key: cord-0808765-7njlt0ce
authors: La Regina, Domenico Paolo; Nenna, Raffaella; Schramm, Dirk; Freitag, Nadine; Goussard, Pierre; Eber, Ernst; Midulla, Fabio
title: The use of pediatric flexible bronchoscopy in the COVID‐19 pandemic era
date: 2021-03-17
journal: Pediatr Pulmonol
DOI: 10.1002/ppul.25358
sha: c04dad13e02009cec6a95cb18172169ecc4a16f1
doc_id: 808765
cord_uid: 7njlt0ce

On March 11, 2020, the World Health Organization (WHO) declared the pandemic because of a novel coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). In January 2020, the first transmission to healthcare workers (HCWs) was described. SARS‐CoV‐2 is transmitted between people because of contact, droplets, and airborne. Airborne transmission is caused by aerosols that remain infectious when suspended in air over long distances and time. In the clinical setting, airborne transmission may occur during aerosol generating procedures like flexible bronchoscopy. To date, although the role of children in the transmission of SARS‐CoV‐2 is not clear the execution of bronchoscopy is associated with a considerably increased risk of SARS‐CoV‐2 transmission to HCWs. The aim of this overview is to summarize available recommendations and to apply them to pediatric bronchoscopy. We performed systematic literature searches using the MEDLINE (accessed via PubMed) and Scopus databases. We reviewed major recommendations and position statements published at the moment by the American Association for Bronchology and Interventional Pulmonology, WHO, European Center for Disease Prevention and Control and expert groups on the management of patients with COVID‐19 to limit transmission among HCWs. To date there is a lack of recommendations for safe bronchoscopy during the pandemic period. The main indications concern adults and little has been said about children. We have summarized available recommendations and we have applied them to pediatric bronchoscopy.

On January 9, 2020, the Chinese Center for Disease Control and Prevention reported that a novel coronavirus had been detected. 1 Since then the virus has spread all over the world, and on March 11, 2020 the World Health Organization (WHO) declared the pandemic. 2 Until May 27, 2020, the worldwide number of confirmed coronavirus disease (COVID)-19 cases had reached 5,488,825 with 349,095 deaths. 3 In this context, children are less affected and have a milder symptomatology, even if currently we do not know the reason. 4 In January 2020, the first transmission to healthcare workers (HCWs) was described and the first reported fatality related to severe acute respiratory syndrome coronavirus 2 (SARS- infection was an otolaryngologist from Wuhan, China. 5 As of April 8, 2020, a total of 22,073 COVID-19 cases among HCWs from 52 countries have been reported to the WHO, 6 

probably under-estimates the true number of SARS-CoV-2 HCW infections globally because to date there has been no systematic reporting of HCW SARS-CoV-2 infections to the WHO. While HCWs represent less than 3% of the population in the large majority of countries, around 14% of COVID-19 cases reported to WHO are among HCWs. In some countries, the proportion can be as high as 35%. However, high quality data are limited, and it is not possible to establish whether HCWs were infected in the workplace or in community settings. Some reviews present more precise data, as in the case of China and Italy. 7 In these countries, HCWs represent about 10% of reported cases. 8, 9 It is likely that nosocomial outbreaks play an important role in amplifying local outbreaks. For this reason, correct management in the hospital environment among HCWs is essential.

Airborne transmission is caused by aerosols that remain infectious when suspended in air over long distances and time. In the clinical setting, airborne transmission may occur during aerosol generating procedures (AGPs) like bronchoscopy (other AGPs are tracheal intubation, noninvasive ventilation (NIV), tracheotomy, manual ventilation before intubation). 10 To date, although the role of children in the transmission of SARS-CoV-2 is not clear, the execution of bronchoscopy is associated with a considerably increased risk of SARS-CoV-2 transmission to HCWs caused by both close contact with the child during the procedure and the possibility of aerosol generation. 12, 13 During the COVID-19 pandemic, the American Association for Bronchology and Interventional Pulmonology (AABIP), WHO, European Center for Disease Prevention and Control (ECDC) and expert groups have offered recommendations and position statements on the management of patients with COVID-19 to limit transmission among HCWs during various procedures, including bronchoscopy. 11, [14] [15] [16] [17] [18] With the current lack of recommendations for pediatric bronchoscopy the aim of this overview is to summarize available recommendations and to apply them to pediatric bronchoscopy.

