience significantly different rates of eczema, food allergy, skin infections, urinary tract infections, or acute gastroenteritis, suggesting a common thread involving the respiratory tract that did not cross over to the gastrointestinal, skin, or urinary tract. We found that age at first nasopharyngeal colonization with any of the three bacterial respiratory pathogens (pneumococcus, Hflu, or Mcat) was significantly associated with the respiratory infection– and asthma-prone clinical phenotype. Specifically, respiratory infection– and asthma-prone children experienced colonization at a significantly earlier age than nonprone children did for all three bacteria. In an analysis of individual conditions, early Mcat colonization significantly associated with pneumonia, sinusitis, and asthma susceptibility; Hflu with pneumonia, sinusitis, influenza, and allergic rhinitis; and pneumococcus with sinusitis.
Since early colonization with the three bacterial respiratory pathogens was strongly associated with respiratory illnesses and asthma, nasopharyngeal microbiome analysis was performed on an available subset of samples. Bacterial diversity trended lower in infection- and asthma-prone children, consistent with dysbiosis in the respiratory infection– and asthma-prone clinical phenotype. Nine different bacteria genera were found to be differentially abundant when comparing respiratory infection– and asthma-prone and nonprone children, pointing the way to possible interventions to make the respiratory infection– and asthma-prone child nasopharyngeal microbiome more like the nonprone child.
As I have written previously in this column, recent accumulating data have shed light on the importance of the human microbiome in modulating immune homeostasis and disease susceptibility.6 My group is working toward generating new knowledge for the long-term goal of identifying new therapeutic strategies to facilitate a protective, diverse nasopharyngeal microbiome (with appropriately tuned intranasal probiotics) to prevent respiratory pathogen colonization and/or subsequent progression to respiratory infection and asthma. Also, vaccines directed against colonization-enhancing members of the microbiome may provide a means to indirectly control respiratory pathogen nasopharyngeal colonization.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He has no conflicts to declare. Contact him at [email protected]
References
1. Man WH et al. Nat Rev Microbiol. 2017;15(5):259-70.
2. Pichichero ME. J Infect. 2020;80(6):614-22.
3. Ren D et al. Clin Infect Dis. 2019;68(9):1566-74.
4. Pichichero ME et al. Pediatr Infect Dis J. 2013;32(11):1163-8.
5. Chapman T et al. PLoS One. 2020 Dec 11;15(12).
6. Blaser MJ. The microbiome revolution. J Clin Invest. 2014;124:4162-5.
Some children are more susceptible to viral and bacterial respiratory infections in the first few years of life than others. However, the factors contributing to this susceptibility are incompletely understood. The pathogenesis, development, severity, and clinical outcomes of respiratory infections are largely dependent on the resident composition of the nasopharyngeal microbiome and immune defense.1
Respiratory infections caused by bacteria and/or viruses are a leading cause of death in children in the United States and worldwide. The well-recognized, predominant causative bacteria are Streptococcus pneumoniae (pneumococcus), nontypeable Haemophilus influenzae (Hflu), and Moraxella catarrhalis (Mcat). Respiratory infections caused by these pathogens result in considerable morbidity, mortality, and account for high health care costs. The clinical and laboratory group that I lead in Rochester, N.Y., has been studying acute otitis media (AOM) etiology, epidemiology, pathogenesis, prevention, and treatment for over 3 decades. Our research findings are likely applicable and generalizable to understanding the pathogenesis and immune response to other infectious diseases induced by pneumococcus, Hflu, and Mcat since they are also key pathogens causing sinusitis and lung infections.
Previous immunologic analysis of children with AOM by our group provided clarity in differences between infection-prone children manifest as otitis prone (OP; often referred to in our publications as stringently defined OP because of the stringent diagnostic requirement of tympanocentesis-proven etiology of infection) and non-OP children. We showed that about 90% of OP children have deficient immune responses following nasopharyngeal colonization and AOM, demonstrated by inadequate innate responses and adaptive immune responses.2 Many of these children also showed an increased propensity to viral upper respiratory infection and 30% fail to produce protective antibody responses after injection of routine pediatric vaccines.3,4
In this column, I want to share new information regarding differences in the nasopharyngeal microbiome of children who are respiratory infection prone versus those who are non–respiratory infection prone and children with asthma versus those who do not exhibit that clinical phenotype. We performed a retrospective analysis of clinical samples collected from 358 children, aged 6 months to 5 years, from our prospectively enrolled cohort in Rochester, N.Y., to determine associations between AOM and other childhood respiratory illnesses and nasopharyngeal microbiota. In order to define subgroups of children within the cohort, we used a statistical method called unsupervised clustering analysis to see if relatively unique groups of children could be discerned. The overall cohort successfully clustered into two groups, showing marked differences in the prevalence of respiratory infections and asthma.5 We termed the two clinical phenotypes infection and asthma prone (n = 99, 28% of the children) and non–infection and asthma prone (n = 259, 72% of the children). Infection- and asthma-prone children were significantly more likely to experience recurrent AOM, influenza, sinusitis, pneumonia, asthma, and allergic rhinitis, compared with non–infection- and asthma-prone children (Figure).
The two groups did not experience significantly different rates of eczema, food allergy, skin infections, urinary tract infections, or acute gastroenteritis, suggesting a common thread involving the respiratory tract that did not cross over to the gastrointestinal, skin, or urinary tract. We found that age at first nasopharyngeal colonization with any of the three bacterial respiratory pathogens (pneumococcus, Hflu, or Mcat) was significantly associated with the respiratory infection– and asthma-prone clinical phenotype. Specifically, respiratory infection– and asthma-prone children experienced colonization at a significantly earlier age than nonprone children did for all three bacteria. In an analysis of individual conditions, early Mcat colonization significantly associated with pneumonia, sinusitis, and asthma susceptibility; Hflu with pneumonia, sinusitis, influenza, and allergic rhinitis; and pneumococcus with sinusitis.
