Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine (FAKHRAVAC®) in healthy adults aged 18-55 years: Randomized, double-blind, placebo-controlled, phase I clinical trial.

Background: The FAKHRAVAC®, an inactivated SARS-CoV-2 vaccine, was assessed for safety and immunogenicity. Methods and findings: In this double-blind, placebo-controlled, phase I trial, we randomly assigned 135 healthy adults between 18 and 55 to receive vaccine strengths of 5 or 10 µg/dose or placebo (adjuvant only) in 0-14 or 0-21 schedules. This trial was conducted in a single center in a community setting. The safety outcomes in this study were reactogenicity, local and systemic adverse reactions, abnormal laboratory findings, and Medically Attended Adverse Events (MAAE). Immunogenicity outcomes include serum neutralizing antibody activity and specific IgG antibody levels.The most frequent local adverse reaction was tenderness (28.9%), and the most frequent systemic adverse reaction was headache (9.6%). All adverse reactions were mild, occurred at a similar incidence in all six groups, and were resolved within a few days. In the 10-µg/dose vaccine group, the geometric mean ratio for neutralizing antibody titers at two weeks after the second injection compared to the placebo group was 9.03 (95% CI: 3.89-20.95) in the 0-14 schedule and 11.77 (95% CI: 2.77-49.94) in the 0-21 schedule. The corresponding figures for the 5-µg/dose group were 2.74 (1.2-6.28) and 5.2 (1.63-16.55). The highest seroconversion rate (four-fold increase) was related to the 10-µg/dose group (71% and 67% in the 0-14 and 0-21 schedules, respectively). Conclusions: FAKHRAVAC® is safe and induces a strong humoral immune response to the SARS-CoV-2 virus at 10-µg/dose vaccine strength in adults aged 18-55. This vaccine strength was used for further assessment in the phase II trial.Trial registrationThis study is registered with https://www.irct.ir; IRCT20210206050259N1.

Effect of fluvoxamine on preventing neuropsychiatric symptoms of post COVID syndrome in mild to moderate patients, a randomized placebo-controlled double-blind clinical trial.

BACKGROUND: Shortly after the Coronavirus disease 2019 (COVID-19) pandemic, a considerable number of recovered patients reported persisting symptoms, especially neuropsychological manifestations, which were later named post-COVID syndrome (PCS). Immune dysregulation was suggested as one of the main mechanisms for PCS. Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) that is mostly used to treat depression, anxiety disorders, and obsessive-compulsive disorder, has been suggested as an anti-COVID drug due to its anti-inflammatory effects, mainly through the sigma-1 receptor. Therefore, we aimed to evaluate fluvoxamine's effect on PCS neuropsychiatric symptoms. METHOD: In this double-blind randomized clinical trial, we included confirmed mild to moderate COVID-19 outpatients using polymerase chain reaction (PCR) by an infectious disease specialist. The presence of severe COVID-19 symptoms was evaluated by the infectious disease specialist and included dyspnea, SpO2 < 94% on room air, PaO2/FiO2 < 300 mm Hg, a respiratory rate > 30 breaths/min, and lung infiltrates > 50%. Then we performed permuted block randomization and assigned patients 1:1 into two groups to either receive fluvoxamine 100 mg tablet or a placebo daily for 10 days. Eligible patients were evaluated after 12 weeks for the presence of fatigue, as the primary, and other PCS symptoms as secondary outcomes. RESULTS: We screened a total of 486 patients from March to June 2022. After 12 weeks, 42 patients receiving fluvoxamine and 43 patients receiving Placebo were evaluated for PCS. Patients had a mean age of 38.5 ± 14.1 and 48% of them were women. Fatigue was significantly lower in the fluvoxamine group (p-value 0.026). No significant differences were observed in other symptoms. CONCLUSION: We concluded that taking fluvoxamine during active COVID-19 can reduce the chance of fatigue but the advantage of fluvoxamine was not observed for other symptoms. Further studies are necessary to confirm these preliminary results.

COVID-19 and its implications on the clinico-radiological course of multiple sclerosis: A case-control study.

Background: Multiple sclerosis (MS) is an immune-mediated disease that has been related to several risk factors such as various viral infections. We carried out this study in order to establish a relationship between COVID-19 infection and MS severity. Methods: In a case-control study, we recruited patients with relapsing-remitting multiple sclerosis (RRMS). Patients were divided into two groups based on positive COVID-19 PCR at the end of the enrollment phase. Each patient was prospectively followed for 12 months. Demographical, clinical, and past medical history were collected during routine clinical practice. Assessments were performed every six months; MRI was performed at enrollment and 12 months later. Results: Three hundred and sixty-two patients participated in this study. MS patients with COVID-19 infection had significantly higher increases in the number of MRI lesions (p: 0.019, OR(CI): 6.37(1.54-26.34)) and EDSS scores (p: 0.017), but no difference was found in total annual relapses or relapse rates. COVID-19 infections were positively correlated with EDSS progression (p: 0.02) and the number of new MRI lesions (p: 0.004) and predicted the likelihood of the number of new MRI lesions by an odds of 5.92 (p: 0.018). Conclusion: COVID-19 may lead to higher disability scores in the RRMS population and is associated with developing new Gd-enhancing lesions in MRI imaging. However, no difference was observed between the groups regarding the number of relapses during follow-up.