We performed systematic literature searches using the MEDLINE (accessed via PubMed) and Scopus databases, searching for relevant terms related to "COVID-19" or "SARS-CoV-2" and one of the following: "children," "transmission," "healthcare workers," "aerosol generating procedures," "bronchoscopy" published until December 2020. We have analyzed the situation reports and interim guidance of WHO, ECDC technical reports, Institute of Health data, major recommendations and position statements published by the AABIP and expert groups on the management of patients with COVID-19 to limit transmission among HCWs.

Except one Italian report of Higher Institute of Health, all articles analyzed are in English language.

3.1 | SARS-CoV-2 infection: differences between children and adults

The first confirmed pediatric case of SARS-CoV-2 infection was reported in Shenzhen on January 20. 19 Epidemiological studies suggest that children comprise only 1%-2% of all SARS-CoV-2 cases. 20, 21 Some studies have suggested that children are as likely as adults to become infected with SARS-CoV-2, 22 though more recent studies have reported that children are less likely to get infected after contact with a SARS-CoV-2 positive person. [23] [24] [25] In particular, it has been suggested that children and adolescents have similar viral loads and may therefore be as likely to transmit SARS-CoV-2 as adults. 26, 27 Moreover, viral load seems to be similar between asymptomatic and symptomatic individuals. 28, 29 According to available data, compared with adults, children infected with SARS-CoV-2 have milder disease that occurs after 1-14 days of incubation (median: 5-6 days). Fever and cough are the most common clinical manifestations, sometimes accompanied by fatigue, myalgia, nasal congestion, runny nose, sneezing, sore throat, headache, dizziness, vomiting, and abdominal pain. [30] [31] [32] [33] A minority of children with COVID-19 require hospitalization, however, younger children are vulnerable to the disease and may experience severe outcomes, 34 but the risk of death is very low. The percentage of asymptomatic infected children is about 4%-15%. 32, [35] [36] [37] To date, there are many theories about why children are less involved and have milder symptoms compared to adults. These include (1) differences density, affinity and distribution of ACE-2 receptors compared to adults; (2) trained immunity; and (3) preexisting immunity to endemic coronaviruses. In addition, factors that put adults at higher risk compared to children are: (1) a higher pre- 

Based on current evidence, SARS-CoV-2 is transmitted between people via droplets, aerosols and contact (including both direct, indirect and close contact like contact for more than 15 min and less than one meter of distance). Aerosols and droplets are expelled when a person coughs, sneezes, talks or sings. 39, 40 The large particles (>5-10 μm), called droplets, remain airborne only briefly before settling because of gravity. Speech and breathing also produce smaller and much more numerous particles (<5 μm), known as aerosol particles. These particles are carried by air currents and dispersed by diffusion and air turbulence. Inhaled droplets and aerosol particles have different sites of deposition in the respiratory system. Inhaled aerosolized particles can penetrate to the depths of the lungs depositing in the alveoli, whereas inhaled droplets are deposited in the upper respiratory tract. 41 Aerosols from infected persons may therefore pose an inhalation threat even at considerable distances and in enclosed spaces, particularly if there is poor ventilation. For this reason, it is important to ensure adequate ventilation of enclosed spaces where such persons are known to be or may recently have been and wear a suitable mask whenever it is thought that infected persons may be nearby. and collection of sputum. Some reviews report a higher risk of transmission for tracheal intubation followed by NIV, tracheotomy and manual ventilation before intubation. 10, 42 These reviews showed that bronchoscopy is a procedure with an increased risk, but confidence intervals were wide. A study on influenza A H1N1 reported an increased detection of viral aerosols following bronchoscopy and airway suctioning. 43 Also, bacteria have been detected in ambient air after bronchoscopy, but HCW transmission was not studied. 44 Considering the very small number of studies and the inconsistent and imprecise results, more stringent measures should be taken to prevent the spread of SARS-Cov-2 to HCWs. 45 infection. 46 Moreover, health institutions should educate the patients to wear a facemask, if available, during transport and at screening in the hospital, 47 wash hands at hospital entrance with soap and water or alcohol-based hand rub and maintain social distance by staying at least one meter away, whenever possible, from anyone.

