Rana F. Hamdy is a member of the editorial advisory board of 

. She is also an Assistant Professor of Pediatrics, George Washington University School of Medicine and Health Sciences; Pediatric Infectious Diseases Attending, Director, Antimicrobial Stewardship Program, Associate Fellowship Program Director, Children’s National Hospital, Washington, DC

Rana F. Hamdy, MD

Since March 2021, when it was first encountered in the United States, the B.1.617.2 (Delta) variant of SARS-CoV-2 has spread rapidly; as of November, Delta represents the predominant strain causing COVID-19 in the United States.

 How does this variant differ from others, and how does it affect pediatric patients? The following answers provide a round- up of the currently available information on this strain of the virus.

What is the COVID-19 Delta variant? How did it become the predominant variant in the United States?

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, is an RNA virus. This type of virus is prone to mutation, especially when it infects a large number of individuals. As we all know, mutations are errors that occur during the process of viral replication: The more opportunities a virus has to replicate, the more chances it has to mutate.

 This is not a unique feature of COVID-19; it also occurs with other viruses, such as the influenza virus.

Mutations happen at random, and most have no effect on viral function. Some may even cause the virus to weaken and become less contagious. However, a mutation that confers the ability to be more transmissible can rapidly take over and become the dominant form among susceptible hosts. The Delta variant has multiple mutations, which are thought to make this variant more transmissible and prone to avoid the human immune system.

How does the epidemiology of the Delta variant differ from that of prior strains of SARS-CoV-2?

After the introduction of the vaccines, incidence of COVID-19 in the United States steadily decreased among all age groups. In children, the weekly Average incidence rates in early June 2021, the lowest of the year, were 1.7, 1.9, and 2.9 per 100,000 persons for 0 to 4, 5 to 11, and 12 to 17 years, respectively. As the Delta variant rose to dominance in July 2021, a rapid incidence increase was observed, reaching rates as high as 16.2, 28.5, and 32.7 per 100,000 persons for the 3 respective age groups by August 2021.

 Other factors that could have contributed to this peak include relaxation of masking mandates and physical distancing, as well as school openings.

Is the COVID-19 Delta variant more transmissible in children? How about in vaccinated children?

The Delta variant is more than twice as transmissible as the original COVID-19 strain and 40% to 60% more than the Alpha variant.

 Unvaccinated individuals of all ages are at increased risk of contracting the Delta variant.

Vaccinated individuals can become infected with COVID-19. Also known as breakthrough infections, these cases have been more frequently observed since the Delta variant surge. Because these individuals are contagious, it is important to follow isolation precautions.

 Thankfully, vaccination effectively reduces the overall risk of infection with COVID-19 by 6-fold.

Does the Delta variant cause more severe disease in children?

The increase in transmissibility and rising number of hospitalizations led to the concern that children were getting sicker. To determine if higher rates of severe disease were observed, a Coronavirus Disease 2019-Associated Hospitalization Surveillance Network team looked at pediatric hospitalization data before (March 1, 2020, to June 19, 2021) and after (June 20 to July 31, 2021) Delta became the predominant strain. The authors found no significant difference in intensive care admission, highest level of respiratory support, or mortality between the 2 periods.

 These data provide reassurance that although the Delta variant led to a larger number of infected children, the severity of disease is not greater compared with that of other variants. Data need to be further updated with subsequent reports including the latest surveillance information to determine other important potential complications in children, such as the incidence of multisystem inflammatory syndrome in children or persistent post–COVID-19 symptoms, better known as “long COVID.”

How can we protect children from the Delta variant?

Vaccination is effective in preventing COVID-19 infection, especially the more severe manifestations. With the Delta variant, new cases of infection were observed in both vaccinated and unvaccinated individuals. Findings published in the 

 showed that one of the current available vaccines (BNT162b2; Pfizer/BioNTech) has slightly lower effectiveness against the Delta variant compared with the Alpha variant (88% vs 93.7%, respectively).

 A subsequent report by the Centers for Disease Control and Prevention (CDC) stated that the Moderna vaccine’s efficacy was 92% in adults during the Delta variant surge.

