Since the beginning of the pandemic, numerous clinical cases, research, and reviews have been published in this regard. Regarding the first-line DMTs, Glatiramer Acetate [3] causes blockage of MHC-II in immunological synapsis and shift from Th1 to Th2 immune responses [39]. antibody titer. However, more studies are needed to help understand how this virus works, paying special attention to long COVID and the neurological symptoms that it causes. Keywords: SARS-CoV-2, Multiple sclerosis, Disease-modifying therapies, Immunity, Adjuvant treatments, Neuro-COVID Introduction On March 11, 2020, the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) as a pandemic, just 3?months after the appearance of the first cases in Wuhan (China) [1]. On May 26, 2022, the cases confirmed by the WHO are 524,339,768 and 6,281,260 deaths have been registered worldwide [2]. This pandemic has placed enormous pressure on medical resources and, in most countries, health care systems have had to reconfigure to manage the increase in severe COVID-19 cases and reduce the risk of vulnerable patients [3, 4]. The genome of the type 2 coronavirus that causes severe acute respiratory syndrome (SARS-CoV-2) comprises 13 to 15 open reading frames (ORF), of which 12 are fundamental, encompassing 11 genes that code for proteins (Fig.?1) [5, 6]. This virus consists of four main structural proteins [7]. The spike protein (S) enables the attachment and entry of SARS-CoV-2 to the host cells; The membrane protein (M) is a component of the viral membrane; the nucleocapsid protein Rabbit Polyclonal to TEF (N) binds to viral RNA and supports the formation of the nucleocapsid and the envelope protein (E) that plays a role in viral assembly, release, and pathogenesis (Fig.?2) [8, 9]. When infection occurs, the first responders are alveolar macrophages [9]. This signal causes transcription factors such as IRF3/7 (interferon regulation factor) and NF-B (nuclear factor kappa B) to be activated and the production of type I and III interferon (IFN) BJE6-106 begins, as well as the secretion of interleukin 6 (IL-6) and interleukin 1 (IL-1), which induces the recruitment of neutrophils and cytotoxic T cells [7, 10]. CD4?+?T cells aid in the adaptive BJE6-106 response, by stimulating CD8?+?T cells and B cells [11]. In addition, they induce a Th1 response [12], which plays a dominant role in the adaptive immune response to viral infections [9, 11]. This response causes an increase in the secretion of pro-inflammatory cytokines, IFN- and Tumor Necrosis Factor alpha (TNF-) [12]. Th17 cells produce IL-17, even more monocytes, macrophages, and neutrophils are recruited, and more cytokines are stimulated [9, 13, 14]. In certain cases, the levels of these cytokines are very high, due to a dysregulated immune response of the host, causing what is known as Cytokine Storm. Open in a separate window Fig. 1 SARS-CoV-2 genomic organization. Image made with Inkscape based on the article made by Dos Santos 2021 [5] Open in a separate window Fig. 2 Structure of SARS-CoV-2 with the main structural proteins. Image made with Inkscape based on the article made by Dos Santos 2021 [5] SARS-CoV-2 has become a serious challenge for many areas of medicine, including neurology [15]. In this sense, since the beginning of the pandemic, there has been a special concern for those people suffering from Multiple Sclerosis (MS), especially those who are being treated with disease-modifying therapies (DMTs) [16], since it is believed that these patients may be at higher risk of infection or of having a more BJE6-106 severe course of COVID-19 than the general population. This disease affects 2.5 million people in the world [17], being the most common cause of non-traumatic disability in young adults [18] between 20 and 30?years of age [19] (Fig.?3). Open in a BJE6-106 separate window Fig. 3 Cellular and molecular mechanisms involved in multiple sclerosis. BBB bloodCbrain barrier, central nervous system, T-cell receptor, major histocompatibility complex II, vascular cell adhesion molecule 1, cells T helper 1, T helper 17,.