Novel coronavirus disease 2019 (COVID-19) outbreak in children in Iran: Atypical CT manifestations and mortality risk of severe COVID-19 infection

Mamishi, Setareh; Heydari, Hassan; Aziz-Ahari, Alireza; Shokrollahi, Mohammad Reza; Pourakbari, Babak; Mahmoudi, Shima; Movahedi, Zahra

doi:10.1016/j.jmii.2020.07.019

Cited by 30 publications

(35 citation statements)

References 20 publications

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“…'s study, 71% of cases showed lymphopaenia [26]. The majority of cases at admission had markedly elevated inflammatory markers including ESR and CRP and mildly decreased albumin that was similar to previous reports [2, 3, 5, 12, 13, 15, 26, 27]. Hypoalbuminaemia was found in 64.5% of patients that was higher than previous report [15].…”

Section: Discussionsupporting

confidence: 84%

Multisystem inflammatory syndrome associated with SARS-CoV-2 infection in 45 children: a first report from Iran

et al. 2020

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During the coronavirus disease 2019 (COVID-19) pandemic, a new phenomenon manifesting as a multisystem inflammatory syndrome in children (MIS-C) which has a similar clinical presentation to Kawasaki disease, toxic shock syndrome and severe sepsis has emerged. Although the number of MIS-C reports is increasing, rare reports in Asia is still available. To our knowledge, this study is the largest series of published MIS-C cases in Iran. We performed a retrospective study of all patients with case definition for MIS-C admitted to the three paediatric hospitals in Iran. All of these hospitals are located within the most active COVID-19 pandemic areas (Tehran, Qom and Mazandaran) in Iran. Demographic characteristics, clinical data, laboratory findings, imaging and echocardiographic findings, treatment and outcomes were collected. Between 7 March and 23 June 2020, 45 children were included in the study. The median age of children was 7 years (range between 10 months and 17 years). Common presenting symptoms include fever (91%), abdominal pain (58%), nausea/vomiting (51%), mucocutaneous rash (53%), conjunctivitis (51%) and hands and feet oedema (40%) with median duration of symptoms prior to presentation of 5 (interquartile range (IQR) 3, 7) days. Fifty-three percent of children showed lymphopaenia. Overall, the majority of cases at admission had markedly elevated inflammatory markers erythrocyte sedimentation rate (ESR) (95.5%) and C-reactive protein (CRP) (97%). Ferritin was abnormal in 11 out of 14 tested patients (73%), and it was highly elevated (>500 ng/ml) in 47% of cases. Median fibrinogen level was 210 (IQR 165, 291) mg/dl, D-dimer was 3909 (IQR 848, 4528) ng/ml and troponin was 0.6 (IQR 0.1, 26) ng/ml, respectively. Twenty out of 31 patients (64.5%) had hypoalbuminaemia. In addition, hyponatraemia was found in 64% of cases. Twenty-five patients (56%) presented with cardiac involvement and acute renal failure was observed in 13 cases (29%). Pleural, ascitic, ileitis and pericardial effusions were found in 18%, 11%, 4% and 2% of cases, respectively. In conclusion, this is a first large case series of hospitalised children who met criteria for MIS-C in Iran. There was a wide spectrum of presenting signs and symptoms; evidence of inflammation with abnormal values of CRP, ESR, D-dimer, ferritin and albumin; and multi-organ involvement.

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Section: Discussionsupporting

confidence: 84%

Multisystem inflammatory syndrome associated with SARS-CoV-2 infection in 45 children: a first report from Iran

et al. 2020

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“…Since December 2019, when COVID-19 was first reported from China, numerous studies were published to clarify the pathogenesis of the disease and various hypotheses have been proposed in this regard [ 17 , 18 , 19 ]. Among the proposed mechanisms underlying the worsening of the disease, the strongest is immune system dysfunction [ 20 ]. Recent findings hypothesize that virus-induced immune system dysregulation can lead to T cell exhaustion [ 4 , 21 ] and cytokine storm [ 22 , 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

