Changing Disease Course of Crimean-Congo Hemorrhagic Fever in Children, Turkey.

Crimean-Congo hemorrhagic fever (CCHF), endemic in certain regions of the world, is listed as a priority disease with pandemic potential. Since CCHF was first identified in Turkey, children have been known to experience milder disease than adults. However, during the COVID-19 pandemic, we observed an unusually severe disease course, including hemophagocytic lymphohistiocytosis (HLH). We examined cytokine/chemokine profiles of 9/12 case-patients compared with healthy controls at 3 time intervals. Interferon pathway-related cytokines/chemokines, including interleukin (IL) 18, macrophage inflammatory protein 3α, and IL-33, were elevated, but tumor necrosis factor-α, IL-6, CXCL8 (formerly IL-8), and cytokines acting through C-C chemokine receptor 2 and CCR5 were lower among case-patients than controls. Interferon pathway activation and cytokines/chemokines acting through CCR2 and CCR5 improved health results among children with severe CCHF. Children can experience severe CCHF, including HLH, and HLH secondary to CCHF can be successfully treated with intravenous immunoglobulin and steroid therapy.

The difference of the inflammatory milieu in MIS-C and severe COVID-19.

BACKGROUND: Coronavirus disease 19 (COVID-19) may have a severe course in children. Multisystem inflammatory syndrome in children (MIS-C) is the post-COVID complication characterized by an exaggerated inflammation, observed in children. However, data on the underlying pathophysiology are sparse. We therefore aimed to assess the cytokine and chemokine profiles of children with MIS-C and compare these to life-threatening severe SARS-CoV-2 and healthy controls (HCs) to shed light on disease pathophysiology. METHODS: Samples of 31 children with MIS-C, 10 with severe/critical COVID-19 and 11 HCs were included. Cytokine and chemokine profiles were studied and compared in between groups. RESULTS: Most cytokines and chemokines related to IL-1 family and IFN-γ pathway (including IL-18 and MIG/CXCL9) and IL-17A were significantly higher in the MIS-C group when compared to the severe/critical COVID-19 group and HCs. IP-10/CXCL10 and IL-10 were higher in both MIS-C patients and severe/critical COVID-19 compared to HCs. CONCLUSION: Our results suggest that IL-1 and IFN-γ pathways play an important role in the pathophysiology of MIS-C. IMPACT: This study defines a pattern of distinctive immune responses in children with MIS-C and in patients with severe/critical COVID-19. As the COVID-19 pandemic continues, biomarkers to identify MIS-C risk are needed to guide our management that study results may shed light on it.

Management of acute abdomen during the active disease course of COVID-19 and multisystem inflammatory syndrome in children.

PURPOSE: To evaluate the management of children with severe gastrointestinal symptoms during the disease course of COVID-19 and multisystem inflammatory syndrome (MIS-C). METHODS: After ethical approval, we reviewed the medical records, retrospectively, of children with COVID-19 or MIS-C requiring surgical consultation for severe gastrointestinal symptoms. RESULTS: The subjects comprised 15 children, 13 with MIS-C and 2 with COVID-19. Twelve children (80%) had been in known close contact with a person with SARS-CoV-19 and 13 were positive for Anti-SARS-CoV-2 IgG. All the children had experienced fever for at least 1 day and had signs of involvement of two or more systems. Three patients required surgical intervention: one underwent surgical exploration with a presumptive diagnosis of acute appendicitis in the referring center and was transported to our center following clinical deterioration, where a diagnosis of MIS-C was confirmed; and the remaining two developed appendicitis during hospitalization for COVID-19. All three patients had a longer duration of abdominal pain, a higher number of lymphocytes, and a lower level of inflammatory markers than the non-surgically managed patients. None of the patients presenting with MIS-C underwent surgical exploration. CONCLUSION: Gastrointestinal involvement may mimic acute abdomen in children with COVID-19. Thus, children presenting with acute abdomen in the pandemic era require careful evaluation and prompt diagnosis to avoid unnecessary surgical intervention.

Chest imaging for COVID-19: a single-center comparative results in pediatric patients.

