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      Collateral effects of COVID‐19 pandemic in pediatric hematooncology: Fatalities caused by diagnostic delay

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          To the Editor: Coronavirus disease COVID‐19 has deeply modified national health services with a profound impact on hospitals, and in particular emergency and intensive care unit (ICU) activities. As recently reported in Italy, pediatric emergency accesses substantially decreased likely due to the instructions to prevent overcrowding in emergency rooms and spread of SARS‐CoV‐2 infection and to fear of the infection. 1 At the Santobono‐Pausilipon Hospital (Naples), pediatric emergency accesses in March 2020 were only one‐fifth of those registered in 2019 in the same period. Likewise, a marked reduction of consultations also occurred in family pediatric clinics. 2 We report here three children who arrived at hospital with life‐threatening conditions at the onset of acute lymphoblastic leukemia (ALL) between March 14 and April 10, 2020. First case: A 2‐year‐old child arrived at the emergency department with a 15‐day history of fatigue, pallor, and dyspnea, in a comatose state with severe anemia, respiratory distress, hematemesis, and metabolic acidosis. Chest X‐ray showed interstitial pneumonia. Blood tests showed the following results: hemoglobin 2.7 g/dL, WBC count 185 000/μL, platelets (PTL) 10 000/μL, and LDH 3609 U/L. Peripheral blood was diagnostic for CD10, CD19, and CD58 positive ALL (B‐lineage ALL). The patient, admitted at the ICU, intubated, transfused with RBC, PTL, and plasma, died 12 h after arrival at the hospital due to progressive worsening of clinical conditions. The nasal swab was negative for SARS‐CoV‐2 and positive for adenovirus. Second case: A 5‐year‐old child arrived at the emergency department with a 1‐month history of respiratory distress. Imaging showed a mediastinal mass compressing the brachiocephalic vein, the aorta, the pulmonary trunk, and the left pulmonary artery; tracheal deviation;compression of the left main bronchus; left lung atelectasis; and pleural effusion. Blood tests showed the following results: hemoglobin 14.5 g/dL, WBC count 37 000/μL, PTL 294 000/μL, LDH 6153 U/L, creatinine 1.9 mg/dL. Peripheral blood was diagnostic for CD5, CD7, CyCD3, and CD8 positive ALL (T‐ALL). Steroid treatment was started. Clinical conditions deteriorated rapidly with cardiac and renal failure. The patient, admitted to ICU 2 h after arrival at the hospital and intubated, died 24 h later. The nasal swab was negative for SARS‐CoV‐2. Third case: A 4‐year‐old child arrived at the hospital with 1‐month history of fever, cough, and shortness of breath, treated at home with antibiotics and steroids without improvement. Imaging showed a mediastinal mass compressing the left brachiocephalic, azygos and superior cava veins, and right pulmonary artery and vein; mild tracheal deviation; compression of the left main bronchus; pericardial and pleural effusion; nephro‐hepato‐splenomegaly and ascites. Due to signs of cardiac tamponade, pericardiac and pleural drainage were placed and the patient was admitted to ICU and intubated. Blood tests showed the following results: normal hemoglobin, WBC, and PTL counts; LDH 2732 U/L, creatinine 2.98 mg/dL, K 8 mEq/L, and Ca 5.4 mEq/L. Bone marrow was diagnostic for CD2, CD5, CD7, CD99, and CyCD3 positive ALL (T‐ALL). Treatment with steroids was started. Due to progressive renal failure, hemodialysis was performed for 9 days. Clinical conditions improved with rapid shrinking of mediastinal masses and resolution of pericardial and pleural effusion. The patient was thus extubated and treatment for ALL was instituted with good response to induction therapy. The nasal swab was negative for SARS‐CoV‐2. The three cases of ALL are described here, two of them fatal, arrived at the hospital in critical condition, most likely as a consequence of fear of COVID‐19. Delay in diagnosis of neoplastic disease is a well‐known problem in low‐ to middle‐income countries (LMIC), but is quite rare in high‐income countries (HIC). Actually, this combination of events never occurred in the past at the Santobono‐Pausilipon Hospital, where, at the time of writing, no SARS‐CoV‐2‐positive cases have been identified among children treated for cancer. Considering low prevalence of virus spreading in children and that SARS‐CoV‐2‐positive children are generally asymptomatic or have a very mild course of the disease, there is a substantial risk that collateral effects of COVID‐19 pandemic, that is, delays in diagnosis, chemotherapeutic treatments, and treatment of chemotherapy complications, may be worse than those posed by the disease itself. 3 , 4 , 5 Recently, the major pediatric cancer scientific associations have expressed great concern on the risk that fear to access to medical care raised by COVID‐19 may cause these delays not only in LMIC but also in HIC with dramatic consequences we are not used to face. 6 , 7 Our experience confirms the occurrence of these collateral effects, indicating that there is a need of awareness of this risk and careful medical attention to assure timely diagnoses and adequate treatment adherence in childhood cancer. CONFLICT OF INTEREST The authors declare that there is no conflict of interest.

