Neurologic manifestations in children with COVID-19 from a tertiary center in Turkey and literature review.

BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic caused by highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although respiratory disease and multisystem inflammatory syndrome in children (MIS-C) are main clinical presentations in children, numerous neurological manifestations are being described increasingly. We aimed to investigate new onset neurological symptoms associated with SARS-CoV-2 in pediatric patients in order to establish a possible relationship as well as to understand the underlying pathophysiological mechanisms between SARS-CoV-2 infection and neurological findings. METHODS: We analyzed retrospectively children who had neurologic manifestations temporally associated with SARS-CoV-2 infection at Hacettepe University Ihsan Dogramaci Children's Hospital. We performed a literature search between March 20, 2020 and March 30, 2021. Articles that report children with COVID-19 related neurological manifestations were included. RESULTS: We have observed 15 consecutive cases with new onset neurological manifestations along with confirmed SARS-CoV-2 infection. Age at hospitalization ranged from three months to 17 years. Ten patients had central nervous system involvement, and most common manifestation was encephalopathy (5/10), which is also one of the most common manifestations of the patients mentioned in the relevant 39 articles we reviewed. CONCLUSION: Children with COVID-19 can present with neurologic findings such as encephalopathy, seizures, cerebrovascular events as well as abnormal eye movements. Clinical suspicion and awareness are required to show the association between neurologic manifestations and COVID-19.

Caution on Plasma Cytokine Findings in 2019 Novel Coronavirus Cases

In the initial 41 cases of 2019 novel coronavirus published in Lancet, elevated blood IL-10 cytokine data from these patients and four healthy subjects were presented as argument to not consider immunosuppressive therapy. We propose this is an erroneous interpretation of the cytokine measures, as parallel increases in pro- and anti-inflammatory cytokines indicate an intact immune axis and do not diminish the potential role of immunosuppression. We show data in healthy control subjects strong correlations between pro- and anti-inflammatory cytokines, and immunosuppressive therapies should be considered in 2019 novel coronavirus cases. Funding: This study was funded by NIH K01AG42498 (WW) and R01AG54046 (WTH). The funders have no role in the data analysis or manuscript preparation. Declaration of Interest: WTH has served as a consultant to ViveBio LLC, Biogen Inc., and AARP Inc.;received research support from Fujirebio USA;and has a patent on CSF-based diagnosis of FTLD-TDP (assigned to Emory University).

Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19.

A wide spectrum of clinical manifestations has become a hallmark of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although the immunological underpinnings of diverse disease outcomes remain to be defined. We performed detailed characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks of extrafollicular B cell activation and shared B cell repertoire features previously described in autoimmune settings. Extrafollicular activation correlated strongly with large antibody-secreting cell expansion and early production of high concentrations of SARS-CoV-2-specific neutralizing antibodies. Yet, these patients had severe disease with elevated inflammatory biomarkers, multiorgan failure and death. Overall, these findings strongly suggest a pathogenic role for immune activation in subsets of patients with COVID-19. Our study provides further evidence that targeted immunomodulatory therapy may be beneficial in specific patient subpopulations and can be informed by careful immune profiling.

Antibody Profiles According to Mild or Severe SARS-CoV-2 Infection, Atlanta, Georgia, USA, 2020.

Among patients with coronavirus disease (COVID-19), IgM levels increased early after symptom onset for those with mild and severe disease, but IgG levels increased early only in those with severe disease. A similar pattern was observed in a separate serosurveillance cohort. Mild COVID-19 should be investigated separately from severe COVID-19.

Caution on Plasma Cytokine Findings in 2019 Novel Coronavirus Cases.

In the initial 41 cases of 2019 novel coronavirus published in Lancet, elevated blood IL-10 cytokine data from these patients and four healthy subjects were presented as argument to not consider immunosuppressive therapy. We propose this is an erroneous interpretation of the cytokine measures, as parallel increases in pro- and anti-inflammatory cytokines indicate an intact immune axis and do not diminish the potential role of immunosuppression. We show data in healthy control subjects strong correlations between pro- and anti-inflammatory cytokines, and immunosuppressive therapies should be considered in 2019 novel coronavirus cases. Funding: This study was funded by NIH K01AG42498 (WW) and R01AG54046 (WTH). The funders have no role in the data analysis or manuscript preparation. Declaration of Interest: WTH has served as a consultant to ViveBio LLC, Biogen Inc., and AARP Inc.; received research support from Fujirebio USA; and has a patent on CSF-based diagnosis of FTLD-TDP (assigned to Emory University).

Encephalopathy and Encephalitis Associated with Cerebrospinal Fluid Cytokine Alterations and Coronavirus Disease, Atlanta, Georgia, USA, 2020.

There are few detailed investigations of neurologic complications in severe acute respiratory syndrome coronavirus 2 infection. We describe 3 patients with laboratory-confirmed coronavirus disease who had encephalopathy and encephalitis develop. Neuroimaging showed nonenhancing unilateral, bilateral, and midline changes not readily attributable to vascular causes. All 3 patients had increased cerebrospinal fluid (CSF) levels of anti-S1 IgM. One patient who died also had increased levels of anti-envelope protein IgM. CSF analysis also showed markedly increased levels of interleukin (IL)-6, IL-8, and IL-10, but severe acute respiratory syndrome coronavirus 2 was not identified in any CSF sample. These changes provide evidence of CSF periinfectious/postinfectious inflammatory changes during coronavirus disease with neurologic complications.