Adverse outcomes and maternal complications in pregnant women with severe-critical COVID-19: a tertiary center experience.

OBJECTIVES: This study aimed to present perinatal outcomes, clinical challenges, and basic ICU management in pregnant women with severe-critical COVID-19 at our tertiary referral center. METHODS: In this prospective cohort study, patients were divided into two groups, whether they survived or not. Clinical characteristics, obstetric and neonatal outcomes, initial laboratory test results and radiologic imaging findings, arterial blood gas parameters at ICU admission, and ICU complications and interventions were compared between groups. RESULTS: 157 of the patients survived, and 34 of the patients died. Asthma was the leading health problem among the non-survivors. Fifty-eight patients were intubated, and 24 of them were weaned off and discharged healthfully. Of the 10 patients who underwent ECMO, only 1 survived (p<0.001). Preterm labor was the most common pregnancy complication. Maternal deterioration was the most common indication for a cesarean section. Higher neutrophil-to-lymphocyte-ratio (NLR) values, the need for prone positioning, and the occurrence of an ICU complication were important parameters that influenced maternal mortality (p<0.05). CONCLUSIONS: Overweight pregnant women and pregnant women with comorbidities, especially asthma, may have a higher risk of mortality related to COVID-19. A worsening maternal health condition can lead to increased rates of cesarean delivery and iatrogenic prematurity.

Investigation of SARS-CoV-2 using RT-PCR in vaginal swab samples of female patients with a diagnosis of severe COVID-19.

OBJECTIVE: It is important to determine the presence of SARS-CoV-2 in the vaginal fluid samples of reproductive-aged women with severe disease during the acute stage of the disease and to determine the risks of transmission by sexual or vertical transmission. MATERIAL AND METHODS: Adult women with confirmed severe COVID-19 who were admitted to Ankara City Hospital intensive care unit (ICU) between December 1st, 2020, and January 1st, 2021, were enrolled in the study. Vaginal swab samples were collected within 48 h in the ICU using Dacron or rayon swabs and tested for SARS-CoV-2 using reverse transcription real-time polymerase chain reaction (RT PCR). RESULTS: Thirty women of reproductive age were included in the study, five (16.7%) of whom were pregnant. The mean age was 44.9 (±10.5) years. The most common symptoms were headache (100%), muscle soreness (86.7%), cough (76.7%), fever (60%), and nausea and vomiting (20%). Nineteen (63.3%) patients had underlying medical conditions. The time interval from obtaining vaginal swab samples to admission to the ICU was 48 h. The time between vaginal sampling and PCR positivity ranged from 2 to 18 days. SARS-CoV-2 was not detected in any vaginal samples. CONCLUSION: Our study showed that women with severe COVID-19 did not have SARS-CoV-2 in their vaginal fluids. Investigation of the presence of SARS-CoV-2 in vaginal secretions may help in determining the risks of sexual transmission and vertical transmission from mother to baby. Information on this subject is still limited. Larger studies on comprehensive biological samples are needed.

Development and validation of COVID-19 associated candidemia score (CAC-Score) in ICU patients.

BACKGROUND: The development of candidemia is a highly fatal condition in severe COVID-19 infection. OBJECTIVES: This study aimed to develop a candidemia prediction score in COVID-19 patient based on the patient's clinical characteristics, and healthcare-related factors during intensive care units (ICU) follow-up. PATIENTS/METHODS: Severe COVID-19 patients hospitalised in ICU in Ankara City Hospital during the one-year period (August 15, 2020, and August 15, 2021) were included. After univariate analysis, multivariate analysis was applied using variable selection approach to investigate the effects of variables together and to create a score model for candidemia. Statistically significant factors were included in the development process of candida prediction score. RESULTS: Of 1305 COVID-19 ICU patients, 139 had a candidemia episode. According to the final model, four variables, presence of central venous catheter (CVC) (OR 19.07, CI 8.12-44.8, p < .0001), multifocal colonisation (OR 2.28, CI 1.39-3.72, p 0.001), length of ICU stays ≥14 days (OR 3.62, CI 2.42-5.44, p < .0001) and corticosteroids (OR 0.51, CI 0.34-0.76, p 0.0011) were the only statistically significant independent risk factors for candidemia. Score model was demonstrated by a nomogram, and the risk for candidemia was calculated to be high in patients who scored ≥56 points by using the criteria [CVC = 51, multifocal colonisation = 14, prolonged hospitalisation = 23, no steroid use = 12 points]. The AUC of the score is 0.84 (CI 0.81-0.87). CONCLUSION: We developed and validated an easy-to-use clinical prediction score for candidemia in severe COVID-19 infection. In COVID-19 ICU patients, the risk of candidemia is high if one of the other risk factors is present together with CVC.

