The association of decreased HLA-G+ immune cell frequencies with critical COVID-19 patients.

INTRODUCTION: COVID-19 (coronavirus disease-2019) is an infectious disease caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Immune dysregulation causes inflammation and massive production of inflammatory mediators that worsen the patients' status. Here, regulatory immune cells may ameliorate inflammation and improve the severity of the disease. MATERIALS AND METHODS: A total of 76 participants were enrolled in this study and divided into 3 groups as follows: patients with moderate/severe COVID-19 (n = 25), patients with critical COVID-19 (n = 26), and healthy controls (n = 25). After blood collection, peripheral blood mononuclear cells (PBMCs) were isolated and stained by FITC-conjugated anti-CD4 monoclonal antibodies (mABs), PE-conjugated anti-HLA-G mABs, PerCPCy5.5-conjugated anti-CD14 mABs, and APC-conjugated anti-CD8 mABs. RESULTS: Critical COVID-19 patients had a significantly lower frequency of CD4+ HLA-G+ T lymphocytes compared with moderate/severe COVID-19 patients (p value < 0.001; SMD, -1.27; 95% CI [-1.86, -0.66]) and healthy controls (p value < 0.05; SMD, -0.69; 95% CI [-1.25, -0.12]). Critical COVID-19 patients had a significantly lower frequency of CD14+ HLA-G+ monocytes compared with moderate/severe COVID-19 patients (p value < 0.001; SMD, -2.09; 95% CI [-2.77, -1.41]) and healthy controls (p value < 0.05; SMD, -0.83; 95% CI [-1.40, -0.25]). However, there was no difference between the groups regarding the frequency of CD8+ HLA-G+ T lymphocytes. CONCLUSION: The increased amount of immunomodulatory HLA-G+ cells may reduce the severity of the disease in moderate/severe COVID-19 patients compared with critical COVID-19 patients.

A Large Retrospective Study of Epidemiological Characteristics of COVID-19 Patients in the North of Iran: Association between SARS-CoV-2 RT-PCR Ct Values with Demographic Data.

Objectives: To avoid worsening from mild, moderate, and severe diseases and to reduce mortality, it is necessary to identify the subpopulation that is more vulnerable to the development of COVID-19 unfavorable consequences. This study aims to investigate the demographic information, prevalence rates of common comorbidities among negative and positive real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) patients, and the association between SARS-CoV-2 cycle threshold (Ct) at hospital admission, demographic data, and outcomes of the patients in a large population in Northern Iran. Methods: This large retrospective cross-sectional study was performed from 7 March to 20 December 2020. Demographic data, including gender, age, underlying diseases, clinical outcomes, and Ct values, were obtained from 8,318 cases suspected of COVID-19, who were admitted to four teaching hospitals affiliated to Babol University of Medical Sciences (MUBABOL), in the north of Iran. Results: Since 7 March 2020, the data were collected from 8,318 cases suspected of COVID-19 (48.5% female and 51.5% male) with a mean age of 53 ± 25.3 years. Among 8,318 suspected COVID-19 patients, 3,250 (39.1%) had a positive rRT-PCR result; 1,632 (50.2%) patients were male and 335 (10.3%) patients died during their hospital stay. The distribution of positive rRT-PCR revealed that most patients (464 (75.7%)) had a Ct between 21 and 30 (Group B). Conclusion: Elderly patients, lower Ct, patients having at least one comorbidity, and male cases were significantly associated with increased risk for COVID-19-related mortality. Moreover, mortality was significantly higher in patients with diabetes, kidney disease, and respiratory disease.

The survival rate of liver transplantation in children: a systematic review and meta-analysis.

Liver transplantation is a life-saving treatment for children who are in liver failure. The survival rate index is used to assess the success rate of liver transplantation. The study aimed to assess the survival rate of liver transplantation in children. We searched 5 international databases in this study, including Medline/PubMed, ProQuest, Scopus, Web of Knowledge, and Google Scholar, for published articles by the end of 2020. Also, meta-regression analysis was performed based on the year of the study, and subgroup analysis was performed according to continents. A total of 425 titles were reviewed. Based on the results, 96 articles were entered in the meta-analysis. Established on the random-effect model, the survival rates of 1, 3, 5, and 10 years of transplantation were 86.62%, 77.74%, 73.95%, and 68.60%, respectively. Also, based on the meta-regression results, there was a relationship between the year of the study and the survival rate, as the study year gets more recent, the survival rate is increased. This study can provide documented and comprehensive evidence which can be the basis of many policies and decisions in various sectors of health development, including evaluating treatment options and health interventions in transplantation.