Since early colonization with the three bacterial respiratory pathogens was strongly associated with respiratory illnesses and asthma, nasopharyngeal microbiome analysis was performed on an available subset of samples. Bacterial diversity trended lower in infection- and asthma-prone children, consistent with dysbiosis in the respiratory infection– and asthma-prone clinical phenotype. Nine different bacteria genera were found to be differentially abundant when comparing respiratory infection– and asthma-prone and nonprone children, pointing the way to possible interventions to make the respiratory infection– and asthma-prone child nasopharyngeal microbiome more like the nonprone child.
As I have written previously in this column, recent accumulating data have shed light on the importance of the human microbiome in modulating immune homeostasis and disease susceptibility.6 My group is working toward generating new knowledge for the long-term goal of identifying new therapeutic strategies to facilitate a protective, diverse nasopharyngeal microbiome (with appropriately tuned intranasal probiotics) to prevent respiratory pathogen colonization and/or subsequent progression to respiratory infection and asthma. Also, vaccines directed against colonization-enhancing members of the microbiome may provide a means to indirectly control respiratory pathogen nasopharyngeal colonization.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He has no conflicts to declare. Contact him at [email protected]
References
1. Man WH et al. Nat Rev Microbiol. 2017;15(5):259-70.
2. Pichichero ME. J Infect. 2020;80(6):614-22.
3. Ren D et al. Clin Infect Dis. 2019;68(9):1566-74.
4. Pichichero ME et al. Pediatr Infect Dis J. 2013;32(11):1163-8.
5. Chapman T et al. PLoS One. 2020 Dec 11;15(12).
6. Blaser MJ. The microbiome revolution. J Clin Invest. 2014;124:4162-5.
Some children are more susceptible to viral and bacterial respiratory infections in the first few years of life than others. However, the factors contributing to this susceptibility are incompletely understood. The pathogenesis, development, severity, and clinical outcomes of respiratory infections are largely dependent on the resident composition of the nasopharyngeal microbiome and immune defense.1
Respiratory infections caused by bacteria and/or viruses are a leading cause of death in children in the United States and worldwide. The well-recognized, predominant causative bacteria are Streptococcus pneumoniae (pneumococcus), nontypeable Haemophilus influenzae (Hflu), and Moraxella catarrhalis (Mcat). Respiratory infections caused by these pathogens result in considerable morbidity, mortality, and account for high health care costs. The clinical and laboratory group that I lead in Rochester, N.Y., has been studying acute otitis media (AOM) etiology, epidemiology, pathogenesis, prevention, and treatment for over 3 decades. Our research findings are likely applicable and generalizable to understanding the pathogenesis and immune response to other infectious diseases induced by pneumococcus, Hflu, and Mcat since they are also key pathogens causing sinusitis and lung infections.
Previous immunologic analysis of children with AOM by our group provided clarity in differences between infection-prone children manifest as otitis prone (OP; often referred to in our publications as stringently defined OP because of the stringent diagnostic requirement of tympanocentesis-proven etiology of infection) and non-OP children. We showed that about 90% of OP children have deficient immune responses following nasopharyngeal colonization and AOM, demonstrated by inadequate innate responses and adaptive immune responses.2 Many of these children also showed an increased propensity to viral upper respiratory infection and 30% fail to produce protective antibody responses after injection of routine pediatric vaccines.3,4
In this column, I want to share new information regarding differences in the nasopharyngeal microbiome of children who are respiratory infection prone versus those who are non–respiratory infection prone and children with asthma versus those who do not exhibit that clinical phenotype. We performed a retrospective analysis of clinical samples collected from 358 children, aged 6 months to 5 years, from our prospectively enrolled cohort in Rochester, N.Y., to determine associations between AOM and other childhood respiratory illnesses and nasopharyngeal microbiota. In order to define subgroups of children within the cohort, we used a statistical method called unsupervised clustering analysis to see if relatively unique groups of children could be discerned. The overall cohort successfully clustered into two groups, showing marked differences in the prevalence of respiratory infections and asthma.5 We termed the two clinical phenotypes infection and asthma prone (n = 99, 28% of the children) and non–infection and asthma prone (n = 259, 72% of the children). Infection- and asthma-prone children were significantly more likely to experience recurrent AOM, influenza, sinusitis, pneumonia, asthma, and allergic rhinitis, compared with non–infection- and asthma-prone children (Figure).
The two groups did not experience significantly different rates of eczema, food allergy, skin infections, urinary tract infections, or acute gastroenteritis, suggesting a common thread involving the respiratory tract that did not cross over to the gastrointestinal, skin, or urinary tract. We found that age at first nasopharyngeal colonization with any of the three bacterial respiratory pathogens (pneumococcus, Hflu, or Mcat) was significantly associated with the respiratory infection– and asthma-prone clinical phenotype. Specifically, respiratory infection– and asthma-prone children experienced colonization at a significantly earlier age than nonprone children did for all three bacteria. In an analysis of individual conditions, early Mcat colonization significantly associated with pneumonia, sinusitis, and asthma susceptibility; Hflu with pneumonia, sinusitis, influenza, and allergic rhinitis; and pneumococcus with sinusitis.
Since early colonization with the three bacterial respiratory pathogens was strongly associated with respiratory illnesses and asthma, nasopharyngeal microbiome analysis was performed on an available subset of samples. Bacterial diversity trended lower in infection- and asthma-prone children, consistent with dysbiosis in the respiratory infection– and asthma-prone clinical phenotype. Nine different bacteria genera were found to be differentially abundant when comparing respiratory infection– and asthma-prone and nonprone children, pointing the way to possible interventions to make the respiratory infection– and asthma-prone child nasopharyngeal microbiome more like the nonprone child.