Comparison of anakinra and tocilizumab in management of severe COVID-19: a retrospective cohort study.

BACKGROUND: Studies regarding effectiveness of anakinra and tocilizumab treatments in coronavirus disease 2019 (COVID-19) have contradictory results. Furthermore, there is scarce comparative data regarding superiority of any agent. To further elucidate any superiority between these two agents, we retrospectively investigated and compared outcomes in hospitalized COVID-19 patients of our inpatient cohort who received anakinra or tocilizumab. METHODS: This study was designed as a single-center, retrospective, cross-sectional cohort study. Hospitalized patients with confirmed diagnosis of COVID-19 who had Brescia-COVID respiratory severity scale score ≥3 and hyperinflammation (defined as elevation of C reactive protein ≥50 g/L or ferritin ≥700 ng/mL) and received anakinra or tocilizumab in addition to standard care were enrolled in the study. Length of hospital stay after initiation of antiinflammatory treatment, need for mechanical ventilation, need for intensive care unit admission, mortality were set as primary outcomes and compared between tocilizumab and anakinra recipients after propensity score matching. RESULTS: One hundred and six patients were placed in each group after propensity score matching. In the anakinra group, relative risk reduction for intensive care unit admission was 50% when compared to the tocilizumab group and the number needed to treat to avert an intensive care unit admission was 3 (95% CI, 2-5). In terms of mortality, a 52% relative risk reduction was observed with anakinra treatment and the number needed to treat to avert an intensive care unit admission was 8 (95% CI, 4-50). Significantly more patients were observed to receive glucocorticoids in the anakinra group. DISCUSSION: Anakinra administration in severe COVID-19 patients was significantly associated with better survival and greater clinical improvement compared to the tocilizumab administration in our study. Increased rate of glucocorticoid use in the anakinra group might have contributed to better outcomes.

Secondary bacterial infections of the respiratory tract in COVID-19 patients.

INTRODUCTION: Secondary Bacterial Infections (SBIs) of the respiratory system are one of the biggest medical concerns in patients undergoing hospitalization with a diagnosis of COVID-19. This study aims to provide relevant data for the initiation of appropriate empirical treatment after examining the etiology and antimicrobial resistance of SBIs in COVID-19 patients under care in the Intensive Care Units (ICUs) in the largest pandemic hospital of our country. METHODOLOGY: Between March 16, 2020 and December 31, 2021, 56,993 COVID patients were hospitalized, of which 7684 were admitted to ICUs. A total of 1513 patients diagnosed with SBIs have been included in this study. During the course of the study, demographic data, clinical course, etiology and antimicrobial resistance data of all patients were collected. RESULTS: The most common causative agents of SBIs were inferred as Acinetobacter baumanii (35.1%), Staphylococcus aureus (15.2%), Klebsiella pneumoniae (12.3%) and Pseudomonas aeruginosa (10.4%). The isolation rates of carbapenem-resistant and colistin-resistant A. baumannii, K. pneumoniae and P. aeruginosa were 83.7%; 42.7%, 79.2%, and 5.6%, 42.7%, 1.7%, respectively. Acinetobacter pittii clustering was seen in one of the ICUs in the hospital. Multidrug resistant 92 (5.4%) Corynebacterium striatum isolates were also found as a causative agent with increasing frequency during the study period. CONCLUSIONS: SBI of the respiratory system is one of the major complications in patients hospitalized with COVID-19. The antimicrobial resistance rates of the isolated bacteria are generally high, which indicates that more accurate use of antibacterial agents is necessary for SBIs in patients hospitalized with COVID-19 diagnosis.