A brief review of influenza virus infection.

Influenza is an acute viral respiratory infection that affects all age groups and is associated with high mortality during pandemics, epidemics, and sporadic outbreaks. Nearly 10% of the world's population is affected by influenza annually, with about half a million deaths each year. Influenza vaccination is the most effective method for preventing influenza infection and its complications. The influenza vaccine's efficacy varies each season based on the circulating influenza strains and vaccine uptake rates. Currently, three antiviral drugs targeting the influenza virus surface glycoprotein neuraminidase are available for treatment and prophylaxis of disease. Given the significant burden of influenza infection globally, this review is focused on the latest findings in the etiology, epidemiology, transmission, clinical manifestation, diagnosis, prevention, and treatment of influenza.

Neonatal Outcomes in Pregnant Women Infected with COVID-19 in Babol, North of Iran: A Retrospective Study with Short-Term Follow-Up.

During the coronavirus disease 2019 (COVID-19) pandemic, the number of pregnant women and neonates suffering from COVID-19 increased. However, there is a lack of evidence on clinical characteristics and neonatal outcomes in pregnant women with COVID-19. We evaluated short-term outcomes (4 weeks postdischarge) and symptoms in neonates born to mothers infected with COVID-19. In this retrospective cohort study, we included all neonates born to pregnant women with COVID-19 admitted to Ayatollah Rohani Hospital, Babol, Iran, from February 10 to May 20, 2020. Clinical features, treatments, and neonatal outcomes were measured. Eight neonates were included in the current study. The mean gestational age and birth weight of newborns were 37 ± 3.19 weeks (30₊6-40) and 3077.50 ± 697.64 gr (1720-3900), respectively. Apgar score of the first and fifth minutes in all neonates was ≥8 and ≥9 out of 10, respectively. The most clinical presentations in symptomatic neonates were respiratory distress, tachypnea, vomiting, and feeding intolerance. This manifestation and high levels of serum C-reactive protein (CRP) in three infants are common in neonatal sepsis. The blood culture in all of them was negative. They have been successfully treated with our standard treatment. Our pregnant women showed a pattern of clinical characteristics and laboratory results similar to those described for nonpregnant COVID-19 infection. This study found no evidence of intrauterine or peripartum transmission of COVID-19 from mother to her child. Furthermore, the long-term outcomes of neonates need more study.

Multicenter Cryptococcal Antigen Screening of HIV-Infected Patients in Iran.

Early diagnosis and targeted preemptive antifungal treatment are crucial in reducing cryptococcal meningitis (CM)-related mortality in individuals living with human immunodeficiency virus (HIV). The present study was performed to determine cryptococcal antigenemia and outcomes among HIV-infected patients in Iran. This multicenter prospective study was conducted between October 2016 and December 2018. For the purpose of the study, blood samples were randomly collected from 177 profoundly immunosuppressed (CD4+ counts < 200 cells/µL) HIV-positive individuals in six major cities of Iran. The patients were antiretroviral therapy-naive or had received inadequate medication. The stored sera were screened for cryptococcal antigen (CrAg), using point-of-care lateral flow assay (IMMY® diagnostics, Norman, OK, US). Overall, out of the 174 asymptomatic patients, 3 (1.72%) cases were CrAg-positive using the LFA in serum. Accordingly, the prevalence of cryptococcal antigenemia was 7.14%, 0%, and 1.2% in the patients with the CD4+ counts of < 50, 50-100, and 100-200 cells/µL, respectively. The median age of the patients with antigenemia was 36 years (age range 8-55 years). The median CD4+ count of the cohort was 98 cells/µL (range 14-200 cells/µL). Routine screening of Iranian HIV-infected patients with CD4+ count of < 50 cells/µL before initiating antiretroviral therapy is justified. It is suggested to conduct more inclusive research throughout the whole country on more patients to recommend screening cryptococcal antigen strongly.

Helicobacter pylori infection in children: an overview of diagnostic methods.

