What we knew about COVID-19 when the pandemic began, what we know now.
It is now 2021, and our understanding of the novel coronavirus first reported in Wuhan, China in December 2019 has drastically expanded due largely to the extensive number of individuals who have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide, as well as those who have exhibited symptoms of disease from this virus (COVID-19). Currently, the increase in incidence throughout the country is significantly impacting our health care system capacity. Whereas children in general have been reported to experience less disease from infection with SARS-CoV-2, the nationwide surge in cases has led to an increase in pediatric hospitalizations, as well as cases of multisystem inflammatory syndrome in children (MIS-C). Despite a growing number of cases throughout the United States, we have greatly improved our understanding of infection control measures to curb transmission, have better access to personal protective equipment (PPE), and have improved testing availability to aid in mitigating transmission. We must now reduce community, household, and workplace transmission to relieve the strain that an ill and reduced workforce is having on the health care system.
What we know right now: SARS-CoV-2 infection in children
Due to variation in public health reporting, accurate numbers of SARS-CoV-2 infected pediatric patients are a challenge to obtain. However, available data show a consistent increase in pediatric patients that tested positive for SARS-CoV-2 over the past year, and particularly the past several months. As of November 19, 2020, the American Academy of Pediatrics/Children’s Hospital Association (AAP/CHA) Children and COVID-19: State Data Report1 reported 1,183,609 cumulative child cases, representing 11.8% of total cases reported and 1572.6 cases per 100,000 children. Fifty-seven percent of these cases were reported since September 2020.
Despite climbing numbers of pediatric SARS-CoV-2 infections, children continue to be proportionally less affected by infection than adults. Although children represent about 22% of the United States population, they represent only 1.8% of total hospitalizations related to SARS-CoV-2.1 The scope of asymptomatic infections in children is challenging to fully represent due to the retrospective nature of current reports, but estimates range between 5% and 35%.2,3 Children presenting to care with symptoms and subsequently diagnosed with SARS-CoV-2 infection most commonly have fever or cough.2-4 There is variation in representation of other complaints, including pharyngitis, rhinorrhea, congestion, headache, or gastrointestinal (GI) complaints. Children with some underlying medical conditions (obesity, asthma or chronic lung disease, and immunosuppression) are at greater risk for severe illness from SARS-CoV-2 infection.5-7 This does not, however, discount the potential for healthy children to develop severe disease or require hospitalization.
Although rates of severe illness due to SARS-CoV-2 are generally lower in children than adults, a hyperinflammatory syndrome associated with SARS-CoV-2 infection has been identified as MIS-C.8 As of December 9, 2020, 23 of these cases in the United States resulted in death.9 More than 75% of reported cases of MIS-C occurred in children of Hispanic/Latino or Black, non-Hispanic reported race/ethnicity and the average age was 8 years.9 The most common symptoms reported for children with MIS-C include GI complaints (abdominal pain, vomiting, diarrhea), rash, and conjunctival injection. Whereas some MIS-C patients may present with symptoms overlapping with Kawasaki disease or toxic shock syndrome, multiple case series of patients with MIS-C demonstrate clear differences between these patients, including age distribution, prominence of GI symptoms, the degree of multisystem organ involvement, and cardiogenic shock with myocardial dysfunction.10,11 Multiple studies are ongoing to better understand the pathophysiology of this inflammatory syndrome.
Infection prevention in community and health care settings
Understanding of SARS-CoV-2 transmission has increased exponentially throughout the pandemic. Basic concepts of infection prevention such as wearing face coverings/masks, hand hygiene, not working when ill, and social distancing have proved to be of the utmost importance for the health care setting and for the public, including our patients and their families. Although children who cannot remove their mask in case of an emergency or those with sensory sensitivities should not use face coverings, children aged as young as 2 years can learn to don them when out in public or at school. The epidemiologic curve in relation to social distancing and masking guidance over the past 10 months supports the use of these infection prevention methods. Additionally, household contact with an individual with SARS-CoV-2 is a risk factor for transmission, likely due to individuals exposing one another during the pre-symptomatic period and lack of use of face coverings within the household.3,12-14
In-school learning is dependent upon the level of community transmission and ability to mitigate transmission of infections. School attendance is important not only for education, but also for food security, access to other services, and physical activity. If open, schools should enforce the basic principles described above: Masking and social distancing (depending on the age group), as well as extensive cleaning of the environment. Creation of cohorts of students and teachers (“pods”) within schools has helped alleviate the need to close an entire school in some circumstances. Testing, contact tracing, and school or class closure policies are contingent upon local transmission rates and other factors. Unlike other viruses such as influenza, younger children appear to be less affected by and less likely to spread SARS-CoV-2 than older children.15,16 Age-based schooling recommendations may therefore be an appropriate consideration, with greater emphasis on the ability of younger school-aged children to continue in-person learning even if this cannot be maintained in older age groups.
