Safety and efficacy of RCP recombinant spike protein covid-19 vaccine compared to Sinopharm BBIBP: A phase III, non-inferiority trial.

Background: We conducted a phase III, non-inferiority trial comparing safety and efficacy of RCP recombinant spike protein Covid-19 vaccine to BBIBP (Sinopharm). Methods: Adult Iranian population received RCP or BBIBP in a randomized, double blind and an additional non-randomized open labeled trial arms. Eligible participants signed a written informed consent and received two intramuscular injections three weeks apart. In the randomized arm, an intranasal dose of vaccine or adjuvant-only preparation were given to the RCP and BBIBP recipients at day 51 respectively. Participants were actively followed for up to 4 months for safety and efficacy outcomes. Primary outcome was PCR + symptomatic Covid-19 disease two weeks after the second dose. The non-inferiority margin was 10% of reported BBIBP vaccine efficacy (HR = 1.36). Results: We recruited 23,110 participants (7224 in the randomized and 15,886 in the non-randomized arm). We observed 604 primary outcome events during 4 months of active follow-up including 121 and 133 in the randomized and 157 and 193 cases in the non-randomized arms among recipients of RCP and BBIBP respectively. Adjusted hazard ratios for the primary outcome in those receiving RCP compared with BBIBP interval were 0.91 (0.71-1.16) and 0.62 (0.49-0.77) in the randomized and non-randomized arms respectively. The upper boundary of 99.1% confidence interval of HR = 0.91 (0.67-1.22) remained below the margin of non-inferiority in the randomized arm after observing the early stopping rules using O'Brien Fleming method. Conclusion: Our study showed that the RCP efficacy is non-inferior and its safety profile is comparable to the BBIBP.

Human Immunodeficiency Virus-1 Drug Resistance Mutations in Iranian Treatment-experienced Individuals.

BACKGROUND: Human immunodeficiency virus-1 infection still remains a global health threat. While antiretroviral therapy is the primary treatment option, concerns about the emergence of drug-resistance mutations and treatment failure in HIV-infected patients persist. OBJECTIVE: In this study, we investigated the development of drug resistance in HIV-1-infected individuals receiving antiretroviral therapy for 6-10 years. METHODS: In this cross-sectional study, we evaluated 144 people living with HIV-1 who had received antiretroviral therapy for at least 6 years. Plasma specimens were collected, and the HIV-1 viral load and drug-resistance mutations were assessed using molecular techniques. RESULTS: The demographic and epidemiological characteristics of the participants were also analyzed: Twelve [8.3%) of the studied patients showed a viral load over 1000 copies per/mL, which indicates the suboptimal response to antiretroviral therapy. Significant correlations were found between viral load and CD4 count, as well as epidemiological factors, such as vertical transmission, history of imprisonment, and needle stick injuries. Drug resistance mutations were detected in 10 (83.3%) of patients who failed on antiretroviral therapy, with the most common mutations observed against nucleoside reverse transcriptase inhibitors (5 (41.7%)) and non-nucleoside reverse transcriptase inhibitors (9 (75%)). Phylogenetic analysis revealed that 12 patients who failed treatment were infected with CRF35_AD. CONCLUSION: Our study provides important insights into the characteristics and development of drug resistance in HIV-1-infected individuals receiving long-term antiretroviral therapy in Iran. The findings underline the need for regular viral load monitoring, individualized treatment selection, and targeted interventions to optimize treatment outcomes and prevent the further spread of drug-resistant strains.

Immunogenicity and safety of RAZI recombinant spike protein vaccine (RCP) as a booster dose after priming with BBIBP-CorV: a parallel two groups, randomized, double blind trial.

