Factors Associated with Mortality in Patients with Coronavirus Disease (COVID-19) in Babol, North of Iran.

BACKGROUND: The spectrum of the clinical features of coronavirus disease 2019 (COVID-19) spans from asymptomatic or mild disease to severe respiratory failure, while different factors are related to its mortality rate. This research aimed to determine the clinical and laboratory characteristics and the associated factors of mortality in patients with COVID-19. MATERIALS AND METHODS: Data were collected from hospitalized patients (May to June 2020), and COVID-19 was confirmed in patients by real-time polymerase chain reaction (PCR). The patient group was classified into survivor and deceased groups. The chi-square and the independent t-test with Statistical Package for the Social Sciences (SPSS) software program, version 18, were used for analysis. RESULTS: Mean age, hemoglobin, serum C-reactive protein (CRP), alkaline phosphatase (ALP), white blood cells, and level of procalcitonin in non-survivors were significantly higher than in survivors. Serum tumour necrosis factor-alpha (TNF-a) had a significant relationship with D-dimer (p = 0.0006). The risk of mortality in patients with serum CRP > 100 mg/dl was significantly higher than those with CRP < 100 mg/dl (odds ratio (OR) = 4.8 (95 % CI, 1.33-12.44, p = 0.01). CONCLUSION: COVID-19 has different clinical features and can be an asymptomatic, mild, or severe disease. Thus, findings about the disease and the consequent outcomes differ in patients. Further studies are needed to evaluate the clinical features and consequences of COVID-19 infection.

Pneumocystis jirovecii pneumonia complicated a case of SARS-CoV-2 infection and multiple sclerosis after treatment with rituximab.

Although immunodeficient patients are less prone to develop Coronavirus disease 2019 (COVID-19)-mediated cytokine storm, secondary infections can cause serious complications in this vulnerable population. They are more likely to develop opportunistic infections that can mimic the symptoms of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Herein, we presented a 27-year-old male patient of SARS-CoV-2 infection, who was complicated with Pneumocystis jirovecii pneumonia (PJP), following treatment with rituximab. First, he was hospitalized for 5 days with fever, cough, and dyspnea due to COVID-19 infection, and treated with remdesivir and glucocorticoid. Then, he has been referred to our center with cough, dyspnea, body pain, and fever. Due to persistent fever, the progression of pulmonary lesions, and reduced oxygen saturation, we began treatment with piperacillin + tazobactam, vancomycin, and levofloxacin. Nevertheless, the patient's fever did not stop after the aforementioned empiric treatment and his condition got worse and he was admitted to the intensive care unit. The result of BAL fluid, tested for P. jirovecii by RT-PCR, turned out to be positive. Therefore, we started trimethoprim-sulfamethoxazole and dexamethasone, which improved his condition. We hope this article helps clinicians consider causes other than COVID-19, especially opportunistic infections such as PJP, in patients with respiratory symptoms and fever.

Impact of Negative Fluid Balance on Mortality and Outcome of Patients with Confirmed COVID-19.

Purpose: Maintaining the proper fluid balance is a fundamental step in the management of hospitalized patients. The current study evaluated the impact of negative fluid balance on outcomes of patients with confirmed COVID-19. Methods: We considered the negative fluid balance as a higher output fluid compared to the input fluid. The fluid balance was categorized into four groups (group 4: -850 to -500 ml/day; group 3: -499 to -200 ml/day, group 2: -199 to 0 ml/day, and group 1 : 1 to 1000 ml/day) and included ordinally in the model. The outcomes were all-cause mortality, length of hospitalization, and improvement in oxygen saturation. Results: The fluid balance differed significantly among nonsurvivors and survivors (MD: -317.93, 95% CI: -410.21, -225.69, and p < 0.001). After adjusting for potential confounders, there was a significantly lower frequency of mortality in patients with negative fluid balance compared to the controls (aRR: 0.69, 95% CI: 0.57, 0.84, and p < 0.001). Similarly, the length of hospitalization was significantly shorter in the negative fluid balance group in comparison to the control group (aMD: -1.01, 95% CI: -1.74, -0.28, and p=0.006). Conclusion: We determined that the negative fluid balance was associated with favorable outcomes in COVID-19 patients. The negative fluid balance was associated with the reduced mortality rate and length of hospitalization as well as improvement in oxygen saturation. Moreover, the NT-proBNP >781 pg/mL and fluid balance >-430 mL might be the predictors for positive fluid balance and mortality, respectively.

