Novel paediatric presentation of COVID-19 with ARDS and cytokine storm syndrome without respiratory symptoms

Pain, Clare; Felsenstein, Susanna; Cleary, Gavin; Mayell, Sarah; Conrad, Karsten; Harave, Srikrishna; Duong, Phuoc; Sinha, Ian; Porter, David A.; Hedrich, Christian M.

doi:10.1016/s2665-9913(20)30137-5

Cited by 58 publications

(69 citation statements)

References 12 publications

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“…Following IVMP treatment patients rapidly became afebrile in 20/22 (90.9%). Children on a treatment regimen containing corticosteroids from dose one or biologics [ 45 ] became afebrile significantly more rapidly when compared to those who received IVIG alone (median 1 versus 2 days, p = 0.015); many of which thereafter required a second dose which was mostly accompanied by steroids ( Figure 7 ).…”

Section: Resultsmentioning

confidence: 99%

“…Lymphopenia [ 41 , 42 ], thrombocytopenia and circulating immune complexes have been reported, all distinct from classical KD [ 41 , 43 ]. Lastly, coagulopathy associated with antiphospholipid antibodies has been repeatedly described in PIMS-TS and COVID-19 [ 44 , 45 ] and contributes to a hypercoagulable state [ 46 ]. Therapeutically, the hyperinflammatory state in PIMS-TS and severe COVID-19 has been addressed by a variety of immunomodulatory approaches, including corticosteroids, intravenous immunoglobulins (IVIG), cytokine blocking strategies targeting IL-6 (tocilizumab [ 47 , 48 ]) or IL-1 (anakinra [ 45 , 49 ]) and adjunctive anticoagulant treatments [ 50 ].…”

Section: Introductionmentioning

confidence: 99%

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Presentation, Treatment Response and Short-Term Outcomes in Paediatric Multisystem Inflammatory Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS)

Felsenstein

Willis

Lythgoe

et al. 2020

JCM

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The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the pathogen responsible for Coronavirus Disease 2019 (COVID-19). Whilst most children and young people develop mild symptoms, recent reports suggest a novel paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Case definition and classification are preliminary, treatment is empiric and disease-associated outcomes are unclear. Here, we report 29 patients with PIMS-TS who were diagnosed, admitted and treated in the English North West between March and June 2020. Consistent with patterns observed internationally, cases peaked approximately 4 weeks after the initial surge of COVID-19-like symptoms in the UK population. Clinical symptoms included fever (100%), skin rashes (72%), cardiovascular involvement (86%), conjunctivitis (62%) and respiratory involvement (21%). Some patients had clinical features partially resembling Kawasaki disease (KD), toxic shock syndrome and cytokine storm syndrome. Male gender (69%), black, Asian and other minority ethnicities (BAME, 59%) were over-represented. Immune modulating treatment was used in all, including intravenous immunoglobulin (IVIG), corticosteroids and cytokine blockers. Notably, 32% of patients treated with IVIG alone went into remission. The rest required additional treatment, usually corticosteroids, with the exception of two patients who were treated with TNF inhibition and IL-1 blockade, respectively. Another patient received IL-1 inhibition as primary therapy, with associated rapid and sustained remission. Randomized and prospective studies are needed to investigate efficacy and safety of treatment, especially as resources of IVIG may be depleted secondary to high demand during future waves of COVID-19.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Presentation, Treatment Response and Short-Term Outcomes in Paediatric Multisystem Inflammatory Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS)

Felsenstein

Willis

Lythgoe

et al. 2020

JCM

Self Cite

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“…In children, the increased inflammatory markers include IL-6, IL-1, and C-reactive protein along with procalcitonin in serum (52). In a case study, a 14-year-old child with cytokine storm was treated with anakinra (IL-1 receptor antagonist) in order to stabilize the respiratory illness and other clinical symptoms (100). Transcriptomic analysis of PBMC and BALF showed that a number of immune regulators were upregulated, particularly CXCL10, with respect to BALF.…”