BACKGROUND: The immunity induced by primary vaccination is effective against COVID-19; however, booster vaccines are needed to maintain vaccine-induced immunity and improve protection against emerging variants. Heterologous boosting is believed to result in more robust immune responses. This study investigated the safety and immunogenicity of the Razi Cov Pars vaccine (RCP) as a heterologous booster dose in people primed with Beijing Bio-Institute of Biological Products Coronavirus Vaccine (BBIBP-CorV). METHODS: We conducted a randomized, double-blind, active-controlled trial in adults aged 18 and over primarily vaccinated with BBIBP-CorV, an inactivated SARS-CoV-2 vaccine. Eligible participants were randomly assigned (1:1) to receive a booster dose of RCP or BBIBP-CorV vaccines. The primary outcome was neutralizing antibody activity measured by a conventional virus neutralization test (cVNT). The secondary efficacy outcomes included specific IgG antibodies against SARS-CoV-2 spike (S1 and receptor-binding domain, RBD) antigens and cell-mediated immunity. We measured humoral antibody responses at 2 weeks (in all participants) and 3 and 6 months (a subgroup of 101 participants) after the booster dose injection. The secondary safety outcomes were solicited and unsolicited immediate, local, and systemic adverse reactions. RESULTS: We recruited 483 eligible participants between December 7, 2021, and January 13, 2022. The mean age was 51.9 years, and 68.1% were men. Neutralizing antibody titers increased about 3 (geometric mean fold increase, GMFI = 2.77, 95% CI 2.26-3.39) and 21 (GMFI = 21.51, 95% CI 16.35-28.32) times compared to the baseline in the BBIBP-CorV and the RCP vaccine groups. Geometric mean ratios (GMR) and 95% CI for serum neutralizing antibody titers for RCP compared with BBIBP-CorV on days 14, 90, and 180 were 6.81 (5.32-8.72), 1.77 (1.15-2.72), and 2.37 (1.62-3.47) respectively. We observed a similar pattern for specific antibody responses against S1 and RBD. We detected a rise in gamma interferon (IFN-γ), tumor necrosis factor (TNF-α), and interleukin 2 (IL-2) following stimulation with S antigen, particularly in the RCP group, and the flow cytometry examination showed an increase in the percentage of CD3 + /CD8 + lymphocytes. RCP and BBIBP-CorV had similar safety profiles; we identified no vaccine-related or unrelated deaths. CONCLUSIONS: BBIBP-CorV and RCP vaccines as booster doses are safe and provide a strong immune response that is more robust when the RCP vaccine is used. Heterologous vaccines are preferred as booster doses. TRIAL REGISTRATION: This study was registered with the Iranian Registry of Clinical Trial at www.irct.ir , IRCT20201214049709N4. Registered 29 November 2021.

Phase II, Safety and Immunogenicity of RAZI Cov Pars (RCP) SARS Cov-2 Vaccine in Adults Aged 18-70 Years; A Randomized, Double-Blind Clinical Trial.

BACKGROUND: This study explores the safety and immunogenicity of the Razi-Cov-Pars (RCP) SARS Cov-2 recombinant spike protein vaccine. METHOD: In a randomized, double-blind, placebo-controlled trial, adults aged 18-70 were randomly allocated to receive selected 10 µg/200 µl vaccine strengths or placebo (adjuvant). It included two intramuscular injections at days 0 and 21, followed by an intranasal dose at day 51. Immediate and delayed solicited local and systemic adverse reactions after each dose up to a week, and specific IgG antibodies against SARS Cov-2 spike antigens two weeks after the 2nd dose were assessed as primary outcomes. Secondary safety outcomes were abnormal laboratory findings and medically attended adverse events (MAAE) over six months follow up. Secondary immunogenicity outcomes were neutralizing antibody activity and cell-mediated immune response. RESULT: Between May 27th and July 15th, 2021, 500 participants were enrolled. Participants' mean (SD) age was 37.8 (9.0), and 67.0 % were male. No immediate adverse reaction was observed following the intervention. All solicited local and systemic adverse events were moderate (Grade I-II). Specific IgG antibody response against S antigen in the vaccine group was 5.28 times (95 %CI: 4.02-6.94) the placebo group with a 75 % seroconversion rate. During six months of follow-up, 8 SAEs were reported, unrelated to the study intervention. The participants sustained their acquired humoral responses at the end of the sixth month. The vaccine predominantly resulted in T-helper 1 cell-mediated immunity, CD8+ cytotoxic T-cell increase, and no increase in inflammatory IL-6 cytokine. CONCLUSION: RCP vaccine is safe and creates strong and durable humoral and cellular immunity. TRIAL REGISTRATION: (IRCT20201214049709N2).

"Struggle against Bitter Life": Lived Experience of Iranian Nurses with HIV/AIDS.