BACKGROUND: Chest computed tomography (CT) appears to be an important radiological modality for the diagnosis of COVID-19 in adults. Studies comparing the findings of such children with those of other viral infections have not been reported either. The aim of this study was to present comparative imaging findings of 75 pediatric COVID-19 patients and four patients with other viral upper respiratory tract infections. We also aimed to demonstrate the possible association between the radiological and laboratory findings in the COVID group. METHODS: From 11 March 2020 to 20 June 2020, 79 children (aged < 18 years) were enrolled. COVID-19 was detected by RT-PCR or antibody testing. A plain chest X-ray was obtained from all subjects. Non-contrast chest CT was performed for symptomatic patients. RESULTS: Seventy-five patients had COVID-19 and 4 were infected with other pathogens i.e. adenovirus, rhinovirus, parainfluenza virus B, respiratory syncytial virus. The ages of the patients (36 M, 43 F) ranged from 7 months to 17 years old. The sensitivity of chest X-ray (as compared to RT-PCR) was 10.67% (95 CI%: 4.72 - 19.94%). From 23 chest CT`s five of them were normal and nine of them had only nodules ( < 5mm). The sensitivity of CT was 78.26% (95CI%: 54.30 - 92.54%), false-negative rate was 21.7%. CONCLUSIONS: The sensitivity of chest CT was found to be low and any significant correlations could have not been depicted, between the radiological parameters and the presence of lymphopenia. Clinical follow-up combined with corresponding pathogen detection, and chest CT of the symptomatic COVID-19 patients might be a feasible/prompt protocol in children.

SARS-CoV-2 seropositivity among pediatric health care personnel after the first peak of the pandemic: nationwide surveillance in Turkey.

BACKGROUND: Understanding SARS-CoV-2 seroprevalence among health care personnel is important to explore risk factors for transmission, develop elimination strategies and form a view on the necessity and frequency of surveillance in the future. METHODS: We enrolled 4927 health care personnel working in pediatric units at 32 hospitals from 7 different regions of Turkey in a study to determine SARS Co-V-2 seroprevalence after the first peak of the COVID-19 pandemic. A point of care serologic lateral flow rapid test kit for immunoglobulin (Ig)M/IgG was used. Seroprevalence and its association with demographic characteristics and possible risk factors were analyzed. RESULTS: SARS-CoV-2 seropositivity prevalence in health care personnel tested was 6.1%. Seropositivity was more common among those who did not universally wear protective masks (10.6% vs 6.1%). Having a COVID-19-positive co-worker increased the likelihood of infection. The least and the most experienced personnel were more likely to be infected. Most of the seropositive health care personnel (68.0%) did not suspect that they had previously had COVID-19. CONCLUSIONS: Health surveillance for health care personnel involving routine point-of-care nucleic acid testing and monitoring personal protective equipment adherence are suggested as important strategies to protect health care personnel from COVID-19 and reduce nosocomial SARS-CoV-2 transmission.

Oxidant and antioxidant balance in patients with COVID-19.

BACKGROUND: A crucial balance exists between oxidant and antioxidant mechanisms in the functional immune system. We aimed to evaluate the contributions of balance between these systems to coronavirus disease 2019 (COVID-19), a devastating pandemic caused by viral infection. METHOD: We analyzed serum oxidant and antioxidant stress parameters according to the clinical and demographic characteristics of children and adults with COVID-19 and compared them against the values of healthy controls. Serum native thiol (NT), total thiol (TT), disulfide, total antioxidant status, total oxidant status, and ischemia-modified albumin levels were evaluated and compared between groups. RESULTS: A total of 79 children and 74 adults were evaluated in the present study, including 46 children and 40 adults with COVID-19, 33 healthy children, and 34 healthy adults. TT, NT, and disulfide levels were significantly lower in the adult COVID-19 group than in all other groups (p = .001, p = .001, and p = .005, respectively). Additionally, TT and NT levels were significantly lower in both pediatric and adult COVID-19 cases with severe disease course than mild/moderate course. TT and NT levels were identified as predictors for the diagnosis of the adult COVID-19 cases and as independent predictors for disease severity in both children and adults with COVID-19. CONCLUSION: Parameters that reveal the oxidant and antioxidant capacity, including TT and NT, appear to be good candidates for the accurate prediction of the clinical course among patients with COVID-19.

Longitudinal Follow-up of Antibody Responses in Pediatric Patients With COVID-19 up to 9 Months After Infection.