Section: Cytokine Productionmentioning

confidence: 99%

Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past

et al. 2020

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After the 1918 flu pandemic, the world is again facing a similar situation. However, the advancement in medical science has made it possible to identify that the novel infectious agent is from the coronavirus family. Rapid genome sequencing by various groups helped in identifying the structure and function of the virus, its immunogenicity in diverse populations, and potential preventive measures. Coronavirus attacks the respiratory system, causing pneumonia and lymphopenia in infected individuals. Viral components like spike and nucleocapsid proteins trigger an immune response in the host to eliminate the virus. These viral antigens can be either recognized by the B cells or presented by MHC complexes to the T cells, resulting in antibody production, increased cytokine secretion, and cytolytic activity in the acute phase of infection. Genetic polymorphism in MHC enables it to present some of the T cell epitopes very well over the other MHC alleles. The association of MHC alleles and its downregulated expression has been correlated with disease severity against influenza and coronaviruses. Studies have reported that infected individuals can, after recovery, induce strong protective responses by generating a memory T-cell pool against SARS-CoV and MERS-CoV. These memory T cells were not persistent in the long term and, upon reactivation, caused local damage due to cross-reactivity. So far, the reports suggest that SARS-CoV-2, which is highly contagious, shows related symptoms in three different stages and develops an exhaustive T-cell pool at higher loads of viral infection. As there are no specific treatments available for this novel coronavirus, numerous small molecular drugs that are being used for the treatment of diseases like SARS, MERS, HIV, ebola, malaria, and tuberculosis are being given to COVID-19 patients, and clinical trials for many such drugs have already begun. A classical immunotherapy of convalescent plasma transfusion from recovered patients has also been initiated for the neutralization of viremia in terminally ill COVID-19 patients. Due to the limitations of plasma transfusion, researchers are now focusing on developing neutralizing antibodies against virus particles along with immuno-modulation of cytokines like IL-6, Type I interferons (IFNs), and TNF-α that could help in combating the infection. This review highlights the similarities of the coronaviruses that caused SARS and MERS to the novel SARS-CoV-2 in relation to their pathogenicity and immunogenicity and also focuses on various treatment strategies that could be employed for curing COVID-19.

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“…( 26 , 27 , 28 ) KD produces inflammatory and cytokine responses, which resemble those noted after infection with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ( 29 ) Accordingly, multiple reports are emerging throughout the world that children are exhibiting symptoms from Multisystem Inflammatory Syndrome in Children (MIS-C), which resemble those for Kawasaki disease during the pandemic. ( 30 , 31 , 32 , 33 )…”

Section: Discussionmentioning

confidence: 99%

Kawasaki Disease and Clinical Outcome Disparities Among Black Children

Padilla

Collins

Idigo

et al. 2021

The Journal of Pediatrics

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Study design ICD codes were used to identify children with Kawasaki disease admitted to a tertiary Southeast U.S. center. Subjects diagnosed and treated according to AHA criteria were included. Demographic, laboratory, clinical and echocardiographic data from EMR (2000-2015) were compared between Blacks and Whites. Results Data from 369 subjects (52% Whites and 48% Blacks) were included in our analysis. No significant differences related to timely admission, IVIG treatment or, coronary artery abnormalities during hospitalization were observed, Blacks showed lower IVIG response rates for those administered IVIG within 10 days of fever onset (86.6% vs 95.6%, P = 0.007). Blacks received more ancillary drugs (9.6% vs 2.6%, P value 0.003), and endured longer hospitalizations (5±3.9 v s 3.4±2.2 days, P = 0.001). Blacks presented with higher C-reactive protein, erythrocyte sedimentation rate and; lower hemoglobin, albumin and, sodium. Blacks showed a greater proportion of persistent coronary artery abnormalities at follow-up when compared with Whites (14.5% vs 6.3%, P = .03, second follow-up ECHO; 21.2% vs 6.9%, P = 0.01 third follow-up ECHO). Conclusion Black children with Kawasaki disease had higher IVIG refractory prevalence, severe inflammation, received more ancillary treatments and, longer hospitalizations than White children. Despite no racial differences in time to diagnosis or initial treatment, there was higher coronary artery abnormality persistence among Black children at follow-up.

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Novel paediatric presentation of COVID-19 with ARDS and cytokine storm syndrome without respiratory symptoms

Cited by 58 publications

References 12 publications

Presentation, Treatment Response and Short-Term Outcomes in Paediatric Multisystem Inflammatory Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS)

Presentation, Treatment Response and Short-Term Outcomes in Paediatric Multisystem Inflammatory Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS)

Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past

Kawasaki Disease and Clinical Outcome Disparities Among Black Children

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