107
views
0
recommends
+1 Recommend
2 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Hyperinflammatory shock in children during COVID-19 pandemic

      letter

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          South Thames Retrieval Service in London, UK, provides paediatric intensive care support and retrieval to 2 million children in South East England. During a period of 10 days in mid-April, 2020, we noted an unprecedented cluster of eight children with hyperinflammatory shock, showing features similar to atypical Kawasaki disease, Kawasaki disease shock syndrome, 1 or toxic shock syndrome (typical number is one or two children per week). This case cluster formed the basis of a national alert. All children were previously fit and well. Six of the children were of Afro-Caribbean descent, and five of the children were boys. All children except one were well above the 75th centile for weight. Four children had known family exposure to coronavirus disease 2019 (COVID-19). Demographics, clinical findings, imaging findings, treatment, and outcome for this cluster of eight children are shown in the table . Table Demographics, clinical findings, imaging findings, treatment, and outcome from PICU Age; weight; BMI; comorbidities Clinical presentation Organ support Pharmacological treatment Imaging results Laboratory results Microbiology results PICU length of stay; outcome Initial PICU referral Patient 1 (male, AfroCaribbean) 14 years; 95 kg; BMI 33 kg/m2; no comorbidities 4 days >40°C; 3 days non-bloody diarrhoea; abdominal pain; headache BP 80/40 mmHg; HR 120 beats/min; RR 40 breaths per min; work of breathing; SatO2 99% NCO2 MV, RRT, VA-ECMO Dopamine, noradrenaline, argipressin, adrenaline milrinone, hydroxicortisone, IVIG, ceftriaxone, clindamycin RV dysfunction/elevate RVSP; ileitis, GB oedema and dilated biliary tree, ascites, bilateral basal lung consolidations and diffuse nodules Ferritin 4220 μg/L; D-dimers 13·4 mg/L; troponin 675 ng/L; proBNP >35 000; CRP 556 mg/L; procalcitonin>100 μg/L; albumin 20 g/L; platelets 123 × 109 SARS-CoV-2 positive (post mortem) 6 days; demise (right MCA and ACA ischaemic infarction) Patient 2 (male, AfroCaribbean) 8 years; 30 kg; BMI 18 kg/m2; no comorbidities 5 days >39°C; non-bloody diarrhoea; abdominal pain; conjunctivitis; rash BP 81/37 mmHg; HR 165 beats/min; RR 40 breaths/min; SVIA MV Noradrenaline, adrenaline, IVIG, infliximab, methylprednisolone, ceftriaxone, clindamycin Mild biventricular dysfunction, severely dilated coronaries; ascites, pleural effusions Ferritin 277 μg/L; D-dimers 4·8 mg/L; troponin 25 ng/L; CRP 295 mg/L; procalcitonin 8·4 μg/L; albumin 18 g/L; platelets 61 × 109 SARS-CoV-2 negative; likely COVID-19 exposure from mother 4 days; alive Patient 3 (male, Middle-Eastern) 4 years; 18 kg; BMI 17 kg/m2; no comorbidities 4 days >39°C; diarrhoea and vomiting; abdominal pain; rash; conjunctivitis BP 90/30 mmHg; HR 170 beats/min; RR 35 breaths/min; SVIA MV Noradrenaline, adrenaline, IVIG ceftriaxone, clindamycin Ascites, pleural effusions Ferritin 574 μg/L; D-dimers 11·7 mg/L; tropinin 45 ng/L; CRP 322 mg/L; procalcitonin 10·3 μg/L; albumin 22 g/L; platelets 103 × 109 Adenovirus positive; HERV positive 4 days; alive Patient 4 (female, AfroCaribbean) 13 years; 64 kg; BMI 33 kg/m2; no comorbidities 5 days >39°C; non-bloody diarrhoea; abdominal pain; conjunctivitis BP 77/41 mmHg; HR 127 beats/min; RR 24 breaths/min; SVIA HFNC Noradrenaline, milrinone, IVIG, ceftriaxone, clindamycin Moderate-severe LV dysfunction; ascites Ferritin 631 μg/L; D-dimers 3·4 mg/L; troponin 250 ng/L; proBNP 13427 ng/L; CRP 307 mg/L; procalcitonin 12·1 μg/L; albumin 21 g/L; platelets 146 × 109 SARS-CoV-2 negative 5 days; alive Patient 5 (male, Asian) 6 years; 22 kg; BMI 14 kg/m2; autism, ADHD 4 days >39°C; odynophagia; rash; conjunctivitis BP 85/43 mmHg; HR 150 beats/min; RR 50 breaths/min; SVIA NIV Milrinone, IVIG, methylprednisolone, aspirin, ceftriaxone Dilated LV, AVVR, pericoronary hyperechogenicity Ferritin 550 μg/L; D-dimers 11·1 mg/L; troponin 47 ng/L; NT-proBNP 7004 ng/L; CRP 183 mg/L; albumin 24 g/L; platelets 165 × 109 SARS-CoV-2 positive; likely COVID-19 exposure from father 4 days; alive Patient 6 (female, AfroCaribbean) 6 years; 26 kg; BMI 15 kg/m2; no comorbidities 5 days >39°C; myalgia; 3 days diarrhoea and vomiting; conjunctivitis BP 77/46 mmHg; HR 120 beats/min; RR 40 breaths/min; SVIA NIV Dopamine, noradrenaline, milrinone, IVIG, methylprednisolone, aspirin, ceftriaxone, clindamycin Mild LV systolic impairment Ferritin 1023 μg/L; D-dimers 9·9 mg/L; troponin 45 ng/L; NT-proBNP 9376 ng/L; CRP mg/L 169; procalcitonin 11·6 μg/L; albumin 25 g/L; platelets 158 SARS-CoV-2 negative; confirmed COVID-19 exposure from grandfather 3 days; alive Patient 7 (male, AfroCaribbean 12 years; 50kg; BMI 20 kg/m2; alopecia areata, hayfever 4 days >39°C; 2 days diarrhoea and vomiting; abdominal