key: cord-1001347-es6y6pf9
authors: Gupta, Shipra; Smith, Layne; Diakiw, Adriana
title: Avoidance of COVID-19 for Children and Adolescents and Isolation Precautions
date: 2021-05-21
journal: Pediatr Clin North Am
DOI: 10.1016/j.pcl.2021.05.011
sha: fbefab0b803bda24fdc53b75dff74fc0cd8bce1a
doc_id: 1001347
cord_uid: es6y6pf9

Limiting exposure to SARS-CoV-2 virus has been the major principle guiding public health measures. Masking, social distancing as well as frequent hand hygiene have been the chief non-pharmaceutical interventions as preventive strategies for all age groups. Advancement in vaccine development and vaccination of large populations offer a glimmer of hope for containing and ending this pandemic. However, until immunization is widespread in the community masking, social distancing, and frequent handwashing as well as early detection and isolation of infected persons should be continued to curb the spread of illness.

"Prevention is better than cure" has been the dictum driving the public health response to the novel coronavirus which was first reported in China towards the end of 2019. 1 Full-length genomic sequencing from virus identified from infected patients were 96% identical to a bat coronavirus. The novel coronavirus shared 79.6% sequence identity with the Severe Acute Respiratory Syndrome (SARS) coronavirus and, therefore, was named SARS-CoV-2. 2 The virus has since spread worldwide and was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. 3, 4 Initial emphasis had been on containment measures to curb community spread with widespread lockdowns, school closures and non-pharmaceutical interventions like masking and social distancing.

There have been multiple reports of familial clusters and studies on household transmission. [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] However, there is limited guidance on prevention measures once a household member is diagnosed or exposed to the virus. This review highlights available data on transmission of SARS-CoV-2 and reviews preventive measures to reduce transmission of the virus both in the community and household setting.

The acquisition of SARS-CoV-2 occurs when susceptible host comes in contact with respiratory secretions from an infected individual. Most transmission occurs through large droplets and occasionally small droplets via airborne spread. [15] [16] [17] [18] Airborne transmission can occur in enclosed spaces, poorly ventilated areas with improper air handling and prolonged or higher exposure dose of respiratory J o u r n a l P r e -p r o o f particles as with expiratory exertion during exercise or singing. [19] [20] [21] [22] Theoretically, transmission can occur through contaminated surfaces, however, this is infrequent. Virus has been detected in stool specimens, however, viable virus has not been isolated from stool samples. 23 The incubation period for SARS-CoV-2 is up to 14 days from the time of exposure and about 50% of exposed have symptoms by day 4 or 5 and 98% by day 12 from exposure. [24] [25] [26] [27] [28] [29] The window of contagiousness for a symptomatic individual starts about 2-3 days prior to onset of symptoms and peaks at symptoms onset and decline over the following 7 days for the majority of cases. [30] [31] [32] [33] Therefore, presymptomatic transmission appears to be a significant driver of spread of infection in the community and households. Early on during the pandemic asymptomatic carriers were thought to be significant spreaders especially in the household setting. 34, 35 However, recent data from Wuhan, China showed that there was no SARS-CoV-2 virus detected by polymerase chain reaction (PCR) in 1,174 close household contacts of the 300 asymptomatic cases. 36 The role of asymptomatic spreaders remains controversial with recent modeling data suggesting that 50% of new infections were estimated to have been acquired from asymptomatic spreaders. 37 The period of contagiousness for asymptomatic individuals is not clearly understood and for purposes of contact tracing the cut-off of 48 hours prior to the positive test date is applied for identification of individuals who had potential exposure.

Secondary attack rate (SAR) is defined as the proportion of infections that occur among susceptible individuals following contact with an infected case within the incubation period. 38 The SAR for SARS-CoV-2 varies in different contact and exposure settings. Recent meta-analysis showed a pooled SAR for SARS-CoV-2 in diverse contact settings of 7% (95% CI: 3%-12%). 39 This study also highlighted low SAR in healthcare facilities, public transport and work settings as compared to the high SAR in households and exposures in social gatherings.

