key: cord-0787719-l405c850 authors: Ravikumar, Namita; Nallasamy, Karthi; Bansal, Arun; Angurana, Suresh Kumar; Basavaraja, G. V.; Sundaram, Manu; Lodha, Rakesh; Gupta, Dhiren; Jayashree, Muralidharan title: Novel Coronavirus 2019 (2019-nCoV) Infection: Part I - Preparedness and Management in the Pediatric Intensive Care Unit in Resource-limited Settings date: 2020-04-25 journal: Indian Pediatr DOI: 10.1007/s13312-020-1785-y sha: 88b5c94473256dc08e78e5344fd415773224045a doc_id: 787719 cord_uid: l405c850 First reported in China, the 2019 novel coronavirus has been spreading across the globe. Till 26 March, 2020, 416,686 cases have been diagnosed and 18,589 have died the world over. The coronavirus disease mainly starts with a respiratory illness and about 5-16% require intensive care management for acute respiratory distress syndrome (ARDS) and multi-organ dysfunction. Children account for about 1-2% of the total cases, and 6% of these fall under severe or critical category requiring pediatric intensive care unit (PICU) care. Diagnosis involves a combination of clinical and epidemiological features with laboratory confirmation. Preparedness strategies for managing this pandemic are the need of the hour, and involve setting up cohort ICUs with isolation rooms. Re-allocation of resources in managing this crisis involves careful planning, halting elective surgeries and training of healthcare workers. Strict adherence to infection control like personal protective equipment and disinfection is the key to contain the disease transmission. Although many therapies have been tried in various regions, there is a lack of strong evidence to recommend anti-virals or immunomodulatory drugs. T he year 2020 started with the emergence of the 2019 novel corona virus (2019-nCoV) as a threat to the world; shortly afterwards the World Health Organization (WHO) declared it a pandemic. Having begun in China, globalization and travel led its spread all over the globe, overwhelming the healthcare resources and resulting in high mortality and morbidity. About 5% of adults, especially those with comorbidities, were critically ill and required intensive care unit (ICU) care [1] . People of all ages were found to be susceptible but severe illness was rare in children [2] . Most of the experience of critical care management of pediatric patients with coronavirus disease 2019 (COVID-19) is derived from the affected children of present epidemic in China, as well as from the previous coronaviral outbreaks viz. Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). We write this review as a guidance statement for preparedness and managing children with suspected or confirmed COVID-19 requiring intensive care in a resource-limited setting like India. Global: Till March 26, 2020, a total of 416,686 confirmed cases from 197 countries with 18,589 deaths have been reported by WHO. China has reported the maximum cases with a total of 81,869, followed by Italy with 69,176 cases. However, mortality is more in Italy with 6,820 (9.9%) deaths followed by China having 3,287 (4%) deaths. The United States of America has surpassed Spain and Germany over the last few days with 51,914 cases and 673 deaths [3] . Indian scenario: A total of 606 cases with 10 deaths have been reported from India as on March 26, 2020 as reported by the WHO. Among these cases, only one child from Kerala has been tested positive. The 2019-nCoV belongs to a group of enveloped positive-sense RNA viruses in the family, Coronaviridae with 4 genera viz., alpha, beta, gamma and delta. Human coronaviruses (HCoV) belong to alpha and beta genus First reported in China, the 2019 novel coronavirus has been spreading across the globe. Till 26 March, 2020, 416,686 cases have been diagnosed and 18,589 have died the world over. The coronavirus disease mainly starts with a respiratory illness and about 5-16% require intensive care management for acute respiratory distress syndrome (ARDS) and multi-organ dysfunction. Children account for about 1-2% of the total cases, and 6% of these fall under severe or critical category requiring pediatric intensive care unit (PICU) care. Diagnosis involves a combination of clinical and epidemiological features with laboratory confirmation. Preparedness strategies for managing this pandemic are the need of the hour, and involve setting up cohort ICUs with isolation rooms. Re-allocation of resources in managing this crisis involves careful planning, halting