One-year prevalence and the association between SARS-CoV-2 cycle threshold, comorbidity and outcomes in population of Babol, North of Iran (2020-2021).

Background: The present study aimed to investigate the one-year prevalence of SARS-CoV-2, common comorbidities and demographic information among negative- and positive rRT-PCR in health care workers (HCW), hospitalized and outpatients. Also, the association between SARS-CoV-2 cycle threshold (Ct) and the outcomes of patients were analyzed in Babol, northern Iran. Methods: This large retrospective cross-sectional study was performed between March 2020 and March 2021. The records of 19232 hospitalized, outpatients and HCW suspected to COVID-19 were collected from teaching hospitals in the North of Iran. Results: Out of the 19232 suspected to COVID-19 patients, 7251 (37.7%) had a positive rRT-PCR result; 652 (9%), 4599 (63.4%) and 2000 (27.6%) of those were categorized as HCW, hospitalized and outpatients, respectively. Moreover, between the hospitalized and the outpatient group, 10.2 and 0.8% cases died, whereas no death cases were reported in the HCW. Furthermore, it seems that death rate was significantly different between the three groups of Ct value, the highest mortality in those with Ct between 21 and 30 (group B=7.6%) and the lowest in the group with the highest Ct (between 31 and 40 = 5.5%) (p<0.001). Conclusion: In summary, 37.7% of cases were positive for SARS-CoV-2; of which, 63.4, 27.6 and 9% were hospitalized, outpatients and HCW, respectively. With regard to the mortality rate in hospitalized patients and the significant association with Ct under 20 and 30, it seems that the early detection and the initial quantification of SARS-CoV-2 in the first week of the conflict and therapeutic considerations to reduce the relative load can reduce the mortality rate.

Association between Influenza vaccination and severity of lung involvement at CT images of the patients with COVID-19 infection: an Iranian retrospective case-control study.

Background: Frequent waves of corona virus disease (COVID-19) and lack of specific drugs against that, warrant studies to reduce the morbidity and mortality of this pandemic disease. In this study, we investigated the association between influenza vaccination and the severity and outcome of COVID-19 disease in Iranian patients living in the North. Methods: This retrospective case-control study was performed on186 patients with COVID-19 infection between March and April, 2020. Patients with positive PCR were divided into two groups of case and control; Patients with moderate to severe and normal to mild lung involvement, respectively. The lung opacities in all of the 5 lobes were evaluated on chest CT images using a CT severity scoring system. The history of influenza vaccination during the fall of 2019-2020 was determined by a phone call. Statistical analysis was done using the chi-square test, student's t-test, and logistic regression. The significance level was p<0.05. Results: The mean age of patients was 54.67±15.05years. Most patients had pulmonary manifestations including ground-glass opacity (57%), consolidation (80%) and pleural effusion (3.2%). Adjusting for age, gender, and history of underlying disease, vaccination is an effective factor in the severity of pulmonary involvement (AOR=0.39; 95%CI: (0.21, 0.73); P=0.003). Furthermore, the chance of ICU admission decreased via influenza vaccination (OR=0.21, P=0.001). Conclusion: The results showed that the severity of COVID-19 pulmonary involvement and outcome as ICU admission, and severe symptoms in patients with history of influenza vaccination were significantly lower than those without history of vaccination. This strategy can be used to prevent and reduce the complications of COVID-19.

Comparing the outcomes of treatment with INF-ß 1-a (interferon beta-1a) and IFN-ß 1-b (interferon beta-1b) among COVID-19 inpatients.