Crowded indoor environments and close contact among household members is a high risk setting for transmission of SARS-CoV-2. Initial reports out of China described SAR of 12.4% among household contacts when defined on the basis of close relatives and 17.1% when they shared the same residential address. 8 Recent systemic review and meta-analysis estimated household SAR of 16.6% (95% CI 14.0%-19.3%). 40 Most published literature reports increased SAR from symptomatic index cases as compared to asymptomatic index cases as well as in spouses as compared to other family contacts. 40, 41 Lewis et al. reported that 31 out of the 58 households from Utah and Wisconsin had secondary transmission and 52 of 188 household contacts tested positive by either PCR-assay or serologic testing giving a secondary infection rate of 28%. 9 This study was done during March-April 2020 when there was relatively low community prevalence at the study sites to reduce risk of additional community exposure.

Higher secondary infection rate of 53% (95% CI: 46%-60%) were detected in households in a study done in Tennessee and Wisconsin thru April-September 2020. 6 Various retrospective studies have identified black ethnicity, male gender, smoking and obesity as risk factors associated with higher risk of infections. [42] [43] [44] Higher rates of infection have been reported in older household contacts (age≥60) as compared to younger contacts. 5 

Prolonged shedding of respiratory viruses after viral illness has been described in children younger than 5 years when compared with older participants. 46 With most children having none to mild symptoms it was thought that children could serve as a silent reservoir for SARS-CoV-2. However, multiple studies of outbreaks in familial clusters have shown that children are rarely the index case and are often identified J o u r n a l P r e -p r o o f after an adult has tested positive. Similar findings were confirmed from outbreaks at childcare facilities which was linked to index cases in adults. 47 In a large multicenter cross-sectional investigation in Germany the estimated SARS-CoV-2 seroprevalence was low in parents and 3-fold lower in children. 48 Follow up interviews with families of children who were hospitalized for COVID-19 illness were performed 6 weeks after the child became ill showed there were no reported illness in the household and one case of child-to-child transmission. 49

Schools across the United States were preemptively closed to in-person classes and transitioned to virtual learning early on during the pandemic to mitigate spread of SARS-CoV-2. However, as months passed certain states allowed in-person learning options along with the remote option. With the help of the local health department and guidance from Centers for Disease Control and Prevention (CDC) there have been multiple reports published for safe reopening of schools. A recent study from Mississippi showed that attending school or childcare 2 weeks prior to testing date was not associated with an increased probability of a positive SARS-CoV-2 test. 47 Parents of cases and controls reported 64 % and 76% consistent mask use respectively for both children and staff at school or childcare facility. Most of the children (<18 years) who tested positive for SARS-CoV-2 were more likely to have attended gatherings with people outside their household 14 days prior to testing positive. Similar results were reported from North Carolina schools over a period of 9 weeks with extensive contact tracing where there was limited secondary transmission and zero child-to-adult transmission noted within the school. 50 These studies highlight that in-person teaching at schools can be achieved with consistent mask wearing, hand hygiene and maintaining a distance of 6 feet as well as screening and early detection of infection.

J o u r n a l P r e -p r o o f

Non-pharmaceutical interventions recommended to reduce transmission of SARS-CoV-2 include mask wearing, social distancing, hand hygiene, disinfection of frequently touched surfaces, improved ventilation, self-isolation, and quarantine.

Face masks are thought to reduce viral transmission from both the source and target of infection; they reduce the exhalation of respiratory particles by an infected person 51, 52 and reduce the inhalation of these particles by a susceptible host 52, 53 . Evidence supporting facemask use comes from epidemiological data, observational studies, mathematical models, and laboratory studies.