pain; rash; odynophagia; headache BP 80/48 mmHg; HR 125 beats/min; RR 47 breaths/min; SatO2 98%; HFNC FiO2 0.35 MV Noradrenaline, adrenaline, milrinone, IVIG, methylprednisolone, heparin, ceftriaxone, clindamycin, metronidazole Severe biventricular impairment; ileitis, ascites, pleural effusions Ferritin 958 μg/L; D-dimer 24·5 mg/L; troponin 813 ng/L; NT-proBNP >35 000 ng/L; CRP 251 mg/L; procalcitonin 71·5 μg/L; albumin 24 g/L; platelets 273 × 109 SARS-CoV-2 negative 4 days; alive Patient 8 (female, AfroCaribbean) 8 years; 50 kg; BMI 25 kg/m2; no comorbidities 4 days >39°C; odynophagia; 2 days diarrhoea and vomiting; abdominal pain BP 82/41 mmHg; HR 130 beats/min; RR 35 breaths/min; SatO2 97% NCO2 MV Dopamine, noradrenaline, milrinone, IVIG, aspirin, ceftriaxone, clindamycin Moderate LV dysfunction Ferritin 460 μg/L; D-dimers 4·3 mg/L; troponin 120 ng/L; CRP 347 mg/L; procalcitonin 7·42 μg/L; albumin 22 g/L; platelets 296 × 109 SARS-CoV-2 negative; likely COVID-19 exposure from parent 7 days; alive ACA= anterior cerebral artery. ADHD=attention deficit hyperactivity disorder. AVR=atrioventricular valve regurgitation. BMI=body mass index. BP=blood pressure. COVID-19=coronavirus disease 2019. CRP=C-reactive protein. FiO2=fraction of inspired oxygen. HERV=human endogenous retrovirus. HFNC=high-flow nasal canula. HR=heart rate. IVIG=human intravenous immunoglobulin. LV=left ventricle. MCA=middle cerebral artery. MV=mechanical ventilation via endotracheal tube. NIV=non-invasive ventilation. PICU=paediatric intensive care unit. RA=room air. RR=respiratory rate. RRT=renal replacement therapy. RV=right ventricle. RVSP=right ventricular systolic pressure. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. SatO2=oxygen saturation. SVIA=self-ventilating in air. VA-ECMO=veno-arterial extracorporeal membrane oxygenation. Clinical presentations were similar, with unrelenting fever (38–40°C), variable rash, conjunctivitis, peripheral oedema, and generalised extremity pain with significant gastrointestinal symptoms. All progressed to warm, vasoplegic shock, refractory to volume resuscitation and eventually requiring noradrenaline and milrinone for haemodynamic support. Most of the children had no significant respiratory involvement, although seven of the children required mechanical ventilation for cardiovascular stabilisation. Other notable features (besides persistent fever and rash) included development of small pleural, pericardial, and ascitic effusions, suggestive of a diffuse inflammatory process. All children tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on broncho-alveolar lavage or nasopharyngeal aspirates. Despite being critically unwell, with laboratory evidence of infection or inflammation 3 including elevated concentrations of C-reactive protein, procalcitonin, ferritin, triglycerides, and D-dimers, no pathological organism was identified in seven of the children. Adenovirus and enterovirus were isolated in one child. Baseline electrocardiograms were non-specific; however, a common echocardiographic finding was echo-bright coronary vessels (appendix), which progressed to giant coronary aneurysm in one patient within a week of discharge from paediatric intensive care (appendix). One child developed arrhythmia with refractory shock, requiring extracorporeal life support, and died from a large cerebrovascular infarct. The myocardial involvement 2 in this syndrome is evidenced by very elevated cardiac enzymes during the course of illness. All children were given intravenous immunoglobulin (2 g/kg) in the first 24 h, and antibiotic cover including ceftriaxone and clindamycin. Subsequently, six children have been given 50 mg/kg aspirin. All of the children were discharged from PICU after 4–6 days. Since discharge, two of the children have tested positive for SARS-CoV-2 (including the child who died, in whom SARS-CoV-2 was detected post mortem). All children are receiving ongoing surveillance for coronary abnormalities. We suggest that this clinical picture represents a new phenomenon affecting previously asymptomatic children with SARS-CoV-2 infection manifesting as a hyperinflammatory syndrome with multiorgan involvement similar to Kawasaki disease shock syndrome. The multifaceted nature of the disease course underlines the need for multispecialty input (intensive care, cardiology, infectious diseases, immunology, and rheumatology). The intention of this Correspondence is to bring this subset of children to the attention of the wider paediatric community and to optimise early recognition and management. As this Correspondence goes to press, 1 week after the initial submission, the Evelina London Children's Hospital paediatric intensive care unit has managed more than 20 children with similar clinical presentation, the first ten of whom tested positive for antibody (including the original eight children in the cohort described above).