BACKGROUND: IFNßs are known as one of the most promising drugs used for COVID-19 treatment. This study aimed to investigate the effects of treatment with INF-ß 1-a (interferon beta-1a) and IFN-ß 1-b (interferon beta-1b) on COVID-19 inpatients. METHODS: In this study, we retrospectively evaluated the clinical treatment outcomes of 100 patients with COVID-19 who received IFN-ß 1-a and IFN-ß 1-b during their hospitalization period. The rate of discharge from the hospital was considered equal to the clinical improvement and then evaluated as a primary outcome. Moreover, mortality, ICU admission and length of ICU stay, frequency of intubation and use of mechanical ventilation, duration of hospitalization, laboratory factors, and medications were assessed as secondary outcomes. RESULTS: The median discharge time of IFN-ß 1a recipients was approximately equal to that of IFN-ß 1-b recipients as 9 (5-10) days and 7 (5-11) days, respectively (HR = 2.43, P = 0.75). Mortality rate was also estimated as 10% among IFN-ß 1-a recipients and 14% among IFN-ß 1-b recipients, which was not statistically significant (p = 0.190). ICU hospitalization rate for the IFN-ß 1-a recipients and IFN-ß 1-b recipients was 26% and 36%, respectively. In addition, no significant difference was found between these two intervention groups in terms of ICU length of stay (1 (0-2) vs. 1 (0-4.25(, respectively,) P = 0.357). There was no significant difference between the two study groups in terms of frequency of mechanical ventilation and length of hospital stay. CONCLUSION: There was no significant difference between the two groups in terms of shortening the disease time, clinical improvements and other outcomes.

Posttreatment Downregulation of Type III Interferons in Patients with Acute Brucellosis.

There is a limited number of clinical studies on interferon (IFN) levels in human brucellosis. The novel group of interferons, type III interferons, which consists of four IFN-λ (lambda) molecules called IFN-λ1 or interleukin-29 (IL-29), IFN-λ2 or IL-28A, IFN-λ3 or IL-28B, and IFN-λ4, is not fully known. This study is one of the first studies of IL-28A and IL-29 levels in brucellosis cases at the end of their treatment course. A total of 33 acute brucellosis patients were included in this study. We considered changes in the levels of IL-28A and IL-29 in cases with acute brucellosis before and after treatment with standard therapy that referred to the Ayatollah Rohani Hospital in Babol, northern Iran. Of 33 included patients, 22 (66.6%) were males, and 11 (33.4%) were females. The range of patients' age was 49.21 ± 17.70 years. Serum IL-29 and IL-28A (acute form: 56.4 ± 30.32 pg/mL and 48.73 ± 27.72 pg/mL, respectively, and posttreatment: 40.15 ± 20.30 pg/mL and 38.79 ± 22.66 pg/mL, respectively) levels were elevated significantly in acute brucellosis than after treatment (p < 0.05). These findings indicate that considering biomarker levels in brucellosis patients may indicate the chronicity of infection. In conclusion, we suggest that IL-29 and IL-28A levels may be valuable biomarkers for follow-up patients with brucellosis.

C-Reactive Protein as a Prognostic Indicator in COVID-19 Patients.

While some biomolecules have been explored to identify potential biomarkers for the prognosis of COVID-19 patients, there is no reliable prognostic indicator of the disease progression and severity. We aimed to evaluate the ability of the C-reactive protein (CRP) to predict COVID-19 infection outcome. This retrospective study was conducted on 429 patients diagnosed with COVID-19 between March 30, 2020, and April 30, 2020. The study population was divided into severe (n = 175) and nonsevere cases (n = 254). Data on demographic characteristics, clinical features, and laboratory findings on admission were collected. The proportion of patients with increased CRP levels was significantly higher in severe cases than in nonsevere patients. Analysis of the receiver operating characteristic (ROC) curve found that CRP could be used as an independent factor in predicting the severity of COVID-19. Also, patients with CRP >64.75 mg/L were more likely to have severe complications. In conclusion, CRP serum levels can predict the severity and progression of illness in patients with COVID-19.

Reduced frequency of T helper 17 and T helper 1 cells and their association with critical coronavirus disease 2019.