Like SARS and Middle Eastern Respiratory Syndrome (MERS) Coronavirus, SARS-CoV-2 is a member of the Betacoronavirus genus, but it resembles the 2009 H1N1 influenza virus in its high degree of upper respiratory tract shedding, its propensity for asymptomatic and presymptomatic transmission and the scope of its global spread. 54 The WHO sponsored a systematic review and meta-analysis that concluded that facemask use could significantly decrease the risk of SARS-CoV-2 infection. 55 with face mask use was 96.6%, with selected countries in North America, Europe, and Asia having similar population density, but without universal masking. They found that the incidence of SARS-CoV-2 was significantly lower in HSKAR. 58 A cross-sectional population level study in the United States showed that self-reported face mask use was correlated with increased odds of transmission control, and that the effect of mask use was higher with increased levels of physical distancing. 59 Laboratory studies of airborne transmission provide additional evidence for the role of mask wearing in preventing the spread of COVID-19. Ueki et al. examined the efficacy of cotton, surgical, and N95 of masks in blocking the transmission of infectious droplets and aerosols of SARS-CoV-2 using an airborne transmission simulator. They found that all types of masks were protective against transmission of infectious particles, with a stronger effect noted when the mask was worn by the source of the virus. 52 A study of the aerosol filtration efficiency of cloth masks showed that snugly fitted masks could provide good protection from a range of aerosol particle sizes. Filtration efficiency was significantly higher in masks made from multiple layers of tightly woven fabric, particularly when different types of fabric were combined in the same mask. Of note, filtration efficiency in poorly fitted masks was found to decrease by more than 60%, highlighting the importance of proper mask fitting to reduce transmission of respiratory particles. 53 Current evidence-based guidelines from the CDC emphasize the importance of consistent and correct face mask use to decrease transmission of SARS-CoV-2 virus in the community. The CDC recommends using fabric masks made with two or three layers of tightly woven, breathable fabric (such as cotton), or disposable, single-use non-medical masks. Regardless of the type of mask used, it should be snugly fitted around the nose and chin, without large gaps at the sides or top. Masks with exhalation valves or vents should not be used, as they may allow passage of respiratory particles. In order to prevent critical supply shortages, surgical masks and respirators should be avoided in the community setting. Outside J o u r n a l P r e -p r o o f the home, face masks should be while indoors in public places, and in crowded outdoor areas where interpersonal distance is less than 6 feet. 60

Studies of COVID-19 outbreaks occurring in community settings outside the home have shown that increased infection risk is associated with close contact with other members of the community, particularly in enclosed spaces. 60 A contact tracing study of train passengers in China found that risk of SARS-CoV-2 transmission increased with spatial proximity to the index case, as well as increased duration of shared travel time. 61 Epidemiological studies lend support to public health guidance on physical distancing to slow the spread of the pandemic. The WHO's systematic review and meta-analysis of non-pharmaceutical measures to prevent SARS-CoV-2 transmission found that the risk of viral infection decreased as interpersonal distancing increased, and concluded that physical separation of at least 1 meter was beneficial, but separation of 2 meters might be more effective in decreasing the risk of infection. 55 The COVID-19 Pandemic Pulse Study evaluated self-reported movement patterns and non- Based on the available evidence regarding transmission patterns, unnecessary interactions with persons outside one's household should be limited while SARS-CoV-2 is circulating in the community. 60 When outside the home, physical distance of ≥6 feet should be maintained from non-household members.

Unnecessary exposure to indoor environments should be avoided, particularly those associated with increased transmission risk, such as indoor restaurant dining, worship services, and exercise classes.

Non-essential use of public transportation should be avoided whenever possible. Since there is emerging evidence of SARS-CoV-2 transmission occurring in large outdoor gatherings, exposure to crowded outdoor venues should also be avoided. 60, 64 Limiting contact with other members of the community is especially important for persons at high risk for severe COVID-19 illness, and those who share a household with someone at high risk. With the advent of widespread immunization for COVID-19, the CDC has issued revised guidelines for indoor visits or small gatherings in private residences. Fully significantly decreased transmission of influenza, but hand hygiene alone did not. 69 It should be noted, however, that these reviews considered the impact of hand hygiene on transmission of respiratory J o u r n a l P r e -p r o o f viruses but not SARS-CoV-2. These results may not correspond to the real-world transmission dynamics of SARS-CoV-2, which is significantly more stable than influenza virus. 70 Since SARS-CoV-2 is a lipid-enveloped RNA virus, it is susceptible to inactivation by agents which disrupt the integrity of its lipid envelope, such as alcohol and hand soap. 72 A review of commonly used hand sanitizers found that most alcohol-based hand sanitizers were successful at inactivating enveloped viruses, including coronavirus, but that washing with soap and water was superior to sanitizers in removing pathogens and debris from hands. 73 For household disinfection, the authors recommend a 1:50 dilution of standard household bleach;