To facilitate the early identification of suspected cases, healthcare facilities should:

• encourage HCWs to have a high level of clinical suspicion;

• establish a well-equipped screening station at the entrance to the facility, supported by trained staff;

• institute the use of screening questionnaires according to the updated case definition. 48 Clinical screening includes a system for assessing all patients at admission, allowing to stratify patients and to recognize possible • Suspected case:

A patient with acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough or shortness of breath), and one of following three items:

(1) A history of travel or residence in a location reporting community transmission of SARS-CoV-2 during the 14 days before symptom onset;

(2) Contact with a confirmed or probable COVID-19 case in the last 14 days before symptom onset; LA REGINA ET AL.

(3) Absence of an alternative diagnosis that fully explains the clinical presentation and requiring hospitalization;

• Probable case:

A suspected case for whom testing for SARS-CoV-2 is inconclusive or a suspected case for whom testing could not be performed for any reason.

• Confirmed case:

A person with laboratory confirmation of SARS-CoV-2 infection, irrespective of clinical signs and symptoms.

One or more negative results do not rule out the possibility of SARS-CoV-2 infection. Some reviews reported negative predictive values of PCR tests; values were between 65% and above 90%. [51] [52] [53] If a negative result is obtained from a patient with a high index of suspicion for SARS-CoV-2 infection, particularly when only upper respiratory tract specimens were collected, additional specimens from the lower respiratory tract should be considered, for example, by bronchoscopy. 54 

Protection of our frontline HCWs is paramount and PPE-including medical masks, gloves, gowns, and eye protection must be prioritized for HCWs and others caring for COVID-19 patients. In view of the global PPE shortage, strategies that can facilitate optimal PPE availability include minimizing the need for PPE in healthcare settings, ensuring rational and appropriate use of PPE, and coordinating PPE supply chain management mechanisms. Recommendations for PPE in patient rooms/wards are as follows:

(1). For HCWs with direct contact to COVID-19 patients, in the absence of AGPs, the following items are required: medical mask (consider respirator N95 or FFP2 or FFP3 standard if available), gown, gloves, eye protection (goggles or face shield).

(2). For HCWs with direct contact to COVID-19 patients, in settings where AGPs are frequently in place, the following items are required: respirator N95 or FFP2 or FFP3 standard, or equivalent, gown, gloves, eye protection and apron.

Bronchoscopy is used to explore the airways, to obtain biological samples and for treatment purposes 55-57 (e.g., foreign body extraction, removal or reduction of an endobronchial tumor, insertion of a stent). Indications for bronchoscopy differ between children and adults. In the pandemic it would be useful to differentiate three categories of pediatric bronchoscopies: urgent, semi-urgent, and elective (Table 1) .

All airway endoscopies are generating aerosol and are therefore considered high risk procedures for pathogen transmission to HCWs. 10 For this reason, all patients should be screened for SARS-Cov-2 infection. In urgent settings we suggest the rapid molecular test, for which less variation compared with rapid antigen tests, and an average sen- 13 There is consensus with this policy, preventing potential transmission of SARS-CoV-2 between patients and HCWs, which has been advocated by various groups. [13] [14] [15] [16] [17] 46, 47, 60, 61 

In communities with a high prevalence of SARS-CoV-2 infections, proper isolation precautions should always be applied, using a room Bronchoscopy has a limited role in the diagnosis of SARS-CoV-2 infection and should only be considered in intubated patients if upper respiratory samples are negative. 13 If bronchoscopy is performed in such instances, a minimum of 2-3 ml of specimen into a sterile, leak proof container for specimen collection is recommended. 59 with negative pressure settings or a designated airborne infection isolation room (AIIR). This also applies for routine flexible bronchoscopies in asymptomatic patients.

All patients with indications for bronchoscopy will be required to 5. Put on a face shield or goggles (face shields may be safe to use, but they distort the view, which is problematic during interventional bronchoscopy. Consider use of modified diving masks since they work very well in this setting 65 ).

