Neurological complications and pathophysiological pathways of the novel coronavirus SARS-CoV-2: a systematic review

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for Coronavirus Disease 2019 (COVID-19), has been increasingly recognized for its neurological disorders. This systematic review aimed to synthesize current evidence on the spectrum of neurological complications associated with SARS-CoV-2 infection and the pathophysiological mechanisms. A search of scientific literature was performed across databases including Web of Science, PubMed, and Scopus from 2019 to 2025. The quality of included studies was assessed using AMSTAR 2 for systematic reviews, JBI Checklist for case reports, and NOS for cohort and case-control studies. The findings demonstrated that SARS-CoV-2 caused neurological symptoms in the Central Nervous System (CNS) and Peripheral Nervous System (PNS). The involvement of CNS included encephalitis, stroke, encephalopathy, myelitis, neuroinflammation, and demyelinating disorders. The PNS disorders such as Guillain–Barré syndrome (GBS), peripheral neuropathy, anosmia, and ageusia, were also frequently observed. Autonomic dysfunction and musculoskeletal complications like myositis were reported. The pathophysiological mechanisms included direct viral neuroinvasion, disruption of the blood–brain barrier, immune-mediated responses, and systemic inflammation. SARS-CoV-2 revealed neurotropic potential and can impact the nervous system through multifaceted mechanisms. Neurological involvement is both common and clinically significant, often correlating with disease severity and poorer outcomes. COVID-19, the disease caused by the SARS-CoV-2 virus, can affect not just the lungs but also the brain and nerves. Many people with COVID-19 experience problems with their nervous system, which includes the brain (central nervous system) and the nerves throughout the body (peripheral nervous system). These problems range from mild symptoms like headaches, loss of smell or taste, and muscle pain, to more serious conditions such as strokes, seizures, and inflammation of the brain. About one in three people with COVID-19 May have some type of neurological symptom. The virus may reach the brain in several ways. It can directly enter the brain, possibly by crossing the protective barrier known as the blood–brain barrier. It may also cause damage indirectly by triggering widespread inflammation or by causing the immune system to attack the body’s own nerve tissues. The studies of brain scans, spinal fluid, and tissue from autopsies have found signs of the virus in the brain and evidence of inflammation and immune system involvement. Testing spinal fluid for the virus using standard methods like PCR often comes back negative, which means other signs such as increased inflammatory markers might be more useful for diagnosis. Some of the long-term brain-related symptoms people report after recovering from COVID-19, like tiredness, memory issues, and trouble sleeping, may be linked to hormonal changes caused by the virus.