Dynamic Changes of Lymphocyte Subsets in the Course of COVID-19

Rezaei

Marjani

Mahmoudi

et al. 2021

Int Arch Allergy Immunol

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Background: Although the pathophysiology of coronavirus disease 2019 (COVID-19) is not clearly defined, among the proposed mechanisms, immune system dysfunction is more likely than others. The aim of this study was to clarify the characteristics and clinical significance of dynamic changes of lymphocyte subsets in the course of COVID-19. Methods: In this prospective study, the levels of peripheral lymphocyte subsets including CD4+, CD8+, CD4+CD25+FOXP3+, CD38+, CD3+HLA-DR+, CD19+, CD20+, and CD16+CD56+ cells were measured by flow cytometry in 52 confirmed hospitalized patients with COVID-19 at the day of admission and after 7 days of care. Clinical response was defined as improvement in symptoms (fever, dyspnea, and cough as well as blood oxygen saturation), and patients who met these criteria after 1 week of admission were classified as early responders; others who survived and finally discharged from the hospital were classified as late responders and patients who died were categorized as nonresponders. Immunophenotyping of studied cell changes on the first day of admission and 7 days after treatment were compared. Besides, the correlation between cellular subset variation and clinical response and outcome were analyzed. Results: Total counts of white blood cell, T cells, CD4+ T cells, CD8+ T cells, CD38+ lymphocytes, and CD3+HLA-DR+ lymphocytes were significantly increased in both early and late responders. No statistically significant difference was observed in CD4+/CD8+ ratio, B cells, FOXP3+Treg lymphocytes, and FOXP3 median fluorescence intensity among studied groups. According to the multivariate analysis, an increase in CD4+ T cells (p = 0.019), CD8+ T cells (p = 0.001), and administration of interferon (p < 0.001) were independent predictors of clinical response. Conclusion: We found an increasing trend in total T cells, T helpers, cytotoxic T cells, activated lymphocytes, and natural killer cells among responders. This trend was not statistically significant among nonresponders. The findings of this study may enhance our knowledge about the pathogenesis of COVID-19.

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“…The subjects of the study were hospitalized children with SARS-CoV-2 pneumonia confirmed using SARS-CoV-2 real-time RT-PCR of nasopharyngeal swab samples according to the CDC diagnostic panel (12,16). The subjects were admitted to the Children's Medical Center, an Iranian referral hospital, between March 7th and June 10th of 2020.…”

Section: Patient Selectionmentioning

confidence: 99%

“…A number of hematological abnormalities have been observed in the laboratory features of COVID-19 (7,(10)(11)(12)(13). Several studies concerning changes of lymphocyte subsets and their correlation with the severity and outcome of the disease have been reported in adults (10,14,15).…”

Section: Introductionmentioning

confidence: 99%

Effects of Coronavirus Disease 2019 (COVID-19) on Peripheral Blood Lymphocytes and Their Subsets in Children: Imbalanced CD4+/CD8+ T Cell Ratio and Disease Severity

et al. 2021

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Introduction: While pathogenesis in COVID-19 is not fully known and the effects between SARS-CoV-2 and the immune system are complicated, it is known that lymphopenia, hyper-inflammatory responses, and cytokines play an important role in the pathology of COVID-19. While some hematological abnormalities have been described among the laboratory features of COVID-19, there have not been studies reported on lymphocyte subset analyses in children. The aim of this study was to describe lymphocyte subsets in pediatric patients with mild/moderate or severe COVID-19.Methods: The subjects in the study were children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia confirmed with the real-time RT-PCR. The subjects were admitted to the Children's Medical Center, affiliated with the Tehran University of Medical Sciences, between March 7th and June 10th of 2020. The complete blood counts and lymphocyte subpopulations were analyzed for each patient.Results: The study included 55 hospitalized patients with confirmed SARS-CoV-2 infection (34 patients (62%) with an observed mild/moderate case of the disease and 21 patients (38%) with severedisease). Lymphocyte counts were found to be lower in patients with a severe case (mean ± SD 1.6 ± 0.9 in the severe group vs. 2.3 ± 2.2 in the mild group). Compared to the group with mild/moderate pneumonia, children with severe pneumonia had an increased count of CD8+ T cell and a lower percentage of CD4+ T cell. However, the differences between the groups were negligible. Interestingly, the severe group had a lower CD4+/CD8+ T cell ratio compared to the mild group (1.1 ± 0.47 vs. 1.4 ± 0.8, p-value: 0.063). CD4+/CD8+ T cell ratio <2, 1.5, and 1 was found in 48 (87%), 40 (73%), and 19 cases (35%). All of the seven cases in which the subject passed (13%) had CD4+/CD8+ T cell ratio of <2, 86% had CD4+/CD8+ T cell ratio of <1.5, and 29% had CD4+/CD8+ T cell ratio of <1.Conclusion: The CD4+/CD8+ T cell ratio was lower in patients with severe COVID-19 compared to those with mild/moderate form of disease. However, although a decline in CD4+/CD8+ ratio may serve as a useful metric in analyzing of the derangement in immune responses in patients with severe COVID-19, further study with larger sample sizes is highly recommended.

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Novel coronavirus disease 2019 (COVID-19) outbreak in children in Iran: Atypical CT manifestations and mortality risk of severe COVID-19 infection

Cited by 30 publications

References 20 publications

Multisystem inflammatory syndrome associated with SARS-CoV-2 infection in 45 children: a first report from Iran

Multisystem inflammatory syndrome associated with SARS-CoV-2 infection in 45 children: a first report from Iran

Dynamic Changes of Lymphocyte Subsets in the Course of COVID-19

Effects of Coronavirus Disease 2019 (COVID-19) on Peripheral Blood Lymphocytes and Their Subsets in Children: Imbalanced CD4+/CD8+ T Cell Ratio and Disease Severity

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