 Findings of a study evaluating the trends in COVID-19–related emergency department (ED) visits and hospitalizations since the Delta variant surge showed that ED visits and hospitalizations were more than 3 times higher in US states with the lowest vaccination coverage (< 50%) compared with those with the highest coverage (> 70%). This effect was seen even in children younger than 12 years, showing that immunizing eligible individuals in the community provides protection to the youngest. At the time this article was drafted, the US Food and Drug Administration had recently approved the Pfizer/BioNTech vaccine for emergency use in children aged 5 to 11 years old and is currently being evaluated by the CDC Advisory Committee on Immunization Practices (ACIP) for further recommendations to the general public.

Our health authorities continue to recommend masking and social distancing in addition to vaccination. Findings of a comparison study of Arizona schools (kindergarten through grade 12) with variable mask policies from July to August 2021 showed that those with no mask requirement had 3.5 higher odds of a school-associated COVID-19 outbreak compared with schools that had required masking since the beginning of the school year.

 Similar results were observed in a larger study including 520 school districts across the United States.

 These studies show that a multilayered approach is still needed to stop the transmission of COVID-19.

Are there any additional variants that we should be concerned about? How about other emerging infections?

Public health networks and national authorities are constantly monitoring the evolution of SARS-CoV-2 worldwide. The World Health Organization (WHO) closely follows the emergence and progression of new variants that emerge globally and the CDC monitors these variants’ threat to the United States. Any variant shown to have genetic changes that might pose a future risk but without clear evidence of impact is labeled by the WHO as “variants under monitoring” and enhanced monitoring and assessments are undertaken to actively seek new evidence about potential impact. At least 15 such variants have been identified worldwide, most recently the B.1.630 variant identified first in the Dominican Republic in October 2021. If an identified variant has mutations that provide a higher transmissibility, immune escape, or severity of disease, and has shown at a community level to have increasing transmission and relative prevalence, it is categorized as a “variant of interest” (VOI), which for the WHO currently includes the Lambda and Mu variants. Given their limited prevalence and expansion within the US, they are not considered VOI by the CDC. The most concerning variants are labeled by the WHO as “variants of concern (VOC)”, which are those that have been proven to have a significant impact in global public health. This group currently includes the Delta variant, in addition to other previously described variants like Alpha (first identified in the United Kingdom), Beta (first identified in South Africa), and Gamma (first identified in Brazil).

 Within the United States, the Delta variant has been considered a VOC since July 2020. In contrast, given their declining prevalence, Alpha, Beta and Gamma variants are considered “variants being monitored” as of September 2021 by the CDC.

There are also an increasing number of subvariants—descendent lineages from each variant—being identified and closely monitored. “Delta plus”, formally known as AY.4.2, is a sub-lineage of the Delta variant that has additional mutations, including 2 in the spike protein region. The WHO has reported an increasing number of viral isolates identified as AY.4.2 predominantly in the United Kingdom, but distributed across 42 countries including the United States.

 More information is needed to determine the potential impact of this subvariant.

In addition to SARS-CoV-2, there are reports of a surge of highly pathogenic avian influenza type A (H5N6) in China. H5N6, first described in 2014, is a zoonotic infection transmitted by infected birds that can cause severe disease in humans. Only 52 cases of H5N6 have been diagnosed since 2014, but, alarmingly, 25 of these occurred during 2021. In addition, the first case outside of China was identified this year, in Laos. The CDC has conducted a risk assessment of the pandemic potential of this infection and has determined that, to date, the risk for human-to-human transmission is low.

 The WHO is monitoring H5N6, as well as other avian influenza viruses.

The Delta variant is the current predominant strain of COVID-19 in the United States and has demonstrated increased transmissibility when compared with prior variants. The most current data have not shown an increase in severity of COVID-19 infections among pediatric patients. Pediatricians should continue to spread awareness of the risks of COVID-19 infection and the known measures for prevention. Vaccination, social distancing, and masking continue to be our greatest tools to protect both children and adults.