As I have written previously in this column, recent accumulating data have shed light on the importance of the human microbiome in modulating immune homeostasis and disease susceptibility.6 My group is working toward generating new knowledge for the long-term goal of identifying new therapeutic strategies to facilitate a protective, diverse nasopharyngeal microbiome (with appropriately tuned intranasal probiotics) to prevent respiratory pathogen colonization and/or subsequent progression to respiratory infection and asthma. Also, vaccines directed against colonization-enhancing members of the microbiome may provide a means to indirectly control respiratory pathogen nasopharyngeal colonization.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He has no conflicts to declare. Contact him at [email protected]
References
1. Man WH et al. Nat Rev Microbiol. 2017;15(5):259-70.
2. Pichichero ME. J Infect. 2020;80(6):614-22.
3. Ren D et al. Clin Infect Dis. 2019;68(9):1566-74.
4. Pichichero ME et al. Pediatr Infect Dis J. 2013;32(11):1163-8.
5. Chapman T et al. PLoS One. 2020 Dec 11;15(12).
6. Blaser MJ. The microbiome revolution. J Clin Invest. 2014;124:4162-5.
Extensive limb swelling after vaccines – including SARS-CoV-2 vaccine
A 19-month-old boy comes to the office with a large firm erythematous swelling of his anterior left thigh that reaches from just below the inguinal crease to the patella. He got his routine immunizations 2 days prior to this visit including the fourth DTaP dose in his left thigh. Clinicians who care for children and who give routine immunizations occasionally see such an adverse effect following immunization (AEFI). These large local reactions have been described for many decades and occur after many vaccines.
What is extensive limb swelling (ELS)? ELS is defined as erythema/swelling crossing a joint or extending mostly joint to joint. It is a subset of large local AEFIs. ELS is generally firm and often erythematous with varying degrees of pain. ELS is now most frequent after pneumococcal conjugate vaccines (PCV) and DTaP, with a 1%-4% rate after DTaP boosters.1-3 ELS and other large local swelling reactions occur at nearly any age.1 And yet there is still much that is not known about their true pathogenesis. Likewise, there are no accurate predictors of which vaccinees will develop large inflammatory processes at or near the site of immunization.
ELS after standard vaccines
The largest report to date on AEFI of all ages, including ELS, covered 1990-2003.1 Two upfront caveats are: This study evaluated ELS before PCVs were available, and in adults, repeat 23-valent pneumococcal polysaccharide vaccine was the most common cause of ELS in this study, comprising 45% of all adult ELS.
Considering all ages, ELS onset was nearly always greater than 1 hour and was less than 24 hours post vaccine in almost 75% of patients. However, for those aged under 2 years, onset in less than 24 hours was even more frequent (84%). Interestingly, concomitant fever occurred in less than 25% regardless of age. In adults, ELS after tetanus- and diphtheria-containing vaccines occurred mostly in women (75%); whereas for ELS under 8 years of age, males predominated (about 60%). Of note, tetanus- and diphtheria-containing vaccines were the most frequent ELS-inducing vaccines in children, that is, 75% aged under 8 years and 55% for those aged 8-17 years. Focusing on pediatric ELS after DTaP by dose, 33% were after the fourth, 31% after the fifth, 12% after the second, 10% after the first, and 3% after the third dose. In the case above, ELS was after the fourth dose.
Clinicians caring for children know how to manage ELS after DTaP or PCVs. They understand that ELS looks scary and is uncomfortable but is not dangerous and requires no specific treatment. Supportive management, that is, pain reliever, cool compresses, and TLC, are warranted. ELS is not a contraindication to subsequent immunization with the same vaccine. That said, large local reactions or ELS do occur with subsequent doses of that same vaccine at varying rates up to 66% of the time. Management is the same with repeat episodes, and no sequelae are expected. Supportive management only is standard unless one suspects a very rare Arthus reaction. If central necrosis occurs or swelling evolution/resolution is not per expectations, referral to a vaccine expert can sort out if it is an Arthus reaction, in which case, subsequent use of the same vaccine in not recommended.
ELS and SARS-CoV-2 vaccines
With SARS-CoV-2 vaccines now authorized for adolescents and expected in a few months for younger children, large local AEFI reactions related to pediatric SARS-CoV-2 vaccines are expected, given that “COVID arm” is now well described in adults.4 Overall, ELS/large local reactions have been reported more frequently with the Moderna than Pfizer mRNA vaccine.4 In the almost 42% of adults having ELS post first dose, repeat ELS post second dose often appears sooner but also resolves more quickly, with no known sequelae.5
Some biopsies have shown delayed-type hypersensitivity reactions (DTH) (superficial perivascular and perifollicular lymphocytic infiltrates with rare eosinophils and scattered mast cells),6,7 while others show no DTH but these patients have findings of immediate hypersensitivity findings and negative skin testing to the vaccine.8 With regard to sex, Dutch ELS data in White adults reveal 90% occur in females – higher than the 75% female rate after standard vaccines.7 Onset of ELS data show that Pfizer mRNA vaccinees had onset on average at 38 hours (range, <1 hr to 12 days). Boston data mostly in White adults reveal later onset (median, 6 days; range, 2-12 days).4 In contrast, adults of color appear to have later onset (mean, 8 days; range, 4-14 days).9
In addition to the local swelling, patients had concurrent injection-site AEFIs of pain (65%), warmth (63%), and pruritus (26%), plus myalgia (51%), headache (48%), malaise (45%), fatigue (43%), chills (33%), arthralgia (30%), and fever (28%).7
What should we tell families about pediatric ELS before we give SARS-CoV-2 vaccines to children? Clinical pediatric SARS-CoV-2 vaccine trials are smaller “immunologic bridging” studies, not requiring proof of efficacy. So, the precise incidence of pediatric ELS (adult rate is estimated under 1/100,000) may not be known until months after general use. Nevertheless, part of our counseling of families will need to include ELS/large local reactions. Unless new data show otherwise, the spiel that clinicians have developed to counsel about the rare chance of ELS after routine vaccines should also be useful to inform families of the rare chance of ELS post SARS-CoV-2 vaccine.
The bottom line is that the management of pediatric ELS after SARS-CoV-2 vaccines should be the same as after standard vaccines. And remember, whether the reactions are DTH or not, neither immediate local injection-site reactions nor DTH reactions are contraindications to subsequent vaccination unless anaphylaxis or Arthus reaction is suspected.10,11
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. He said he had no relevant financial disclosures. Email him at [email protected].