6. Perform hand hygiene before putting on gloves. Gloves should cover the cuff (wrist) of the gown.

Staff's exposure time should be reduced by permitting patient and caregiver to enter the bronchoscopy theater only after all preparations are complete. 65 To reduce HCWs' exposure only essential people should be present during induction, bronchoscopy and when waking up the patient. This provides their filtration capacity which is effective to 99.97% of 0.1 micron particles. 67 Thus, we can consider them as an adjunctive means for decontamination of SARS-CoV-2 aerosols in clinical areas or procedure rooms. [68] [69] [70] The Chinese Thoracic Society has provided specific precautions:

to reduce cough and sputum, patients should be properly sedated before bronchoscopy (e.g., with muscle relaxants). In our opinion, this precaution can be applied only in patients without significant airway obstruction. Alfentanil 10 μg/kg should be used to obtund airway reflexes and the response to a possible placement of an endotracheal tube or a laryngeal mask airway (LMA). 65 Spontaneous breathing should be utilized to reduce aerosol generation.

Patients under local anesthesia and without intubation should wear masks to cover their mouths. To clear the coughed droplets of a patient it is possible to use a suction tube in the mouth (Figure 2 ).

For patients undergoing NIV, a NIV mask with a bronchoscope inlet to perform bronchoscopy through the inlet can be used, avoiding ventilation or oxygen administration during the examination ( Figure 3 ). Alternatively, a three-way connector allowing to insert the bronchoscope through the suction hole ( Figure 4A ) or a double swivel elbow adapter with suction port may be used. In intubated patients the bronchoscope can be inserted through a port used to suction reducing the risk of aerosol efflux ( Figure 4B ). 71 In patients with an LMA, a Rusch Mainz Universal Adapter should be placed between the anesthetic breathing circuit and the LMA to ensure a sealed channel for both bronchoscopy and 

The data that support the findings of this study are available from the corresponding author upon reasonable request. 

World Health Organization. Coronavirus disease (COVID-2019) situation reports. situation report -1

Director-General's opening remarks at the media briefing on COVID-19 -11

World Health Organization. Coronavirus disease (COVID-2019) situation reports. situation report -128

Will children reveal their secret? The coronavirus dilemma

Practical aspects of otolaryngologic clinical services during the 2019 novel coronavirus epidemic: an experience in Hong Kong

World Health Organization. Coronavirus disease (COVID-2019) situation reports. situation report -82

World Health Organization. Keep health workers safe to keep patients safe

Geneva: WHO; 2020

Sorveglianza integrata COVID-19 in Italia: Aggiornamento 09 Aprile 2020. Rome: Istituto superiore di sanità

Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review

Infection prevention and control of epidemic and pandemic prone acute respiratory infections in health care WHO Guidelines

The role of children in transmission of SARS-CoV-2: a rapid review

Asymptomatic COVID-19 infection in a child with nasal foreign body

American Association for Bronchology and Interventional Pulmonology (AABIP) Statement on the Use of Bronchoscopy and Respiratory Specimen Collection in Patients with Suspected or Confirmed COVID-19 Infection

World Health Organization. Rational use of personal protective equipment for coronavirus disease (COVID-19) and considerations during severe shortages. Interim guidance

Contact tracing: public health management of persons, including healthcare workers, having had contact with COVID-19 cases in the European Union -second update

Protecting healthcare workers from SARS-CoV-2 infection: practical indications

Management of patients with SARS-CoV-2 infections and of patients with chronic lung diseases during the COVID-19 pandemic (as of 9

A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-toperson transmission: a study of a family cluster

Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the chinese center for disease control and prevention

Children with Covid-19 in pediatric emergency departments in Italy

Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study

Age specificity of cases and attack rate of novel coronavirus disease (COVID-19)

Frequency of children vs adults carrying severe acute respiratory syndrome coronavirus 2 asymptomatically

Susceptibility to SARS-CoV-2 infection among children and adolescents compared with adults: a systematic review and metaanalysis

SARS-CoV-2 viral load in the upper respiratory tract of children and adults with early acute COVID-19

