SARS-CoV-2 antibody response after BBIBP-CorV (Sinopharm) vaccination in cancer patients: A case-control study.

Background: Long-term safety and efficacy of BBIBP-CorV vaccine especially in individuals with chronic diseases, like cancer, is under investigation. In the present prospective study, we aimed to evaluate severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibody response with BBIBP-CorV vaccine in Iranian cancer patients. Methods: All the patients registered to receive BBIBP-CorV (Sinopharm) vaccine were divided into two groups of with (cases = 107) and without (controls = 45) history of cancer. Serum levels of SARS-CoV anti-spike recombinant receptor binding domain (anti-sRBD) and anti-nucleocapsid (anti-N) IgG serum levels were measured on days 0 (phase 0), 28-32 (phase I), and 56-64 (phase II) of vaccination. The data were analyzed using SPSS, version 22. Results: Totally, 152 individuals (67.1% females) with the mean age of 46.71 ± 15.36 years were included. Solid cancers included 87.8% of the cancer cases (46.7% gynecological and 31.8% gastrointestinal cancer). At Phases I and II, positive anti-sRBD IgG and anti-N IgG were significantly lower among the cases in total analysis. Side effects were not significantly different between the cases and controls. The lowest positive anti-sRBD IgG test was observed among the cancer patients who were simultaneously receiving chemotherapy (35.3%). Anti-sRBD IgG and anti-N IgG serum levels significantly increased at phases I and II in total analysis and in each group. In addition, serum anti-sRBD IgG increased during the three phases and it was significantly higher in the control group. Conclusion: Full vaccination of COVID-19 by BBIBP-CorV in immunocompromised patients such as cancer patients is safe and effective and could induce antibody response but in lower levels compared to healthy people. Probable causes to have minor antibody response found in males, older ages, individuals with BMI ≥ 25, those without past history of COVID-19 and with hematologic cancers. No significant side effects after vaccination were seen.

Recombinant Production of a Novel Fusion Protein: Listeriolysin O Fragment Fused to S1 Subunit of Pertussis Toxin.

Background: Some resources have suggested that genetically inactivated pertussis toxoid (PTs) bear a more protective effect than chemically inactivated products. This study aimed to produce new version of PT, by cloning an inactive pertussis toxin S1 subunit (PTS1) in a fusion form with N-terminal half of the listeriolysin O (LLO) pore-forming toxin. Methods: Deposited pdb structure file of the PT was used to model an extra disulfide bond. Codon-optimized ORF of the PTS1 was used to make recombinant constructs of PTS1 and LLO-PTS1 in the pPSG-IBA35 vector. The recombinant PTS1 and LLO-PTS1 proteins were expressed in BL21 DE3 and SHuffle T7 strains of E. coli and purified by affinity chromatography. Cytotoxic effects of the recombinant proteins were examined in the MCF-7 cell line. Results: The purity of the products proved to be more than 85%, and the efficiency of the disulfide bond formation in SHuffle T7 strain was higher than BL21 DE3 strain. No cytotoxicity of the recombinant proteins was observed in MCF-7 cells. Soluble recombinant PTS1 and LLO-PTS1 proteins were produced in SHuffle T7 strain of E. coli with high efficiency of disulfide bonds formation. Conclusion: The LLO-PTS1 with corrected disulfide bonds was successfully expressed in E. coli SHuffle T7 strain. Due to the safety for human cells, this chimeric molecule can be an option to prevent pertussis disease if its immunostimulatory effects would be confirmed in the future.

Guillain-Barré syndrome as a parainfectious manifestation of SARS-CoV-2 infection: A case series.

The global SARS-CoV-2 pandemic posed an unprecedented challenge to almost all fields of medicine and Neurology is not an exception. Collecting information about its complications and related conditions will help clinicians to become more confident in managing this disease. Guillain-Barre Syndrome (GBS) is mostly described as a post-infectious phenomenon and its occurrence during acute phase of illness is of interest. GBS has recently been reported during the active phase of COVID-19 for the first time. Severity and fast progression of GBS associated with COVID-19 have also been shown in recent studies. Here we report three cases of GBS during the active phase of COVID-19 with severe symptoms and fast progression to quadriplegia and facial diplegia over 2 days, which led to death in one case due to severe autonomic dysfunction. We suggest SARS-CoV-2 might be associated with rather a severe, rapidly progressive and life-threatening phenotype of GBS.