          Related collections

          Most cited references2

          • Record: found
          • Abstract: found
          • Article: not found

          The Science Underlying COVID-19: Implications for the Cardiovascular System

          Corona Virus Disease 2019 (COVID-19) pandemic has impacted health and economy worldwide on an unprecedented scale. Patients have diverse clinical outcomes, but those with pre-existing cardiovascular (CV) disease, hypertension, and related conditions incur disproportionately worse outcome. The high infectivity of the SARS-CoV-2 virus is in part related to new mutations in the receptor binding domain, and acquisition of a furin cleavage site in the S spike protein. The continued viral shedding in the asymptomatic and pre-symptomatic individuals enhances its community transmission. The virus uses the ACE2 receptor for internalization, aided by TMPRSS2 protease. The tissue localization of the receptors correlates with COVDI-19 presenting symptoms and organ dysfunction. Virus-induced ACE2 down regulation may attenuate its function, diminish its anti-inflammatory role, and heightened angiotensin II effects in the predisposed patients. Lymphopenia occurs early and is prognostic, potentially associated with reduction of the CD4+ and some CD8+ T cells. This leads to imbalance of the innate/acquired immune response, delayed viral clearance, and hyper stimulated macrophages and neutrophils. Appropriate type I interferon pathway activation is critical for virus attenuation, and balanced immune response. Persistent immune activation in predisposed patients, such as the elderly and those with CV risk, can lead to hemophagocytosis like syndrome, with uncontrolled amplification of cytokine production, leading to multi-organ failure and death. In addition to the airways and lungs, the cardiovascular system is often involved in COVID-19 early, reflected in the release of highly sensitive troponin and natriuretic peptides, which are all extremely prognostic, particularly in those showing continued rise, along with cytokines such as IL-6. Inflammation in the vascular system can result in diffuse microangiopathy with thrombosis. Inflammation in the myocardium can result in myocarditis, heart failure, cardiac arrhythmias, acute coronary syndrome, rapid deterioration and sudden death. Aggressive support based on early prognostic indicators with expectant management can potentially improve recovery. Appropriate treatment for heart failure, arrhythmias, acute coronary syndrome and thrombosis remain important. Specific evidence based treatment strategies for COVID-19 will emerge with ongoing global collaboration on multiple approaches being evaluated. To protect the wider population, antibody testing and effective vaccine will be needed to make COVID-19 history.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Clinical Analysis of Kawasaki Disease Shock Syndrome

