Possible Role of Selective Serotonin Reuptake Inhibitors (SSRIs) in Clinical Outcome of COVID-19 Patients

In February 2020, the World Health Organization officially named the disease caused by the new corona virus as COVID-19 (Corona Virus Disease 2019). For COVID-19 patients, there are usually four phases of the disease. The first one is virus reproduction phase. The second phase is accompanied with mild symptoms and usually includes flu-like symptoms. The third phase is associated with the development of acute respiratory distress syndrome (ARDS) and is characterized by its symptoms. The fourth phase is associated with high fever, systemic inflammatory responses, especially in the lungs, and eventual respiratory failure. COVID-19 is associated with upregulations of inflammatory cytokines. In the acute phase of COVID-19, the function of TCD4+ cells are impaired and the production of interferon-gamma (IFN-γ) and Tumor Necrosis Factor-alpha (TNF-α) in these cells is reduced. With impaired immune function, virus replication continues, and damaged lung cells induce excessive inflammatory responses and overproduction of inflammatory cytokines such as TNF-α, IL-1β, and IL-6 from immune cells. This eventually induce cytokine storm with systemic inflammatory responses and end organ damage. The level of inflammatory cytokines such as IL-1β, IL-6 and IL-10 in COVID-19 patients has been reported to be higher in COVID-19 patients admitted in ICU. The lack of effective treatment for the severe infection caused by COVID-19 has led scientists and physicians to repurpose popular medications that are indicated for other similar conditions. No effective modality to successful management of this viral disease has yet been identified. Immunosuppressive and anti-inflammatory drugs have been suggested for acute patients with cytokine storms and severe lung involvement. Recently, due to the anti-inflammatory effects of selective serotonin reuptake inhibitors (SSRIs), their therapeutic effects have been proposed for COVID-19 patients. This group of drugs are usually prescribed to treat depressive disorders. SSRIs have been shown to reduce inflammation and the expression of inflammatory cytokines such as TNF⍺ and IL-1β. The decrease in inflammatory cytokines such as IL-1β and TNF-α in the cerebral tissue has been shown as a result of sertraline administration, indicating the anti-inflammatory effects of this drug. In another study, Fluvoxamine could lower IL-1β, IL-6, and TNFα expression in the striatum in depressed mice. Much attention is paid to sertraline due to its very low anticholinergic activity which is especially desirable for the elderly with coronary heart diseases. Moreover, the anti-inflammatory properties of this compound is attributed to prevention of the expression of pro-inflammatory cytokines. Recently, it was demonstrated that treatment of patients with major depression with SSRIs could reduce the expression of inflammatory cytokines, such as IL-10, TNF-α, and IL-6 in these patients. The expression of these inflammatory mediators increase in critically ill COVID-19 patients. Therefore, the use of this class of medications in the management of COVID-19 patients could be considered, especially for acute patients with cytokine storms. In a recently published study, the use of antidepressants SSRI and paroxetine and SNRI venlafaxine in hospitalized patients due to COVID-19 reduced the risk of intubation and death. This therapeutic effect on COVID-19 could be attributed to the inhibition of acid sphingomyelinase activity, which prevents epithelial cell from being infection by SARS-CoV2. It has also been suggested that S1A (σ-1- receptor) agonists can prevent cytokine storms in severe COVID-19. SSRIs, especially fluvoxamine and to a lesser extent sertraline have a moderate to high affinity for this receptor. Antidepressants are associated with decreased plasma levels of pro-inflammatory cytokines which elevate in COVID-19. Furthermore, the antiviral activity of some antidepressants such as fluoxetine has been reported in COVID-19 patients. In a randomized clinical trial on adult outpatients with COVID-19, administration of 100 mg of fluvoxamine reduced the likelihood of clinical deterioration over 15 days. This has been attributed to the high affinity of fluvoxamine for S1R, which reduces the inflammatory responses. It seems that SSRIs are potential candidates for COVID-19 due to their anti-inflammatory properties. Future clinical studies will determine the exact role of this class of medications in clinical outcomes of COVID-19 patients