Antecedentes: La esclerosis múltiple (EM) es una enfermedad inmunomediada que se ha relacionado con varios factores de riesgo, como diversas infecciones virales. Realizamos este estudio para establecer una relación entre la infección por COVID-19 y la gravedad de la EM. Métodos: En un estudio de casos y controles, reclutamos pacientes con esclerosis múltiple remitente-recurrente (EMRR). Los pacientes se dividieron en dos grupos según la PCR positiva para COVID-19 al final de la fase de inscripción. Cada paciente fue seguido prospectivamente durante 12 meses. Los antecedentes demográficos, clínicos y médicos anteriores se recogieron durante la práctica clínica habitual. Las evaluaciones se realizaron cada 6 meses. La resonancia magnética se realizó en el momento de la inscripción y 12 meses después. Resultados: Trescientos sesenta y dos pacientes participaron en este estudio. Los pacientes con EM con infección por COVID-19 tuvieron aumentos significativamente más altos en el número de lesiones de resonancia magnética (p = 0,019; OR = 6,37 [IC 95%: 1,54-26,34]) y puntajes EDSS (p = 0,017), pero no se encontraron diferencias en el total de recaídas anuales o en las tasas de recaída. Las infecciones por COVID-19 se correlacionaron positivamente con la progresión de EDSS (p = 0,02) y la cantidad de nuevas lesiones en la resonancia magnética (p = 0,004) y predijeron la probabilidad de la cantidad de nuevas lesiones en la resonancia magnética con una probabilidad de 5,92 (p = 0,018). Conclusión: COVID-19 puede conducir a puntajes de discapacidad más altos en la población de EMRR y está asociado con el desarrollo de nuevas lesiones realzadas con Gd en imágenes de resonancia magnética. Sin embargo, no se observó diferencia entre los grupos en cuanto al número de recaídas durante el seguimiento.

COVID-19 and its implications on the clinico-radiological course of multiple sclerosis: A case-control study.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease that has been related to several risk factors such as various viral infections. We carried out this study in order to establish a relationship between COVID-19 infection and MS severity. METHODS: In a case-control study, we recruited patients with relapsing-remitting multiple sclerosis (RRMS). Patients were divided into two groups based on positive COVID-19 PCR at the end of the enrollment phase. Each patient was prospectively followed for 12 months. Demographical, clinical, and past medical history were collected during routine clinical practice. Assessments were performed every six months; MRI was performed at enrollment and 12 months later. RESULTS: Three hundred and sixty-two patients participated in this study. MS patients with COVID-19 infection had significantly higher increases in the number of MRI lesions (p: 0.019, OR(CI): 6.37(1.54-26.34)) and EDSS scores (p: 0.017), but no difference was found in total annual relapses or relapse rates. COVID-19 infections were positively correlated with EDSS progression (p: 0.02) and the number of new MRI lesions (p: 0.004) and predicted the likelihood of the number of new MRI lesions by an odds of 5.92 (p: 0.018). CONCLUSION: COVID-19 may lead to higher disability scores in the RRMS population and is associated with developing new Gd-enhancing lesions in MRI imaging. However, no difference was observed between the groups regarding the number of relapses during follow-up.

Thalamic hemi-chorea: a rare complication after receiving the adenoviral vector-based COVID-19 vaccine: a case report.

Lacunar strokes occur when a branch of a large cerebral artery is blocked. The thalamus is often affected, causing uncontrollable motions. A 72-year-old previously healthy man presented with involuntary motions in the right limbs, which were present at rest, and exacerbated during voluntary actions. He had received the first dose of the adenoviral vector-based coronavirus disease 2019 vaccine (ChAdOx1 nCoV-19) 9 days ago. Severe thrombocytopenia and elevated levels of lactate dehydrogenase, ferritin, C-reactive protein, and D-dimer were found, without any evidence of connective tissue disease. Electromyography demonstrated typical choreiform movements, and the brain magnetic resonance imaging indicated a small high signal lesion on the left side of the thalamus. Detection of the immunoglobulin G antibodies against platelet factor 4 in the blood, negative heparin-induced platelet activation (HIPA) test, and positive modified HIPA test confirmed the thalamic stroke due to the vaccine-induced prothrombotic immune thrombocytopenia (VIPIT). He was admitted to the intensive care unit and received nadroparin, sodium ozagrel, edaravone, methylprednisolone, and haloperidol. His hemi-chorea improved gradually over 2 weeks, and he was discharged after 21 days with rehabilitation advice. VIPIT due to the ChAdOx1 nCoV-19 is a novel immune-mediated response that needs clinicians' awareness and further investigations.

