Comparing clinical presentation, viremia, and immunological factors at various severity presentations in hospitalized children affected by COVID-19: A cross-sectional study.

Background and Aims: Although SARS-CoV-2 infection usually leads to mild COVID-19 in children, sometimes it causes serious complications, especially in those with underlying diseases. Several factors have been identified in determining disease severity in adults, and limited studies have been conducted in children. The prognostic implications of SARS-CoV-2 RNaemia as an important factor in determining disease severity in children are not well understood. Methods: In this study, we aimed to prospectively assess the relationship between disease severity and immunological factors and viremia in 47 COVID-19 hospitalized children. In this research, 76.5% of children experienced mild and moderate COVID-19, while 23.5% experienced severe and critical forms of the disease. Results: The presence of underlying diseases in different groups of pediatric patients differed significantly from each other. On the other hand, clinical symptoms such as vomiting and chest pain as well as laboratory parameters including erythrocyte sedimentation rate were significantly different in different groups of patients. Viremia was seen in only two children, and this had no significant relationship with the severity of COVID-19. Conclusion: In conclusion, our data confirmed that COVID-19 severity differed in SARS-CoV-2 infected children. Some clinical presentation and lab data parameters were different in various presentation of patients. Viremia was not associated with severity in our study.

A case report of severe systemic infection with neurological HFMD symptoms followed by an accidental puncture of thumb during HFMD sample collection.

A 34-year-old female clinical virology assistant was punctured with a contaminated lancet used for sampling from a suspected Hand, Foot, and Mouth disease (HFMD) patient. Five days after a puncture, the disease symptoms manifested, including high fever, ague, and stiff neck. Skin rashes suddenly appeared after day 6. Stiff neck and fever were relieved two days after the rash appeared, and rashes disappeared gradually by the next five days. Samples for molecular detection and virus cultivation were taken from the patient. Real-time PCR found the enteroviral RNA in the throat swab and skin rashes. The specific CPE of Enteroviruses appeared on the Vero cell line after three days of incubation. In this case transmission occurs through needle injury and results in the systemic disease, so unusual and unexpected viral transmission should be considered when dealing with samples.

Role of Cytomegalovirus in the Development of Posttransplant Lymphoproliferative Disorders With or Without Epstein-Barr Virus Infection.

OBJECTIVES: Many studies have revealed the role of Epstein-Barr virus infection, in combination with chronic immunosuppression, as the main factor in the development of posttransplant lymphoproliferative disorder malignancy. Although many studies have been published on other confounding factors involved in posttransplant lymphoproliferative disorders, the role of coinfection with both cytomegalovirus and Epstein-Barr virus has not been investigated. We evaluated the role of cytomegalovirus infection as a risk factor in transplant recipients who were simultaneously infected with Epstein-Barr virus. MATERIALS AND METHODS: In the current retrospective study, 143 recipients of various solid-organ transplants at Namazi Hospital from April 2018 to March 2019 were assessed for coinfection with cytomegalovirus and Epstein-Barr virus with the TaqMan real-time polymerase chain reaction assay. We collected clinical and pathology details from their medical records. RESULTS: Of the 143 patients, 81 (57%) were male. Children under 5 years old were the largest group with 32% prevalence, and the most common organ transplant in this study was liver transplant. The prevalence of cytomegalovirus and Epstein-Barr virus coinfection was 12.6% (18/143 patients), of whom 50% experienced posttransplant lymphoproliferative disorder (9/18 patients) during 18 months after transplant. The incidence of posttransplant lymphoproliferative disorder was significantly higher among patients coinfected with cytomegalovirus and Epstein-Barr virus than among patients without coinfection. We observed a significant correlation between cytomegalovirus viral loads, as well as Epstein-Barr virus genome load, in posttransplant lymphoproliferative disorder development. CONCLUSIONS: Coinfection with cytomegalovirus and Epstein-Barr virus, as well as the genome load of each virus, can serve as a strong predictive factor of posttransplant lymphoproliferative disorder in solidorgan transplant recipients.