References
1. Woo EJ and the Vaccine Adverse Event Reporting System Working Group. Clin Infect Dis 2003;37:351-8.
2. Rennels MB et al. Pediatrics 2000;105:e12.
3. Huber BM, Goetschel P. J Pediatr. 2011;158:1033.
4. Blumenthal KG et al. N Engl J Med. 2021;384:1273-7.
5. McMahon DE et al. J Amer Acad Dermatol. 2021;85(1):46-55. 6. Johnston MS et al. JAMA Dermatol. 2021;157(6):716-20 .
7. ELS associated with the administration of Comirnaty®. WHO database Vigilyze (cited 2021 Feb 22). Available from https://vigilyze.who-umc.org/.
8. Baeck M et al. N Engl J Med. 2021 Jun. doi: 10.1056/NEJMc2104751.
9. Samarakoon U et al. N Eng J Med. 2021 Jun 9. doi: 10.1056/NEJMc2108620.
10. Kelso JM et al. J Allergy Clin Immunol. 2012;130:25-43.
11. Zafack JG et al. Pediatrics. 2017;140(3):e20163707.
A 19-month-old boy comes to the office with a large firm erythematous swelling of his anterior left thigh that reaches from just below the inguinal crease to the patella. He got his routine immunizations 2 days prior to this visit including the fourth DTaP dose in his left thigh. Clinicians who care for children and who give routine immunizations occasionally see such an adverse effect following immunization (AEFI). These large local reactions have been described for many decades and occur after many vaccines.
What is extensive limb swelling (ELS)? ELS is defined as erythema/swelling crossing a joint or extending mostly joint to joint. It is a subset of large local AEFIs. ELS is generally firm and often erythematous with varying degrees of pain. ELS is now most frequent after pneumococcal conjugate vaccines (PCV) and DTaP, with a 1%-4% rate after DTaP boosters.1-3 ELS and other large local swelling reactions occur at nearly any age.1 And yet there is still much that is not known about their true pathogenesis. Likewise, there are no accurate predictors of which vaccinees will develop large inflammatory processes at or near the site of immunization.
ELS after standard vaccines
The largest report to date on AEFI of all ages, including ELS, covered 1990-2003.1 Two upfront caveats are: This study evaluated ELS before PCVs were available, and in adults, repeat 23-valent pneumococcal polysaccharide vaccine was the most common cause of ELS in this study, comprising 45% of all adult ELS.
Considering all ages, ELS onset was nearly always greater than 1 hour and was less than 24 hours post vaccine in almost 75% of patients. However, for those aged under 2 years, onset in less than 24 hours was even more frequent (84%). Interestingly, concomitant fever occurred in less than 25% regardless of age. In adults, ELS after tetanus- and diphtheria-containing vaccines occurred mostly in women (75%); whereas for ELS under 8 years of age, males predominated (about 60%). Of note, tetanus- and diphtheria-containing vaccines were the most frequent ELS-inducing vaccines in children, that is, 75% aged under 8 years and 55% for those aged 8-17 years. Focusing on pediatric ELS after DTaP by dose, 33% were after the fourth, 31% after the fifth, 12% after the second, 10% after the first, and 3% after the third dose. In the case above, ELS was after the fourth dose.
Clinicians caring for children know how to manage ELS after DTaP or PCVs. They understand that ELS looks scary and is uncomfortable but is not dangerous and requires no specific treatment. Supportive management, that is, pain reliever, cool compresses, and TLC, are warranted. ELS is not a contraindication to subsequent immunization with the same vaccine. That said, large local reactions or ELS do occur with subsequent doses of that same vaccine at varying rates up to 66% of the time. Management is the same with repeat episodes, and no sequelae are expected. Supportive management only is standard unless one suspects a very rare Arthus reaction. If central necrosis occurs or swelling evolution/resolution is not per expectations, referral to a vaccine expert can sort out if it is an Arthus reaction, in which case, subsequent use of the same vaccine in not recommended.
ELS and SARS-CoV-2 vaccines
With SARS-CoV-2 vaccines now authorized for adolescents and expected in a few months for younger children, large local AEFI reactions related to pediatric SARS-CoV-2 vaccines are expected, given that “COVID arm” is now well described in adults.4 Overall, ELS/large local reactions have been reported more frequently with the Moderna than Pfizer mRNA vaccine.4 In the almost 42% of adults having ELS post first dose, repeat ELS post second dose often appears sooner but also resolves more quickly, with no known sequelae.5
Some biopsies have shown delayed-type hypersensitivity reactions (DTH) (superficial perivascular and perifollicular lymphocytic infiltrates with rare eosinophils and scattered mast cells),6,7 while others show no DTH but these patients have findings of immediate hypersensitivity findings and negative skin testing to the vaccine.8 With regard to sex, Dutch ELS data in White adults reveal 90% occur in females – higher than the 75% female rate after standard vaccines.7 Onset of ELS data show that Pfizer mRNA vaccinees had onset on average at 38 hours (range, <1 hr to 12 days). Boston data mostly in White adults reveal later onset (median, 6 days; range, 2-12 days).4 In contrast, adults of color appear to have later onset (mean, 8 days; range, 4-14 days).9
In addition to the local swelling, patients had concurrent injection-site AEFIs of pain (65%), warmth (63%), and pruritus (26%), plus myalgia (51%), headache (48%), malaise (45%), fatigue (43%), chills (33%), arthralgia (30%), and fever (28%).7
What should we tell families about pediatric ELS before we give SARS-CoV-2 vaccines to children? Clinical pediatric SARS-CoV-2 vaccine trials are smaller “immunologic bridging” studies, not requiring proof of efficacy. So, the precise incidence of pediatric ELS (adult rate is estimated under 1/100,000) may not be known until months after general use. Nevertheless, part of our counseling of families will need to include ELS/large local reactions. Unless new data show otherwise, the spiel that clinicians have developed to counsel about the rare chance of ELS after routine vaccines should also be useful to inform families of the rare chance of ELS post SARS-CoV-2 vaccine.