1. Delta variant: what we know about the science. Centers for Disease Control and Prevention. Updated August 26, 2021. Accessed October 25, 2021. 

https://www.cdc.gov/coronavirus/2019-ncov/variants/delta-variant.html

2. SARS-CoV-2 variant classifications and definitions. Centers for Disease Control and Prevention. Updated October 4, 2021. Accessed October 24, 2021. 

https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html

3. Hagen A. How dangerous is the Delta variant (B.1.617.2)? American Society of Microbiology. July 30, 2021. Accessed October 24, 2021. 

https://asm.org/Articles/2021/July/How-Dangerous-is-the-Delta-Variant-B-1-617-2

4. Siegel DA, Reses HE, Cool AJ, et al. Trends in COVID-19 cases, emergency department visits, and hospital admissions among children and adolescents aged 0–17 years — United States, August 2020–August 2021. 

. 2021;70(36):1249-1254. doi:10.15585/mmwr.mm7036e1

5. COVID data tracker. Centers for Disease Control and Prevention. March 28, 2020. Accessed November 1, 2021. https://covid.cdc.gov/covid-data-tracker/#rates-by-vaccine-status

6. Delahoy MJ, Ujamaa D, Whitaker M, et al; COVID-NET Surveillance Team. Hospitalizations associated with COVID-19 among children and adolescents — COVID-NET, 14 States, March 1, 2020–August 14, 2021. 

. 2021;70(36):1255-1260. doi:10.15585/mmwr.mm7036e2

7. Lopez Bernal J, Andrews N, Gower C, et al. Effectiveness of Covid-19 vaccines against the B.1.617.2 (Delta) variant. 

. 2021;385(7):585-594. doi:10.1056/NEJMoa2108891

8. Grannis SJ, Rowley EA, Ong TC, et al; VISION Network. Interim estimates of COVID-19 vaccine effectiveness against COVID-19–associated emergency department or urgent care clinic encounters and hospitalizations among adults during SARS-CoV-2 B.1.617.2 (Delta) variant predominance — nine states, June–August 2021. 

. 2021;70(37):1291-1293. doi:10.15585/mmwr.mm7037e2

9. FDA authorizes Pfizer-BioNTech COVID-19 vaccine for emergency use in children 5 through 11 years of age. News release. US Food and Drug Administration. October 29, 2021. Accessed November 1, 2021. 

https://www.fda.gov/news-events/press-announcements/fda-authorizes-pfizer-biontech-covid-19-vaccine-emergency-use-children-5-through-11-years-age

10. Jehn M, McCullough JM, Dale AP, et al. Association between K–12 school mask policies and school-associated COVID-19 outbreaks — Maricopa and Pima counties, Arizona, July–August 2021. 

. 2021;70(39):1372-1373. doi:10.15585/mmwr.mm7039e1

11. Budzyn SE, Panaggio MJ, Parks SE, et al. Pediatric COVID-19 cases in counties with and without school mask requirements — United States, July 1–September 4, 2021. 

. 2021;70(39):1377-1378. doi:10.15585/mmwr.mm7039e3

12. World Health Organization. Tracking SARS-CoV-2 variants. Accessed November 3, 2021. 

https://www.who.int/emergencies/emergency-health-kits/trauma-emergency-surgery-kit-who-tesk-2019/tracking-SARS-CoV-2-variants

13. World Health Organization. Weekly epidemiological update on COVID-19 - 26 October 2021. Accessed November 3, 2021. 

https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---26-october-2021

14. CDC Update on A(H5N6) Bird Flu: How is the U.S. CDC monitoring A(H5N6) Infections and contributing to global pandemic preparedness? Centers for Disease Control and Prevention. Published November 1, 2021. Accessed November 3, 2021.

 https://www.cdc.gov/flu/spotlights/2021-2022/H5N6.htm

15. Bui CHT, Kuok DIT, Yeung HW, et al. Risk assessment for highly pathogenic avian influenza A(H5N6/H5N8) Clade 2.3.4.4 Viruses - Volume 27, Number 10—October 2021 - Emerging Infectious Diseases journal - CDC. doi:10.3201/eid2710.210297

16. World Health Organization. Regional Office for the Western Pacific. 

. WHO Regional Office for the Western Pacific; 2021. Accessed November 3, 2021.

 https://apps.who.int/iris/handle/10665/34114

Articles

Experts answer pediatricians’ and parents’ top questions about this COVID-19 strain’s impact on children.