Human Herpesvirus 6 as an Indicator of Cytomegalovirus Infection and Its Attributable Disease Symptoms in Liver Transplant Recipients.

OBJECTIVES: Human ß-herpes viruses, including cytomegalovirus and human herpesvirus 6, can become activated in liver transplant patients. Here, we evaluated the effects of human herpesvirus 6 infection as an independent factor on cytomegalovirus infection and the occurrence of associated diseases in liver transplant patients. MATERIALS AND METHODS: In this cross-sectional study, 46 patients who underwent deceased-donor liver transplant at Nemazi Hospital, Shiraz University of Medical Sciences (Shiraz, Iran) were prospectively monitored for cytomegalovirus and human herpesvirus 6 infections during 3 months posttransplant. Taq-man real-time polymerase chain reaction assay as an accurate and rapid test and pp65-anigenemia as the standard test were used to monitor cytomegalovirus infections, whereas human herpesvirus 6 infection was monitored by Taq-man real-time polymerase chain reaction assay. We also followed clinical findings from laboratory data and symptoms of cytomegalovirus infections. RESULTS: Active cytomegalovirus infection was detected in 23 liver transplant recipients (50%), of which 17 (74%) were diagnosed with cytomegalovirus-related diseases. Active human herpesvirus 6 infection was detected in 25 patients (54%). Thirteen of 17 cytomegalovirussymptomatic patients had coinfection with human herpesvirus 6. In 10 ofthe 13 patients with coinfection, human herpesvirus 6 DNAemia appeared significantly earlier by 9 days than cytomegalovirus infection. In the pp65 antigenemia test, the mean number of cytomegalovirus-infected polymorphonuclear cells was 42.47 ± 5.41, which was correlated with incidence of clinical presentation. In symptomatic patients, average serum and polymorphonuclear cell viral loads of cytomegalovirus were 12064.59 copies/mL and 6735 copies/2 × 105 cells,respectively, with significant differences between the loads and cytomegalovirusattributable disease symptoms. Average human herpesvirus 6 DNA burden in serum samples of symptomatic patients was 11283 copies /mL, which was statistically related to cytomegalovirus-attributable disease symptoms. CONCLUSIONS: We found that human herpesvirus 6 infection is often associated with cytomegalovirus reactivation and cytomegalovirus-attributable disease symptoms.

Hepatitis C virus genotypes in patients with chronic hepatitis C infection in southern Iran from 2016 to 2019.

Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). The treatment of HCV infection has become more complicated due to various genotypes and subtypes of HCV. The treatment of HCV has made significant advances with direct-acting antivirals. However, for the choice of medicine or the combination of drugs for hepatitis C, it is imperative to detect and discriminate the crucial HCV genotypes. The main objective of this study was to determine the pattern of circulating HCV genotypes in southern Iran, from 2016 until 2019. The other aim of the study was to determine possible associations of patients' risk factors with HCV genotypes. A total of 803 serum samples were collected in 4 years (2016-2019) from patients with HCV antibody positive results. A total of 728 serum samples were HCV-RNA positive. The prevalence of HCV genotypes was detected using the genotype-specific RT-PCR test for serum samples obtained from 615 patients. The HCV genotype 1 (G1) was the most prevalent (48.8%) genotype in the area, with G1a, G1b, and mixed G1a/b representing 38.4%, 10.1%, and 0.3%, respectively. Genotype 3a was the next most prevalent (47.2%). Mixed genotypes 1a/3a were detected in 22 (3.6%) and finally G4 was found in 3 (0.5%) patients. The other HCV genotypes were not detected in any patient. Genotype 1 (1a and 1b alone, 1a/1b and 1a/3a coinfections) is the most prevalent HCV genotype in southern Iran. HCV G1 shows a significantly higher rate in people under 40 years old.

Seroprevalence of viral hepatitis A, B, C, D and E viruses in the Hormozgan province southern Iran.