There is very little knowledge about the immune responses, particularly cellular immunity to coronavirus disease 2019 (COVID-19). The main objective of this study was to evaluate the frequency of T helper (Th) cell subtypes, including Th1, Th17, and Treg cells, in moderate-to-severe and critical COVID-19 patients compared to healthy controls. Twenty-nine moderate-to-severe and 13 critical patients confirmed for COVID-19, and 15 healthy subjects were included in this study. Interferon-γ (IFN-γ)-producing Th1 and interleukin-17A-producing Th17 and Treg cells in peripheral blood were measured with flow cytometry. The frequency of Th1 and Th17 was significantly decreased in critical patients compared to healthy subjects (aMD: -2.76 and - 2.34) and moderate-to-severe patients (aMD: -1.89 and - 1.89), respectively (p < 0.05). Differences were not significant between moderate-to-severe patients and healthy subjects for both Th1 (p = 0.358) and Th17 (p = 0.535), respectively. In contrast, significant difference was not observed between study subjects regarding the frequency of Treg cells. Patients with critical COVID-19 had a markedly lower Th1/Treg and Th17/Treg ratios compared with the controls and moderate-to-severe cases. Our study showed a dysregulated balance of Th1 and Th17 cells and its relation to the severity of COVID-19.

Conjunctival polymerase chain reactions in COVID-19 patients and its correlation with clinical and paraclinical indexes.

BACKGROUND AND OBJECTIVES: This study aimed to detect SARS-CoV-2 in conjunctival samples of COVID-19 patients to investigate the transmission route of COVID-19 and its correlation with laboratory indexes. MATERIALS AND METHODS: In this cross-sectional study, 44 COVID-19 patients were tested for conjunctival PCR in Ayatollah Rouhani hospital of Babol, Iran, in January and February 2021. The conjunctival samples were collected using a conjunctival swab and suspended in a viral transport medium. After RNA extraction and cDNA synthesis, real-time PCR was performed to investigate the SARS-CoV-2 genome in samples. The ocular manifestations and laboratory indexes were evaluated for all patients. RESULTS: Among 44 COVID-19 patients, 6 samples (13.63%) were positive in terms of conjunctival PCR. The mean ± SD age of conjunctival PCR-positive patients was 76.17 ± 16.61-year-old, while conjunctival PCR-negative COVID-19 patients were aged 57.54 ± 13.61-year-old (p <0.05). D-dimer serum level is significantly higher in conjunctival PCR-positive COVID-19 patients (4001.00 ± 3043.36 µg/ml) compared to normal individuals (496.80 ± 805.92 µg/ml, p <0.01). CONCLUSION: Our study showed that the conjunctiva and tear contain the SARS-CoV-2 in COVID-19 patients as a possible transmission route.

Clinical and laboratory findings from patients with COVID-19 pneumonia in Babol North of Iran: a retrospective cohort study.

BACKGROUND: In December 2019, China has experienced an outbreak of novel coronavirus disease 2019 (COVID-19). Coronavirus has now spread to all of the continents. We aimed to consider clinical characteristics, laboratory data of COVID-19 that provided more information for the research of this novel virus. METHODS: We performed a retrospective cohort study on the clinical symptoms and laboratory findings of a series of the 100 confirmed patients with COVID-19. These patients were admitted to the hospitals affiliated to Babol University of Medical Sciences (Ayatollah Rohani, Shahid Beheshti and Yahyanejad hospitals) form 25 February 2020 to 12 March 2020. RESULTS: Nineteen patients died during hospitalization and 81 were discharged. Non-survivor patients had a significantly higher C-reactive protein (CRP) (MD: 46.37, 95% CI: 20.84, 71.90; P = 0.001), white blood cells (WBCs) (MD: 3.10, 95% CI: 1.53, 4.67; P < 0.001) and lower lymphocyte (MD: -8.75, 95% CI: -12.62, -4.87; P < 0.001) compared to survivor patients Data analysis showed that comorbid conditions (aRR: 2.99, 95% CI: 1.09, 8.21, P = 0.034), higher CRP levels (aRR: 1.02, 95% CI: 1.01, 1.03, P = 0.044), and lower lymphocyte (aRR: 0.82, 95% CI: 0.73, 0.93, P = 0.003) were associated with increased risk of death. CONCLUSIONS: Based on our findings, most non-survivors are elderly with comorbidities. Lymphopenia and increased levels of WBCs along with elevated CRP were associated with increased risk of death. Therefore, it is best to be regularly assessed these markers during treatment of COVID-19 patients.

