Neurological manifestations of SARS-CoV-2: complexity, mechanism and associated disorders

Tyagi, Kritika; Rai, Prachi; Gautam, Anuj; Kaur, Harjeet; Kapoor, Sumeet; Suttee, Ashish; Jaiswal, Pradeep Kumar; Sharma, Akanksha; Singh, Gurpal; Barnwal, Ravi Pratap

doi:10.1186/s40001-023-01293-2

Cited by 5 publications

References 147 publications

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Elevated level of circulating calprotectin correlates with severity and high mortality in patients with COVID‐19

Zhang,

Liu

et al. 2024

Immunity Inflam & Disease

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BackgroundPatients with coronavirus disease‐2019 (COVID‐19) are characterized by hyperinflammation. Calprotectin (S100A8/S100A9) is a calcium‐ and zinc‐binding protein mainly secreted by neutrophilic granulocytes or macrophages and has been suggested to be correlated with the severity and prognosis of COVID‐19.AimTo thoroughly evaluate the diagnostic and prognostic utility of calprotectin in patients with COVID‐19 by analyzing relevant studies.MethodsPubMed, Web of Science, and Cochrane Library were comprehensively searched from inception to August 1, 2023 to retrieve studies about the application of calprotectin in COVID‐19. Useful data such as the level of calprotectin in different groups and the diagnostic efficacy of this biomarker for severe COVID‐19 were extracted and aggregated by using Stata 16.0 software.ResultsFifteen studies were brought into this meta‐analysis. First, the pooled standardized mean differences (SMDs) were used to estimate the differences in the levels of circulating calprotectin between patients with severe and non‐severe COVID‐19. The results showed an overall estimate of 1.84 (95% confidence interval [CI]: 1.09–2.60). Diagnostic information was extracted from 11 studies, and the pooled sensitivity and specificity of calprotectin for diagnosing severe COVID‐19 were 0.75 (95% CI: 0.64–0.84) and 0.88 (95% CI: 0.79–0.94), respectively. The AUC was 0.89 and the pooled DOR was 18.44 (95% CI: 9.07–37.51). Furthermore, there was a strong correlation between elevated levels of circulating calprotectin and a higher risk of mortality outcomes in COVID‐19 patients (odds ratio: 8.60, 95% CI: 2.17–34.12; p < 0.1).ConclusionThis meta‐analysis showed that calprotectin was elevated in patients with severe COVID‐19, and this atypical inflammatory cytokine might serve as a useful biomarker to distinguish the severity of COVID‐19 and predict the prognosis.

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Elevated level of circulating calprotectin correlates with severity and high mortality in patients with COVID‐19

Zhang,

Liu

et al. 2024

Immunity Inflam & Disease

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Neurological manifestations of acute SARS-CoV-2 infection in pediatric patients: a 3-year study

Vivisenco,

Lescaie,

Dragomirescu

et al. 2024

Preprint

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Purpose This study analyzed the neurological manifestation profiles of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across pandemic waves in pediatric patients. Methods This retrospective study analyzed the data of patients aged 0–18 years who were diagnosed with acute SARS-CoV-2 infection and admitted to a pediatric tertiary hospital between March 1, 2020, and February 28, 2023. The presence of neurological manifestations was established based on the symptoms noted in each patient chart. The relationships between neurological manifestations and pandemic waves or age groups were assessed using the chi-square test. Results This study included 1677 patients. Neurological manifestations were noted in 10% (n = 168) of patients with a 3.2 years median age (interquartile range: 1–11.92). Neurological manifestations were significantly associated with the pandemic waves (p = 0.006) and age groups (p < 0.001). Seizures were noted in 4.2% of cases and reached an increasing frequency over time (p = 0.001), but were not associated with age groups. Febrile seizures accounted for the majority of seizures. Headache was reported in 2.6% of cases and had similar frequencies across the pandemic waves and age groups. Muscular involvement was noted in 2% of cases and reached a decreasing frequency over time (p < 0.001) and showed different frequencies among the age groups. Conclusions Neurological manifestations of acute SARS-CoV-2 infection exhibit distinct patterns, depending on the pandemic wave and patient age group. The Wuhan and Omicron waves involved the nervous system more often than the other waves; however, this was probably through different mechanisms.

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“Multisystem Inflammatory Syndrome in Children”-Like Disease after COVID-19 Vaccination (MIS-V) with Potential Significance of Functional Active Autoantibodies Targeting G-Protein-Coupled Receptors (GPCR-fAAb) for Pathophysiology and Therapy

Schmidt,

Hébert,

Wallukat

et al. 2023

Children

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Background: An infection with SARS-CoV-2 can trigger a systemic disorder by pathological autoimmune processes. A certain type of this dysregulation is known as Multisystemic inflammatory syndrome in children (MIS-C). However, similar symptoms may occur and have been described as Multisystemic inflammatory syndrome after SARS-CoV-2 Vaccination (MIS-V) following vaccination against SARS-CoV-2. We report the case of a 12-year-old boy who was identified with MIS-C symptoms without previous SARS-CoV-2 infection after receiving two doses of the Pfizer–BioNTech COVID-19 vaccine approximately one month prior to the onset of symptoms. He showed polyserositis, severe gastrointestinal symptoms and, consequently, a manifestation of a multiorgan failure. IgG antibodies against spike proteins of SARS-CoV-2 were detected, indicating a successful vaccination, while SARS-CoV-2 Nucleocapsid protein antibodies and SARS-CoV-2 PCR were not detected. Several functional, active autoantibodies against G-protein-coupled receptors (GPCR-fAAb), previously associated with Long COVID disease, were detected in a cardiomyocyte bioassay. Immunosuppression with steroids was initiated. Due to side effects, treatment with steroids and later interleukin 1 receptor antagonists had to be terminated. Instead, immunoadsorption was performed and continued with tacrolimus and mycophenolic acid therapy, leading to improvement and discharge after 79 days. GPCR-fAAb decreased during therapy and remained negative after clinical curing and under continued immunosuppressive therapy with tacrolimus and mycophenolic acid. Follow-up of the patient showed him in good condition after one year. Conclusions: Infection with SARS-CoV-2 shows a broad and severe variety of symptoms, partly due to autoimmune dysregulation, which, in some instances, can lead to multiorgan failure. Despite its rarity, post-vaccine MIS-C-like disease may develop into a serious condition triggered by autoimmune dysregulation. The evidence of circulating GPCR-fAAb and their disappearance after therapy suggests a link of GPCR-fAAb to the clinical manifestations. Thus, we hypothesize a potential role of GPCR-fAAb in pathophysiology and their potential importance for the therapy of MIS-C or MIS-V. However, this observation needs further investigation to prove a causative correlation.

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Neurological manifestations of SARS-CoV-2: complexity, mechanism and associated disorders

Cited by 5 publications

References 147 publications

Elevated level of circulating calprotectin correlates with severity and high mortality in patients with COVID‐19

Elevated level of circulating calprotectin correlates with severity and high mortality in patients with COVID‐19

Neurological manifestations of acute SARS-CoV-2 infection in pediatric patients: a 3-year study

“Multisystem Inflammatory Syndrome in Children”-Like Disease after COVID-19 Vaccination (MIS-V) with Potential Significance of Functional Active Autoantibodies Targeting G-Protein-Coupled Receptors (GPCR-fAAb) for Pathophysiology and Therapy

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