The bottom line is that the management of pediatric ELS after SARS-CoV-2 vaccines should be the same as after standard vaccines. And remember, whether the reactions are DTH or not, neither immediate local injection-site reactions nor DTH reactions are contraindications to subsequent vaccination unless anaphylaxis or Arthus reaction is suspected.10,11
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. He said he had no relevant financial disclosures. Email him at [email protected].
References
1. Woo EJ and the Vaccine Adverse Event Reporting System Working Group. Clin Infect Dis 2003;37:351-8.
2. Rennels MB et al. Pediatrics 2000;105:e12.
3. Huber BM, Goetschel P. J Pediatr. 2011;158:1033.
4. Blumenthal KG et al. N Engl J Med. 2021;384:1273-7.
5. McMahon DE et al. J Amer Acad Dermatol. 2021;85(1):46-55. 6. Johnston MS et al. JAMA Dermatol. 2021;157(6):716-20 .
7. ELS associated with the administration of Comirnaty®. WHO database Vigilyze (cited 2021 Feb 22). Available from https://vigilyze.who-umc.org/.
8. Baeck M et al. N Engl J Med. 2021 Jun. doi: 10.1056/NEJMc2104751.
9. Samarakoon U et al. N Eng J Med. 2021 Jun 9. doi: 10.1056/NEJMc2108620.
10. Kelso JM et al. J Allergy Clin Immunol. 2012;130:25-43.
11. Zafack JG et al. Pediatrics. 2017;140(3):e20163707.
A 19-month-old boy comes to the office with a large firm erythematous swelling of his anterior left thigh that reaches from just below the inguinal crease to the patella. He got his routine immunizations 2 days prior to this visit including the fourth DTaP dose in his left thigh. Clinicians who care for children and who give routine immunizations occasionally see such an adverse effect following immunization (AEFI). These large local reactions have been described for many decades and occur after many vaccines.
What is extensive limb swelling (ELS)? ELS is defined as erythema/swelling crossing a joint or extending mostly joint to joint. It is a subset of large local AEFIs. ELS is generally firm and often erythematous with varying degrees of pain. ELS is now most frequent after pneumococcal conjugate vaccines (PCV) and DTaP, with a 1%-4% rate after DTaP boosters.1-3 ELS and other large local swelling reactions occur at nearly any age.1 And yet there is still much that is not known about their true pathogenesis. Likewise, there are no accurate predictors of which vaccinees will develop large inflammatory processes at or near the site of immunization.
ELS after standard vaccines
The largest report to date on AEFI of all ages, including ELS, covered 1990-2003.1 Two upfront caveats are: This study evaluated ELS before PCVs were available, and in adults, repeat 23-valent pneumococcal polysaccharide vaccine was the most common cause of ELS in this study, comprising 45% of all adult ELS.
Considering all ages, ELS onset was nearly always greater than 1 hour and was less than 24 hours post vaccine in almost 75% of patients. However, for those aged under 2 years, onset in less than 24 hours was even more frequent (84%). Interestingly, concomitant fever occurred in less than 25% regardless of age. In adults, ELS after tetanus- and diphtheria-containing vaccines occurred mostly in women (75%); whereas for ELS under 8 years of age, males predominated (about 60%). Of note, tetanus- and diphtheria-containing vaccines were the most frequent ELS-inducing vaccines in children, that is, 75% aged under 8 years and 55% for those aged 8-17 years. Focusing on pediatric ELS after DTaP by dose, 33% were after the fourth, 31% after the fifth, 12% after the second, 10% after the first, and 3% after the third dose. In the case above, ELS was after the fourth dose.
Clinicians caring for children know how to manage ELS after DTaP or PCVs. They understand that ELS looks scary and is uncomfortable but is not dangerous and requires no specific treatment. Supportive management, that is, pain reliever, cool compresses, and TLC, are warranted. ELS is not a contraindication to subsequent immunization with the same vaccine. That said, large local reactions or ELS do occur with subsequent doses of that same vaccine at varying rates up to 66% of the time. Management is the same with repeat episodes, and no sequelae are expected. Supportive management only is standard unless one suspects a very rare Arthus reaction. If central necrosis occurs or swelling evolution/resolution is not per expectations, referral to a vaccine expert can sort out if it is an Arthus reaction, in which case, subsequent use of the same vaccine in not recommended.
ELS and SARS-CoV-2 vaccines
With SARS-CoV-2 vaccines now authorized for adolescents and expected in a few months for younger children, large local AEFI reactions related to pediatric SARS-CoV-2 vaccines are expected, given that “COVID arm” is now well described in adults.4 Overall, ELS/large local reactions have been reported more frequently with the Moderna than Pfizer mRNA vaccine.4 In the almost 42% of adults having ELS post first dose, repeat ELS post second dose often appears sooner but also resolves more quickly, with no known sequelae.5
Some biopsies have shown delayed-type hypersensitivity reactions (DTH) (superficial perivascular and perifollicular lymphocytic infiltrates with rare eosinophils and scattered mast cells),6,7 while others show no DTH but these patients have findings of immediate hypersensitivity findings and negative skin testing to the vaccine.8 With regard to sex, Dutch ELS data in White adults reveal 90% occur in females – higher than the 75% female rate after standard vaccines.7 Onset of ELS data show that Pfizer mRNA vaccinees had onset on average at 38 hours (range, <1 hr to 12 days). Boston data mostly in White adults reveal later onset (median, 6 days; range, 2-12 days).4 In contrast, adults of color appear to have later onset (mean, 8 days; range, 4-14 days).9
In addition to the local swelling, patients had concurrent injection-site AEFIs of pain (65%), warmth (63%), and pruritus (26%), plus myalgia (51%), headache (48%), malaise (45%), fatigue (43%), chills (33%), arthralgia (30%), and fever (28%).7
What should we tell families about pediatric ELS before we give SARS-CoV-2 vaccines to children? Clinical pediatric SARS-CoV-2 vaccine trials are smaller “immunologic bridging” studies, not requiring proof of efficacy. So, the precise incidence of pediatric ELS (adult rate is estimated under 1/100,000) may not be known until months after general use. Nevertheless, part of our counseling of families will need to include ELS/large local reactions. Unless new data show otherwise, the spiel that clinicians have developed to counsel about the rare chance of ELS after routine vaccines should also be useful to inform families of the rare chance of ELS post SARS-CoV-2 vaccine.