Incidence and risk factors for COVID-19 associated candidemia (CAC) in ICU patients.

BACKGROUND: Critically ill COVID-19 patients have a high risk for the development of candidemia due to being exposed to both well-defined classical risk factors and COVID-19-specific risk factors in ICU. OBJECTIVES: In this study, we investigated the incidence of candidemia in critically COVID-19 patients, and the independent risk factors for candidemia. PATIENTS/METHODS: COVID-19 patients hospitalised in ICU during 1-year period (August 2020 to August 2021) were included. Clinical and laboratory characteristics of all COVID-19 patients, applied treatments, and invasive procedures that may predispose to candidemia were recorded. RESULTS: Of 1229 COVID-19 patients, 63 developed candidemia. Candidemia incidence rate was 4.4 episodes per 1000 ICU days. The most common species was Candida albicans (52.3%). Only 37 patients (58.7%) received antifungal therapy. The presence of central venous catheter (OR 4.7, 95% CI 1.8-12.2, p < .005), multifocal candida colonisation (OR 2.7, 95% CI 1.4-5.2, p < .005), a prolonged ICU stay (≥14 days) (OR 1.9, 95% CI 1.08-3-37, p < .05), the absence of chronic lung disease (OR 0.4, 95% CI 0.1-0.9, p < .05) and the absence of corticosteroid use (OR 0.3, 95% CI 0.14-0.52, p < .0001) were significantly associated with candidemia. CONCLUSIONS: Our study filled the knowledge gap in the literature about the impact of COVID-19-associated risk factors for the development of candidemia. The classical risk factors for candidemia had a significant effect on candidemia, and contrary to expectations, corticosteroids had a protective effect against the development of candidemia. The results of these studies showing interesting effects of corticosteroids in critically ill COVID-19 patients should be confirmed by further studies.

Are angiotensin converting enzyme (ACE1/ACE2) gene variants associated with the clinical severity of COVID-19 pneumonia? A single-center cohort study.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic has been unceasingly ongoing worldwide. Recent bioinformatics analysis and epidemiologic studies have highlighted that the functional polymorphisms on the angiotensin converting enzyme (ACE) gene may have an impact on the clinical progress of COVID-19. In this study, we aimed to determine the impact of the ACE1 gene I/D polymorphism and ACE2 peptidase-2 domain variants on disease severity. METHODS: Hundred patients with confirmed COVID-19 related pneumonia [50 patients with severe disease in intensive care unit (ICU) and 50 patients not in ICU] were compared on the basis of genetic and clinical characteristics. Genomic DNA was purified from peripheral blood lymphocytes with an automated QIA symphony DSP DNA Mini-Kit. The Sanger sequencing analysis was performed. The frequencies of ACE1 gene polymorphism and ACE2 PD variants were compared in patients hospitalized in ICU and those not in ICU. The Statistical Package for Social Sciences version 22.0 was used for statistical analysis. RESULTS: The sequencing analysis of the ACE2 gene exon 1 and 2 revealed none of the polymorphisms investigated or any other variants in the present cohort. The frequencies of the ACE1 ID, DD, and II genotypes were 51%, 31%, and 18%, respectively. The frequency of the D allele was similar between the ICU and non-ICU groups (50.4% versus 49.6%). Older age and the presence of advanced stage radiologic abnormalities on admission were detected as independent predictors of ICU requirement. CONCLUSION: No effect of any ACE1 gene polymorphism on predicting ICU requirement was detected. To the best of our knowledge, this is the first study investigating the impact of ACE gene polymorphisms on clinical severity of COVID-19 in a Turkish cohort.

Development and validation of nomogram to predict severe illness requiring intensive care follow up in hospitalized COVID-19 cases.