Children differ from adults regarding Helicobacter pylori (H. pylori) infection in many terms. H. pylori infection represents a key factor in the pathogenesis of duodenal ulcer and chronic gastritis in children. H. pylori infection causes some extraintestinal diseases as well as gastrointestinal diseases. Although, among these illnesses in children, symptoms like recurrent abdominal pain are not specific. Moreover, the role of the pathogen in the growth faltering, iron deficiency anemia, and asthma still remains controversial. A reliable method to detect H. pylori infection is a crucial issue, sand is still a matter of active debate. The tests applied for H. pylori diagnosis are grouped as either invasive or non-invasive methods. Invasive methods consist of endoscopic evaluation, the rapid urease test (RUT), histology, and bacterial culture. Non-invasive tests include the urea breath test (UBT), stool antigen test (SAT), serology, and molecular diagnostic approaches. Use of endoscopy is a pre-requisite for all invasive methods and poses difficulties in children as it is a difficult procedure and requires patient's cooperation. For this reason, the non-invasive tests have been commonly used in children, although their accuracy is not very reliable in some cases. Invasive tests may be opted to confirm the diagnosis as and when needed. This review presents the diagnostic tests used to detect H. pylori infection in children.

Diagnostic methods for Helicobacter pylori infection: ideals, options, and limitations.

Helicobacter pylori (H. pylori) resides in the stomach, colonizes gastric epithelium, and causes several digestive system diseases. Several diagnostic methods utilizing invasive or non-invasive techniques with varying levels of sensitivity and specificity are developed to detect H. pylori infection. Selection of one or more diagnostic tests will depend on the clinical conditions, the experience of the clinician, cost, sensitivity, and specificity. Invasive methods require endoscopy with biopsies of gastric tissues for the histology, culture, and rapid urease test. Among non-invasive tests, urea breath test and fecal antigen tests are a quick diagnostic procedure with comparable accuracy to biopsy-based techniques and are methods of choice in the test and treatment setting. Other techniques such as serological methods to detect immunoglobulin G antibodies to H. pylori can show high accuracy as other non-invasive and invasive biopsies, but do not differentiate between current or past H. pylori infections. Polymerase chain reaction (PCR) is an emerging option that can be categorized as invasive and non-invasive tests. PCR method is beneficial to detect H. pylori from gastric biopsies without the need for the cultures. There is no other chronic gastrointestinal infection such as H. pylori with a set of comparable diagnostic methodologies. Despite the availability of multiple diagnostic methods, it remains unclear on the choice of any one method as the gold standard for detecting H. pylori infection, especially in epidemiological studies. In this work, we review the principal diagnostic methods used to detect H. pylori infection and their advantages and disadvantages, and applications in clinical practice.

Exposure to Ascaris lumbricoides infection and risk of childhood asthma in north of Iran.

BACKGROUND: Asthma and Ascaris lumbricoides infection are common health issues affecting 250 and 700 million people worldwide, respectively. The relationship between ascariasis and asthma is a matter of substantial interest and research. METHODS: We performed a case-control study to evaluate whether the exposure to Ascaris infection is associated with asthma in children. We also assessed potential risk factors for Ascaris infection and asthma in study area. We enrolled 145 asthmatic children and 115 healthy controls. The Global Initiative for Asthma guideline was used to evaluate asthma symptoms and severity in study participants. Ascaris infection was assessed by the presence of anti-Ascaris IgG ≥ 11 IU/mL measured by enzyme-linked immunosorbent assay. RESULTS: We have found a significant relationship between exposure to Ascaris and asthma (odds ratio, 2.92; 95% CI 1.04-8.18; P value = 0.034), and this relationship remained significant after adjustment for covariates (adjusted OR, 3.36; 95% CI 1.04-13%; P value = 0.047). Ascaris infection was more frequent in children with mild sustainable asthma (13.2%; 15/113) than in children with moderate sustainable asthma (6.2%, 2/32), although there was a non-significant difference between these groups (OR, 2.3; 95% CI 0.5-10.1; P value = 0.35). Based on results of a multi-regression analysis, contact with soil (OR, 6.7; 95% CI 1.9-23.5), and drinking unsafe water (OR, 4.2; 95% CI 1.2-14.2) were significant risk factors for Ascaris infection in the study area. CONCLUSION: Results of this study suggest that A. lumbricoides infection might affect susceptibility to asthma in children. These results could be useful in prevention, early diagnosis and management of childhood asthma.

Zika virus: epidemiology, clinical aspects, diagnosis, and control of infection.