BACKGROUND: Viral hepatitis is a global public health problem affecting millions of people worldwide, causing thousands of deaths due to acute and persistent infection, cirrhosis, and liver cancer. Providing updated serologic data can improve both surveillance and disease control programs. This study is aimed to determine the seroprevalence of markers for viral hepatitis (A, B, C, D and E) and the epidemiology of such infections in the general population of southern Iran's Hormozgan province. METHODS: Between 2016 and 2017, a total of 562 individuals with ages ranging from 1 to 86 years, who visited governmental public laboratories for routine check-ups, were tested for the presence of serological markers to hepatitis virus types A to E using enzyme-linked immunosorbent assays. RESULTS: The overall anti-hepatitis A virus (HAV) antibody seroprevalence was 93.2% (524/562). The prevalence of anti-hepatitis E virus (HEV) antibodies was 15.8% (89/562) among which 1.6% (9/562) of the seropositive individuals also had evidence of recent exposure to the virus (IgM positivity). Two and a half percent (14/562) were positive for hepatitis B surface (HBs) antigen, whereas 11.6% (65/562) tested positive for anti-hepatitis B core (HBc) antibodies. Among anti-HBc positive patients, 11% (7/65) had HBs Ag and 5% (3/65) were positive for anti-hepatitis D virus (HDV) antibodies. The prevalence of anti-hepatitis C virus (HCV) antibodies was 0.7% (4/562). The seroprevalence of anti-HAV, HEV IgG, anti-HBc antibodies, and HBs Ag increased with age. CONCLUSION: The present study confirms a high seroprevalence of HAV infection among the examined population and reveals high levels of endemicity for HEV in the region. Planned vaccination policies against HAV should be considered in all parts of Iran. In addition, improvements on public sanitation and hygiene management of drinking water sources for the studied area are recommended.

Molecular diagnosis of genital tract infections among HIV-positive women in Iran.

BACKGROUND AND OBJECTIVES: Human immunodeficiency virus (HIV)-infected women are usually at a higher risk of sexually transmitted infections (STIs) than others. The objective of this study was to characterize the prevalence of human papilloma virus (HPV), herpes simplex virus (HSV), Chlamydia trachomatis (CT), and Neisseria gonorrhoeae (NG), and associated risk factors among HIV-infected women in Fars province, Iran. MATERIALS AND METHODS: In this cross-sectional study, cervical swab samples were collected from 71 HIV-infected women, aged 17-45 years (mean ± standard deviation: 31.11 ± 6.58 years), and tested for HPV, HSV, CT, and NG using PCR assays. RESULTS: Overall, 77.5% of patients were positive for the tested STIs with the following distribution: 36 (50.7%) HPV, 7 (9.9%) HSV, 4 (5.6%) NG, and 27 (38%) CT. From those, 39 (55%) were positive for only one infection, while 16 (22.5%) were positive for multiple infections. We observed that the prevalence of all tested STIs increased by age, except for HSV which showed a slight decrease, although not statistically significant. Socio-economic factors such as low educational level, multiple sex partners, and being a sex worker significantly correlated with higher positive prevalence of STIs in the studied population. CONCLUSION: A high prevalence of STIs was observed among HIV-infected women in this region. These data might prompt policy makers and STI experts to focus on providing a comprehensive sex education, including participation in screening programs for STIs among high-risk groups.

Comparison of HCV viral load and its genotype distributions in HCV mono- and HIV/HCV co-infected illicit drug users.