Objectives: The impact of HIV/AIDS on the healthcare system in many countries, particularly in developing countries is significant. Due to the high prevalence of HIV/AIDS in these countries, remarkable number of nurses have contracted HIV through their work. HIV/AIDS poses a major threat to people's physical and emotional health status as well as their social well-being and it has overwhelming effects on personal and social lives of HIV-positive people. HIV-positive nurses, like other patients, are subject to many stresses, but because of their special professional and social conditions they may bear more psychological and social burdens. Materials and methods: A hermeneutic phenomenological approach was used to examine the everyday experiences of nurses who suffer HIV/AIDS. To conduct the study, six methodical steps which developed by van Manen (1990) applied in the process of the inquiry. Eight HIV-positive nurses were recruited and selected through a purposive sampling method. Data was collected by conducting 12 face-to-face in-depth semi-structured interviews with participants, two women and six men who became HIV-infected through occupational exposure. A thematic analysis method was used to extract themes and sub-themes. Results:Through thematic analysis of transcriptions, two main themes 'past, not passed' and 'struggle against bitter life' emerged. We found that the daily life of HIV/AIDS nurses is like a limbo between the past and the present. They are constantly trying to push themselves from this limbo of death to life. Conclusion:According to the results, participants were immersed in bitter memories of their past, which has always cast a dark shadow over their lives. Their lived space surrounded by many bitterness and adversities, yet they have the enthusiasm to move on with their lives and struggle day-to-day to maintain their relative health and have their job as a nurse. As result, management of HIV/AIDS is not only about fighting the virus, but it imposes many issues and problems on nurses, which should be given more attention and support.

The effect of oral probiotics on CD4 count in patients with HIV infection undergoing treatment with ART who have had an immunological failure.

INTRODUCTION: Probiotics are live microorganisms that, when administered in appropriate colonies, can delay the destruction of the immune system and contribute to the maintenance of immunity in HIV patients. Probiotics play an important role in stimulating natural killer T cells, strengthening the functional gut barrier, and reducing systemic inflammation. METHODS: This study was a randomized double-blind clinical trial involving 30 patients treated with antiretroviral therapy who had experienced immunological failure despite HIV viral suppression. Patients were divided into two equal groups of 15, group (B) received two probiotic capsules daily with a colony count of 109 CFU per capsule containing seven strains, after 3 months they were examined for CD4+ counts by flow cytometry, and after a 1-month washout period the participants who had received probiotics were switched to placebo, and the participants who had received placebo were given probiotics for 3 months, and they were examined for CD4+ counts 7 months after the start of the study. RESULTS: In the first group (A), administration of the placebo resulted in a decrease in CD4 count in the first 3 months (from 202.21 to 181.79, p value < .001), which may be due to the natural history of the disease. After probiotics administration, CD4 count increased significantly (from 181.79 to 243.86, p value < .001). Overall, after 7 months of study, there was a significant increase in the mean CD count from 202.21 to 243.86 (p value < .001). In the second group (B), the administration of probiotics in the first 3 months of the study resulted in a significant increase in the mean CD4 count (from 126.45 to 175.73, p value < .001). Termination of treatment with probiotics resulted in a significant decrease (from 175.73 to 138.9, p value < .001) but overall the CD4 count at the end of the study was significantly higher than at baseline (p value < .001).

Comparison of the Onset and End of Specific and Major Side Effects in Iranian Teenage Participants Vaccinated With COVID-19 Vaccine: Sinopharm and Soberana.

Background: Clinical trials were conducted on children on side effects after vaccination. We tried to assess the frequency and onset of the main symptoms in children who were vaccinated. We aimed to evaluate early and delayed adverse effects after coronavirus disease 2019 (COVID-19) vaccine among Iranian pediatrics and adolescents in a national survey. Methods: This cross-sectional study included people <18 years who received the Soberana (PastoCoVac) and Sinopharm vaccines since 2021. The basic information was gender, age, type of vaccine, and reaction after vaccination besides the main events that occurred for them. The required data were collected via a predetermined checklist by trained interviewers through phone calls by their parents or legal guardians. The independent t test and Fisher exact test were used. P values less than 0.05 were considered significant. Results: A total of 11,042 participants (age range, 10-18 years) consisting of 5374 boys (47.8%) and 5768 girls (52.2%) were studied and 88.1% of the children (n = 9727) were vaccinated by Sinopharm and 11.9% (n = 1315) by Soberana. The data of kidney-related side effects had delayed improvement of side effects after the Sinopharm compared with the Soberana vaccines (P = 0.012). Cardiovascular and hematological side effects showed early-onset (P = 0.006) and delayed improvement of side effects (P = 0.002) after the Soberana vaccine compared with the Sinopharm vaccine. Neurological side effects showed delayed improvement of side effects after the Soberana vaccine compared with the Sinopharm vaccine (P = 0.027). Joint-related side effects showed early-onset (P = 0.004) and delayed improvement of side effects (P = 0.023) after the Soberana vaccine compared with the Sinopharm vaccine. Respiratory side effects showed delayed improvement of side effects after the Soberana vaccine compared with the Sinopharm vaccine (P = 0.013), and dermatological side effects showed early-onset (P = 0.050) and delayed improvement of side effects (P = 0.035) after the Soberana vaccine compared with the Sinopharm vaccine. There was not any statistically significant difference regarding gastrointestinal side effects between the 2 vaccines (P > 0.05). Conclusion: The cardiovascular and hematological, joint-related (non-neurologic musculoskeletal) and dermatological side effects after the Soberana vaccine appear earlier and end later compared with the Sinopharm vaccine. Improvement of renal side effects in the Sinopharm vaccine group and improvement of neurological and respiratory side effects in the Soberana vaccine group occurred with delay compared with other vaccines.