Zika virus (ZIKV) is an emerging pathogen of huge public health significance to human beings. Although majority of infections are benign with self-limiting symptoms, the recent outbreak has established an association with the increased incidence of some congenital anomalies such as microcephaly. In other words, due to the large extent of the virus and mosquito vectors, the infection has become a thoughtful health problem for human societies, though now, there are no antiviral therapies or vaccines against this virus. In spite of extensive research carried out by scientists, not so much information has been gathered about this viral infection. In the current review, we prepared an overview of the remarkable progress made in understanding about the epidemiology, immunology, clinical presentation, and diagnosis methods of ZIKV infection.

Amoebiasis in Iran: a systematic review and meta-analysis.

A comprehensive meta-analysis study was performed to estimate the reliable national prevalence and molecular epidemiology of amoebiasis in Iran. Nine English and Persian databases were searched to achieve the relevant studies. Pooled estimates were generated and meta-regression was performed. We identified 71 eligible articles involving 330 930 subjects from 25 provinces to be included in the final analysis. Moreover, 17 studies compromising 462 polymerase chain reaction (PCR)-positive isolates performed molecular analysis to inter-species differentiation. The pooled prevalence of Entamoeba infection among Iranian population was about 1% (95% CI 0.8-2.0%). Moreover, regarding Human Development Index (HDI), a higher prevalence was observed in undeveloped provinces. Out of 462 PCR-positive isolates, 83% (95% CI 69-94%) and 12% (95% CI 3-24%) were Entamoeba dispar, Entamoeba histolytica, respectively. In subgroup analysis based on molecular results, in general, population prevalence of Entamoeba dispar and E. histolytica were 91% (95% CI 80-99%) and 7%, (95% CI 0-19%), respectively, while prevalence of these species in patients with gastrointestinal disorders were 75% (95% CI 45-96%) and 18% (95% CI 1-43%), respectively. Our findings indicate the low burden of amoebiasis in Iran. E. dispar, that is mostly non-pathogenic, was identified as most prevalent species. Nevertheless, we suggest more public health interventions in areas with lower HDI.

Strongyloides stercoralis: detection of parasite-derived DNA in serum samples obtained from immunosuppressed patients.

Strongyloidiasis is an important neglected disease, which is life threatening in immunocompromised patients. This study aimed to evaluate the frequency of Strongyloides stercoralis infection among immunosuppressed subjects living in endemic communities by conventional PCR of the 18S rRNA and Cox1 genes to detect cell-free DNA in the patients' serum samples. Fresh stool and serum samples were obtained from participants. The stool samples were examined using parasitological methods. Total DNA was extracted from the serum samples and S. stercoralis larvae isolated from patient fecal samples. Conventional PCR to amplify a 101 bp fragment of the 18S rRNA gene was carried out for all extracted DNA, and then positive samples were further evaluated for a 121 bp fragment of the Cox1 gene. The PCR products of selected samples were sequenced and BLAST analysis was performed. Out of 120 patients, 57 and 63 cases had autoimmune disorders and cancer, respectively. The 101 bp fragments of the 18S rRNA were successfully amplified in 36 out of 120 (30%) serum samples. The PCR products of five samples were sequenced and compared with reference sequences in GenBank, which showed 97% identity and 90% coverage. In conclusion, to the best of our knowledge, this is the first molecular study for the detection of S. stercoralis cell-free DNA in human serum samples. These results provide useful insights for future studies and show that serum is an alternative specimen and may be useful in molecular diagnosis of diseases, particularly in immunosuppressive patients.

Joint modeling of longitudinal and competing risks for assessing blood oxygen saturation and its association with survival outcomes in COVID-19 patients.

BACKGROUND: The objective of the present study is to evaluate the association between longitudinal and survival outcomes in the presence of competing risk events. To illustrate the application of joint modeling in clinical research, we assessed the blood oxygen saturation (SPO2) and its association with survival outcomes in coronavirus disease (COVID-19). MATERIALS AND METHODS: In this prospective cohort study, we followed 300 COVID-19 patients, who were diagnosed with severe COVID-19 in the Rohani Hospital in Babol, the north of Iran from October 22, 2020 to March 5, 2021, where death was the event of interest, surviving was the competing risk event and SPO2 was the longitudinal outcome. Joint modeling analyses were compared to separate analyses for these data. RESULT: The estimation of the association parameter in the joint modeling verified the association between longitudinal outcome SPO2 with survival outcome of death (Hazard Ratio (HR) = 0.33, P = 0.001) and the competing risk outcome of surviving (HR = 4.18, P < 0.001). Based on the joint modeling, longitudinal outcome (SPO2) decreased in hypertension patients (ß = -0.28, P = 0.581) and increased in those with a high level of SPO2 on admission (ß = 0.75, P = 0.03). Also, in the survival submodel in the joint model, the risk of death survival outcome increased in patients with diabetes comorbidity (HR = 4.38, P = 0.026). CONCLUSION: The association between longitudinal measurements of SPO2 and survival outcomes of COVID-19 confirms that SPO2 is an important indicator in this disease. Thus, the application of this joint model can provide useful clinical evidence in the different areas of medical sciences.