elective surgeries and training of healthcare workers. Strict adherence to infection control like personal protective equipment and disinfection is the key to contain the disease transmission. Although many therapies have been tried in various regions, there is a lack of strong evidence to recommend anti-virals or immunomodulatory drugs. R R R R T T T T T I I I I I C C is between 2.2 to 3.6, which is comparable to SARS-CoV but higher than MERS-CoV [6] . Less severe affection in children: Children less than 10 years of age accounted for 1% of the total cases [1] . The median age among pediatric cases was 6.7 years [7] . The lesser proportion of severe cases among children has been attributed to lesser opportunities for exposure and immaturity of angiotensin converting enzyme 2 receptors, which are proposed to be the binding sites for coronaviruses [8, 9] . The overall case fatality rate as per China Centre for Disease Control and Prevention (CDC) is 2.3%, which is much lower compared to SARS (9.6%) and MERS (34%) but significantly higher compared to the latest H1N1 influenza pandemic (0.001 -0.007%) [1] . However, as per WHO, the global case fatality rate is as high as 4.4% with absolute number of deaths already higher than the total fatality of SARS and MERS combined [10] . The case fatality reported from Italy is 7.2% which has gone up to 9.8% as per WHO (as on March 26, 2020) [11] . The common clinical features reported in the critically ill patients include fever (98%), cough (77%), dyspnea (63%), malaise (35%), myalgia, headache, nausea, vomiting and diarrhea [12] . A prospective study from China involving 171 children with confirmed COVID-19 reported fever (41%) with a median duration of 3 days (1-16), cough (48%), pharyngeal erythema (46%) tachypnea (28%) and diarrhea (8.8%). The cohort had 15% asymptomatic, 19% upper respiratory infection, and 65% pneumonia. Only 3 children (1.7%) required care and mechanical ventilation. All three of them had comorbidities, and one died [7] . The severe and critical categories require admission and management in ICU. Among adults, 7% of patients admitted with SARS-CoV-2 pneumonia required ICU care. The mean age of these ICU patients was 60 years with male: female ratio of 2:1 and 50% had chronic illness. Majority had Multi-organ dysfunction syndrome (MODS) with ARDS (67%), acute kidney injury (29%), liver dysfunction (29%) and cardiac injury (23%). Of the ICU admissions, 71% required mechanical ventilation, 35% vasoactive support, 17% renal replacement therapy and 11% ECMO. Mortality was as high as 61% among the critically ill [12] . As per unpublished data from Italy, 16% of admitted patients with COVID-19 needed ICU care [13] . In the Chinese pediatric cases, 5.9% of all pediatric cases belonged to the severe or critical categories. Based on the experience in managing community-acquired pneumonia, high-risk pediatric population includes children with underlying conditions such as congenital heart disease, broncho-pulmonary hypoplasia, airway/lung anomalies, severe malnutrition, and immunocompromised state; however, more information is needed in the setting of COVID-19 [2] . Case definitions for suspected, probable and confirmed COVID-19 cases as given by WHO are in Box I [16] . The largest series on children analyzing suspected and confirmed COVID cases is from the electronic data base of Chinese CDC [17] . Cases were suspected based on the presence of clinical features and exposure history. They also identified high-risk cases and categorized into groups based on severity (Box II). Laboratory testing of suspected cases is based on clinical and epidemiological factors. Screening protocol should be adapted to local situation and may change with the evolution of the outbreak scenario in the local population. Recent testing strategy in India (as on March 20, 2020) given by ICMR is as per algorithm in Fig. 1 [18] . Specimen handling for molecular testing would require Biosafety 2 (BSL-2) or equivalent facilities. VOLUME 57 __ APRIL 15, 2020 RAVIKUMAR, ET AL. Attempts to culture the virus require minimum of BSL-3 facilities [19] . Upper respiratory specimens: nasopharyngeal and oropharyngeal swabs; both swabs are placed together in a viral transport medium and transported to the laboratory in ice. Lower respiratory specimens: sputum and/or endotracheal aspirate or bronchoalveolar lavage in patients with more severe respiratory disease (obtained with