Evaluation of the Sensitivity of Prominent Biomarkers Involvement in Diagnosing the Severity of Lung Damage in Patients with COVID-19.

Background: COVID-19 has become the greatest pandemic of the century. Considering the role of some hematologic and biochemical factors and their alterations due to the activity of the immune system, the current study aimed to evaluate LDH/CRP/ESR/RDW in patients with COVID-19 and their relationship with the severity of lung involvement based on CT scan findings. Methods: In this cross-sectional study, some biomarkers (LDH/CRP/ESR/RDW) were measured in 158 patients who were admitted to the intensive care unit (ICU) or hospitalized in the infectious diseases ward of Rasoul-e-Akram and Firoozgar hospitals or attended to the outpatient clinics. The diagnosis was confirmed by a positive RT-PCR test in all patients. The severity of lung involvement was determined by CT scan findings for comparison. Data were collected and analyzed through SPSS version 22. Results: Regarding the severity of lung damage according to the CT scan, 17.7% of the patients were normal, 19% had less than 25% involvement, 17% had 25% -50% involvement, 33.5% had 50% -75% involvement, and 12% had more than 75% involvement. Considering the increasing severity of lung damage based on CT scans, the levels of RDW, ESR, CRP, and LDH significantly increased in parallel. The diagnostic value of RDW (cut-off point: 12.6, Sen: 73.1% (95%CI: 65.1-79.5), Sp: 53.6% (95%CI: 45.7-61.7), ESR (cut-off point: 49, Sen: 46.9% (95%CI: 38.2-54.5)), Sp: 85.7% (95%CI: 789.-90.5)), CRP (cut-off point: 23, Sen: 62.8% (95%CI: 54.6-70.4), Sp: 77.7% (95%CI: 70.3-84.1)) and LDH (cut-off point: 550, Sen: 65.1% (95%CI: 57.2-72.5), Sp: 85.7% (95%CI: 78.9-90.5)) were significant in diagnosing the severity of lung involvement (P < 0.05). Conclusion: The use of RDW, ESR, CRP, and LDH biomarkers could be effective in predicting the severity of lung damage in patients with COVID-19.

Evaluation of MicroRNA Expression Pattern (miR-28, miR-181a, miR-34a, and miR-31) in Patients with COVID-19 Admitted to ICU and Diabetic COVID-19 Patients.

INTRODUCTION: MicroRNAs, or miRNAs, with regulatory performance in inflammatory responses and infection are the prevalent manifestations of severe coronavirus disease (COVID-19). This study aimed to evaluate whether PBMC miRNAs are diagnostic biomarkers to screen the ICU COVID-19 and diabetic COVID-19 subjects. METHODS: Candidate miRNAs were selected through previous studies, and then the PBMC levels of selected miRNAs (miR-28, miR-31, miR-34a, and miR-181a) were measured via quantitative reverse transcription PCR. The diagnostic value of miRNAs was determined by the receiver operating characteristic (ROC) curve. The bioinformatics analysis was utilized to predict the DEM genes and relevant bio-functions. RESULTS: The COVID-19 patients admitted to ICU had significantly greater levels of selected miRNAs compared to non-hospitalized COVID-19 and healthy people. Besides, the mean miR-28 and miR-34a expression levels in the diabetic COVID-19 group were significantly upregulated when compared with the non-diabetic COVID-19 group. ROC analyses demonstrated the role of miR-28, miR-34a, and miR-181a as new biomarkers to discriminate the non-hospitalized COVID-19 group from the COVID-19 patients admitted to ICU samples, and also miR-34a can probably act as a useful biomarker for screening diabetic COVID-19 patients. Using bioinformatics analyses, we found the performance of target transcripts in many bioprocesses and diverse metabolic routes such as the regulation of multiple inflammatory parameters. DISCUSSION: The difference in miRNA expression patterns between the studied groups suggested that miR-28, miR-34a, and miR-181a could be helpful as potent biomarkers for diagnosing and controlling COVID-19.

Immunogenicity and Safety of a Combined Intramuscular/Intranasal Recombinant Spike Protein COVID-19 Vaccine (RCP) in Healthy Adults Aged 18 to 55 Years Old: A Randomized, Double-Blind, Placebo-Controlled, Phase I Trial.