Evaluation of the efficacy of oral nano-silymarin formulation in hospitalized patients with COVID-19: A double-blind placebo-controlled clinical trial.

Considering the outbreak pandemic of Coronavirus Disease 2019 (COVID-19), the lack of effective therapeutic strategies for the management of this viral disease, and the increasing evidence on the antiviral potential of silymarin, this study aimed to investigate the effectiveness of silymarin nanomicelles on the symptom's resolution time, laboratory parameters, and liver enzymes in patients with COVID-19. The participants were assigned to the nano-silymarin (n = 25) (receiving SinaLive soft gel, containing 70 mg silymarin as nanomicelles) or placebo groups (n = 25) three times daily for two weeks. Patients' symptoms and laboratory findings were assessed at baseline and during the follow-up period (one week and one month after the beginning of the treatment). No significant differences were observed between the two groups in terms of symptoms resolution time, laboratory parameters, and hospitalization duration (p > 0.05). However, the alanine aminotransferase level decreased significantly in the treatment group, compared to the placebo group (p < 0.001). Concomitant use of dexamethasone and remdesivir with silymarin might make the effects of silymarin on the improvement of patients' condition unclear. Further clinical trials are recommended with diverse dosages and larger sample sizes.

The effect of IGF-1 plasma concentration on COVID-19 severity.

BACKGROUND: The severity and fatality of Coronavirus disease 2019 (COVID-19) infection are not the same in the infected population. The host immune response and Immune-stimulating factors appear to play a role in COVID-19 infection outcome. insulin-like growth factor-1 (IGF-1) affects the immune system by controlling the endocrine system. Recently, the effect of IGF-1 levels on COVID-19 prognosis has been considered. OBJECTIVE: To investigate the difference between circulating IGF-1 and inflammatory cytokines concentration among COVID-19 patients, infected patients admitted to the Intensive Care Unit (ICU) (n = 40; 35 ± 5 y) and patients with mild cases of COVID-19 (n = 40; 35 ± 5 y) were screened prior to participation in the study. There was no significant difference between the groups in terms of gender and preexisting inflammatory state. Collected samples were evaluated by ELISA for IGF-1 and IL-6. RESULTS: The study outcomes included a significant decrease in IGF-1 and an increase in IL-6 serum concentration, as an inflammatory marker, for infected patients admitted to the Intensive Care Unit (ICU) (P ≤ 0.001). Finally, there was a significant increase in the IGF-1 and a decrease in the IL-6 serum concentration of hospitalized patients. DISCUSSION: it appears that inflammatory cytokines (IL-6) serum concentration in the severe form of corona virus-based infections causes reduced defenses because of suppressed IGF-1. CONCLUSIONS: Our findings show that lower IGF-1 concentrations are associated with a Severe form of COVID-19 disease. It seems, IGF-1 supplementation or anti-inflammatory treatment rescued the severe form of COVID-19 infection. Further studies are required to determine how to design COVID-19 therapeutic strategies targeting the IGF-1 pathway.

Frequency of HLA Alleles in a Group of Severe COVID-19 Iranian Patients.

BACKGROUND: Human Leukocyte Antigen (HLA) system composed of a group of related proteins with important functions in the immune system. Several studies have reported that there is a significant association between specific HLA alleles and the susceptibility to different infectious diseases. This study aimed to detect the specific HLA alleles that cause higher susceptibility to COVID-19, we analyzed the HLA allele frequency distribution in Iranian patients with a severe form of COVID-19. METHODS: Overall, 48 severe cases of COVID-19 that were hospitalized and required intensive care unit (ICU) admission between Oct and Dec 2020 were included in this study. Genomic DNA was extracted from the peripheral blood samples and HLA typing (Locus A, B, and DR) was performed for the patients. RESULTS: After analyzing and comparing the results with a reference group of 500 Iranian individuals, a significant association was found for HLA-B*38, HLA-A*68, HLA-A*24, and HLA-DRB1*01. CONCLUSION: These results may be valuable for studying the potential association of specific HLA alleles with susceptibility to COVID-19 and mortality due to the disease.

Use of Azelastine and Sodium Chloride Spray for Prevention of Sinusitis in ICU Admitted Patients: A Randomized Clinical Trial.