Cytochrome P450 Genes (CYP2E1 and CYP1A1) Variants and Susceptibility to Chronic Hepatitis B Virus Infection.

Hepatitis B virus (HBV) infection is a worldwide health concern which is associated with significant morbidity and mortality. Both viral and host factors have a significant effect on infection, replication and pathogenesis of HBV. The aim of this study was to investigate the effect of CYP2E1 and CYP1A1 genetic variants on susceptibility to HBV. 143 individuals including 54 chronic HBV patients and 89 healthy controls were enrolled in the genotyping procedure. rs2031920 and rs3813867 at CYP2E1 as well as rs4646421 and rs2198843 at CYP1A1 loci were studied in all subjects using PCR-RFLP (restriction fragment length polymorphism) analysis. Both variants at CYP2E1 locus were monomorphic in all studied subjects. Genotype frequency of rs4646421 was significantly different between chronic HBV patients and healthy blood donors (P = 0.04, OR 4.31; 95% CI 1.04-17.7). Furthermore, individuals carrying at least one C allele (CC or CT genotypes) for rs4646421 seemed to have a decrease risk of hepatitis in comparison with TT genotype (P = 0.039). Our results showed a relationship between rs4646421 TT genotype (rare genotype) and the risk for developing chronic HBV infection (four times higher). Further studies are needed to examine the role of CYP1A1 polymorphism in susceptibility to chronic HBV infection.

Diagnosis of Clostridium difficile infection by toxigenic culture and PCR assay.

BACKGROUND AND OBJECTIVES: Clostridium difficile is responsible for 15-25% of nosocomial antibiotic associated diarrhea (AAD) cases and all cases of pseudomembranous colitis. C. difficile has two major virulence factors, toxin A (enterotoxin) and toxin B (cytotoxin). The aim of this study was to determine the frequency of C. difficile strains in patients with diarrhea in Babol' hospitals with toxigenic culture and PCR assay. MATERIALS AND METHODS: One hundred stool specimens were taken from diarrheal patients in hospitals of the city of Babol. All patients had a history of antibiotic use. The samples were cultured on CCFA medium. In the next stage, toxigenic culture was performed for isolated C. difficile strains. Then, PCR assay was used to identify gdh, tcdA and tcdB genes among isolated C. difficile strains. RESULTS: From the 100 stool samples, eight (8%) samples were positive in C. difficile culture. In toxigenic culture, two (2%) of these strains had cytopathic effects on Vero cells. All eight strains had the gdh gene. This gene is specific for C. difficile. Two strains that had cytopathic effects on toxigenic culture were positive for toxin genes. CONCLUSION: The frequency of toxigenic strains in different parts of the world is variable, and needs to be continually investigated. In the present study, the PCR method had a good correlation with toxigenic culture. Thus, it can replace the laborious and costly cell culture method.

Serum and alveolar procalcitonin had a weak diagnostic value for ventilator-associated pneumonia in patients with pulmonary infection score ≥ 6.