BACKGROUND: Because of shared modes of transmission, patients with hepatitis C virus (HCV) infection are often co-infected with other types of hepatitis viruses and/or HIV. We studied HCV viral load and its genotype patterns among HCV mono- and HCV/HIV co-infected Illicit Drug Users in Fars province-Iran. METHODS: Totally, 580 HCV seropositive IDUs referred to Prof. Alborzi Clinical Microbiology Research Center, Shiraz, Iran, without receiving any anti-HCV treatment, were enrolled. After their HCV infections were reconfirmed by one step rapid diagnostic test, HCV RNA level and HCV genotypes were determined by Taq-man real-time PCR assays. Their HIV serostatus was determined and seropositive patients were excluded from the group. In addition, 104 HIV/HCV co-infected IDUs referred from Shiraz Behavioral Diseases Consultation Center (SBDC) were assessed for HCV RNA level and HCV genotype patterns, as well. RESULTS: The overall estimated HIV prevalence was 6.7% (39/580) among HCV seropositive IDUs. Genotype 1, the most prevalent genotype in both groups, was detected in 69% and 49% of co- and mono-infected IDUs, respectively. Median HCV viral load was significantly higher in HIV/HCV co-infected patients, compared with that among HCV mono-infected counterparts. CONCLUSIONS: Given the higher baseline HCV viral load and GT1 attributed to poorer treatments response, HCV treatment must be more considered among HCV/HIV co-infected IDUs, compared to those mono-infected with HCV.

Construction of AAV-rat-IL4 and Evaluation of its Modulating Effect on Aß (1-42)-Induced Proinflammatory Cytokines in Primary Microglia and the B92 Cell Line by Quantitative PCR Assay.

BACKGROUND: Interleukin-4 (IL-4), as the most prominent anti-inflammatory cytokine, plays an important role in modulating microglial activation and inflammatory responses in Alzheimer's disease (AD), a chronic inflammatory disorder. OBJECTIVES: The current study aimed to develop a new recombinant Adeno-associated viral (rAAV) vector that delivers IL-4 and then assess the counterbalancing effect of the new construct along with recombinant IL-4 (rIL-4) protein in in-vitro models of AD. MATERIALS AND METHODS: The rAAV-IL4 was originally prepared and then employed along with rIL-4 protein to counter Amyloid ß (1-42)-induced proinflammatory cytokines in a primary microglia cell culture and the B92 rat microglia continuous cell line, using relative Real-Time PCR assay. RESULTS: Aß (1-42) stimulated the production of the proinflammatory cytokines IL6, IL1ß, TNFα, and IL18 in both the primary microglia cell culture and the B92 cell line. Both the rAAV-IL4 construct and the rIL-4 protein were found to inhibit production of the most important Aß (1-42)-induced proinflammatory cytokine mRNAs in the two types of cells with different patterns. CONCLUSIONS: It seems that the new construct can serve as an appropriate option in the modulation of Aß-induced proinflammatory cytokine gene expression and microglia activation in patients affected by AD.

Epstein-Barr virus DNAemia in Iranian liver transplant recipients and assessment of its variation in posttransplant lymphproliferative disorder patients by quantitative polymerase chain reaction assay.

OBJECTIVES: Epstein-Barr virus primary infection and/or reactivation may play a major role in the incidence of posttransplant lymphoproliferative disorder in organ recipients. We assessed Epstein-Barr virus viral load in liver transplant patients suspected of having Epstein-Barr virus/ posttransplant lymphoproliferative disorder at specified times after transplant and evaluated the clinical findings and posttransplant complications. MATERIALS AND METHODS: In the 696 patients who underwent liver transplant in this retrospective study, Epstein-Barr virus viral load was examined intermittently in 127 liver transplant recipients who were suspected to have Epstein-Barr virus infection/disease. Sampling was performed during 4 years from July 2009 to May 2013 using real-time polymerase chain reaction assay. Clinical and pathologic data were gathered by reviewing medical records. RESULTS: There were 78 of the 127 suspected patients (61%) who exhibited Epstein-Barr virus DNAemia and 19 patients had posttransplant lymphoproliferative disorder. The median EBV viral load of posttransplant lymphoproliferative disorder patients was significantly higher than unaffected patients. Posttransplant lymphoproliferative disorder was diagnosed clinically in 34 subjects (4.9%). Estimated mortality rate of posttransplant lymphoproliferative disorder patients was 35% during 1.5-year follow-up after transplant. CONCLUSIONS: Monitoring Epstein-Barr virus load may enable detection of Epstein-Barr virus infection/disease in liver transplant patients suspected of having the virus, even several weeks before the onset of any clinical manifestations, especially in pediatric patients who have high incidence and mortality from posttransplant lymphoproliferative disorder.