What we now know about the COVID-19 Delta variant

On November 26, 2021, the World Health Organization (WHO) designated the B.1.1.529 variant a variant of concern (VOC), and assigned its name the Greek letter Omicron. 

The B.1.1.529 variant, which was first reported to the WHO from South Africa on November 24, 2021, with the first case reported in the United States (California) on December 1, 2021, contains around 50 mutations, of which more than 30 are in the spike protein of the SARS-CoV-2 virus. These include some of the mutations also found in the Delta and Alpha variants which have been linked to increased transmissibility. A sharp rise in cases of SARS-CoV-2 over the last 2 weeks of November 2021 in South Africa, specifically in the Gauteng province, raise concern because of 1)the rapidity with which number of daily cases is increasing is a faster rate than with any of the past 3 waves experienced in South Africa, and 2)the rapidity with which the B.1.1.529 variant took to represent the majority of SARS-CoV-2 cases (accounting for 90% of SARS-CoV-2 cases in just 2 weeks, compared to the 3 months it took for the Delta variant to become the predominant variant during the previous wave). These epidemiologic data support the concern for increased transmissibility of this variant compared to previous VOCs. 

As of December 1, the Omicron variant has been detected in 20 countries around the world, including the United States. Studies are underway to understand if this variant is associated with a different severity of disease compared to other SARS-CoV-2 variants. Anecdotes from clinicians in South Africa do not suggest increased severity of disease, but additional information is needed. Studies are also underway to understand the effectiveness of current vaccines in protecting against the Omicron variant. The mutations in the B.1.1.529 variant are not impacted by the currently used PCR test, so ability to detect infection with this variant are not expected to be impacted.

1. World Health Organization, News. Accessed November 30, 2021, Available at: 

https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern

2. Nature News. 25 November 2021. Heavily mutated Omicron variant puts scientists on alert. Accessed November 30, 2021. Available at: 

https://www.nature.com/articles/d41586-021-03552-w

3. COVID-19 Statistics for Republic of South Africa. National Institute for Communicable Diseases. Latest Confirmed Cases of COVID-19 in South Africa (30 November 2021). Available at: 

https://www.nicd.ac.za/latest-confirmed-cases-of-covid-19-in-south-africa-30-november-2021/

An update from infectious disease expert, Rana F. Hamdy, MD, on the Omicron variant of COVID-19.

What you need to know right now about the COVID-19 Omicron variant

In their “New bugs, new drugs” session from the virtual 2020 American Academy of Pediatrics National Conference & Exhibition, Rana El Feghaly, MD, and Jennifer Goldman, MD, associate professors of Pediatrics at UMKC School of Medicine and Children’s Mercy Hospital in Kansas City, Missouri, used a case-based format to highlight several important clinical pearls relating to optimizing antimicrobial use in the outpatient and inpatient pediatrics settings.

Community-based quality improvement initiatives should focus on decreasing inappropriate testing for Group A

El Feghaly provided key points from the Centers for Disease Control and Prevention (CDC) 2019 report on Antibiotic Threats in the United States: More than 2.8 million antibiotic-resistant infections occur each year in the United States,

 and many of those resistant infections considered to be serious threats are acquired in the community setting, like methicillin-resistant 

. Studies from nationally representative databases have found that at least one-third of all antibiotics prescribed nationally in the outpatient setting are unnecessary, and an additional 20% may be inappropriate. Two of the top 8 diagnoses leading to antibiotic prescriptions include viral upper respiratory tract infections and bronchitis, conditions for which antibiotics should never be prescribed.

(GAS) pharyngitis is one high-impact target in the ambulatory pediatrics setting that can lead to significant decrease in inappropriate antibiotic prescriptions.