BACKGROUND: Measuring the serum and alveolar procalcitonin level as inflammatory marker in the diagnosis of ventilator-associated pneumonia (VAP) has been taken into account. In this study, serum and alveolar procalcitonin levels in patients with suspected VAP and patients with confirmed VAP were compared. METHODS: This cross-sectional study was conducted using 50 intubated intensive care unit (ICU) patients, connected to ventilator, from October 2014 to April 2015. 50 patients with clinical pulmonary infection score ≥6 were divided into two groups. Patients whose bronchoalveolar lavage (BAL) has shown the growth of more than 104 CFU/mL were included in confirmed VAP group and other patients were included in suspected VAP group. Serum and alveolar procalcitonin levels were measured and compared between both groups. RESULTS: Mean age of patients was 69.10 ± 42.13 with a range of 16-90 years, out of which 23 patients were male (46%) and 27 patients were female (54%). Moreover, patients' mean clinical pulmonary infection score was reported to be 7.02 ± 1.07. There was a significant relationship between serum and alveolar procalcitonin in suspected patients and patients with an approved form of pneumonia (p = 0.001 and 0.027). Area under the curve for alveolar procalcitonin was 0.683 (sensitivity = 57%; specificity = 80%) and for serum procalcitonin 0.751 (sensitivity = 71%; specificity = 73%) for the diagnosis of VAP. CONCLUSION: According to the results of the present study, we can diagnose ventilator-associated pneumonia earlier and more accurately by measuring procalcitonin level (particularly alveolar type) in intensive care unit patients.

Histological grading and staging of liver and its relation to viral loads in chronic anti-HBe positive hepatitis.

BACKGROUND: Hepatitis activity index (HAI) and fibrosing stage are two important findings during the evaluation of liver samples in patients with chronic hepatitis B. The aim of this study was to determine the HAI and fibrosing stage in patients with anti-HBe positive chronic hepatitis B. METHODS: Liver biopsy slides of 72 patients were evaluated at the Department of Pathology in two teaching hospitals of Babol University of Medical Sciences, Iran, from April 2006 to August 2011. Total HAI or grading as well as its components including piecemeal necrosis, confluent necrosis, spoty necrosis, portal inflammation and fibrosis scores or staging in considering with viral loads more or less than 10(5) copies/ml were enumerated according to Ishak scoring system. RESULTS: The mean age of these patients was 34.4±12 years. Fifty-six patients had viral load> 10(5) copies/ml. Piecemeal necrosis and grading scores with viral load (10(3),10(3)-10(5) and >10(5) copies/ml) were 0.8±0.7, 0.9±0.4, 1.8±1 and 3.8±1.9, 4.4±2, 5.9±2.6, respectively (p=0.005 and p=0.04, respectively). There was not any significant difference with fibrosis stage regarding different viral loads. In total, 18 cases had fibrosis scores > 1 and 24 cases had confluent necrosis. HAI≥4 was seen in 29 (60.4%) of the 48 cases without confluent necrosis and in 23 out of 24 cases with confluent necrosis (p=0.007). CONCLUSION: The results show that piecemeal necrosis and higher grading scores are associated with higher viral loads. The presence of confluent necrosis is associated with more severe diseases.

Seroepidemiology of varicella zoster virus in healthcare workers in Babol, Northern Iran.

BACKGROUND: Varicella zoster virus (VZV) infection is one of the nosocomial infections and healthcare workers (HCWs) are at high risk group who work in the hospital with likelihood of varicella acquisition or transmission. This study evaluated the VZV seroprevalence in this high risk population in Babol, Iran. METHODS: Serological testing for VZV using enzyme linked immunosorbent assay (ELISA) was performed on 459 HCWs in Ayatollah Rouhani Hospital, Babol, Northern Iran from 2011 to 2012. A questionnaire was completed including age, gender, place of residence, marital status, history of chickenpox, educational level, working experience and risk of exposure. The data were collected and analyzed. RESULTS: The mean age of these subjects was 32.2±1.1 years. Four hundred-sixteen (90.6%) cases were females and 43 (9.4%) were males. The overall positive seroprevalence of VZV was 94.6%. No statistically significant differences were observed between age, gender, place of residence, risk of exposure, marital status, educational level, working experience and seropositivity. The seropositivity of varicella was seen in 278 (95.5%) of 297 cases with positive history and in 30 (81.1%) of 37 cases who did not (p=0.005). CONCLUSION: The results show that a positive history of VZV is associated with positive seroprevalence but can not be a reliable indicator of the immunity, therefore, serological screening should be considered for all the HCWs.