Culture-Competent SARS-CoV-2 in nasopharynx of symptomatic neonates, children, and adolescents

SARS-CoV-2 infections among children in the biospecimens from respiratory virus-exposed kids (brave kids) study. medRxiv

Clinical course and molecular viral shedding among asymptomatic and symptomatic patients with SARS-CoV-2 infection in a community treatment center in the Republic of Korea

COVID-19 epidemic: disease characteristics in children

Novel coronavirus disease (COVID-19) in children

Covid-19 in children: a brief overview after three months experience

Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults

Clinical and epidemiological characteristics of children with COVID-19

Clinical characteristics of COVID-19 in children: a systematic review

Epidemiology of COVID-19 among children in China

COVID-19 in Children: initial characterization of the pediatric disease

Why is COVID-19 less severe in children? A review of the proposed mechanisms underlying the age-related difference in severity of SARS-CoV-2 infections

Transmission of SARS-CoV-2: implications for infection prevention precautions

Visualizing speechgenerated oral fluid droplets with laser light scattering

Droplets and aerosols in the transmission of SARS-CoV-2

Bronchoscopy, laryngoscopy, and esophagoscopy during the COVID-19 pandemic

Influenza Aerosols in UK Hospitals during the H1N1 (2009) pandemic-the risk of aerosol generation during medical procedures

Bacteria emitted in ambient air during bronchoscopy-a risk to health care workers?

Aerosol-generating procedures and infective risk to healthcare workers from SARS-CoV-2: the limits of the evidence

SARS-CoV-2 viral load in upper respiratory specimens of infected patients

Triage of Suspected COIVD-19 Patients in non-US Healthcare Settings

Infection prevention and control during health care when COVID-19 is suspected. Interim guidance

From SARS to avian influenza preparedness in Hong Kong

World Health Organization. Global surveillance for COVID-19 caused by human infection with COVID-19 virus. Interim guidance

The Interpretation of SARS-CoV-2 Diagnostic Tests

What Is the predictive value of a single nasopharyngeal SARS-CoV-2 PCR swab test in a patient with COVID-like symptoms and/or significant COVID-19 exposure? Open Forum Infect Dis

Cochrane COVID-19 Diagnostic Test Accuracy Group Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection

World Health Organization. Laboratory testing for coronavirus disease (COVID-19) in suspected human cases

ERS statement: interventional bronchoscopy in children

ERS Statement on Tracheomalacia and Bronchomalacia in Children

Pediatric flexible and rigid bronchoscopy in European centers-Availability and current practice

Risk of bacterial exposure to the endoscopist's face during endoscopy

World Health Organization. Laboratory testing for 2019 novel Coronavirus (2019-nCov) in suspected human cases. Interim Guidance

COVID-19 and the risk to health care workers: a case report

Practice of endoscopy during COVID-19 pandemic: position statements of the Asian Pacific Society for Digestive Endoscopy (APSDE-COVID statements

COVID-19 E-Book "International pulmonologist's consensus on covid-19

European Centre for Disease Prevention and Control. Personal protective equipment (PPE) needs in healthcare settings for the care of patients with suspected or confirmed 2019-nCoV

Practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-nCoV) patients

Bronchoscopy in children with COVID-19: a case series

Clinical management of severe acute respiratory infection (SARI) when Covid-19 disease is suspected. Interim guidance

SARS: clearing the air

Management of patients infected with airborne-spread diseases: an algorithm for infection control professionals

High-efficiency particulate air filters in the era of COVID-19: function and efficacy

Considerations for optimizing the supply of powered air-purifying respirators (PAPRs): for healthcare practitioners (HCP)

Expert consensus on preventing nosocomial transmission during respiratory care for critically Ill patients infected by 2019 novel coronavirus pneumonia. ZhonghuaJie He He Hu Xi Za Zhi

Pediatric laryngoscopy and bronchoscopy during the COVID-19 pandemic: a four-center collaborative protocol to improve safety with perioperative management strategies and creation of a surgical tent with disposable drapes

Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1

The use of pediatric flexible bronchoscopy in the COVID-19 pandemic era