The global prevalence of methicillin-resistant Staphylococcus aureus colonization in residents of elderly care centers: a systematic review and meta-analysis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a difficult to treat infection, particularly in residents of elderly care centers (ECCs). Despite the substantial burden of MRSA, an inadequate number of studies have analyzed MRSA prevalence in ECCs. OBJECTIVES: We conducted a worldwide systematic review and meta-analysis on the prevalence and risk factors of MRSA in ECCs. METHODS: We searched MEDLINE/PubMed, EMBASE, Web of Science, and Scopus databases and the gray literature sources for all studies published between January 1980 and December 2022 on the prevalence of MRSA in ECCs. A random-effects model was utilized to estimate pooled prevalence rates at 95% confidence intervals (CI). Moreover, the data were analyzed based on World Health Organization-defined regions, income, and human development index levels. RESULTS: In total, 119 studies, including 164,717 participants from 29 countries, were found eligible for meta-analysis. The pooled global prevalence of MRSA was 14.69% (95% CI 12.39-17.15%; 16,793/164,717). Male gender [prevalence ratio (PR) = 1.55; 95% CI 1.47-1.64], previous MRSA infection (PR = 3.71; 95% CI 3.44-4.01), prior use of antibiotics (PR = 1.97; 95% CI 1.83-2.12), hospitalized within the previous year (PR = 1.32; 95% CI 1.20-1.45), have had any wound (PR = 2.38; 95% CI 2.23-2.55), have used urinary catheter (PR = 2.24; 95% CI 2.06-2.43), have used any medical device (PR = 1.78; 95% CI 1.66-1.91), and those with diabetes (PR = 1.55; CI 1.43-1.67) were more likely to be colonized by MRSA than other patients. CONCLUSION: Screening programs and preventive measures should target MRSA in ECCs due to the high global prevalence rates.

Domestic Violence Against Women During the COVID-19 Pandemic and Its Relationship to Demographic and Family Factors: A Cross-Sectional Study in Iran.

BACKGROUND: During the COVID-19 pandemic, we have witnessed increased complaints from third parties about violent conditions through social media. This study aimed to determine the prevalence of domestic violence (DV) against women following exposure to the COVID-19 pandemic and its relevance to some related factors. MATERIALS AND METHODS: This study was conducted from July 2020 to May 2021 on married women of Babol, Iran. Eligible women entered into the study in a multi-stage cluster random sampling method. Data collection tools included demographic and family data, questionnaire HITS (Hurt, Insult, Threaten and Scream). Relationships were estimated using the Univariate and multivariate regression models.  Results: The mean age of 488 women and their spouses was 34.62 ± 9.14 and 38.74 ± 9.07, respectively. Of the total female participants, 37 (7.6%), 68 (13.9%), and 21 (4.3%) were victims of total violence, verbal abuse, and physical violence, respectively. Ninety-five women (19.5) had a history of coronavirus infection. Women who were satisfied with their income and husbands were university educated, their chances of DV were reduced by 72% (95% CI (0.09-0.85), OR = 0.28) and 67% (95% CI (0.11-0.92), OR = 0.33) respectively. Drug abuse by husbands increased the likelihood of DV by up to 4 times (OR = 4.00), and more contact with their husbands at home due to home quarantine was more than twice as likely to have DV (OR = 2.64).  Conclusion: Since the level of domestic violence was lower than before the coronavirus pandemic, it seems that most Iranian women were more under the support of their husbands during the coronavirus pandemic to endure the fear and panic caused by the pandemic. Women whose husbands had a university education and sufficient income had less domestic violence.

Survival rate of vaginal cancer in Asian countries: a systematic review and meta-analysis.

