**1. Introduction – COVID-19 options for treatment**

The coronavirus disease 2019 (COVID-19) is an acute respiratory infection related to the new RNA virus coronavirus 2, that produces severe acute respiratory syndrome (SARS-CoV-2) [1]. Since the first SARS-CoV-2-infected patients were reported in Wuhan, China, in December 2019, the number of individuals infected with COVID-19 has risen significantly around the world [2]. In January 2020, the World Health Organization (WHO) announced that COVID-19 had been labeled as a public health pandemic disease worldwide [3]. Likewise, during the last three years, individuals worldwide face a large wave of COVID-19 produced by SARS-CoV-2 variants (i.e., delta, lambda, mu, and omicron) on a widespread globe. In January 2022, the World Health Organization (WHO) published an updated report about enhancing the response to the new mutation called Omicron SARS-CoV-2 variant [4]. To focus more on COVID-19 symptoms, after the incubation period (2–14 days), three phases of COVID-19 symptoms appeared [1]. The first stage, known as the acute COVID-19 stage (stage I) characterized by mild to moderate symptoms including fever or chills,

cough, shortness of breath fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or running nose, nausea, and diarrhea [2]. The prevalence of mild to moderate symptoms is significant in SARS-CoV-2-infected individuals [5]. Post-acute viral syndromes are acknowledged as prolonged and multiorgan effects [6]. The second stage (stage II) is less common and characterized by severe clinical stages such as dyspnea accompanied by hypoxemia [7, 8]. As a consequence of severe clinical symptoms, stage III can occur, including serious difficulties such as arrhythmias, septic shock, and multi-organ failures, ultimately resulting in intubation or death [2]. A high proportion of COVID-19 non survivors had preexisting cardiovascular illness and multi organ dysfunction [9].

SARS-CoV-2 infection appears to have harmful effects on the central nervous system (CNS), leading to psychiatric and neurological symptoms [10]. Brain-related manifestations were reported in individuals with and without neuropsychiatric diseases [11]. Existing in vitro and in vivo studies support the notion of SARS-CoV-2-related neuroinvasive risks. These risks were transported mainly through olfaction and the trigeminal pathways [12]. According to national longitudinal research in China, depression, anxiety, and insomnia were the most common psychiatric disorders associated with the COVID-19 pandemic [13]. Another study indicated that the prevalence of neurological manifestations was reasonably noted, including encephalopathy, delirium, seizures, Guillain-Barré-syndrome, and motor dysfunctions [14]. Another review reported that the emergence of psychiatric disorders occurs within three months in COVID-19 survivors [6].

COVID-19 outbreaks present challenges for therapeutic and drug management in clinical conditions and complications. Recently, several researchers emphasized medication repurposing as an approaching method to establish a fast-track line for discovering therapeutic treatments for COVID-19 patients worldwide [15–18]. Drug repurposing, also known as drug reuse, is defined as exploring new indications for existing drugs. This approach limits the cost of both research and development significantly [19]. Serendipitously revealed a substantial number of current identified repurposed drugs [20]. The repurposing strategy provided promising treatment candidates in other viral pandemics outbreaks, including ZIKA, Ebola, and dengue [21].

Zhang et al summarized the current potential therapeutic approaches for diseases related to COVID-19 infection and explain their mechanisms of action, safety, and effectiveness such as antiviral drugs, convalescent plasma, spike Protein-Angiotensin-Converting enzyme 2 blockers, chloroquine, hydroxychloroquine, human monoclonal antibody, mesenchymal stem cells, inhaled nitric oxide (iNO), and corticosteroids [22]. Another review highlighted alternative treatment approaches such as mesenchymal stem cells, human monoclonal antibodies, and complementary Chinese medicine [20].

A comprehensive and systematic research about the repurposing of drugs in COVID-19 was conducted by Srivastava and Singh (2021), the results revealed that no drugs passed clinical trials or were approved by the FDA for COVID-19 [23]. In fact, various reports that clinical trials regarding the potential therapeutic possibilities, such as hydroxychloroquine, lopinavir-ritonavir, and ivermectin, showed that choices were unsuccessful in the treatment of COVID-19 patients [24–27]. Although COVID-19 vaccines were successfully developed and massively distributed, there is a lack of effective treatment [28].

Most significantly, there are cumulative clinical data linked with the use of antidepressants, including the selective serotonin reuptake inhibitor (SSRI) and the serotonin-norepinephrine reuptake inhibitor (SNRI) with a reduced risk of clinical complications in SARS-CoV-2-infected patients [18]. In line with this, a randomized *Perspective Chapter: New Use of the SSRI Fluvoxamine in the Treatment of COVID-19 Symptoms DOI: http://dx.doi.org/10.5772/intechopen.105023*

controlled trial showed that patients who received fluvoxamine had a decreased risk of clinical deterioration compared to those who received placebo during the early period of infection [29]. Following that, an observational study done by Hoertel et al. discovered that the antidepressants, such as SSRIs and SNRIs, may be associated with a lower risk of intubation or death in SARS-CoV-2-infected hospitalized patients [30]. This advantage was not reported with other antipsychotics. For example, a multicenter observational study indicated that administration of haloperidol was not associated with a reduced risk of intubation or death in hospitalized COVID-19 patients [31].

Fluvoxamine has advantages over other repurposing drugs such as positive safety profiles, widespread availability, inexpensive, accessible mode of administration as immediate-release tablets and controlled-release capsules, and use for children and adolescents [32, 33]. The available dosage form of fluvoxamine is both immediaterelease tablets and controlled-release capsules. The main therapeutic indication of fluvoxamine is to treat patients with obsessive-compulsive disorder (OCD). The pharmacokinetic properties of fluvoxamine include long half-life of about 9–28 hours according to its dosage form. The clinical guideline recommended the therapeutic dose of fluvoxamine between 100–300 mg/day [34]. Fluvoxamine indication is related to COVID-19 was clarified on the US National Institutes of Health (NIH) COVID-19 Guidelines Panel on April 23, 2021, despite the fact that evidence for fluvoxamine effectiveness was lacking. Recently, a retrospective cohort study of COVID-19 patients treated with SSRIs using electronic health records of 87 health care centers across the US was done in November 2021 by Oskotsky et al. [35]. The study participants were COVID-19 patients receiving fluoxetine only (n = 470), COVID-19 patients receiving fluoxetine or fluvoxamine (n = 481), and COVID-19 patients receiving other SSRIs (n = 2898) compared with matched untreated control COVID-19 patients. The results showed that the patients who received any SSRI had a lower risk of death. In contrast, there was no significant relationship between SSRIs other than fluoxetine or fluvoxamine and the risk of mortality [35]. Finally, fluvoxamine might be used as a preventive medication for patients infected with SARS-CoV-2 in the early stages [16, 36]. In this chapter, we review the fluvoxamine mechanisms of action in COVID-19 and discuss the studies that focus on the impact of the use of fluvoxamine in minimizing the possible complication during COVID-19 infection. Here, we review two main mechanisms mediated by fluvoxamine, the serotonin and the sigma-1 receptor-related mechanisms.