alternatively, a solution of 62-70% ethanol may be used for disinfection of small surfaces. 74 Current guidance for prevention of COVID-19 from WHO recommends the use of 0.1% sodium hypochlorite solution or 70%-90% ethanol for household disinfection. 75

Respiratory particles emitted by humans span a continuum of sizes, from large droplets to tiny aerosols.

Conventional wisdom holds that droplets >5 μm in diameter fall to the ground within 1-2 meters of the source, while smaller aerosols remain suspended in the air; however, this is now understood to be a false dichotomy. The duration of time that a particle remains suspended in the air depends not only on its diameter, but also on the velocity at which it is emitted, and a host of environmental factors, including the temperature, humidity, speed, and direction of ambient airflow. 76 It is not surprising, therefore, that both proximity and ventilation have emerged as key determinants of transmission risk for SARS-CoV-2. 68 A mathematical model of indoor transmission found that increasing ventilation rate was correlated with decreasing infection probability. Of note, the model also predicted that mask wearing indoors significantly decreased infection probability, even at lower rates of air exchange. 77 Using the principles of fluid mechanics, Bhagat et al. assessed the impact of ventilation on the movement of infectious particles in an enclosed space, and concluded that displacement ventilation was most effective in removing contaminated air and decreasing the exposure risk. Displacement ventilation consists of exhaust fans or vents installed on or near the ceiling of the room, 78 and can be found in the kitchens and bathrooms of most modern homes. To decrease transmission through direct contact and fomites, the CDC advises that household members wash their hands frequently with soap and water for at least 20 seconds, or use hand sanitizer J o u r n a l P r e -p r o o f containing at least 60% alcohol, and avoid touching their eyes, nose or mouth with unwashed hands.

Frequently touched surfaces, such as light switches, doorknobs, desks, tables, electronics, sinks, faucets, and toilets should be cleaned and disinfected daily. If the affected person uses a shared bathroom, they should clean and disinfect it after use if they are able to do so; if not, the caregiver should wait as long as possible before entering the bathroom to clean and disinfect it. Caregivers should wear gloves to prevent contact with the affected person's secretions, bodily fluids, or stool. Gloves should also be worn when handling contaminated items, washing dishes, or doing laundry. Dishes should be washed with soap and hot water, or in a dishwasher. Dirty laundry may be combined with laundry from other household members but should washed and dried on the hottest settings possible. Used gloves, masks, and other contaminated items should be discarded in a trash can with a disposable liner, preferably one set aside for use by the affected person, and gloves should be worn when handling and disposing of contaminated trash. Caregivers should wash their hands after removing gloves. 79 Since the estimated incubation period of SARS-CoV-2 can last up to 14 days, the CDC recommends that caregivers and close household contacts of the affected person quarantine at home for 14 days after their last exposure to the affected person, or 14 days after the affected person meets criteria to end isolation. "Close contact" is defined as being within 6 feet of the infected person for a total of 15 minutes or more, direct physical contact such as hugging or kissing, sharing the same utensils for eating or drinking, or direct exposure to respiratory droplets from coughing or sneezing. Caregivers and close household contacts with a history of laboratory-confirmed COVID-19 infection and recovery within the that low vitamin D level may be associated with COVID-19 infection and complications. 84 Another study of patients in European countries found a significant negative correlation between average vitamin D levels and COVID-19 cases, but not with death. 85 Due to the limited generalizability of these trials and lack of studies in pediatric patients, supplementation with vitamin D to prevent SARS-CoV-2 infection is currently not recommended. However, vitamin D supplementation may be warranted in pediatric patients with known vitamin D deficiency.