Infliximab and Intravenous Gammaglobulin in Hospitalized Severe COVID-19 Patients in Intensive Care Unit.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) may lead to the cytokine storm syndrome which may cause acute respiratory failure syndrome and death. Our aim was to investigate the therapeutic effects of infliximab, intravenous gammaglobulin (IVIg) or combination therapy in patients with severe COVID-19 disease admitted to the intensive care unit (ICU). METHODS: In this observational research, we studied 104 intubated adult patients with severe COVID-19 infection (based on clinical symptoms, and radiographic or CT scan parameters) who were admitted to the ICU of a multispecialty hospital during March 2020 in Tehran, Iran. All cases received standard treatment regimens as local protocol (Oseltamivir + hydroxychloroquine + lopinavir/ritonavir or sofosbuvir or atazanavir ± ribavirin). The cases were grouped as controls (n = 43), infliximab (n = 27), IVIg (n = 23) and combination (n = 11). RESULTS: There was no significant difference between controls and treatment groups in terms of underlying diseases or the number of underlying diseases. The mean age (SD) of cases was 72.42 (16.06) in the control group, 64.52 (12.965) in IVIg, 63.40 (17.57) in infliximab and 64.00 (11.679) in combination therapy; (P = 0.047, 0.031 and 0.11, respectively). Also, 37% in the infliximab group, 26.1% in IVIg, 45.5% in combination therapy, and 62.8% in the control group expired (all P < 0.05). Hazard ratios were 0.31 in IVIg (95% CI: 0.12-0.76, P = 0.01), 0.30 in infliximab (95% CI: 0.13-0.67, P = 0.004), 0.39 in combination therapy (95% CI: 0.12-1.09, P = 0.071). CONCLUSION: According to the findings of this study, it seems that infliximab and IVIg, alone or together, in patients with severe COVID-19 disease can be considered an effective treatment.

Toward an Alum Free Mono-Component Monovalent Pertussis Vaccine: A Cytokine Response Assay.

BACKGROUND: Current evidence indicates the resurgence of whooping cough despite high coverage of whole-cell (wP) and acellular (aP) pertussis vaccines. OBJECTIVE: To investigate the cytokine response to a genetically inactivated protein containing the S1 subunit of pertussis toxin (PTS1) with and without the Listeriolysin O (LLO-PTS1), in comparison with current wP and aP vaccines in the mice model. METHODS: Thirty-six female NMRI mice aged 8 to 12 weeks (25 ± 5 g) were divided into six groups, including control (n=6) and five treated groups (n=6/each). Treated groups received intraperitoneal injection of recombinant PTS1, recombinant fusion LLO-PTS1, aP, wP, and sham (phosphate-buffered saline), whereas the control group did not receive anything. After 60 days, the serum levels of IFN-γ, IL-4, and IL-17 cytokines were evaluated by ELISA method. RESULTS: Our findings showed LLO-PTS1 significantly increased IL-17 and IL-4 cytokines compared with wP and aP vaccines. IFN-γ failed to increase substantially in the LLO-PTS1 group compared to others, but it was non-inferior to standard vaccines. CONCLUSION: Our alum free mono-component monovalent recombinant fusion protein (LLO-PTS1) could bear the capacity to stimulate the release of IFN-γ similar to wP and aP vaccines in the mouse model. Besides, it showed better results in stimulating the release of IL-17 and IL-4 response. This study can be regarded as a platform for further probes in booster pertussis vaccine development.

Angiotensin Converting Enzyme Inhibitors, A Risk Factor of Poor Outcome in Diabetic Patients with COVID-19 Infection.