Objectives: This study aimed to determine the safety and immunogenicity of a combined intramuscular/intranasal recombinant spike protein COVID-19 vaccine (RCP). Methods: We conducted a randomized, double-blind, placebo-controlled, phase I trial. Three vaccine strengths were compared with an adjuvant-only preparation. It included two intramuscular and a third intranasal dose. Eligible participants were followed for adverse reactions. Specific IgG, secretory IgA, neutralizing antibodies, and cell-mediated immunity were assessed. Results: A total of 153 participants were enrolled (13 sentinels, 120 randomized, 20 non-randomized open-labeled for IgA assessment). No related serious adverse event was observed. The geometric mean ratios (GMRs) and 95% CI for serum neutralizing antibodies compared with placebo two weeks after the second injection were 5.82 (1.46-23.13), 11.12 (2.74-45.09), and 20.70 (5.05-84.76) in 5, 10, and 20 µg vaccine groups, respectively. The GMR for anti-RBD IgA in mucosal fluid two weeks after the intranasal dose was 23.27 (21.27-25.45) in the 10 µg vaccine group. The humoral responses were sustained for up to five months. All vaccine strengths indicated a strong T-helper 1 response. Conclusion: RCP is safe and creates strong and durable humoral and cellular immunity and good mucosal immune response in its 10 µg /200 µL vaccine strengths. Trial registration: IRCT20201214049709N1.

Antibiotic use during the first 6 months of COVID-19 pandemic in Iran: A large-scale multi-centre study.

WHAT IS KNOWN AND OBJECTIVE: Although antibiotics are ineffective against viral infections, epidemiological studies have revealed that the COVID-19 pandemic resulted in the overuse of antibiotics and disruption of antimicrobial stewardship programmes. We investigated the pattern of antibiotic use during the first 6 months of the COVID-19 pandemic in Iran. METHODS: A multi-centre retrospective study was designed to investigate the use of 16 broad-spectrum antibiotics in 12 medical centres. The rate of antibiotic use was calculated and reported based on the Defined Daily Dose (DDD) per 100 hospital bed-days. The bacterial co-infection rate was also reported. RESULTS AND DISCUSSION: Totally, 43,791 hospitalized COVID-19 patients were recruited in this study. It was found that 121.6 DDD of antibiotics were used per 100 hospital bed-days, which estimated that each patient received approximately 1.21 DDDs of antibiotics every day. However, the bacterial co-infections were detected only in 14.4% of the cases. A direct correlation was observed between the rate of antibiotic use and mortality (r[142] = 0.237, p = 0.004). The rate of antibiotic consumption was not significantly different between the ICU and non-ICU settings (p = 0.15). WHAT IS NEW AND CONCLUSION: In this study, widespread antibiotic use was detected in the absence of the confirmed bacterial coinfection in COVID-19 patients. This over-consumption of broad-spectrum antibiotics may be associated with increased mortality in hospitalized COVID-19 patients, which can be an alarming finding.

Effectiveness of Plasmapheresis Treatment in the Treatment of Patients with COVID-19 Disease.

Background: According to the World Health Organization, COVID-19 management focuses primarily on infection prevention, case management, case monitoring, and supportive care. However, due to the lack of evidence, no specific anti-SARS-CoV-2 treatment is recommended. This study aimed to evaluate the effectiveness of plasmapheresis treatment in COVID-19 patients with symptoms of pulmonary involvement on the computed tomography (CT) of the lung. Methods: In 2021, an experimental study in critically ill patients admitted to the COVID-19 ward in the Hazrat-e Rasool hospital diagnosed with COVID-19 was conducted in the second phase (pilot study). The diagnosis was confirmed according to clinical signs, CT scan of the lung, and the Polymerase chain reaction (PCR) test. All patients received the usual treatments for COVID-19 disease and underwent plasmapheresis at a dose of 40 cc/kg daily up to 4 doses. All patients were observed for 24 hours for complications of plasmapheresis treatment and simultaneously for symptoms of COVID-19, after which only routine care measures were performed. The next day and 2 weeks after resumption of the treatment, patients experienced COVID-19 symptoms, including shortness of breath, cough, and fever. Blood oxygen saturation, and treatment results were evaluated. Qualitative and rank variables were described using absolute and relative frequencies and quantitative parametric variables were used using mean and confidence interval. Frequencies were compared in groups using the chi-square test. All tests were performed in 2 directions and P > 0.05 was considered statistically significant. Results: Of the 120 patients studied, 79 (65.8%) were men and 41 (34.2%) were women. The mean age was 60.30 ± 15.61 years (22-95 years). The mean hospital stay was 12.89 days ± 7.25 days (2-38 days). Increased blood oxygen saturation levels in patients had an increasing trend. Inflammatory indices had a downward trend in patients. The frequency of plasmapheresis had no significant effect on reducing the downward trend of inflammatory markers. The greatest reduction occurred in the first plasmapheresis. Conclusion: Finally, according to the findings, plasmapheresis is one of the appropriate treatments to improve patients' symptoms and reduce cytokine storm. Recovered patients had lower levels of inflammatory markers than those who died.