aerosol precautions) (a) Respiratory tract or blood samples tested positive for 2019-nCoV nucleic acid using Real-time Reverse Transcriptase -Polymerase Chain Reaction (RT-PCR) (b) Genetic sequencing of respiratory tract or blood samples is highly homologous with the known 2019-nCoV, but this is not done routinely. Serological tests may help in epidemiological investigation but there could be cross reactivity with other coronaviruses. Viral isolation is not done routinely for diagnosis. Rapid diagnostic test kits like Xpert Xpress [20, 21] . Complete blood count: Lymphopenia was seen in 85% of critically ill adults, suggesting it a marker of severe disease while among the overall pediatric cases, it was seen in 3.5% [7, 12] . Infection markers: Elevation of C-reactive protein (CRP) was reported in 20% and procalcitonin in 64% of cases [7] . Radiological findings: Chest radiography (CXR) or computed tomography (CT) are not recommended as a routine for children but only in specific cases presenting with pneumonia and/or acute respiratory distress syndrome (ARDS). Parenchymal abnormalities with peripheral consolidations on CXR have been reported in a small case series from Korea [14] . Ground glass opacities (32%), local patchy shadows (18%) and bilateral patchy shadows (12%) on CT chest were the common findings in children [7] . Bilateral pneumonia (75%), unilateral pneumonia (25%) and multiple mottling and ground-glass opacity (14%) were reported based on CXR and CT findings from adult patients in Wuhan, China [15] . Laboratory markers of organ dysfunction: Elevation of transaminases is seen in 12-14% and d-Dimer in 14% cases [7] . A phased and tiered plan for ICU during the pandemic needs to be made based on the assessment of healthcare burden and resource utilization [13, 22, 23] . A dedicated area for screening and triaging of patients with suspected COVID-19 is essential. Once the patient fits to the case definition and requires admission, unnecessary movement must be avoided and minimum staff should accompany the patient. Ensure that the patient (if self-breathing) and the accompanying persons should be on a 3-ply surgical mask. Severe and critical cases need ICU care for monitoring, ventilation and organ support therapy. Severe acute respiratory illness (SARI): SARI is defined by the presence of cough and fast breathing plus at least one of the following [25] :(i) Oxygen saturation (SpO 2 ) <90%, (ii) severe chest indrawing and grunting, and (iii) altered mental status. SARI is the most common indication for ICU transfer and most guidelines are similar to management of any viral pneumonia with ARDS with an emphasis on minimizing risk of transmission to others, especially healthcare workers [26, 27] . The details on the management of SARI are given in Part II of this write-up and Table I . Septic shock: Management of septic shock in COVID is not very different from the routine. However, the Surviving Sepsis Campaign (SSC) guidelines for COVID-19 recommend conservative fluid strategy, avoiding colloids as resuscitation fluid, and to use low dose steroids in catecholamine refractory shock [28] . In children, epinephrine is the first vasoactive of choice for septic shock. Co-infections like secondary bacterial pneumonia are common, especially in children (50%) and addition of broad spectrum antibiotic to cover gram positive, gram negative, and staphylococcal infection is recommended [29] . Myocarditis: Cardiogenic shock with elevations in hypersensitive Tropnonin-I have been seen in 12% of patients. Management includes inodilators like milrinone, diuretics, immunomodulators (methylprednisolone and IVIG) and circulatory support with ECMO (extracorporeal membrane oxygenation) have also been used in a few cases [30, 31] . Acute kidney injury : This has been reported in 7% and renal replacement therapy may be necessary [32] . Supportive care: This includes conservative fluid management, nutrition, appropriate sedo-analgesia, and prevention and treatment of healthcare associated infections. Although no definitive therapy till date has proven benefit for SARS-CoV2, antiviral drugs like Remdesivir, Lopinavir/Ritonavir are being used in over 50% of the critically ill adults based on in vitro viral inhibition and recovery in SARS and MERS but there is no strong evidence [33] [34] [35] [36] . Chloroquine has been found to increase endosomal pH and hinder virus cell fusion and also interfere with ACE2, a