Introduction: Vaginal cancer is one of the major causes of mortality in women, which mostly takes place in low- and middle-income countries. Assessing the survival rate of vaginal cancer is essential to investigate the success rate of current treatments and screening tools. This study aims to determine the survival rate of vaginal cancer in Asia. Methods: This systematic review was carried out using four international databases, including Medline/Pubmed, ProQuest, Scopus, Web of Knowledge, and also Google Scholar. Articles were investigated up to the end of August 2021. The authors utilized the Newcastle-Ottawa Scale to evaluate the quality of the articles. Evaluating the papers for heterogeneity was performed using the Cochrane test and I² statistic. Meta-regression analysis was also applied based on the year of the study. Results: Three articles (13 records) fulfilled the inclusion criteria. Based on the random model, the overall 5-year survival rate was 74.63%. Also, the rates of survival in relation to the type of treatment including chemotherapy, radiotherapy, or other modalities, were 78.53, 78.44, and 68.54%, respectively. According to meta-regression analysis, no correlation was found between the survival rate and the year of the study. Conclusion: The vaginal cancer survival rate is lower in Asian countries compared to that of developed countries. Increasing patient survival rates in such countries is crucial by implementing newer diagnostic tools, advanced surgical techniques, and goal-oriented treatments. Early diagnosis in lower stages and educating the populations about risk factors and preventative measures are also necessary for raising the rate of survival.

Prevalence of Psychological Distress and Posttraumatic Stress Symptoms and Associated Factors in Hospitalized Iranian COVID-19 Patients.

Objectives: To investigate the prevalence of psychiatric symptoms/distress and posttraumatic stress (PTS) and associated factors among inpatients with COVID-19 before discharge from the hospital. Methods: This cross-sectional study was conducted in two teaching referral hospitals in Babol, Iran from July to November 2020. The subjects were inpatients diagnosed with COVID-19 who were clinically stable. Before their discharge from the hospital, the patients completed three questionnaires: demographic data, Brief Symptom Inventory, and Primary Care Post Traumatic Stress Disorder Screen for Diagnostic and Statistical Manual-5. Results: The subjects were 477 inpatients diagnosed with COVID-19 including 40 (8.4%) admitted to intensive care units. Their average age was 60.5±17.9 years; 53.9% were female. Most had symptoms of significant psychological distress (96.0%) and PTS (8.1%) prior to discharge. A higher level of education (-0.18; standard error (SE) = 0.05; p < 0.001) was a negative predictor of psychiatric distress. The admission to intensive care units (0.86; SE = 0.08; p< 0.001) was a positive predictor of psychiatric distress. Conclusions: Most COVID-19 inpatients suffered significant psychiatric distress and PTS symptoms before discharge. Appropriate mental health crisis interventions are recommended for COVID-19 patients during hospitalization.

A Multiple-Center, Retrospective Study of Characteristics and Outcomes of Hospitalized COVID-19 Patients with Cardiovascular Disease in North Iran.

Background: In this retrospective study, we investigated the outcomes and demographic characteristics of COVID-19 patients with and without a history of CVD. Methods: This large retrospective, multicenter study was performed on inpatients with suspected COVID-19 pneumonia who were admitted across four hospitals in Babol, Northern Iran.Demographic data, clinical data, and cycle threshold value (Ct) results of Real Time PCR were obtained. Then, participants were divided into two groups: (1) cases with CVDs, (2) cases without CVDs. Results: A total of 11097 suspected COVID-19 cases with a mean ± SD age of 53 ±25.3 (range: 0 to 99) years were involved in the present study. Out of whom 4599 (41.4%) had a positive RT-PCR result. Of those, 1558 (33.9%) had underlying CVD. Patients with CVD had significantly more co-morbidities such as hypertension, kidney disease, and diabetes. Moreover, 187 (12%) and 281 (9.2%) of patients with and without CVD died, respectively. Also, mortality rate was significantly high among the three groups of Ct value in patients with CVD, with the highest mortality in those with Ct between 10 and 20 (Group A = 19.9%). Conclusions: In summary, our results highlight that CVD is a major risk factor for hospitalization and the severe consequences of COVID-19. Death in CVD group is significantly higher compared to non-CVD. In addition, the results show that age-related diseases can be a serious risk factor for the severe consequences of COVID-19.

Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine: A Randomized Clinical Trial.