HOMA-IR index in non-diabetic patient, a reliable method for early diagnosis of liver steatosis.

Background: NAFLD is one of the most common liver diseases in the world. HOMA-IR as an indicator of insulin resistance is commonly used in clinical trials in NAFLD patients. The aim of this study was to evaluate the application of HOMA-IR index in the diagnosis of NAFLD. Methods: This study was performed on 54 patients with NAFLD and 54 non-NAFLD patients that referred to Razi Hospital in Rasht during 2019-2020. FibroScan was used to diagnose NAFLD in the patient group and ultrasound was used to rule it out in the control group. Metabolic and hepatic parameters were measured for each patient. Data were entered into SPSS 22 software and the necessary analyses were performed. Results: The mean age of the subjects in the study was 44.01±13.12 years and ranged from 18 to 75 years. 72.2% of people affected by NAFLD were men (p <0.001) .The optimal cut-off point for HOMA-IR in NAFLD was 1.65 with a sensitivity of 89.7% and a specificity of 76.9% in men and 1.90 with a sensitivity of 86.7% and a specificity of 82.9% in women. Overall, the optimal cut-off point for HOMA-IR in NAFLD was 1.75 with a sensitivity of 87.0% and a specificity of 81.5%. In addition, the results showed that there was no significant relationship between steatosis and hepatic fibrosis with HOMA-IR index. Conclusion: The results showed that HOMA-IR can be used as a reliable criterion for early detection of NAFLD.

Pediatric and adolescent COVID-19 vaccination side effects: A retrospective cohort study of the Iranian teenage group in 2021.

To determine the safety and efficacy profile of teenager COVID-19 vaccination. In this retrospective cohort study, contact numbers of parents of teenagers under 18 years of age referred to a teenager vaccination centers in Tehran-Iran to receive the corona vaccine were collected, and the following information was obtained via the phones: demographic information, type of vaccine, and the number of doses received, as well as additional information like complications and required treatments. Eleven thousand forty-two subjects aged 10-18 years, mean age 14.55 ± 1.83 year including 5374 boys and 5768 girls were investigated. 88.1% received the Sinopharm and 11.9% the Soberana vaccine. General side effects, including fatigue, fever and chills, injection site pain and dizziness, and so forth happened in 2978 cases; 7421 children presented with at least one general or organ-specific side effect following vaccination, including potentially critical side effects, such as vascular injuries, respiratory complication, and so forth. 0.1% of the subject needed hospital admission. The breakthrough infection happened in 200 individuals. Our study shows that Sinopharm and Soberana (PastoCoVac) COVID-19 vaccines are generally safe with no serious side effects in less than 18 years old. COVID-19 infection and reinfection can occur after vaccination, but the incidence is actually tolerable and significantly lower than in the unvaccinated group.

Evaluation of the Expression Pattern of 4 microRNAs and their Correlation with Cellular/viral Factors in PBMCs of Long Term Non-progressors and HIV Infected Naïve Individuals.

BACKGROUND: Long-term non-progressors (LTNPs) are small subsets of HIV-infected subjects that can control HIV-1 replication for several years without receiving ART. The exact mechanism of HIV-1 suppression has not yet been completely elucidated. Although the modulatory role of microRNAs (miRNAs) in HIV-1 replication has been reported, their importance in LTNPs is unclear. OBJECTIVE: The aim of this cross-sectional study was to assess the expression pattern of miR-27b, -29, -150, and -221, as well as their relationship with CD4+ T-cell count, HIV-1 viral load, and nef gene expression in peripheral blood mononuclear cells (PBMCs) of untreated viremic patients and in LTNPs. METHODS: MiRNAs expression levels were evaluated with real-time PCR assay using RNA isolated from PBMCs of LTNPs, HIV-1 infected naive patients, and healthy people. Moreover, CD4 T-cell count, HIV viral load, and nef gene expression were assessed. RESULTS: The expression level of all miRNAs significantly decreased in the HIV-1 patient group compared to the control group, while the expression pattern of miRNAs in the LNTPs group was similar to that in the healthy subject group. In addition, there were significant correlations between some miRNA expression with viral load, CD4+ T-cell count, and nef gene expression. CONCLUSION: The significant similarity and difference of the miRNA expression pattern between LNTPs and healthy individuals as well as between elite controllers and HIV-infected patients, respectively, showed that these miRNAs could be used as diagnostic biomarkers. Further, positive and negative correlations between miRNAs expression and viral/cellular factors could justify the role of these miRNAs in HIV-1 disease monitoring.