BACKGROUND: Nosocomial sinusitis is a common and less attended complication in patients admitted to intensive care units (ICU). It can cause several problems, such as prolongation of hospitalization, comorbidity, and mortality in patients. The present study aimed to evaluate the effect of azelastine (second-generation antihistamine) and sodium chloride spray on sinusitis prevention in ICU admitted patients. METHODS: In this randomized, open-label, and parallel clinical trial a total of 126 patients were enrolled (63 patients per arm). Finally, 121 patients (61 patients in the control group and 60 patients in the treatment group) completed the study, and 120 patients entered the final analysis. In the treatment group, during 24 h after the insertion of nasogastric tube azelastine and sodium chloride sprays were administered (one puff from each spray every 12 h) while no intervention was conducted in the control group. Primary and secondary end-points were evaluated within 10 days of the study period. RESULTS: The incidence of sinusitis and pneumonia (18.3% and 16.6% in the control group compared to 8.3% and 3.3% in the treatment group, respectively) in the treatment group showed a decreasing trend; however, only the difference of pneumonia was statistically significant between groups (P = 0.03). In addition to the clinical pulmonary infection score, nasal and tracheal secretions were significantly improved in the treatment group (P = 0.03, P < 0.001, and P = 0.01, respectively). CONCLUSIONS: The findings of the present study offer an inexpensive, low-risk, and efficacious intervention for the prevention of upper respiratory tract infections in ICU patients.

Acute transverse myelitis after SARS-CoV-2 infection: a rare complicated case of rapid onset paraplegia.

A 63-year-old Caucasian male, known case of controlled type 2 diabetes, chronic renal failure, and ischemic heart disease, was presented with weakness and loss of movement in lower limbs, an absent sensation from the chest below, constipation, and urinary retention. About 4 days before these symptoms, he experienced a flu-like syndrome. Suspicious for COVID-19, his nasopharyngeal specimen's reverse transcription-polymerase chain reaction (RT-PCR) resulted positive. Chest X-ray and HRCT demonstrated severe pulmonary involvement. Immediately, he was admitted to the emergency ward, and the treatment was started according to the national COVID-19 treatment protocol. Subsequently, diagnostic measures were taken to investigate the patient's non-heterogeneous peripheral (spinal) neuromuscular manifestations. Brain CT scan and MRI were normal, but spinal MRI with gadolinium contrast showed extensive increased T2 signal involving central gray matter and dorsal columns, extended from C7 to T12 with linear enhancement in the sagittal plane, posteriorly within the mid and lower thoracic cord. The CSF specimen demonstrated pleocytosis, positive RT-PCR for SARS-CoV-2, and elevated IgG index. Clinical presentation, MRI, CSF, and laboratory findings prioritized the acute transverse myelitis (ATM) as a probable complication of COVID-19 infection over other differential diagnoses. Intravenous methylprednisolone and, subsequently, IV human immunoglobulin were added to the treatment regimen. In the end, the complete resolution of dysesthesia, urinary retention, and constipation were achieved. After continuous and extended respiratory and motor rehabilitation programs, he was discharged asymptomatic.

Evaluating the Prevalence of PTSD among Children and Adolescents after Earthquakes and Floods: a Systematic Review and Meta-Analysis.

Our study systematically reviews articles about the prevalence of Post-traumatic Stress Disorder (PTSD) among children and adolescents, aiming to evaluate its prevalence after earthquakes and floods.Three databases (PubMed, Scopus, and Web of Science) were searched for articles published from 1981 to 2019 containing information on PTSD prevalence among survivors of earthquakes and floods. Articles with insufficient data on the prevalence of PTSD or without any available full-text were excluded. Major study variables consist of the prevalence of PTSD of the included studies, gender, and the elapsed time after the disaster. The overall PTSD prevalence was determined using a fixed-effect model for eligible studies. Of 4107 studies listed using our search strategy, 439 underwent full-text review, 59 records included in the systematic review, and 39 records met the criteria for meta-analysis. The pooled prevalence of PTSD among children and adolescent survivors after earthquakes and floods was 19.2% (95%CI = 18.6-19.7%), 30.0% (95%CI = 29.5-30.6%), 24.4% (95%CI = 23.4-25.4%) and 20.4% (95%CI = 19.1-21.7%), in the first, second, third and fourth six-month intervals after the disaster, respectively. Our analysis also revealed that PTSD was more prevalent among girls (p < 0.001). The absence of psychological support for affected areas considerably increases the risk of PTSD among survivors. Our results indicated that children and adolescents, especially girls, are more vulnerable and should be in top priority. The governments should refine their policies on post-disaster services and run early screening, immediate intervention, and ongoing monitoring for PTSD, as well as mental and emotional supports.