Importance: The protein-based SARS-CoV-2 vaccines FINLAY-FR-2 (Soberana 02) and FINLAY-FR-1A (Soberana Plus) showed good safety and immunogenicity in phase 1 and 2 trials, but the clinical efficacy of the vaccine remains unknown. Objective: To evaluate the efficacy and safety of a 2-dose regimen of FINLAY-FR-2 (cohort 1) and a 3-dose regimen of FINLAY-FR-2 with FINLAY-FR-1A (cohort 2) in Iranian adults. Design, Setting, and Participants: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial was conducted at 6 cities in cohort 1 and 2 cities in cohort 2. Participants included individuals aged 18 to 80 years without uncontrolled comorbidities, coagulation disorders, pregnancy or breastfeeding, recent immunoglobulin or immunosuppressive therapy, and clinical presentation or laboratory-confirmed COVID-19 on enrollment. The study was conducted from April 26 to September 25, 2021. Interventions: In cohort 1, 2 doses of FINLAY-FR-2 (n = 13 857) or placebo (n = 3462) were administered 28 days apart. In cohort 2, 2 doses of FINLAY-FR-2 plus 1 dose of FINLAY-FR-1A (n = 4340) or 3 placebo doses (n = 1081) were administered 28 days apart. Vaccinations were administered via intramuscular injection. Main Outcomes and Measures: The primary outcome was polymerase chain reaction-confirmed symptomatic COVID-19 infection at least 14 days after vaccination completion. Other outcomes were adverse events and severe COVID-19. Intention-to-treat analysis was performed. Results: In cohort 1 a total 17 319 individuals received 2 doses and in cohort 2 5521 received 3 doses of the vaccine or placebo. Cohort 1 comprised 60.1% men in the vaccine group and 59.1% men in the placebo group; cohort 2 included 59.8% men in the vaccine group and 59.9% in the placebo group. The mean (SD) age was 39.3 (11.9) years in cohort 1 and 39.7 (12.0) years in cohort 2, with no significant difference between the vaccine and placebo groups. The median follow-up time in cohort 1 was 100 (IQR, 96-106) days and, in cohort 2, 142 (137-148) days. In cohort 1, 461 (3.2%) cases of COVID-19 occurred in the vaccine group and 221 (6.1%) in the placebo group (vaccine efficacy: 49.7%; 95% CI, 40.8%-57.3%) vs 75 (1.6%) and 51 (4.3%) in cohort 2 (vaccine efficacy: 64.9%; 95% CI, 49.7%-59.5%). The incidence of serious adverse events was lower than 0.1%, with no vaccine-related deaths. Conclusions and Relevance: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of the efficacy and safety of FINLAY-FR-2 and FINLAY-FR-1A, 2 doses of FINLAY-FR-2 plus the third dose of FINLAY-FR-1A showed acceptable vaccine efficacy against symptomatic COVID-19 as well as COVID-19-related severe infections. Vaccination was generally safe and well tolerated. Therefore, Soberana may have utility as an option for mass vaccination of the population, especially in resource-limited settings, because of its storage condition and affordable price. Trial Registration: isrctn.org Identifier: IRCT20210303050558N1.

Prognostic accuracy of inflammatory markers in predicting risk of ICU admission for COVID-19: application of time-dependent receiver operating characteristic curves.

OBJECTIVE: Intensive care unit (ICU) admission occurs at different times during hospitalization among patients with COVID-19. We aimed to evaluate the time-dependent receive operating characteristic (ROC) curve and area under the ROC curve, AUC(t), and accuracy of baseline levels of inflammatory markers C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) in predicting time to an ICU admission event in patients with severe COVID-19 infection. METHODS: In this observational study, we evaluated 724 patients with confirmed severe COVID-19 referred to Ayatollah Rohani Hospital, affiliated with Babol University of Medical Sciences, Iran. RESULTS: The AUC(t) of CRP and NLR reached 0.741 (95% confidence interval [CI]: 0.661-0.820) and 0.690 (95% CI: 0.607-0.772), respectively, in the first 3 days after hospital admission. The optimal cutoff values of CRP and NLR for stratification of ICU admission outcomes in patients with severe COVID-19 were 78 mg/L and 5.13, respectively. The risk of ICU admission was significantly greater for patients with these cutoff values (CRP hazard ratio = 2.98; 95% CI: 1.58-5.62; NLR hazard ratio = 2.90; 95% CI: 1.45-5.77). CONCLUSIONS: Using time-dependent ROC curves, CRP and NLR values at hospital admission were important predictors of ICU admission. This approach is more efficient than using standard ROC curves.