            Kawasaki disease shock syndrome (KDSS) refers to Kawasaki disease (KD) patients who present more than 20% decrease in systolic blood pressure compared to healthy individuals of the same age, or to those patients who show peripheral blood circulation perfusion disorder. KDSS may have varied clinical courses and could be easily ignored and misdiagnosed. Yet, this syndrome could be deleterious, especially when combined with coronary artery injury or multiple organ dysfunctions. Therefore, early diagnosis of KDSS through specific clinical manifestations is critical. This manuscript summarizes the clinical features and treatment methods of 11 children with KDSS who were able to fully recover in our hospital. The results shed lights on understanding the early identification of KDSS and could assist in reducing the complications of KD and improving the quality of life in KDSS patients. All patients met the criteria for KD according to the standard of American Academy of Pediatrics and Cardiology Society,[1] and they also met the requirements for concurrent shock of KD proposed by Kanegaye et al. in 2009.[2] We retrospectively reviewed the medical records of 11 children diagnosed with KDSS in our hospital from February 2012 to February 2017. Among these 11 patients, 7 were male and 4 were female. Ages ranged from 1 month to 9 years. Clinical manifestations of shock occurred in the first 3–10 days during the disease course with a mean time of 6.1 days. Five of the 11 patients experienced shock within 5 days of KD onset. These data suggested that patients already exhibited shock even before KD diagnosis could be made. All the 11 cases showed persistent high fever, lymph node enlargement, and cardiac insufficiency. More than 50% of patients had multiple organ dysfunctions as listed in Table 1. Table 1 Clinical presentations of children with Kawasaki disease shock syndrome (n = 11) Clinical presentations Cases (n) Physical examination  Lymphadenectasis 11  Rash 10  Conjunctival hyperemia 10  Joint swelling of the palms or feet 9  Chapped lips 6 Clinical manifestations  Coronary artery dilatation 9  Shock within 5 days 5  Pneumonitis 7 Auxiliary examinations  Hypoalbuminemia 10  Hepatic insufficiency 8  Anemia 8  Hyponatremia 6  Electrocardiogram abnormalities 8  Urine routine abnormalities 5  Hypokalemia 3 Intravenous immunoglobulin (IVIG) and oral administration of aspirin were given in all KDSS patients, and re-treatment with IVIG was done in five patients who presented with IVIG resistance. In addition, all patients received fluid volume resuscitation, vasoactive drugs, and nutrition support treatments. Six patients received additional treatments including respiratory support and methylprednisolone. KDSS is considered a rare disease around the world, yet in the recent years, more interests have focused on the early diagnosis of KDSS. Clinical manifestations of KDSS are atypical.[3 4] It can rapidly develop into shock, and often with strong inflammatory responses which could lead to coronary artery disease and multiple organ dysfunctions. Therefore, early identification is particularly important. Through literature review and examination of our 11 patients, we have summarized the following characteristics for KDSS: (1) It is more common in males; (2) symptoms include lymphadenectasis, hypoalbuminemia, hyponatremia, hepatic insufficiency, anemia, and electrocardiogram abnormalities; the incidence of coronary artery dilatation is high, and some children may have severe gastrointestinal symptoms; (3) inflammatory indicators are significantly increased; (4) patients often present with IVIG resistance; (5) 50% of patients need hormone therapy; and (6) shock appears at an early stage. For the treatment of KDSS, IVIG combined with aspirin and vasoactive drugs is the current standard of care. Recent studies[5] have shown that glucocorticoids combined with a large dose of gamma globulin treatment can reduce the incidence of coronary artery disease in patients with severe KD. In this study, 11 patients were given anti-shock therapy, such as fluid resuscitation, vasoactive drugs, and respiratory support therapy. Further, six children underwent hormone therapy due to inflammatory reactions. In our study, a high dosage of methylprednisolone was given to one patient in the initial treatment. Disease progression was controlled, yet heart rate declined afterward. Arrhythmia occurred with the junctional escape rhythm and the onset of cyanosis followed. Vasoactive drugs could not maintain a normal range of blood pressure; therefore, a temporary pacemaker was implanted. For the other patients in our cohort, vital signs and blood and inflammation indicators returned to normal after shock through interventions. In summary, the cases in our study shared similar clinical manifestations with previously reported cases. However, in addition to standard care, respiratory support and hormone therapy were used in our patients, and temporary pacemakers were implanted when vasoactive drugs could not maintain a normal range of blood pressure. Our study indicated that early diagnosis and comprehensive therapeutic methods based on the disease progression are important in treating KDSS. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
              Bookmark

              Author and article information

              Contributors
              Journal
              Lancet
              Lancet
              Lancet (London, England)
              Elsevier Ltd.
              0140-6736
              1474-547X
              7 May 2020
              7 May 2020
              Affiliations
              [a ]South Thames Retrieval Service for Children, Evelina London Children's Hospital Paediatric Intensive Care Unit, London SE1 7EH, UK
              [b ]Evelina London Children's Hospital, London, UK
              Article
              S0140-6736(20)31094-1
              10.1016/S0140-6736(20)31094-1
              7204765
              32386565
              0489884e-d97f-4859-9f32-9f8663d5fc26
              © 2020 Elsevier Ltd. All rights reserved.

              Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

              History
              Categories
              Article

              Medicine
              Medicine

              Comments

              Comment on this article