Ascorbic acid, or Vitamin C have been studied as potential immunomodulatory. Vitamin C has been evaluated in patient with serious infections and sepsis with inconsistent results. 86, 87 While there are many ongoing clinical trials evaluating its place in therapy, it is currently not routinely recommended for prevention of SARS-CoV-2 in pediatric patients.

Zinc supplementation has also been studied as a preventive as well as management of COVID-19 in ongoing clinical trials. In vitro studies have shown that increased intracellular Zinc concentrations decrease replication in RNA viruses such as rhinoviruses and coronaviruses. 88, 89 Topical

The nose and mouth are significant entry portals for the virus, since infection is primarily transmitted by inhalation of or contact with infected droplets. Additionally, the nasal cavity and nasopharynx contains the highest viral load. Therefore, topical nasal irrigations and oral rinses have been identified as potential options to prevent SARS-CoV-2 infection.

There is currently limited evidence regarding the use of topical therapies in the prevention of SARS-CoV-2 infection specifically. However, available data to support these agents in other viral illnesses may help guide preventive measures for SARS-CoV-2. 90 Regular use of saline nasal irrigation in children has been J o u r n a l P r e -p r o o f shown to prevent symptoms of rhinitis and associated complications. 91 Additionally, use of hypertonic saline nasal irrigation and gargling was associated with decreased duration of illness, over-the-counter medication use, transmission within household contacts, and viral load of many viruses, including rhinovirus, enterovirus, influenza A virus, and coronavirus (not SARS-CoV-2). 92 Povidone-iodine (PVP-1) is another topical agent identified for potential use in the prevention of SARS-CoV-2 infections. PVP-1 is a solution that disrupts microbial metabolic pathways, destabilizes structural components of cell membranes, and leads to irreversible damage to pathogen. PVP-1 has been shown to achieve almost 100% virucidal activity against SARS-CoV-2 within 30 seconds of contact in the laboratory. 93 Another in vitro study found the PVP-1 at diluted concentrations of 0.5%, 1.25%, and 2.5% completely inactivated SARS-CoV-2 within 15 seconds of contact. 94 While neither of these studies were done in humans, a review of PVP-1 use in sinonasal and oral cavities found that PVP-1 is safe to use in the nose up to a strength of 1.25% for 5 months and in the mouth up to a strength of 5% for 6 months. 95 However, the over-the-counter product is commercially available at a strength of 10%, so this product should not be used in the nose or mouth. Until a commercially available diluted solution is available and clinical trials have been completed, PVP-1 should not be used to prevent SARS-CoV-2 infections in children.

There is currently insufficient evidence to support use of topical therapies to prevent COVID-19 in children. Risks associated with these therapies include irritation, loss of smell, and destruction of microorganisms in the nose or mouth that are useful in preventing infection. Additionally, if nasal spray solutions are used on multiple children without sterilizing the bottle or product, spread of disease may increase. There are currently multiple trials underway to determine the safety and efficacy of topical agents in prevention of COVID-19 infection and transmission.

Vaccines offer the best preventive strategy to contain the SARS-CoV-2 pandemic. Several vaccines using different methodology are being developed across the world. Recently, two nucleoside-modified RNA vaccine encoding SARS-CoV-2 spike protein were shown efficacious in preventing COVID-19 illness, including severe disease. 96, 97 These two vaccines received an emergency use authorization (EUA) by the Food and Drug Administration (FDA) and are being used across the United States to vaccinate healthcare workers and people at high risk of severe disease. The Pfizer-BioNTech COVID-19 vaccine and MODERNA COVID-19 vaccine also received an interim recommendation for immunization of individuals ≥16 years of age and ≥18 years respectively. 98, 99 However, there are clinical trials being done to evaluate safety and efficacy in younger children.

There is limited data on the effect of vaccine on asymptomatic transmission and therefore the current recommendation is to continue practicing masking and social distancing until a majority of the population is immunized. 

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