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          Delayed access or provision of care in Italy resulting from fear of COVID-19

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            Delayed access or provision of care in Italy resulting from fear of COVID-19

            During Italy's national lockdown for coronavirus disease 2019 (COVID-19), official hospital statistics in the period March 1–27, 2020, show substantial decreases—ranging from 73% to 88%—in paediatric emergency department visits compared with the same time period in 2019 and 2018 (figure ). Similarly, family paediatricians widely report a considerable reduction in clinic visits, although this is difficult to measure precisely. Figure Visits to paediatric emergency departments across five hospitals in Italy, March 1–27, 2020, compared with the same period in 2018 and 2019 Data are official hospital statistics (courtesy of the authors). Schools and sports activities have been closed since March 1 in Italy, so it is understandable that the numbers of acute infections and traumas among children are lower than usual. In addition, relatively few cases of COVID-19 among children have been reported. 1 As of April 2, the 1624 cases in the paediatric population ( 39°C) and the other presented with severe anaemia (haemoglobin 4·2 mg/dL) and respiratory distress after emergency department access was delayed. One of these patients died several days after hospital admission. One child presented with long-lasting convulsions after three previous episodes of convulsions had been treated at home without medical assistance; the patient was eventually diagnosed with bacterial pneumonia. A 3-year-old girl was admitted to hospital after 6 days at home with very high fever (>39°C), with a sepsis secondary to a pyelonephritis. A neonate was kept home despite vomiting for several days because of hypertrophic pyloric stenosis and arrived in the emergency department in hypovolaemic shock. Another child, aged 2 years, had been vomiting for several days and unable to eat before presenting with severe hypoglycaemia. One child arriving in the emergency department having been unable to pass faeces for more than a week was diagnosed with an abdominal mass of 15 cm diameter, later diagnosed as Wilm's tumour; the diagnosis by telephone from his paediatrician had been functional constipation. An adolescent with cerebral palsy and severe malnutrition got in touch with the hospital after 10 days of fever at home with increased oxygen needs, and died in the ambulance on the way to the hospital. The precise cause of fever and death was not ascertained but the adolescent was negative for COVID-19 infection. Another child with cerebral palsy, tracheotomy, and enteral nutrition died on route to the hospital after 3 days of bloody stools. A child with Mowat Wilson syndrome, in dialysis for chronic renal insufficiency, arrived at the hospital after 3 days of being “less active than usual” with capillary refill time of 4 s, heart rate of 50 beats per min, oxygen saturation level not detectable, mixed acidosis, and creatine 4 mg/dL; the child died after 4 days in the ICU. Of this small series of 12 cases, half of the children were admitted to an ICU and four died. In all cases, parents reported avoiding accessing hospital because of fear of infection with SARS-CoV-2. Furthermore, in five cases, the family had contacted health services before accessing care, but their health provider was unavailable because of the COVID-19 epidemic, or hospital access was discouraged because of the possible risk of infection. All cases were either negative for SARS-CoV-2 or had a clinical presentation (eg, diabetes) that did not justify a diagnostic test according to the national criteria. Notably, no death occurred in the same hospitals during the same period in 2019, and the total yearly number of paediatric deaths in these hospitals ranges from zero to three. These cases are clearly a small sample compared with the overall number of paediatric visits recorded in the five hospitals during this week (12 [2%] of 502). However, since delay in access to care was not monitored systematically, this small case series might underestimate the problem. We believe that further monitoring of access to routine clinical care is needed during the COVID-19 pandemic. There is a need to prevent delays in accessing hospital care and to increase provision of high-quality coordinated care by health-care providers. Both of these aspects should be considered as part of the overall public health impact of the COVID-19 pandemic, as evident in other epidemics,3, 4 and must be adequately monitored. Both the general population and health-care workers need clear guidance and information. Specifically, parents should be made fully aware that the risks of delayed access to hospital care for emergency conditions can be much higher than those posed by COVID-19. Specific duties and obligations of different types of health-care professionals should be clearly defined, taking into consideration the risk level of the working environment, the health-care worker's specialty, the probable harms and benefits of treatment, and competing obligations deriving from workers' multiple roles.4, 5
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              Flash Survey on SARS-CoV-2 Infections in Pediatric Patients on anti-Cancer Treatment