The bottom line is that the management of pediatric ELS after SARS-CoV-2 vaccines should be the same as after standard vaccines. And remember, whether the reactions are DTH or not, neither immediate local injection-site reactions nor DTH reactions are contraindications to subsequent vaccination unless anaphylaxis or Arthus reaction is suspected.10,11
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. He said he had no relevant financial disclosures. Email him at [email protected].
References
1. Woo EJ and the Vaccine Adverse Event Reporting System Working Group. Clin Infect Dis 2003;37:351-8.
2. Rennels MB et al. Pediatrics 2000;105:e12.
3. Huber BM, Goetschel P. J Pediatr. 2011;158:1033.
4. Blumenthal KG et al. N Engl J Med. 2021;384:1273-7.
5. McMahon DE et al. J Amer Acad Dermatol. 2021;85(1):46-55. 6. Johnston MS et al. JAMA Dermatol. 2021;157(6):716-20 .
7. ELS associated with the administration of Comirnaty®. WHO database Vigilyze (cited 2021 Feb 22). Available from https://vigilyze.who-umc.org/.
8. Baeck M et al. N Engl J Med. 2021 Jun. doi: 10.1056/NEJMc2104751.
9. Samarakoon U et al. N Eng J Med. 2021 Jun 9. doi: 10.1056/NEJMc2108620.
10. Kelso JM et al. J Allergy Clin Immunol. 2012;130:25-43.
11. Zafack JG et al. Pediatrics. 2017;140(3):e20163707.
COVID-19 in children and adolescents: Disease burden and severity
My first thought on this column was maybe Pediatric News has written sufficiently about SARS-CoV-2 infection, and it is time to move on. However, the agenda for the May 12th Advisory Committee on Immunization Practice includes a review of the Pfizer-BioNTech COVID-19 vaccine safety and immunogenicity data for the 12- to 15-year-old age cohort that suggests the potential for vaccine availability and roll out for early adolescents in the near future and the need for up-to-date knowledge about the incidence, severity, and long-term outcome of COVID-19 in the pediatric population.
Updating and summarizing the pediatric experience for the pediatric community on what children and adolescents have experienced because of SARS-CoV-2 infection is critical to address the myriad of questions that will come from colleagues, parents, and adolescents themselves. A great resource, published weekly, is the joint report from the American Academy of Pediatrics and the Children’s Hospital Association.1 As of April 29, 2021, 3,782,724 total child COVID-19 cases have been reported from 49 states, New York City (NYC), the District of Columbia, Guam, and Puerto Rico. Children represent approximately 14% of cases in the United States and not surprisingly are an increasing proportion of total cases as vaccine impact reduces cases among older age groups. Nearly 5% of the pediatric population has already been infected with SARS-CoV-2. Fortunately, compared with adults, hospitalization, severe disease, and mortality remain far lower both in number and proportion than in the adult population. Cumulative hospitalizations from 24 states and NYC total 15,456 (0.8%) among those infected, with 303 deaths reported (from 43 states, NYC, Guam, and Puerto Rico). Case fatality rate approximates 0.01% in the most recent summary of state reports. One of the limitations of this report is that each state decides how to report the age distribution of COVID-19 cases resulting in variation in age range; another is the data are limited to those details individual states chose to make publicly available.
Although children do not commonly develop severe disease, and the case fatality is low, there are still insights to be learned from understanding risk features for severe disease. Preston et al. reviewed discharge data from 869 medical facilities to describe patients 18 years or younger who had an inpatient or emergency department encounter with a primary or secondary COVID-19 discharge diagnosis from March 1 through October 31, 2020.2 They reported that approximately 2,430 (11.7%) children were hospitalized and 746, nearly 31% of those hospitalized, had severe COVID disease. Those at greatest risk for severe disease were children with comorbid conditions and those less than 12 years, compared with the 12- to 18-year age group. They did not identify race as a risk for severe disease in this study. Moreira et al. described risk factors for morbidity and death from COVID in children less than 18 years of age3 using CDC COVID-NET, the Centers for Disease Control and Prevention COVID-19–associated hospitalization surveillance network. They reported a hospitalization rate of 4.7% among 27,045 cases. They identified three risk factors for hospitalization – age, race/ethnicity, and comorbid conditions. Thirty-nine children (0.19%) died; children who were black, non-Hispanic, and those with an underlying medical condition had a significantly increased risk of death. Thirty-three (85%) children who died had a comorbidity, and 27 (69%) were African American or Hispanic/Latino. The U.S. experience in children is also consistent with reports from the United Kingdom, Italy, Spain, Germany, France, and South Korea.4 Deaths from COVID-19 were uncommon but relatively more frequent in older children, compared with younger age groups among children less than 18 years of age in these countries.
Acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) do not predominantly target the neurologic systems; however, neurologic complications have been reported, some of which appear to result in long-lasting disability. LaRovere et al. identified 354 (22%) of 1,695 patients less than 21 years of age with acute COVID or MIS-C who had neurologic signs or symptoms during their illness. Among those with neurologic involvement, most children had prior neurologic deficits, mild symptoms, that resolved by the time of discharge. Forty-three (12%) were considered life threatening and included severe encephalopathy, stroke, central nervous system infection/demyelination, Guillain-Barre syndrome or variant, or acute cerebral edema. Several children, including some who were previously healthy prior to COVID, had persistent neurologic deficits at discharge. In addition to neurologic morbidity, long COVID – a syndrome of persistent symptoms following acute COVID that lasts for more than 12 weeks without alternative diagnosis – has also been described in children. Buonsenso et al. assessed 129 children diagnosed with COVID-19 between March and November 2020 in Rome, Italy.5 Persisting symptoms after 120 days were reported by more than 50%. Symptoms like fatigue, muscle and joint pain, headache, insomnia, respiratory problems, and palpitations were most common. Clearly, further follow-up of the long-term outcomes is necessary to understand the full spectrum of morbidity resulting from COVID-19 disease in children and its natural history.