The effect of influenza vaccine on severity of COVID-19 infection: An original study from Iran.

Background: The COVID-19 infection is a novel virus that mainly targets the respiratory system via specific receptors without any coronavirus-targeted therapies. Many efforts have been made to prepare specific vaccines for COVID-19 or use of prefabricated vaccines of other similar viruses, especially severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and influenza (flu). We aimed to evaluate the effects of previous flu vaccine injection on severity of incoming COVID-19 infection. Methods: We conducted a large cross-sectional study of 529 hospitalized Iranian COVID patients to evaluate the severity of disease courses in patients with or without previous flu vaccination history using some main factors like length of hospitalization, need for the intensive care unit (ICU) admission and length of stay in the ICU for comparison between COVID-19 infected patients with or without flu vaccination history. For the quantitative data, we used independent-samples t and Mann-Whitney tests. The qualitative data were calculated using the Fisher exact and chi-square tests in IBM SPSS Statistics version 22 (SPSS Inc) and P value <0.05 was considered statistically significant. Results: There were no significant differences in the demographic data of patients, disease, and severity-related parameters between the 2 groups. It means that there were not any significant differences between patients with and without history of flu vaccination regarding mean days of hospitalization, percentage of needing to be admitted to the ICU, days being admitted to the ICU (8.44±6.36 vs 7.94±8.57; 17% vs 11.5%; and 1.17±3.09 vs 0.92±3.04, retrospectively) (p=0.883, 0.235, and 0.809, respectively). In the laboratory tests, in comparison between patients with and without history of previous flu vaccination, only lymphocytes count in the vaccine positive group was higher than the vaccine negative group (20.82±11.23 vs 18.04±9.71) (p=0.067) and creatine phosphokinase (CPK) levels were higher in the vaccine negative group (146.57±109.72 vs 214.15±332.06) (p=0.006). Conclusion: We did not find any association between flu vaccination and decrease in disease severity in our patients. It seems that patients with previous history of flu vaccination may experience less laboratory abnormalities in some parameters that could be interpreted in favor of lower overall inflammation; however, this study cannot answer this definitely because of its design. As we collected retrospective data from only alive discharged patients and had no healthy control group, we could not discuss the probable effect of the vaccine on the mortality rate or its probable protective role against the infection. We need more well-designed controlled studies with different populations in different geographic areas to address the controversies.

Comparing the effectiveness of Atazanavir/Ritonavir/Dolutegravir/Hydroxychloroquine and Lopinavir/Ritonavir/Hydroxychloroquine treatment regimens in COVID-19 patients.

The purpose of this study was to compare the effectiveness of Atazanavir/Ritonavir/Dolutegravir/Hydroxychloroquine and Lopinavir/Ritonavir/Hydroxychloroquine treatment regimens in COVID-19 patients based on clinical and laboratory parameters. We prospectively evaluated the clinical and laboratory outcomes of 62 moderate to severe COVID-19 patients during a 10-day treatment plan. Patients were randomly assigned to either KH (receiving Lopinavir/Ritonavir [Kaletra] plus Hydroxychloroquine) or ADH (receiving Atazanavir/Ritonavir, Dolutegravir, and Hydroxychloroquine) groups. During this period, clinical and laboratory parameters and outcomes such as intensive care unit (ICU) admission or mortality rate were recorded. Compared to the KH group, after the treatment period, patients in the ADH group had higher activated partial thromboplastin time (aPTT) (12, [95% confidence interval [CI]: 6.97, 17.06), p = <0.01), international normalized ratio (INR) (0.17, [95% CI: 0.07, 0.27), p = <0.01) and lower C-reactive protein (CRP) (-14.29, (95% CI: -26.87, -1.71), p = 0.03) and potassium (-0.53, (95% CI: -1.03, -0.03), p = 0.04) values. Moreover, a higher number of patients in the KH group needed invasive ventilation (6 (20%) vs. 1 (3.1%), p = 0.05) and antibiotic administration (27 (90%) vs. 21(65.6), p = 0.02) during hospitalization while patients in the ADH group needed more corticosteroid administration (9 (28.1%) vs. 2 (6.7%), p = 0.03). There was no difference in mortality rate, ICU admission rate, and hospitalization period between the study groups. Our results suggest that the Atazanavir/Dolutegravir treatment regimen may result in a less severe disease course compared to the Lopinavir/Ritonavir treatment regimen and can be considered as an alternative treatment option beside standard care. However, to confirm our results, larger-scale studies are recommended.

