Post‐COVID‐19 Area Postrema Syndrome With SARS‐CoV‐2 in CSF: A Dual‐Case Report and Review of the Literature
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2026
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| author | Wan Zhu Jing Qian Min Peng Yan Li Jinghan Hu |
| author_facet | Wan Zhu Jing Qian Min Peng Yan Li Jinghan Hu Wan Zhu Jing Qian Min Peng Yan Li Jinghan Hu |
| collection | Wiley Open Access |
| contents | Post‐COVID‐19 Area Postrema Syndrome With SARS‐CoV‐2 in CSF: A Dual‐Case Report and Review of the Literature Wan Zhu Jing Qian Min Peng Yan Li Jinghan Hu Immunity, Inflammation and Disease ABSTRACT Background Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune astrocytopathy characterized by inflammatory demyelinating lesions in the central nervous system. Area postrema syndrome (APS), marked by intractable nausea, vomiting, and hiccups, is a recognized but less common initial manifestation. Post‐infectious autoimmunity triggered by SARS‐CoV‐2 has been increasingly associated with NMOSD pathogenesis; however, the clinical significance of direct viral neuroinvasion and its relationship to divergent patient outcomes remains poorly understood. Methods We report two female patients who developed isolated APS shortly after COVID‐19 infection. Both patients underwent comprehensive neurological evaluation, including brain and spinal magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis with metagenomic next‐generation sequencing (mNGS), and serological testing for aquaporin‐4 immunoglobulin G (AQP4‐IgG), myelin oligodendrocyte glycoprotein immunoglobulin G (MOG‐IgG), and glial fibrillary acidic protein immunoglobulin G (GFAP‐IgG) using cell‐based assays. Clinical outcomes were compared in the context of antibody serostatus and treatment strategies. A review of the relevant literature on post‐COVID NMOSD was also performed. Results Both patients presented with intractable vomiting and hiccups following SARS‐CoV‐2 infection, and MRI demonstrated isolated T2/FLAIR hyperintense lesions in the dorsal medulla consistent with area postrema involvement. SARS‐CoV‐2 RNA sequences were detected in the CSF of both patients via mNGS, suggesting direct viral neuroinvasion or blood–brain barrier compromise. Despite similar initial presentations, their outcomes diverged dramatically. Patient 1 was AQP4‐IgG negative, responded well to immunotherapy with intravenous immunoglobulin and corticosteroids followed by mycophenolate mofetil maintenance, and remained relapse‐free at 12‐month follow‐up with significant lesion regression on MRI. Patient 2 was AQP4‐IgG positive in both serum and CSF, and despite acute treatment, experienced a fatal relapse 6 months later with longitudinally extensive transverse myelitis while on low‐dose prednisone monotherapy. Conclusions Isolated APS may represent an important yet under‐recognized manifestation of post‐COVID‐19 autoimmune neuroinflammation. Detection of SARS‐CoV‐2 in CSF supports a role for direct viral neuroinvasion as a localized inflammatory stimulus. AQP4‐IgG serostatus serves as a critical prognostic determinant: seronegativity is associated with a benign, monophasic course, whereas seropositivity mandates prompt initiation of potent immunosuppressive therapy to prevent devastating relapses. Clinicians should maintain a high index of suspicion for NMOSD in patients with unexplained persistent vomiting following COVID‐19, and perform urgent neuroimaging and antibody testing for early risk stratification. 10.1002/iid3.70421 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/iid3.70421 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_iid3_70421 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2026 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Post‐COVID‐19 Area Postrema Syndrome With SARS‐CoV‐2 in CSF: A Dual‐Case Report and Review of the Literature Wan Zhu Jing Qian Min Peng Yan Li Jinghan Hu Immunity, Inflammation and Disease Post‐COVID‐19 Area Postrema Syndrome With SARS‐CoV‐2 in CSF: A Dual‐Case Report and Review of the Literature Wan Zhu Jing Qian Min Peng Yan Li Jinghan Hu Immunity, Inflammation and Disease ABSTRACT Background Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune astrocytopathy characterized by inflammatory demyelinating lesions in the central nervous system. Area postrema syndrome (APS), marked by intractable nausea, vomiting, and hiccups, is a recognized but less common initial manifestation. Post‐infectious autoimmunity triggered by SARS‐CoV‐2 has been increasingly associated with NMOSD pathogenesis; however, the clinical significance of direct viral neuroinvasion and its relationship to divergent patient outcomes remains poorly understood. Methods We report two female patients who developed isolated APS shortly after COVID‐19 infection. Both patients underwent comprehensive neurological evaluation, including brain and spinal magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis with metagenomic next‐generation sequencing (mNGS), and serological testing for aquaporin‐4 immunoglobulin G (AQP4‐IgG), myelin oligodendrocyte glycoprotein immunoglobulin G (MOG‐IgG), and glial fibrillary acidic protein immunoglobulin G (GFAP‐IgG) using cell‐based assays. Clinical outcomes were compared in the context of antibody serostatus and treatment strategies. A review of the relevant literature on post‐COVID NMOSD was also performed. Results Both patients presented with intractable vomiting and hiccups following SARS‐CoV‐2 infection, and MRI demonstrated isolated T2/FLAIR hyperintense lesions in the dorsal medulla consistent with area postrema involvement. SARS‐CoV‐2 RNA sequences were detected in the CSF of both patients via mNGS, suggesting direct viral neuroinvasion or blood–brain barrier compromise. Despite similar initial presentations, their outcomes diverged dramatically. Patient 1 was AQP4‐IgG negative, responded well to immunotherapy with intravenous immunoglobulin and corticosteroids followed by mycophenolate mofetil maintenance, and remained relapse‐free at 12‐month follow‐up with significant lesion regression on MRI. Patient 2 was AQP4‐IgG positive in both serum and CSF, and despite acute treatment, experienced a fatal relapse 6 months later with longitudinally extensive transverse myelitis while on low‐dose prednisone monotherapy. Conclusions Isolated APS may represent an important yet under‐recognized manifestation of post‐COVID‐19 autoimmune neuroinflammation. Detection of SARS‐CoV‐2 in CSF supports a role for direct viral neuroinvasion as a localized inflammatory stimulus. AQP4‐IgG serostatus serves as a critical prognostic determinant: seronegativity is associated with a benign, monophasic course, whereas seropositivity mandates prompt initiation of potent immunosuppressive therapy to prevent devastating relapses. Clinicians should maintain a high index of suspicion for NMOSD in patients with unexplained persistent vomiting following COVID‐19, and perform urgent neuroimaging and antibody testing for early risk stratification. 10.1002/iid3.70421 http://creativecommons.org/licenses/by/4.0/ |
| title | Post‐COVID‐19 Area Postrema Syndrome With SARS‐CoV‐2 in CSF: A Dual‐Case Report and Review of the Literature |
| topic | Immunity, Inflammation and Disease |
| url | https://onlinelibrary.wiley.com/doi/10.1002/iid3.70421 |