The current picture of COVID infection in children younger than 18 reinforces that children are part of the pandemic. Although deaths in children have now exceeded 300 cases, severe disease remains uncommon in both the United States and western Europe. Risk factors for severe disease include comorbid illness and race/ethnicity with a disproportionate number of severe cases in children with underlying comorbidity and in African American and Hispanic/Latino children. Ongoing surveillance is critical as changes are likely to be observed over time as viral evolution affects disease burden and characteristics.
Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].
References
1. Children and COVID-19: State-Level Data Report. Services AAP.org.
2. Preston LE et al. JAMA Network Open. 2021;4(4):e215298. doi:10.1001/jamanetworkopen.2021.5298
3. Moreira A et al. Eur J Pediatr. 2021;180:1659-63.
4. SS Bhopal et al. Lancet 2021. doi: 10.1016/ S2352-4642(21)00066-3.
5. Buonsenso D et al. medRxiv preprint. doi: 10.1101/2021.01.23.21250375.
My first thought on this column was maybe Pediatric News has written sufficiently about SARS-CoV-2 infection, and it is time to move on. However, the agenda for the May 12th Advisory Committee on Immunization Practice includes a review of the Pfizer-BioNTech COVID-19 vaccine safety and immunogenicity data for the 12- to 15-year-old age cohort that suggests the potential for vaccine availability and roll out for early adolescents in the near future and the need for up-to-date knowledge about the incidence, severity, and long-term outcome of COVID-19 in the pediatric population.
Updating and summarizing the pediatric experience for the pediatric community on what children and adolescents have experienced because of SARS-CoV-2 infection is critical to address the myriad of questions that will come from colleagues, parents, and adolescents themselves. A great resource, published weekly, is the joint report from the American Academy of Pediatrics and the Children’s Hospital Association.1 As of April 29, 2021, 3,782,724 total child COVID-19 cases have been reported from 49 states, New York City (NYC), the District of Columbia, Guam, and Puerto Rico. Children represent approximately 14% of cases in the United States and not surprisingly are an increasing proportion of total cases as vaccine impact reduces cases among older age groups. Nearly 5% of the pediatric population has already been infected with SARS-CoV-2. Fortunately, compared with adults, hospitalization, severe disease, and mortality remain far lower both in number and proportion than in the adult population. Cumulative hospitalizations from 24 states and NYC total 15,456 (0.8%) among those infected, with 303 deaths reported (from 43 states, NYC, Guam, and Puerto Rico). Case fatality rate approximates 0.01% in the most recent summary of state reports. One of the limitations of this report is that each state decides how to report the age distribution of COVID-19 cases resulting in variation in age range; another is the data are limited to those details individual states chose to make publicly available.
Although children do not commonly develop severe disease, and the case fatality is low, there are still insights to be learned from understanding risk features for severe disease. Preston et al. reviewed discharge data from 869 medical facilities to describe patients 18 years or younger who had an inpatient or emergency department encounter with a primary or secondary COVID-19 discharge diagnosis from March 1 through October 31, 2020.2 They reported that approximately 2,430 (11.7%) children were hospitalized and 746, nearly 31% of those hospitalized, had severe COVID disease. Those at greatest risk for severe disease were children with comorbid conditions and those less than 12 years, compared with the 12- to 18-year age group. They did not identify race as a risk for severe disease in this study. Moreira et al. described risk factors for morbidity and death from COVID in children less than 18 years of age3 using CDC COVID-NET, the Centers for Disease Control and Prevention COVID-19–associated hospitalization surveillance network. They reported a hospitalization rate of 4.7% among 27,045 cases. They identified three risk factors for hospitalization – age, race/ethnicity, and comorbid conditions. Thirty-nine children (0.19%) died; children who were black, non-Hispanic, and those with an underlying medical condition had a significantly increased risk of death. Thirty-three (85%) children who died had a comorbidity, and 27 (69%) were African American or Hispanic/Latino. The U.S. experience in children is also consistent with reports from the United Kingdom, Italy, Spain, Germany, France, and South Korea.4 Deaths from COVID-19 were uncommon but relatively more frequent in older children, compared with younger age groups among children less than 18 years of age in these countries.
Acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) do not predominantly target the neurologic systems; however, neurologic complications have been reported, some of which appear to result in long-lasting disability. LaRovere et al. identified 354 (22%) of 1,695 patients less than 21 years of age with acute COVID or MIS-C who had neurologic signs or symptoms during their illness. Among those with neurologic involvement, most children had prior neurologic deficits, mild symptoms, that resolved by the time of discharge. Forty-three (12%) were considered life threatening and included severe encephalopathy, stroke, central nervous system infection/demyelination, Guillain-Barre syndrome or variant, or acute cerebral edema. Several children, including some who were previously healthy prior to COVID, had persistent neurologic deficits at discharge. In addition to neurologic morbidity, long COVID – a syndrome of persistent symptoms following acute COVID that lasts for more than 12 weeks without alternative diagnosis – has also been described in children. Buonsenso et al. assessed 129 children diagnosed with COVID-19 between March and November 2020 in Rome, Italy.5 Persisting symptoms after 120 days were reported by more than 50%. Symptoms like fatigue, muscle and joint pain, headache, insomnia, respiratory problems, and palpitations were most common. Clearly, further follow-up of the long-term outcomes is necessary to understand the full spectrum of morbidity resulting from COVID-19 disease in children and its natural history.
The current picture of COVID infection in children younger than 18 reinforces that children are part of the pandemic. Although deaths in children have now exceeded 300 cases, severe disease remains uncommon in both the United States and western Europe. Risk factors for severe disease include comorbid illness and race/ethnicity with a disproportionate number of severe cases in children with underlying comorbidity and in African American and Hispanic/Latino children. Ongoing surveillance is critical as changes are likely to be observed over time as viral evolution affects disease burden and characteristics.
Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].
References
1. Children and COVID-19: State-Level Data Report. Services AAP.org.
2. Preston LE et al. JAMA Network Open. 2021;4(4):e215298. doi:10.1001/jamanetworkopen.2021.5298
3. Moreira A et al. Eur J Pediatr. 2021;180:1659-63.
4. SS Bhopal et al. Lancet 2021. doi: 10.1016/ S2352-4642(21)00066-3.
5. Buonsenso D et al. medRxiv preprint. doi: 10.1101/2021.01.23.21250375.
My first thought on this column was maybe Pediatric News has written sufficiently about SARS-CoV-2 infection, and it is time to move on. However, the agenda for the May 12th Advisory Committee on Immunization Practice includes a review of the Pfizer-BioNTech COVID-19 vaccine safety and immunogenicity data for the 12- to 15-year-old age cohort that suggests the potential for vaccine availability and roll out for early adolescents in the near future and the need for up-to-date knowledge about the incidence, severity, and long-term outcome of COVID-19 in the pediatric population.
Updating and summarizing the pediatric experience for the pediatric community on what children and adolescents have experienced because of SARS-CoV-2 infection is critical to address the myriad of questions that will come from colleagues, parents, and adolescents themselves. A great resource, published weekly, is the joint report from the American Academy of Pediatrics and the Children’s Hospital Association.1 As of April 29, 2021, 3,782,724 total child COVID-19 cases have been reported from 49 states, New York City (NYC), the District of Columbia, Guam, and Puerto Rico. Children represent approximately 14% of cases in the United States and not surprisingly are an increasing proportion of total cases as vaccine impact reduces cases among older age groups. Nearly 5% of the pediatric population has already been infected with SARS-CoV-2. Fortunately, compared with adults, hospitalization, severe disease, and mortality remain far lower both in number and proportion than in the adult population. Cumulative hospitalizations from 24 states and NYC total 15,456 (0.8%) among those infected, with 303 deaths reported (from 43 states, NYC, Guam, and Puerto Rico). Case fatality rate approximates 0.01% in the most recent summary of state reports. One of the limitations of this report is that each state decides how to report the age distribution of COVID-19 cases resulting in variation in age range; another is the data are limited to those details individual states chose to make publicly available.
Although children do not commonly develop severe disease, and the case fatality is low, there are still insights to be learned from understanding risk features for severe disease. Preston et al. reviewed discharge data from 869 medical facilities to describe patients 18 years or younger who had an inpatient or emergency department encounter with a primary or secondary COVID-19 discharge diagnosis from March 1 through October 31, 2020.2 They reported that approximately 2,430 (11.7%) children were hospitalized and 746, nearly 31% of those hospitalized, had severe COVID disease. Those at greatest risk for severe disease were children with comorbid conditions and those less than 12 years, compared with the 12- to 18-year age group. They did not identify race as a risk for severe disease in this study. Moreira et al. described risk factors for morbidity and death from COVID in children less than 18 years of age3 using CDC COVID-NET, the Centers for Disease Control and Prevention COVID-19–associated hospitalization surveillance network. They reported a hospitalization rate of 4.7% among 27,045 cases. They identified three risk factors for hospitalization – age, race/ethnicity, and comorbid conditions. Thirty-nine children (0.19%) died; children who were black, non-Hispanic, and those with an underlying medical condition had a significantly increased risk of death. Thirty-three (85%) children who died had a comorbidity, and 27 (69%) were African American or Hispanic/Latino. The U.S. experience in children is also consistent with reports from the United Kingdom, Italy, Spain, Germany, France, and South Korea.4 Deaths from COVID-19 were uncommon but relatively more frequent in older children, compared with younger age groups among children less than 18 years of age in these countries.
Acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) do not predominantly target the neurologic systems; however, neurologic complications have been reported, some of which appear to result in long-lasting disability. LaRovere et al. identified 354 (22%) of 1,695 patients less than 21 years of age with acute COVID or MIS-C who had neurologic signs or symptoms during their illness. Among those with neurologic involvement, most children had prior neurologic deficits, mild symptoms, that resolved by the time of discharge. Forty-three (12%) were considered life threatening and included severe encephalopathy, stroke, central nervous system infection/demyelination, Guillain-Barre syndrome or variant, or acute cerebral edema. Several children, including some who were previously healthy prior to COVID, had persistent neurologic deficits at discharge. In addition to neurologic morbidity, long COVID – a syndrome of persistent symptoms following acute COVID that lasts for more than 12 weeks without alternative diagnosis – has also been described in children. Buonsenso et al. assessed 129 children diagnosed with COVID-19 between March and November 2020 in Rome, Italy.5 Persisting symptoms after 120 days were reported by more than 50%. Symptoms like fatigue, muscle and joint pain, headache, insomnia, respiratory problems, and palpitations were most common. Clearly, further follow-up of the long-term outcomes is necessary to understand the full spectrum of morbidity resulting from COVID-19 disease in children and its natural history.
The current picture of COVID infection in children younger than 18 reinforces that children are part of the pandemic. Although deaths in children have now exceeded 300 cases, severe disease remains uncommon in both the United States and western Europe. Risk factors for severe disease include comorbid illness and race/ethnicity with a disproportionate number of severe cases in children with underlying comorbidity and in African American and Hispanic/Latino children. Ongoing surveillance is critical as changes are likely to be observed over time as viral evolution affects disease burden and characteristics.
Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].
References
1. Children and COVID-19: State-Level Data Report. Services AAP.org.
2. Preston LE et al. JAMA Network Open. 2021;4(4):e215298. doi:10.1001/jamanetworkopen.2021.5298
3. Moreira A et al. Eur J Pediatr. 2021;180:1659-63.
4. SS Bhopal et al. Lancet 2021. doi: 10.1016/ S2352-4642(21)00066-3.
5. Buonsenso D et al. medRxiv preprint. doi: 10.1101/2021.01.23.21250375.