Single-pill sofosbuvir and daclatasvir for treating hepatis C in patients co-infected with human immunodeficiency virus.

BACKGROUND: The current recommendation for treating hepatitis C virus (HCV) in HIV patients includes the combination of sofosbuvir (SOF) and daclatasvir (DCV). DCV should be used at different doses to compensate for interactions with antiretroviral therapy (ART). Up to three pills a day might be required which will significantly add to the pill burden of these patients. In this study, we have used a single-tablet approach to treating HCV-HIV coinfection. METHODS: Patients coinfected with HIV and HCV were prospectively enrolled from 10 centers throughout the country. Patients received a single once-daily fixed dose combination (FDC) pill containing 400 mg SOF and 30, 60 or 90 mg DCV depending on the type of ART they were receiving for 12 or 24 weeks. (ClinicalTrials.gov ID: NCT03369327). RESULTS: Two hundred thirty-three patients were enrolled from 10 centers. Twenty-three patients were lost to follow-up and two patients died from causes unrelated to treatment. Two hundred eight patients completed the treatment course of which 201 achieved SVR (96.6%). CONCLUSION: Single-tablet combination of DCV and SOF is an effective and safe treatment for patients coinfected with HIV and HCV. The combination works well in patients on ART in which dose adjustment is required. Patients with cirrhosis, previous treatment failure and various genotypes respond identically. The expenses of genotyping can be saved.

A Reliable Prognostic Marker for Liver Dysfunction in COVID-19 Infection.

BACKGROUND In December 2019, COVID-19 emerged from China and spread to become a pandemic, killing over 1,350,000 up to November 18, 2020. Some patients with COVID-19 have abnormal liver function tests. We aimed to determine the clinical significance of liver chemistries in patients with COVID-19. METHODS We performed a cross-sectional study of 1044 consecutive patients with confirmed COVID-19 in two referral hospitals in Tehran, Iran, from February to April 2020. All cases were diagnosed by clinical criteria and confirmed by characteristic changes in the spiral chest computed tomography (CT) and nucleic acid testing of the nasopharyngeal samples. We evaluated the association between abnormal liver enzymes or function tests and survival, intensive care unit (ICU) admission and fatty liver changes in CT scans. RESULTS The mean age was 61.01 ± 16.77 years, and 57.68% were male. Of 495 patients with elevated alanine transaminase (ALT) levels, 194 had chest CT scans, in which fatty liver disease was seen in 38.1%. 41 patients (21.13%) had moderate to severe, and 33 (17.01%) had borderline fatty liver disease. Bilirubin, albumin, and partial thromboplastin time (PTT), along with other markers such as HCO3, C-reactive protein (CRP), triglyceride, and length of admission, were significantly associated with ICU admission and mortality. Prothrombin time (PT), platelet count, and low-density lipoprotein (LDL) levels were also correlated with mortality. Fasting blood sugar (FBS) and pH were important indices in ICU admitted patients. CONCLUSION Liver function tests accurately predict a worse prognosis in patients with COVID-19. However, liver enzymes were only slightly increased in those who died or needed ICU admission and were not related to the fatty liver changes.

A rare manifestation of extrapulmonary tuberculosis: left ventricular cardiac tuberculoma in an HIV infected male "case report".

Cardiac tuberculosis (TB) is rare and most commonly manifests itself as tuberculous pericarditis. Involvement of other parts of the heart is unusual and descriptions in the literature are confined to case reports regarding mainly pericardial TB and very few cases of cardiac tuberculoma. Tuberculomas are space occupying lesions most commonly found in the brain of immunocompromised individuals. These space occupying lesions previously described only after autopsies are now more diagnosed with the use of advanced imaging techniques. Herein, we describe a first case of pericardial TB manifesting as left ventricular (LV) cardiac tuberculoma in a 34-year-old human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infected male. Upon presentation the patient complained mainly of progressive dyspnoea over the past month. Primary investigations including chest computed tomography (CT) scan and transthoracic echocardiography (TTE) suggested probable diagnosis of cardiac and pericardial TB which was later confirmed by histopathological modalities. The patient received anti-TB therapy along with surgical subtotal pericardiotomy which resulted in improvement of symptoms, complete resolution of the mass and reduction in the size of pericardial thickening. Although very rare it is crucial to bear in mind the importance of having cardiac tuberculoma as differential diagnosis in patients with a cardiac mass and implement the optimum diagnostic and therapeutic courses.