Effect of vitamin C on coagulation factors and endothelium function in patients with sepsis

Objective: Sepsis is one of the leading causes of mortality in intensive care unit. Despite advances in its management, its mortality rate remains high. Recently, high dose of vitamin C in sepsis treatment has attracted the attention of researchers. In the current study, the impacts of 25 mg/kg of vitamin C every 6 hours as a bolus for 3 days were assessed in septic patients in intensive care unit (ICU). Methods: This was a prospective cohort study that was performed on adult patients with diagnosis of sepsis. Patients were assigned to control group (administration of placebo) or intervention group, i.e., those receiving a 25 mg/kg dose of vitamin C every 6 hours as a bolus for 3 days. Clinical data were recorded before and after the experiment. Also, plasma levels of antithrombin III, syndecan-1, fibrin degradation product (FDP), D-dimer, and C-reactive protein (CRP) were measured at 0, 24, 48, and 72 hours. Results: In septic patients receiving vitamin C, a significant upregulation of antithrombin III and significant decreases in the levels of syndecan-1 (at 48 hours; P-value=0.046 and at 72 hours; P-value=0.007), D-dimer and CRP were observed compared to the control. Reductions in sequential organ failure assessment (SOFA) score, in-hospital mortality, and ICU length of stay were seen in septic patients receiving vitamin C. Conclusion: Prescribing high dose of intravenous vitamin C can reduce the mortality of sepsis patients and reduce the length of stay in the ICU

Efficacy of lacosamide in the treatment of non-convulsive seizure and non-convulsive status epilepticus in septic patients: a narrative review

Non-convulsive seizures (NCS) and non-convulsive status epilepticus (NCSE) are of the acute complications of patients admitted to the intensive care unit (ICU), which lead to increased mortality and morbidity. In these cases, immediate treatment with antiepileptic drugs (AEDs) is important to prevent further damage to the brain. AEDs are the first line of treatment, however, most of these medications have many side effects. In the recent years, significant advances have been made in this area and lacosamide is one of the therapeutic options. The intravenous formulation of this drug is most popular due to the lack of drug-drug interaction and properly designed studies which have been conducted in this field. In this review, the latest findings on the effect of lacosamide on acute non-convulsive and generalized-convulsive seizures (G-CS) are evaluated in critically ill patients admitted to the ICU

High Dose of Vitamin C in Septic and Critically Ill Patients with COVID-19: A Narrative Review

The coronavirus disease of 2019 (COVID-19) may be considered sepsis on the basis that all the pathological events and the subsequent organ-to-organ interaction in sepsis also occur in COVID-19. In this article, the authors first discussed the rationale for the use of vitamin C (Vit-C) in sepsis and septic patients. They also reviewed the role of a high dose of Vit-C in COVID-19, which included clinical trials designed for the management of this viral disease. Methods: The researchers explored databases of PubMed, Scopus, ISI Web of Science, and Google Scholar. Data were extracted to assess the effects of Vit-C in septic patients and also the efficacy of supplementation with a high dose of Vit-C regarding the clinical outcomes of patients with COVID-19. Results: Recent research findings indicate that severe inflammatory responses (cytokine storms) and oxidative stress are important causes for the high mortality in COVID-19 patients. It seems, however, that administering high doses of Vit-C can offer a therapeutic benefit. High doses of intravenous Vit-C, with its antioxidant properties and pleiotropic functions, could attenuate the tissue damage caused by excessive levels of free radicals following the cytokine storm and septic shock in severe cases of the disease. Conclusions: Recent literature suggests that high doses of Vit-C have a potential role in reducing mortality and intubation rates in critically ill COVID-19 patients. However, determining the optimal duration and dose of Vit-C in these patients requires further studies