Diagnosing of herpes simplex virus infections in suspected patients using real-time PCR.

BACKGROUND: Herpes simplex virus infections are very common worldwide. The virus can cause infection in various body parts, especially eyes and the nervous system. Therefore, an early diagnosis and highly sensitive method is very helpful. OBJECTIVES: The present study sought to investigate the efficiency of Real-time TaqMan probe PCR in the diagnosis of HSV infection in suspected patients. PATIENTS AND METHODS: In this study, 1566 patients with suspected HSV infections were enrolled. They aged 17 days to 96 years. The collected specimens were classified into four groups; cerebrospinal fluid (CSF) from HSE suspected individuals, samples from eye epithelial scraping, tear fluid or aqueous humor from herpes simplex keratitis (HSK) suspected patients, plasma of immune compromised patients and mucocutaneous collected samples from different body parts. The samples were analyzed by Real-time PCR assays. RESULTS: In total, 44 (5.6%), 118 (26.8%), 23 (11.7%), 13 (44.8%) and 65 (45.5%) of 791 HSE, 407 HSK, 29 skin HSV, 143 oropharyngeal suspected patients and 196 patients with systemic HSV infection HSV had positive results by Real-time PCR assays, respectively. CONCLUSIONS: Real-time PCR assay, due to its high sensitivity and specificity, can help in early diagnosis and more effective treatment for patients. Also, it requires shorter hospital stay and promotes patients' survival.

Cervical Infection with Herpes simplex Virus, Chlamydia trachomatis, and Neisseria gonorrhoeae among Symptomatic Women, Dubai, UAE: A Molecular Approach.

Tragically, genital tract infections are still a major public health problem in many regions. This study was undertaken to determine the prevalence of cervical infection with Herpes simplex virus (HSV), Chlamydia trachomatis (CT), and Neisseria gonorrhoeae (NG) among married women referring to Iranian Hospital, Dubai, UAE. In a retrospective cross-sectional survey, 201 female patients aged 16-80 years who referred to the Obstetrics and Gynecology Department of Iranian Hospital, Dubai, UAE, in 2010 were enrolled. The patients were categorized into three age groups: 15-30 (group I), 31-40 (group II), and ≥41 years old (group III). A cervical swab sample was collected from each woman and the prevalence of cervical infection with HSV, CT, and NG was determined by PCR method. HSV, CT, and NG were detected in 6.5%, 10.4%, and 5.5% of swab samples, respectively. Regarding age, a significant difference was noticed for prevalence of NG and HSV between groups I and III. Because of public health importance of sexual transmitted diseases (STDs), their long-lasting impact on quality of life, and their economic burden, preventing measures and education of women seem necessary.

Determining hepatitis C virus genotype distribution among high-risk groups in Iran using real-time PCR.

AIM: To assess hepatitis C virus (HCV) genotype patterns among high-risk Iranian groups, using real-time RT-PCR. METHODS: In this study, we evaluated the distribution of different HCV genotypes among injection drug users and other high-risk groups over a 4-year period (from 2009 to 2012) using real-time polymerase chain reaction (PCR). Sera from 888 HCV-infected patients residing in southern and southwest Iran were genotyped using real-time PCR with common primers and specific probes. These patients were grouped into distinct exposure categories. Illicit drug users constituted the primary group and were further evaluated for HCV genotype distribution and parameters such as age range. RESULTS: Of the examined HCV-infected patients, 62% were substance abusers, although the route of transmission could not be determined in approximately 30% of these patients. HCV genotyping revealed that Gt1 was the most prevalent genotype among the drug users as well as among patients with thalassemia, hemophilia, solid organ recipients and those on hemodialysis. Mixed infections were only seen in addict groups, where Gt2 genotype was also found. The highest frequencies in HCV-positive addict patients were observed in the 31-40 age group. Our research also showed that the addiction age has increased, whereas the addiction rate has dropped in this region. Most illicit drug users had more than one risk factor such as tattoo and/or a history of imprisonment. CONCLUSION: This study revealed that the most common HCV-infection route and HCV-genotype in southern and southwest Iran was illicit drug abuse and Gt1, respectively.