INTRODUCTION: Antibody response developed within 2-3 weeks after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to decrease over time; however, there is limited data about antibody levels at 6 months or later postinfection, particularly in children. MATERIALS AND METHOD: A prospective multicenter study was performed using 315 samples of 74 confirmed and 10 probable coronavirus disease 2019 pediatric cases. About 20% of these cases were classified as asymptomatic, 74% as mild/moderate and 6% as severe/critical. Patients were included if at least 2 samples were available. The antibody response was classified as either early-period or late-period (14 days-3 months and after 6 months, respectively) for IgG response whereas IgA response was tested on various time intervals, including as early as 4 days up to 3 months. Euroimmun Anti-SARS-CoV-2 IgG and IgA and Genscript SARS-CoV-2 Surrogate Virus Neutralization Kits were used for antibody detection. RESULTS: There was no difference between the early-period and late-period IgG positivity (P = 0.1). However, the median IgG levels were 11.98 in the early periods and 4.05 in the late periods, with a significance of P < 0.001. Although the decrease in IgG levels was significant in asymptomatic and mild/moderate cases (P < 0.008 and P < 0.001, respectively), the decrease in severe/critical cases was moderate (P = 0.285). The sensitivity of the IgG after 15 days was higher than 94%, and the sensitivity of IgA was 88% on days 8-15. CONCLUSION: SARS-CoV-2 IgG antibody levels decreased after 6 months. The decrease was moderate in severe/critical cases. Overall, 95.8% of the patients remained positive up to 9 months after infection. Although the IgA response may be useful early on, the IgG response is useful after 14 days.

Favipiravir use in children with COVID-19 and acute kidney injury: is it safe?

BACKGROUND: The rising number of infections due to Severe Acute Respiratory Syndrome Coronavirus-2 (popularly known as COVID-19) has brought to the fore new antiviral drugs as possible treatments, including favipiravir. However, there is currently no data regarding the safety of this drug in patients with kidney impairment. The aim of this paper, therefore, is to share our experience of the use of favipiravir in pediatric patients affected by COVID-19 with any degree of kidney impairment. METHODS: The study enrolled pediatric patients aged under 18 years and confirmed as suffering from COVID-19 and multisystem inflammatory syndrome in children (MIS-C) with any degree of kidney injury, who were treated with favipiravir at the time of admission. RESULTS: Out of a total of 11 patients, 7 were diagnosed with MIS-C and 4 with severe COVID-19. The median age of the cases was 15.45 (9-17.8) years and the male/female ratio was 7/4. At the time of admission, the median serum creatinine level was 1.1 mg/dl. Nine patients were treated with favipiravir for 5 days, and 2 patients for 5 days followed by remdesivir for 5-10 days despite kidney injury at the time of admission. Seven patients underwent plasma exchange for MIS-C while 2 severely affected cases underwent continuous kidney replacement therapy (CKRT) as well. One severe COVID-19 patient received plasma exchange as well as CKRT. Serum creatinine values returned to normal in mean 3.07 days. CONCLUSIONS: Favipiravir seems a suitable therapeutic option in patients affected by COVID-19 with kidney injury without a need for dose adjustment.

The association of viral load and disease severity in children with COVID-19.

It is still not fully understood how to predict the future prognosis of patients at the diagnosis coronavirus disease 2019 (COVID-19) due to the wide clinical range of the disease. We aimed to evaluate whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load could predict the clinical course of pediatric patients. This study was conducted retrospectively with medical records of pediatric patients who were tested for SARS-CoV2 between April 12 and October 25, 2020 in the University of Health Sciences, Ankara Educating and Training Hospital and Hacettepe University Faculty of Medicine. We evaluated 518 pediatric patients diagnosed with COVID-19 and classified according to severity as asymptomatic (16.2%), mild (59.6%), moderate (20.2%), and critical/severe (3.9%) cases. We analyzed patients in four groups in terms of ages: <4, 5-9, 10-14, and 15-17 years. There was no statistically significant difference in terms of ∆Ct value among age groups, different gender and the existence of underlying diseases in each disease course. The ∆Ct values were relatively lower in the first 2 days of symptoms than after days in all groups. Our study has indicated that children with COVID-19 have similar amount of viral load in all disease courses irrespective of the age and underlying disease. It should be taken into account that, regardless of the severity of the disease, pediatric patients may have a role in the transmission chain.