BACKGROUND: Early identification of severe COVID-19 patients who will need intensive care unit (ICU) follow-up and providing rapid, aggressive supportive care may reduce mortality and provide optimal use of medical resources. We aimed to develop and validate a nomogram to predict severe COVID-19 cases that would need ICU follow-up based on available and accessible patient values. METHODS: Patients hospitalized with laboratory-confirmed COVID-19 between March 15, 2020, and June 15, 2020, were enrolled in this retrospective study with 35 variables obtained upon admission considered. Univariate and multivariable logistic regression models were constructed to select potential predictive parameters using 1000 bootstrap samples. Afterward, a nomogram was developed with 5 variables selected from multivariable analysis. The nomogram model was evaluated by Area Under the Curve (AUC) and bias-corrected Harrell's C-index with 95% confidence interval, Hosmer-Lemeshow Goodness-of-fit test, and calibration curve analysis. RESULTS: Out of a total of 1022 patients, 686 cases without missing data were used to construct the nomogram. Of the 686, 104 needed ICU follow-up. The final model includes oxygen saturation, CRP, PCT, LDH, troponin as independent factors for the prediction of need for ICU admission. The model has good predictive power with an AUC of 0.93 (0.902-0.950) and a bias-corrected Harrell's C-index of 0.91 (0.899-0.947). Hosmer-Lemeshow test p-value was 0.826 and the model is well-calibrated (p = 0.1703). CONCLUSION: We developed a simple, accessible, easy-to-use nomogram with good distinctive power for severe illness requiring ICU follow-up. Clinicians can easily predict the course of COVID-19 and decide the procedure and facility of further follow-up by using clinical and laboratory values of patients available upon admission.

Does hospitalisation of a patient in the intensive care unit cause anxiety and does restriction of visiting cause depression for the relatives of these patients during COVID-19 pandemic?

OBJECTIVES: During the pandemic, anxiety and depression may occur increasingly in the whole society. The aim of this study was to evaluate the possible cause, incidence and levels of anxiety and depression in the relatives of the patients in the intensive care unit (ICU) in accordance with the patients' SARS-CoV-2 polymerase chain reaction (PCR) result. MATERIALS AND METHOD: The study was prospectively conducted on relatives of patients admitted to tertiary intensive care units during COVID-19 pandemic. Sociodemographic characteristics of the patients and their relatives were recorded. "The Turkish version of the Hospital Anxiety and Depression Scale" was applied twice to the relatives of 120 patients to determine the symptoms of anxiety and depression in accordance with the PCR results of the patients (PCR positive n = 60, PCR negative n = 60). RESULTS: The ratios above cut-off values for anxiety and depression among relatives of the patients were 45.8% and 67.5% for the first questionnaire and 46.7% and 62.5% for the second questionnaire, respectively. The anxiety and depression in the relatives of PCR-positive patients was more frequent than the PCR negative (P < .001 for HADS-A and P = .034 for HADS-D). The prevalence of anxiety and depression was significantly higher in female relatives (P = .046 for HADS-A and P = .009 for HADS-A). There was no significant correlation between HADS and age of the patient or education of the participants. The fact that the patients were hospitalised in the ICU during the pandemic was an independent risk factor for anxiety (AUC = 0.746) while restricted visitation in the ICU was an independent risk factor for depression (AUC = 0.703). CONCLUSION: Positive PCR and female gender were associated with both anxiety and depression while hospitalisation in the ICU due to COVID-19 was an independent risk factor for anxiety and restricted visitation in the ICU is an independent risk factor for depression.

A single center experience of intravenous immunoglobulin treatment in Covid-19.