In the health care setting, use of negative pressure rooms, PPE, social distancing, environmental cleaning with focus on high touch surfaces, and hand hygiene decrease the likelihood of transmission of SARS-CoV-2 between patient and provider. Nosocomial transmission is likely more associated with lack of PPE particularly during prolonged exposure and/or performing aerosol-generating procedures (AGP) without the recommended PPE.17 Transmission dynamics of SARS-CoV-2 to date support transmission via direct or indirect contact with secretions, respiratory droplets, or fomites unless a procedure is being performed that may generate aerosol. Use of a face mask and eye protection has been shown to reduce risk of transmission.18 Face masks prevent large droplets from being breathed in, but also to prevent any viral secretions from going out. However, if an AGP is being performed, a respirator (eg, N95 respirator) should be employed to keep generated aerosols from being inhaled. The Infectious Diseases Society of America has published a table of AGPs to aid in decision making around PPE use.19 It is yet unclear whether SARS-CoV-2 can be spread through aerosol other than those generated by medical procedures, though the transmission dynamics of this virus does not match those of known airborne infections such as measles or varicella. Implementation of these infection control strategies can mitigate transmission of SARS-CoV-2 between health care personnel and patients if they are followed.20 Fatigue from using PPE and laxity with social distancing have more recently become real concerns and problems. Universal mask use and social distancing guidelines have been adopted within many health care settings, yet transmission among health care workers has become a new challenge when mask use is inconsistent. A recent Cochrane Review reported that a key facilitator to adherence to infection prevention guidelines among medical personnel was understanding the rationale behind the guide-lines.21 Education of team members is therefore likely the most important approach to take in the coming months as we face PPE fatigue and burnout in health care.
In addition to the continuing SARS-CoV-2 pandemic, we are now within the winter respiratory virus season. Though some reports from the Southern Hemisphere have shown a mild influenza season,22 it is difficult to predict what the United States can expect with influenza or any of the other winter respiratory viruses. Given the overlap of symptoms between SARS-CoV-2 and influenza infections, use of SARS-CoV-2 and influenza testing is crucial. Results will aid in identifying people who require isolation, inform contact tracing efforts, particularly for schools, and for those requiring hospitalization, inform treatment for either virus. Communities with more infection mitigation measures in place and adherence to those measures may have less influenza circulation than typically would be expected. Reinforcing the basics of infection prevention, promoting influenza vaccine for health care providers, patients, and families, in addition to maintaining high rates of routine immunizations will be important to alleviate hospital admission rates and reduce strain on hospital bed availability.
Therapeutics and immunization
Strategies for treatment and immune modulation of the effects of SARS-CoV-2 continue to develop. An Emergency Use Authorization (EUA) was granted by the FDA for the use of hydroxychloroquine for treatment of COVID-19 and revoked in June 2020 due to insufficient data to show efficacy. In parallel, an EUA was granted for the use of remdesivir in May 2020. Recommendation for use is with or without dexamethasone in patients who are hospitalized and require supplemental oxygen23 (Table). In October 2020, remdesivir became the first drug approved by the FDA for treatment of COVID-19 in individuals aged 12 years and 40kg. Safety and efficacy in children aged <12 years has not yet been established, so use in this group remains under EUA. In November, bamlanivimab, a neutralizing monoclonal antibody targeting the spike protein of the SARS-CoV-2 virus was issued an EUA for use in non-hospitalized patients with mild-to-moderate SARS-CoV-2 infection who are at high risk for adverse effects from the infection (Table). In December, as this article was going to press, the Pfizer and BioNTech mRNA vaccine had just been granted EUA: Shortly thereafter, doctors and nurses throughout the country were televised receiving the first vaccines and plans have been made to distribute to additional health care workers. By the time this article is published, a second vaccine, developed by Moderna, might very well have been approved as well.
The Advisory Committee on Immunization Practices recommends a phased approach with initial vaccine being made available to the groups most at-risk for SARS-CoV-2 infection, including inpatient and outpatient health care personnel, first responders, and a variety of other health care personnel.24,25 Initial vaccine uptake will help maintain the health and availability of health care personnel to continue to provide both acute and preventative care to patients. Subsequent phases of vaccination will then be able to mitigate spread among the general community. The Pfizer-BioNTech vaccine is approved for persons aged 16 years and older, and the company has begun trialing vaccine administration for children 12 years of age. Emphasis for now will therefore remain on uptake by adults and older children.
Where are we now?
There have been many successes and many “educational moments” in our journey through the SARS-CoV-2 pandemic. The speed with which our large health care and public health systems, as well as our governments and communities, have had to mobilize and adapt to continually new information is tremendous. Early in the pandemic, focus was primarily on creating protocols and gaining better understanding of the virus and its dynamics. We have confirmed that public health and infection control measures can positively impact infection rates. Our concern in the health care setting has shifted from acquisition of SARS-CoV-2 from our patients to its acquisition from coworkers, community, or household members.
In the coming months, we will be challenged with continuing to care for the growing number of patients with SARS-CoV-2 and increasing rates of hospitalization, as well as managing distribution of new vaccines. We will still encounter school closures, be challenged with our patients’ and colleagues’ mental health, and continue to seek preventative care. However, looking back over the past 11 months, it is evident that we have made tremendous strides in understanding COVID-19, mitigating spread, treating the virus and its sequelae, and connecting scientists to advance our knowledge of this virus and how to combat it.