Therapeutic Approaches to the Neurologic Manifestations of COVID-19

Abstract

As of May 2022, there have been more than 527 million infections with severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) and over 6.2 million deaths from Coronavirus Disease 2019 (COVID-19) worldwide. COVID-19 is a multisystem illness with important neurologic consequences that impact long-term morbidity and mortality. In the acutely ill, the neurologic manifestations of COVID-19 can include distressing but relatively benign symptoms such as headache, myalgias, and anosmia; however, entities such as encephalopathy, stroke, seizures, encephalitis, and Guillain-Barre Syndrome can cause neurologic injury and resulting disability that persists long after the acute pulmonary illness. Furthermore, as many as one-third of patients may experience persistent neurologic symptoms as part of a Post-Acute Sequelae of SARS-CoV-2 infection (Neuro-PASC) syndrome. This Neuro-PASC syndrome can affect patients who required hospitalization for COVID-19 or patients who did not require hospitalization and who may have had minor or no pulmonary symptoms. Given the large number of individuals affected and the ability of neurologic complications to impair quality of life and productivity, the neurologic manifestations of COVID-19 are likely to have major and long-lasting personal, public health, and economic consequences. While knowledge of disease mechanisms and therapies acquired prior to the pandemic can inform us on how to manage patients with the neurologic manifestations of COVID-19, there is a critical need for improved understanding of specific COVID-19 disease mechanisms and development of therapies that target the neurologic morbidities of COVID-19. This current perspective reviews evidence for proposed disease mechanisms as they inform the neurologic management of COVID-19 in adult patients while also identifying areas in need of further research.

Dual-targeting cyclic peptides of receptor-binding domain (RBD) and main protease (Mpro) as potential drug leads for the treatment of SARS-CoV-2 infection

“…Respiratory disease is the hallmark of COVID-19, meanwhile gastrointestinal symptoms, cardiac injury, and neurologic symptoms may occur. SARS-CoV-2 was found in relevant organs including lungs, intestines, heart, and brain ( Akhmerov and Marbán, 2020 ; Yang W. et al, 2020 ; Mao et al, 2020 ; Graham et al, 2022 ). Therefore, to further investigate the safety of MRs 1-4, a MTT assay was conducted to detect the cytotoxicity of MRs 1-4 to A549, FHs 74 Int, AC16, and hCME/CD3 which are in correspondence to the symptoms mentioned above.…”

Case report: Treatment of long COVID with a SARS-CoV-2 antiviral and IL-6 blockade in a patient with rheumatoid arthritis and SARS-CoV-2 antigen persistence

“…Currently, there are only symptomatic treatments for Neuro-PASC (8). We present the first case of a Neuro-PASC patient whose symptoms and antiviral adaptive immune responses were reduced by a 5-day course of nirmatrelvir-ritonavir.…”

“…Neuro-PASC is clinically defined as new neurologic or neurocognitive symptoms persisting for more than 4 weeks after disease onset and is often not concomitant with diagnosis of acute infection (6,7). Currently, there are only symptomatic treatment options for Neuro-PASC (8), demonstrating the urgent need for new therapeutic approaches that address the underlying cause(s).…”

Myeloencephalitis as the only presentation of Omicron SARS-CoV-2 infection

“… 12 In case of an active systemic infection, antiviral could be considered for at least 5–10 days. 12 Agents such as remdesivir or favipiravir were used in several case reports, however, their efficacy in encephalitis is uncertain. 11 13 In our institution, remdesivir is the only viable option despite a penetration rate in CSF of less than 5% in animal models.…”