BACKGROUND: Intravenous immunoglobulins (IVIg) have been used in management of severe Covid-19. Here in this study, we report our single-center experience regarding IVIg treatment in management of severe Covid-19. MATERIALS AND METHOD: Among hospitalized adult Covid-19 patients between April 1 and December 31, 2020, patients with confirmed diagnosis of Covid-19 who had Brescia-COVID respiratory severity scale score ≥ 3, hyperinflammation and received IVIg treatment in addition to standard of care were retrospectively investigated. We grouped IVIg recipients into three according to reasons for IVIg administration: Group 1 patients requiring anti-inflammatory treatment but complicated with secondary infection and/or sepsis , group 2 patients with Covid-19 related complications including progressive disease refractory to other anti-inflammatory agents, myocarditis, adult multisystem inflammatory syndrome, hemophagocytic lymphohystiocytosis like syndrome and group 3 patients with other complications non-specific to Covid-19. Mortality and clinical data was compared among groups. RESULTS: A total of 46 IVIg recipients were enrolled. Group 1 comprised 17 (36.9%), group 2 comprised 18 (39.1%) and group 3 comprised 11 (23.9%) patients. No significant differences in means of age, gender and comorbidities were observed among groups. Mortality was significantly lower in group 3 when compared to group 1 (64.7% vs 18.2%, p = 0.016) and close to significance when compared to group 2 (50% vs 18.2% p = 0.087). CONCLUSIONS: IVIg seemed to be used mostly in severe, refractory and complicated cases in our population. As a rescue agent in severe cases refractory to other anti-inflammatory strategies, 33.7% survival rate was observed with IVIg.

Characteristics of candidemia in COVID-19 patients; increased incidence, earlier occurrence and higher mortality rates compared to non-COVID-19 patients.

Severe COVID-19 patients in ICU are at high risk for candidemia due to exposure to multiple risk factors for candidemia. We aimed to compare the incidence of candidemia in ICU patients with and without COVID-19, and to investigate epidemiologic and clinical characteristics of candidemia patients and risk factors for mortality in candidemia patients. This retrospective study was conducted in patients followed in the ICUs of Ankara City Hospital for 2 years, divided into pre-pandemic and pandemic periods. The incidence (event per 1000 patient-days) and epidemiology of candidemia, clinical and laboratory characteristics of patients were compared in COVID-19 and non-COVID-19 groups. Candidemia incidence was higher in the COVID-19 group (2.16, 95% CI 1.77-2.60) than the non-COVID-19 group (1.06, 95% CI 0.89-0.125) (p < .001). A total of 236 candidemia episodes (105 in COVID-19 patients and 131 in non-COVID-19 patients) were detected during the study periods. COVID-19 cases had a higher rate of corticosteroid use (63.8% vs. 9.9%, p < .001). Epidemiology of candidemia and antifungal susceptibility were similar. Candidemia developed 2 weeks earlier in COVID-19 groups and resulted in higher mortality (92.5% vs. 79.4%, p .005). One-third of candidemia patients died before receiving any antifungal treatment, and this rate was higher in the COVID-19 group. In multivariate logistic regression analysis, corticosteroid use, presence of sepsis and age older than 65 years were independent risk factors for mortality in candidemia patients. Candidemia with high mortality is a more serious problem for COVID-19 patients due to its increased incidence, earlier occurrence and a higher rate of mortality.

Comparing ICU admission rates of mild/moderate COVID-19 patients treated with hydroxychloroquine, favipiravir, and hydroxychloroquine plus favipiravir.

BACKGROUND: In this study, we aimed to compare the intensive care unit (ICU) admission rate of hospitalized mild/moderate COVID-19 patients treated with hydroxychloroquine (HCQ), favipiravir, and HCQ plus favipiravir. METHODS: Single center retrospective designed observational study conducted in Ankara City Hospital. Patients who were hospitalized between March 15, 2020 and June 1, 2020 in COVID-19 inpatient clinics with laboratory confirmed diagnosis of COVID-19 were included in the study. An inverse probability of treatment weighting (IPTW) for multiple treatment groups approach was used to balance the differences in several variables on admission. RESULTS: Among 2441 patients hospitalized with diagnosis of COVID-19 during the study period, 824 were eligible for the analysis. Median age of patients was 42 (18-93 years). Among all, 347 (43.2%) of the patients had mild disease, 470 (56.8%) had pneumonia. Propensity scores ranged from 0.1841 to 0.9381 in the HCQ group, from 0.03643 to 0.29885 in the favipiravir group, and from 0.03542 to 0.56184 in the HCQ plus favipiravir group. After IPTW for multiple treatment groups was applied, all the covariates in the planned propensity score had weighted standardized effect sizes below 10% which were ranged from 0.005 to 0.092. Multivariate analysis of treatment effect (adjusted effect of treatment) was indicated that there is no statistically significant difference between HCQ, favipiravir, and HCQ plus favipiravir treatment. After using combination of SMOTE and Bootstrap resampling approach, we found no statistically significant difference between HCQ and HCQ plus favipiravir groups in terms of ICU admission. However, compared with the HCQ group, ICU admission rate was statistically significantly higher in the favipiravir group. We obtained the similar results after the sensitivity analysis. CONCLUSIONS: HCQ with or without favipiravir treatment is associated with reduced risk of ICU admission compared to favipiravir alone in mild to moderate COVID-19 adult patients.