receptor for binding of SARS-CoV2 [37] . A combination of hydroxychloroquine and azithromycin showed reduction in viral load [38] . VOLUME 57 __ APRIL 15, 2020 RAVIKUMAR, ET AL. Interferons, IVIG, and convalescent plasma from recovered SARS patients are other tested treatment options [39] . Vaccination for RNA viruses (measles, influenza, polio) has shown higher titers of neutralizing antibodies against SARS-CoV [40] (Table II) . Based on the current experience, we may use broad spectrum antibiotics, oseltamivir, protease inhibitors, hydroxychloroquine and azithromycin. Lopinavir/Ritonavir along with Chloroquine should be avoided in combination. In adult patients with COVID-19 pneumonia, onset of symptoms to respiratory failure takes an average of 7 days with peak severity at 10 days. Signs of improvement starts occurring by day 14. However, at the time of reporting of most studies, many patients were still admitted and their course needs to be followed to know the exact prognosis [40] . In the intensive care setting, disinfection of high-touch surfaces like monitors, ventilator screen, other equipment, resuscitation trolleys etc are essential and need to be carried out every 4 hours. Surface decontamination: Alcohol (e.g. isopropyl 70% or ethyl alcohol 70%) can be used to wipe down surfaces where the use of bleach is not suitable for e.g. Mobiles, laptops, keys, pens etc. Disinfection: Freshly prepared1% sodium hypochlorite should be used as a disinfectant for cleaning and disinfection with at least 10 minute contact period. Aerosol: Ensure room disinfection within 20 minutes of any procedure generating aerosol. Social distancing: Maintain at least 1 meter distance unless required for examination or procedure. Contact and droplet precautions: minimize direct contact, ensure hand hygiene, and cough etiquette. Apart from risks related to droplet spread and from contaminated surfaces, ICU professionals face the challenge of acquiring infection during aerosol generating procedures (see table in Part II) . HCW should wear a medical mask and gown when entering a room where patients with suspected or confirmed COVID-19 are admitted and use full personal protective equipment (PPE), which includes N95 mask, goggles or face shield, cap, full sleeve gown and shoe cover, when performing aerosol-generating procedures [41] . The entire PPE is [26] . ICMR recommends prophylactic use of hydroxychloroquine 400 mg twice a day on day 1, followed by 400 mg once weekly for next 7 weeksfor HCW managing suspected or confirmed COVID-19 patients [42] . It is important to minimize the number of people inside the room during high aerosol generating events like cardiopulmonary resuscitation. One airway specialist, one nurse/doctor for chest compression and one nurse for medication are essential. Other assistants may remain outside the room and may enter only if necessary after donning full PPE. Hand bagging needs to be avoided. During any disconnection from ventilator, endotracheal (ET) tube needs to be clamped and/or viral filter attached to the ET tube. In case re-intubation is required, follow the standard procedure described (see Part II in this issue). The COVID-19 pandemic caused by 2019-nCOV has become a serious concern for mankind all over the world. It has challenged and overwhelmed the existing intensive care facilities globally. SARI is the most common indication for intensive care management and is associated with high mortality. The disease so far appears to be less common in children and seems to have a milder course. Preparation for handling crisis during this outbreak is essential for early identification, stratification and management of cases. Prevention by ensuring strict infection control practices minimizes transmission to other patients and healthcare workers, especially in intensive care units. Contributors: NR, KN, AB, SKA: substantial contribution to the conception and design of the work (ii) drafting the work (iii) final approval of the version to be published (iv) agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved; GVB, MS, RL, DG, MJ: substantial contributions to the acquisition and interpretation of data for the work (ii) revising it critically for important intellectual content (iii) Final approval of the version to be published (iv) Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Funding: None; Competing interests: None stated. 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