INTRODUCTION: Diabetes mellitus and hypertension are described as the most common comorbidities among COVID-19 patients. We investigated the adverse effect of ACEIs in diabetic and nondiabetic patients with COVID-19. METHODS: This prospective study consisted of 617 RT-PCR-confirmed COVID-19 inpatients. Demographic and baseline characteristics, underlying comorbid diseases, and antihypertensive drugs were evaluated. Study outcome (in-hospital death) was evaluated with the Kaplan-Meyer method and Cox regression model. Statistical analyses were performed with SPSS software for Windows. P values < .05 were considered significant. RESULTS: Mean ± SD age was 58.49 ± 15.80 (range: 18 to 94) years old. Cox regression analysis revealed that age (adjusted hazard ratio [HR] = 1.04, 95% CI: 1.03 to 1.06), diabetes mellitus (adjusted HR = 2.07, 95% CI: 1.32 to 3.26), immunocompromised patients (adjusted HR = 2.33, 95% CI: 1.29 to 4.21), acute kidney injury (AKI) (adjusted HR = 3.23, 95% CI: 2.01 to 5.19), ICU admission (adjusted HR = 2.48, 95% CI: 1.46 to 4.21), Asthma and COPD (adjusted HR = 2.13, CI:1.6 to 4.28) and ACEI (adjusted HR = 3.08, 95% CI: 1.56 to 6.06), respectively were associated with in-hospital death. Among diabetic patients, ACEI (adjusted HR = 3.51, 95% CI: 1.59 to 7.75), AKI (adjusted HR = 3.32, 95% CI: 1.76 to 6.45) and ICU admission (adjusted HR = 3.64, 95% CI: 1.530 to 8.65) were associated with increased mortality. The Kaplan-Meier survival curve showed a lower survival rate in diabetic patients with ACE inhibitor (adjusted HR = 3.36, 95% CI: 2.25 to 7.71). CONCLUSION: ACEIs may harm the diabetic patient's outcome with COVID-19. Further studies can confirm if ACE inhibitors have an adverse effect on COVID-19 diabetic patient's mortality.

SARS-CoV-2 Molecular and Phylogenetic analysis in COVID-19 patients: A preliminary report from Iran.

BACKGROUND: The aim of the current study was to investigate and track the SARS-CoV-2 in Iranian Coronavirus Disease 2019 (COVID-19) patients using molecular and phylogenetic methods. METHODS: We enrolled seven confirmed cases of COVID-19 patients for the phylogenetic assessment of the SARS-CoV-2 in Iran. The nsp-2, nsp-12, and S genes were amplified using one-step RT-PCR and sequenced using Sanger sequencing method. Popular bioinformatics software were used for sequences alignment and analysis as well as phylogenetic construction. RESULTS: The mean age of the patients in the present study was 60.42 ± 9.94 years and 57.1% (4/7) were male. The results indicated high similarity between Iranian and Chinese strains. We could not find any particular polymorphisms in the assessed regions of the three genes. Phylogenetic trees by neighbor-joining and maximum likelihood method of nsp-2, nsp-12, and S genes showed that there are not any differences between Iranian isolates and those of other countries. CONCLUSION: As a preliminary phylogenetic study in Iranian SARS-CoV-2 isolates, we found that these isolates are closely related to the Chinese and reference sequences. Also, no sensible differences were observed between Iranian isolates and those of other countries. Further investigations are recommended using more comprehensive methods and larger sample sizes.

The prevalence of HBV, HCV and HIV infections among Iranian infertile couples referring to Royan institute infertility clinic: A cross-sectional study.

BACKGROUND: The role of the screening protocol for viral hepatitis and human immuunodeficiency virus (HIV) infections among infertile couples were seldom investigated. OBJECTIVE: The present study was performed to assess the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV infections among infertile couples referring to infertility clinic of Royan Institute. MATERIALS AND METHODS: This analytical cross-sectional study was performed on 21673 infertile couples referring to infertility clinic of Royan Institute between 2009 and 2014. Serological findings for viral hepatitis B, C and HIV infection were gathered herewith demographic data of the study participants through the study checklist. Ultimately, 302 couples who had at least one positive result in their serological tests were included in the statistical analysis. RESULTS: The HBV and HCV infections prevalence among study participants were 0.57% and 0.148% respectively; only two cases had HIV infection. HBV and HCV infections prevalence had significant association with the gender of participants, but there was no significant relationship between these infections and infertility types. CONCLUSION: Viral hepatitis infections screening among infertile couples undergoing assisted reproductive techniques needs more attention.

Prevalence of cryptococcal antigen positivity among HIV infected patient with CD4 cell count less than 100 of Imam Khomeini Hospital, Tehran, Iran.