Efficacy of the delta neutrophil index in predicting 30-day mortality in COVID-19 patients requiring intensive care.

OBJECTIVES: Coronavirus-19 is a rapidly progressing disease that can result in mortality. We aimed to evaluate the efficacy of the delta neutrophil index in predicting mortality in intensive care patients diagnosed with Coronavirus-19. MATERIALS AND METHODS: Patients with a positive polymerase chain reaction test and/or computed tomography findings compatible with the disease were included in the study. The demographic characteristics of the patients, polymerase chain reaction test results, chest computed tomography findings, blood parameters at the time of presentation, 30-day mortality, and the number of days in the intensive care unit were assessed. RESULTS: Of the 388 patients receiving intensive care, 220 (56.7%) were men and 168 (43.3%) were women. The mean age was 70 ± 15 years. The evaluation of mortality, 264 (68%) of the patients survived and 124 (32%) died. The delta neutrophil index, neutrophil lymphocyte ratio, lactate, interleukin-6 and C-reactive protein values were statistically significantly higher and the lymphocyte value was significantly lower in the mortality group (P = .003, .034, .000, .002, .000 and .024, respectively). In the receiver operating characteristic curve analysis, the area under the curve values of the delta neutrophil index, lymphocyte, neutrophil lymphocyte ratio, lactate, interleukin-6 and C-reactive protein levels in predicting mortality were 0.718, 0.416, 0.628, 0.585, 0.701 and 0.684, respectively. CONCLUSION: We consider that the delta neutrophil index can be used as an effective prognostic parameter to show intensive care mortality in patients with Coronavirus-19.

COVID-19 experience of the major pandemic response center in the capital: results of the pandemic's first month in Turkey

Background/aim: The aim of this study is to evaluate the epidemiological and clinical characteristics and parameters that determined the clinical course and prognosis of the COVID-19 patients admitted to Ankara City Hospital during the first month of the pandemic in Turkey. Materials and methods: SARS-CoV-2 PCR positive patients who were hospitalized between March 10 and April 10, 2020 were included. Results: Among 222 patients, mean age was higher in severe acute respiratory illness (SARI)/critical disease group (P < 0.001). Median time from illness onset to admission and presence of comorbidity, especially coronary artery disease and chronic obstructive pulmonary disease, were significantly higher in the SARI/critical disease group (P < 0.05). Cough and fever were the most common symptoms, while anosmia and loss of taste were observed in 8.6% and 7.7% patients, respectively. The mortality rate was 5.4%. A high neutrophil/lymphocyte ratio; low lymphocyte, monocyte, and platelet count; elevated liver enzymes; low GFR; and high levels of muscle enzymes, ferritin, and IL-6 on admission were found to be associated with SARI/critical disease (P < 0.05). Bilateral ground-glass opacity and patchy infiltration were more frequently seen in the SARI/critical disease group (P < 0.001). Patients older than 65 years had an 8-fold increased risk for development of SARI/critical disease. Conclusion: This cohort study regarding COVID-19 cases in Turkey reveals that older age, presence of comorbidity, bilateral infiltration on CT, high neutrophil/lymphocyte ratio, low monocyte and platelet count, elevated liver enzymes, low GFR, high levels of muscle enzymes, and high levels of ferritin and IL-6 on admission are predictors of SARI and severe disease.