              Introduction Since the beginning of COVID-19 pandemics, it is known that the severe course of the disease occurs mostly among elderly, whereas it is rare among children and young adults. Comorbidities, in particular diabetes and hypertension, clearly associated with age, besides obesity and smoke are strongly associated with the need of intensive treatment and a dismal outcome. A weaker immunity of the elderly has been proposed as a possible explanation of this uneven age distribution. Along the same line, anecdotal information from Wuhan, China mentioned a severe course of COVID-19 in a child treated for leukemia. Aim and methods We made a flash survey on COVID19 incidence and severity among children on anticancer treatment. Respondents were asked by email to fill in a short web based survey. Results We received reports from 25 countries, where approximately 10,000 patients at risk are followed. At the time of the survey, over 200 of these children were tested, nine of whom were positive for COVID-19. Eight of the nine cases had asymptomatic to mild disease and one was just diagnosed with COVID-19. We also discuss preventive measures that are in place or should be taken as well as treatment options in immunocompromised children with COVID-19. Conclusion Thus, even children receiving anti-cancer chemotherapy may have a mild or asymptomatic course of COVID-19. While we should not underestimate the risk of developing a more severe course of COVID-19 than observed here, the intensity of preventive measures should not cause delays or obstructions in oncological treatment.

                Author and article information

                Pediatr Blood Cancer
                Pediatr Blood Cancer
                Pediatric Blood & Cancer
                John Wiley and Sons Inc. (Hoboken )
                11 June 2020
                [ 1 ] Department of Pediatric Hemato‐Oncology Santobono‐Pausilipon Hospital Naples Italy
                [ 2 ] Pediatric Hemato‐Oncology University of Milano‐Bicocca Fondazione MBBM/Hospital San Gerardo Monza Italy
                [ 3 ] Intensive Care Unit Santobono‐Pausilipon Hospital Naples Italy
                [ 4 ] Nephrology Unit Santobono‐Pausilipon Hospital Naples Italy
                [ 5 ] Emergency Unit Santobono‐Pausilipon Hospital Naples Italy
                Author notes
                [* ] Correspondence

                Rosanna Parasole, Department of Pediatric Hemato‐Oncology, Santobono‐Pausilipon Hospital, Via Posillipo 226, 80123 Naples, Italy.

                Email: rparasol64@

                © 2020 Wiley Periodicals LLC

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

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                Letter to the Editor
                Letter to the Editor
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