 The GAS carrier rate among asymptomatic children in the United States is approximately 20%. Group A 

 pharyngitis does not present with cough, congestion, rhinorrhea, or conjunctivitis, but viral upper respiratory tract infections do. For this reason, any patient presenting with these viral symptoms should not undergo throat swab for GAS testing, because a positive test is more likely to represent a GAS carrier status in a patient with a viral illness than true GAS pharyngitis. Consensus guidelines also recommend against GAS testing in children aged younger than 3 years unless there is a clear exposure in a household contact, because acute rheumatic fever is rare, and the incidence of GAS pharyngitis is uncommon in this age group.

Clinical criteria alone (such as the Centor Score criteria) are not reliable for identifying a child with GAS pharyngitis, so treating presumptively for GAS pharyngitis in children without obtaining a throat swab for GAS testing is never recommended.

Despite these consensus guideline recommendations, El Feghaly highlights results from a retrospective cohort study she and colleagues performed at Children’s Mercy Hospital showing that 53% of GAS pharyngitis tests ordered were inappropriate (9% were in children aged < 3 years old and 44% in patients with viral symptoms).

 The good news, El Feghaly notes, is that quality improvement initiatives focusing on reducing inappropriate testing for GAS pharyngitis have been successful in reducing inappropriate testing in both the primary care and emergency department settings by implementing algorithms to guide clinicians on when testing is indicated.

 Given how common this condition is, reduction of inappropriate testing for GAS pharyngitis is an important antibiotic stewardship target in the ambulatory pediatric setting.

Documented penicillin allergy results in suboptimal therapy and should always be clarified

Goldman presented national antibiotic resistance data from the CDC highlighting substantial increases over the past twelve years in clindamycin and macrolide resistance among isolates from invasive GAS infections. Group A 

s resistance to clindamycin has increased from <5% in 2006 to 25% in 2018, and GAS resistance to macrolide antibiotics (ie, erythromycin and azithromycin) has increased from 12% in 2006 to 25% in 2018. These data showing that non-penicillin antibiotics provide suboptimal empiric therapy for invasive GAS infections are one example highlighting the importance of clarifying penicillin allergies with patients and their families.

Although documented penicillin allergies are prevalent among 10% of children, true Immunoglobulin E-mediated allergies for which the drug would be contraindicated are present in <1% of children. Understanding the local antibiotic resistance patterns in your patient population is essential to making the best antibiotic choices for empiric and definitive therapy.

El Feghaly and Goldman highlighted here the importance of evaluating both diagnostic testing and antibiotic prescribing practices to address opportunities to improve, knowing the susceptibility patterns of your patient population, and developing facility-specific clinical algorithms to guide diagnostic and treatment of infectious conditions.

1. Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2019. CDC.gov. Updated December 1, 2019. Accessed November 17, 2020. 

https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf

2. Fleming-Dutra K, Hersh A, Shapiro D, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. 

. 2016;315(17):1864. doi:10.1001/jama.2016.4151

3. Linafelter A, Burns A, Lee B, et al. Group A streptococcal pharyngitis testing appropriateness in pediatric acute care settings

. September 4, 2020. Epub ahead of print. doi:10.1097/pec.0000000000002223

4. Norton L, Lee B, Harte L, et al. Improving guideline-based streptococcal pharyngitis testing: a quality improvement initiative. 

. 2018;142(1):e20172033. doi:10.1542/peds.2017-2033

5. Ahluwalia T, Jain S, Norton L, Meade J, Etherton-Still J, Myers A. Reducing streptococcal testing in patients <3 years old in an emergency department. 

. 2019;144(4):e20190174. doi:10.1542/peds.2019-0174

A presentation at the virtual 2020 American Academy of Pediatrics National Conference & Exhibition offered a case-based format to highlight several important clinical pearls relating to optimizing antimicrobial use in the outpatient and inpatient pediatrics settings.

Rana F. Hamdy, MD

Articles

What we now know about the COVID-19 Delta variant

What you need to know right now about the COVID-19 Omicron variant

Optimizing antibiotic use and infectious diagnostic testing