Fig. 1

Possible pathogenesis and therapeutic strategy of GBS associated with SARS-CoV-2 infection. SARS-CoV-2 infection can induce immune-mediated peripheral nerve injury and ultimately lead to GBS likely because of the similar antigenic epitopes between pathogens and human peripheral nerve gangliosides (molecular mimicry and cross-reactivity) (anti-ganglioside antibodies have been detected in serum or CSF of GBS patients). When the S1 protein of the new coronavirus binds to ACE2R of human cells, it is recognized and captured by APC and presented to T cells. CD4 T cells stimulate B cells to produce anti-ganglioside antibodies and CD8 T cells directly kill virus-infected cells. Activated T cells secrete IFN, which stimulate NK cells to kill SARS-CoV-2. Moreover, activated T cells destroy the BNB by secreting IL-1, IL-6, and TNF-α to promote immune cells, complement, and antibodies crossing BNB to entry the CNS. In the peripheral nervous system, macrophages are activated by TNF and IFN-γ secreted by activated T cells. The activated macrophages release inflammatory cytokines to damage the myelin sheaths and axons of peripheral nerves. Besides, the autoantibodies can combine with the specific antigenic epitopes of myelin and axons to activate complement, inducing the formation of MAC, and macrophage migration and recruitment, ultimately leading to peripheral nerve injury. Besides, complement activation, MAC deposition, and infiltration of macrophages participate in the pathogenesis of GBS. In terms of therapy of GBS, IVIG plays a therapeutic role by neutralizing antibodies, blocking Fc receptors on macrophages, inhibiting complement activation and the formation of MAC, and regulating T and B cell functions. PE may work via scavenging autoantibodies, complement, MAC, and cytokines. Complement inhibitors, such as eculizumab, may be a potential therapy, and its therapeutic mechanism is associated with inhibition of complement activation and the formation of MAC. SARS-CoV-2 acute respiratory syndrome coronavirus 2, GBS Guillain-Barré syndrome, CSF cerebrospinal fluid, S1 Spike, ACE2R angiotensin converting enzyme 2 receptor, APC antigen-presenting cell, TNF tumor necrosis factor, IL interleukin, TNF tumor necrosis factor, BNB blood–nerve barrier, CNS central nervous system, MAC membrane attack complex, Mφ macrophages; IVIG Intravenous immunoglobulin, PE plasma exchange⁺⁺