BACKGROUND AND OBJECTIVES: Cryptococcal meningitis is one of the main opportunistic infections associated with human immunodeficiency virus (HIV) infection. Despite the present and increasingly availability of specific treatment for cryptococcosis, the mortality rate of this infection is still high, particularly in patients with advanced immunsupression and advanced cryptococcal diseases. MATERIALS AND METHODS: This Prospective Cohort study was conducted at Imam Khomeini hospital in Tehran, Iran. Serum cryptococcal antigen was detected using the Lateral Flow Assay (LFA) There were 86 HIV-infected patients included in this study. RESULTS: There were 86 HIV-infected patients in this study. The prevalence of positive serum cryptococcal antigen was 0% (0 of 86). CONCLUSION: The prevalence of cryptococcal infection among patients with advanced acquired immunodeficiency syndrome (AIDS) in the Iran is very low (<3%) thus the screening test for cryptococcal antigenemia dose not save lives and is not cost-effective in Iranian population.

Relative frequency of human papillomavirus genotypes and related sociodemographic characteristics in women referred to a general hospital in Tehran, 2014-2015: A cross-sectional study.

BACKGROUND: Human papilloma virus (HPV) is one of the major public health problems and the main causes of cervical cancer. The prevalence HPV infection in developing countries with low financial resources is high. OBJECTIVE: This study aimed to determine the relative frequency of HPV genotypes and its sociodemographic characteristics in women referred to a general hospital in Tehran, Iran from 2014-2015. MATERIALS AND METHODS: This cross-sectional study was performed in 400 women with Pap smear samples, referring to to a general hospital in Tehran, Iran from 2014-2015. The detection of 28 HPV genotypes was performed by using the Multiplex PCR technique. The sociodemographic survey was conducted for each HPV positive woman. RESULTS: HPV-positive infection was detected in 155 (38.75%) women aged 17-85 years. HPV 16 (19.1%) was the most prevalent type, followed by HPV 39 (12.5%) and HPV 18 (8.9%). The highest rate of HPV infection was observed at the age of 36 years (7.7%). The level of education and economic situation of each woman were showed most of HPV-positive women had a high school diploma (34.6%) and average economic situation (67,9%). 60.9% of these women were a housewife, and 67.3% lived in the capital . CONCLUSION: Determination of HPV genotype and risk factor related to HPV infection in each geographical region can lead to the production of effective vaccines against the HPV virus. It can also be useful for disease management and high sensitivity diagnosis of cervical intraepithelial neoplasia.

Urine-Based Nested PCR for the Diagnosis of Mycobacterium tuberculosis: A Comparative Study Between HIV-Positive and HIV-Negative Patients.

BACKGROUND: While tuberculosis (TB) can be diagnosed by microscopy and culture, the sensitivity of Ziehl-Neelsen staining is variable and culture results require 4 - 8 weeks to be determined. Polymerase chain reaction (PCR) and its modifications, including nested PCR, might be promising methods for the rapid diagnosis of TB. OBJECTIVES: This study aimed to evaluate the performance of nested PCR on urine samples of human immunodeficiency virus (HIV)-positive and -negative patients with different manifestations of clinical TB. METHODS: In a prospective study, three early-morning urine samples from 100 patients with pulmonary TB (PTB) or extrapulmonary TB (EPTB) were evaluated using a molecular target with insertion element IS6110, specific to the Mycobacterium tuberculosis genome, and nested PCR was performed. The results were analyzed with SPSS version 22. RESULTS: A total of 100 patients, including 74 (74%) with PTB and 26 (26%) with EPTB, were enrolled. Positive smears were seen in 38 patients (38%). Lymph nodes were the most commonly involved organ in 14 of the 26 (53.8%) EPTB patients (13.5%). Seven (23.1%) of the EPTB patients were HIV-positive. Urine PCR was positive in only 28 patients (28%). Seven HIV-positive patients with PTB showed positive urine PCR results. Moreover, PCR results were positive in only one of the seven HIV-positive subjects with EPTB. Positive PCR results were found in 20 of the 73 HIV-negative patients (27.4%) and in 8 of the 27 HIV-positive patients (29.6%). Therefore, there was no significant difference between the HIV-negative and HIV-positive patients for urine PCR (sensitivity 29.6%, specificity 72.6%; positive and negative predictive values 28% and 72%, respectively; P = 0.138). CONCLUSIONS: Nested PCR showed the same sensitivity in HIV-positive and HIV-negative patients. It can be applied as a rapid technique for the diagnosis of TB.