Neuroimaging findings in children with COVID-19 infection: a systematic review and meta-analysis | Scientific Reports – Nature.com

The emergence of the COVID-19 pandemic caused by the novel coronavirus, SARS-CoV-2, has evolved into a global health crisis. Initially focused on respiratory symptoms, it's now clear that COVID-19 presents a complex clinical picture affecting various organ systems32,33. Neurological manifestations have gained attention for their potential impact on both immediate clinical care and long-term health outcomes34,35. This systematic review and meta-analysis aimed to provide a comprehensive assessment of the abnormal neuroimaging findings in children with COVID-19.

Our findings reveal that a substantial proportion of pediatric COVID-19 patients with neurological symptoms exhibit abnormal neuroimaging findings, with 43.74% of children in the included studies demonstrating such abnormalities. These findings underscore the importance of considering neurological complications in the management of pediatric COVID-19 cases.

In a systematic review conducted by Choi et al. an extensive exploration was undertaken to comprehensively assess the spectrum of COVID-19-related neurological manifestations and associated abnormal neuroimaging findings in adults. Their meta-analysis unveiled that 42.6% of adult patients exhibited abnormal neuroimaging findings, as observed through brain CT or MRI36. With acute to subacute infarcts were the most common (24.0%), followed by cerebral micro hemorrhages (6.9%), acute spontaneous intracerebral hemorrhages (5.4%), and encephalitis/encephalopathy (3.3%)36. It is important to note that their investigation exclusively centered on specific COVID-19-related neuroimaging findings in the adult population and specifically considered MRI and CT as the imaging modalities of interest, although acknowledging that alternate modalities such as OCT, and TCD are also utilized.

In contrast, our study takes a unique approach, focusing exclusively on the pediatric group of COVID-19 patients, which is an area with limited research. Additionally, we aimed to cover a wide range of neuroimaging findings using diverse range of methods commonly used in pediatric cases. This broader scope is in response to the frequent use of various imaging techniques in pediatric clinical settings, extending the depth of our investigation.

In terms of specific neuroimaging abnormalities, our analysis categorized them into neurovascular findings, ADEM-like lesions, encephalitic pattern, myelitis, transient splenial lesions, and other findings. Neurovascular findings, encompassing findings like arterial or venous stroke, exhibited a pooled incidence of 8.22%. ADEM-like lesions showed a pooled incidence of 7.69%. Encephalitic pattern, including findings like Acute Hemorrhagic Necrotizing Encephalitis, showed a pooled incidence of 13.95%. Myelitis had a pooled incidence of 4.60%. Transient splenial lesions, encompassing findings like RESLES and MERS, exhibited a pooled incidence of 16.26%. Other abnormalities, such as PRES, neuritis, and brain edema, had a pooled incidence of 12.03%. These findings emphasize the diversity of neurological involvement in pediatric COVID-19 cases, spanning from inflammatory processes to vascular events.

In a recent systematic review led by Falsaperla et al. in 2023, undertook an exhaustive examination of COVID-19-related neurological manifestations in the pediatric population. Although this study primarily emphasized clinical symptoms, it did not include a meta-analytic assessment. Nevertheless, their conclusions align closely with our own findings, albeit with distinct categorization. Their results highlighted that encephalitis represented the most frequent diagnosis, accounting for 20.83% of cases, followed by seizures (10.42%), GBS (10.42%), cerebrovascular involvement (10.42%), ADEM (8.33%), and encephalopathy (8.33%). Additionally, a fraction of cases exhibited neurological signs secondary to central nervous system lesions (4.17%), and peripheral neuropathy (4.17%)37.

The cellular and molecular basis of SARS-CoV-2's ability to affect the nervous system is not fully understood. In light of this, several theoretical mechanisms have been posited to shed light on the acute and postacute neurological manifestations associated with COVID-19. Firstly, one hypothesis proposes that SARS-CoV-2 exhibits an affinity for infecting olfactory neurons, subsequently spreading through axons and across the synapse, thereby causing central nervous system infection38. Secondly, considering the viral-induced depletion of ACE-2, there is a perturbation in the renin-angiotensin system equilibrium. Consequently, a prothrombotic state may ensue, impairing both large vessel and microvascular blood flow. This vascular dysfunction heightens the risk of thrombotic and hemorrhagic stroke following SARS-CoV-2 infection39. Thirdly, perhaps the most pivotal mechanism at play is immune dysregulation, culminating in autoimmunity and hyperinflammatory responses. The aberrant immune response is recognized as a central contributor to neurological involvement in COVID-19 cases40. Lastly, the cytokine storm and systemic hyperinflammatory responses incited by the virus present an additional avenue through which neurological manifestations may occur. Elevated pro-inflammatory cytokine levels can disrupt normal neuronal function, impede neurotransmitter systems, and induce neuronal damage41,42. Understanding the mechanisms responsible for the neurological manifestations of COVID-19 is crucial for the development of potential therapeutic interventions. These mechanisms can operate independently or in concert within individual patients, giving rise to a range of clinical and neuroimaging presentations that, while varied, often exhibit overlapping features. This underscores the significance of investigating these mechanisms in our pursuit of effective treatments43.

The observed incidence of neurological abnormalities in pediatric COVID-19 patients raises several important clinical and research implications. First, it highlights the necessity for a high index of suspicion for neurological complications in children with COVID-19, especially those presenting with neurological symptoms. Timely neuroimaging assessments and consultations with pediatric neurologists may be essential for early diagnosis and appropriate management.

Second, the findings of this study emphasize the importance of continued research into the long-term consequences of COVID-19 in children. Even in cases where acute neurological symptoms resolve, it remains to be seen whether these children may be at risk of long-term cognitive or neurological sequelae. Longitudinal studies are needed to assess the evolution of these abnormalities and their potential impact on a child's development and quality of life.

To the best of our knowledge, this study represents the first systematic review and meta-analysis of neuroimaging findings in pediatric SARS-CoV-2 cases. Nonetheless, it is important to acknowledge several limitations of this study. Firstly, some of the studies included in our analysis exhibited substantial heterogeneity, attributed to variations in study designs, patient cohorts, and imaging protocols. This inherent diversity, though mitigated through statistical methods, somewhat limits the generalizability of our findings. Secondly, the potential presence of publication bias, although not overtly evident in our assessments, cannot be entirely dismissed. Thirdly, the relatively limited number of studies constrained our ability to conduct more detailed subgroup analyses and explore specific aspects comprehensively. Moreover, in this study, our research commenced on December 1, 2019. It is essential to acknowledge a limitation related to the evolving nature of information about COVID-19 during that early period. Detailed and comprehensive information about COVID-19, including its clinical manifestations and neurological implications, may not have been readily available at the beginning of our study. As a result, some aspects of our analysis may be based on limited data and evolving knowledge in the early stages of the pandemic. Furthermore, establishing a causal relationship between COVID-19 infection and the observed neuroimaging abnormalities remains an ongoing area of investigation. These abnormalities may be influenced by systematic confounding factors such as comorbidities, mechanical ventilation, and the complex pharmacological regimens administered for respiratory distress with hypoxia. These limitations underscore the necessity for future prospective studies that consider comorbidities and conduct more intricate analyses to affirm the potential association between COVID-19 and neuroimaging findings.

Link:

Neuroimaging findings in children with COVID-19 infection: a systematic review and meta-analysis | Scientific Reports - Nature.com