The effects of cichorium intybus extract on the maturation and activity of dendritic cells.

BACKGROUND: Cichorium intybus is a medicinal plant commonly used in traditional medicine for its benefits in immune-madiated disorders. There are several evidences showing that C. intybus can modulate immune responses. In the present study we have investigated the effects of the ethanolic root extract of this plant on the immune system by targeting dendritic cells (DCs). For this purpose, phenotypic and functional maturity of murine DCs after treatment with the extract was analyzed by flow cytometry and mixed lymphocyte reaction (MLR) assay. RESULTS: C. intybus did not change the expression of CD40, CD86 and MHC-II molecules as important co-stimulatory markers on DCs compared to the control, indicating that it could not promote DCs phenotypic maturation. Treatment of DCs with lower concentrations of the extract resulted in an increased production of IL-12 by these cells with no change in IL-10 release. The capacity of treated DCs to stimulate allogenic T cells proliferation and cytokines secretion was examined in the co-cuture of these cells with T cells in MLR. C. intybus at higher concentrations inhibited proliferation of allogenic T cells and in lower concentrations changed the level of cytokines such that IL-4 decreased and IFN-γ increased. CONCLUSIONS: These results indicated that C. intybus extract at higher concentrations can inhibit T cell stimulating activity of DCs, whereas at lower concentrations can modulate cytokine secretion toward a Th1 pattern. These data may in part explain the traditional use of this plant in treatment of immune-mediated disorders.

Pandemic 2009 influenza A (H1N1) infection among 2009 Hajj Pilgrims from Southern Iran: a real-time RT-PCR-based study.

BACKGROUND: Hajj is a mass gathering undertaken annually in Mecca, Saudi Arabia. The 2009 Hajj coincided with both the pandemic influenza A/H1N1 2009 (A(H1N1)pdm09) and seasonal types of influenza A viruses. The interaction between pandemic influenza and Hajj could cause both a high level of mortality among the pilgrims and the spread of infection in their respective countries upon their return home. OBJECTIVE: The present study attempted to determine the point prevalence of A(H1N1)pdm09 among returning Iranian pilgrims, most of whom had been vaccinated for seasonal influenza but not A(H1N1)pdm09. METHODS: Pharyngeal swabs were collected from 305 pilgrims arriving at the airport in Shiraz, Iran. RNA was extracted from the samples and A(H1N1)pdm09 and other seasonal influenza A viruses were detected using TaqMan real-time PCR. For A(H1N1)pdm09-positive samples, the sensitivity to oseltamivir was also evaluated. RESULTS: Subjects included 132 (43.3%) men and 173 (56.7%) women, ranging in age from 24 to 65 years. The A(H1N1)pdm09 virus was detected in five (1.6%) pilgrims and other influenza A viruses in eight (2.6%). All the A(H1N1)pdm09 were sensitive to oseltamivir. CONCLUSIONS: Only five cases were found to be positive for A(H1N1)pdm09, and it seems unlikely that the arrival of infected pilgrims to their homelands would cause an outbreak of a new wave of infection there. Thus, the low morbidity and mortality rates among the pilgrims could be attributed to the characteristics of A(H1N1)pdm09, which causes morbidity and mortality in a way similar to the seasonal influenza infections, absence of high-risk individuals among the Iranian pilgrims, and the instructions given to them about contact and hand hygiene, and respiratory etiquette.