Characteristics and outcomes of carbapenemase harbouring carbapenem-resistant Klebsiella spp. bloodstream infections: a multicentre prospective cohort study in an OXA-48 endemic setting.

A prospective, multicentre observational cohort study of carbapenem-resistant Klebsiella spp. (CRK) bloodstream infections was conducted in Turkey from June 2018 to June 2019. One hundred eighty-seven patients were recruited. Single OXA-48-like carbapenemases predominated (75%), followed by OXA-48-like/NDM coproducers (16%). OXA-232 constituted 31% of all OXA-48-like carbapenemases and was mainly carried on ST2096. Thirty-day mortality was 44% overall and 51% for ST2096. In the multivariate cox regression analysis, SOFA score and immunosuppression were significant predictors of 30-day mortality and ST2096 had a non-significant effect. All OXA-48-like producers remained susceptible to ceftazidime-avibactam.

A model integrating Killer Immunoglobulin-like Receptor (KIR) haplotypes for risk prediction of COVID-19 clinical disease severity.

Associations between inherited Killer Immunoglobulin-like Receptor (KIR) genotypes and the severity of multiple RNA virus infections have been reported. This prospective study was initiated to investigate if such an association exists for COVID-19. In this cohort study performed at Ankara University, 132 COVID-19 patients (56 asymptomatic, 51 mild-intermediate, and 25 patients with severe disease) were genotyped for KIR and ligands. Ankara University Donor Registry (n:449) KIR data was used for comparison. Clinical parameters (age, gender, comorbidities, blood group antigens, inflammation biomarkers) and KIR genotypes across cohorts of asymptomatic, mild-intermediate, or severe disease were compared to construct a risk prediction model based on multivariate binary logistic regression analysis with backward elimination method. Age, blood group, number of comorbidities, CRP, D-dimer, and telomeric and centromeric KIR genotypes (tAA, tAB1, and cAB1) along with their cognate ligands were found to differ between cohorts. Two prediction models were constructed; both included age, number of comorbidities, and blood group. Inclusion of the KIR genotypes in the second prediction model exp (-3.52 + 1.56 age group - 2.74 blood group (type A vs others) + 1.26 number of comorbidities - 2.46 tAB1 with ligand + 3.17 tAA with ligand) increased the predictive performance with a 92.9% correct classification for asymptomatic and 76% for severe cases (AUC: 0.93; P < 0.0001, 95% CI 0.88, 0.99). This novel risk model, consisting of KIR genotypes with their cognate ligands, and clinical parameters but excluding earlier published inflammation-related biomarkers allow for the prediction of the severity of COVID-19 infection prior to the onset of infection. This study is listed in the National COVID-19 clinical research studies database.

Antibody response to two doses of inactivated SARS-CoV-2 vaccine (CoronaVac) in kidney transplant recipients.

BACKGROUND: Coronavirus Disease-19 (COVID-19) has high mortality in kidney transplant recipients (KTR), and vaccination against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is vital for this population. Although the humoral response to messenger RNA vaccines was shown to be impaired in KTR, there is a lack of data regarding the antibody response to inactivated vaccines. We investigated the antibody response to two consequent doses of the inactivated SARS-CoV-2 vaccine (CoronaVac; Sinovac Biotech, China). METHODS: A total of 118 patients from two centers were included. The levels of anti-SARS-CoV-2 immunoglobulin-G antibodies against the nucleocapsid and spike antigens were determined with enzyme immunoassay (DIA.PRO; Milano, Italy) before the vaccine and one month after the second dose of the vaccine. Thirty-three patients were excluded due to antibody positivity in the serum samples obtained before vaccination. RESULTS: Eighty-five patients, 47 of whom were female, with a mean age of 46 ± 12, were included in the statistical analysis. The maintenance immunosuppressive therapy comprised tacrolimus (88.2%), mycophenolate (63.6%), and low-dose steroids (95.3%) in the majority of the patients. After a median of 31 days following the second dose of the vaccine, only 16 (18.8%) patients developed an antibody response. The median (IQR) antibody level was 52.5 IU/ml (21.5-96). Age (48 vs. 38, p = .005) and serum creatinine levels (1.14 vs. 0.91, p = .04) were higher in non-responders and were also found to be independently associated with the antibody response (odds ratio (OR): 0.93, p = 0.012 and 0.15, p = 0.045, respectively) in multivariate analysis. CONCLUSION: In this study, we found the antibody response to the inactivated vaccine to be considerably low (18.8%) in KTR. Increased age and impaired renal function were associated with worse antibody response. Based on the knowledge that mRNA vaccines yield better humoral responses, this special population might be considered for additional doses of mRNA vaccination.

Is pulse oximeter a reliable tool for non-critically ill patients with COVID-19?

INTRODUCTION: Guidelines recommend using a pulse oximeter rather than arterial blood gas (ABG) for COVID-19 patients. However, significant differences can be observed between oxygen saturation measured by pulse oximetry (SpO2 ) and arterial oxygen saturation (SaO2 ) in some clinical conditions. We aimed to assess the reliability of the pulse oximeter in patients with COVID-19. METHODS: We retrospectively reviewed ABG analyses and SpO2 levels measured simultaneously with ABG in patients hospitalised in COVID-19 wards. RESULTS: We categorised total 117 patients into two groups, in whom the difference between SpO2 and SaO2 was ≤4% (acceptable difference) and >4% (large difference). A large difference group exhibited higher neutrophil count, C-reactive protein, ferritin, fibrinogen, D-dimer and lower lymphocyte count. Multivariate analyses revealed that increased fibrinogen, increased ferritin and decreased lymphocyte count were independent risk factors for a large difference between SpO2 and SaO2 . The total study group demonstrated the negative bias of 4.02% with the limits of agreement of -9.22% to 1.17%. The bias became significantly higher in patients with higher ferritin, fibrinogen levels and lower lymphocyte count. CONCLUSION: Pulse oximeters may not be sufficient to assess actual oxygen saturation, especially in COVID-19 patients with high ferritin and fibrinogen levels and low lymphocyte count with low SpO2 measurements.

Clinical characteristics of lung cancer patients with COVID-19: Retrospective case series.

INTRODUCTION: One of the patient groups adversely affected during the COVID19 pandemic is those suffering with cancer. The aim of this study was to evaluate the clinical characteristics and outcomes of lung cancer (LC) patients with COVID-19. MATERIALS AND METHODS: Three thousand seven-hundred and fifty hospitalized patients with a presumptive diagnosis of COVID-19 in a tertiary referral hospital between March 2020-February 2021 were retrospectively evaluated. Among them, 36 hospitalized COVID-19 patients with a history of primary LC were included in the study. Univariate and multivariate analyses were carried out to assess the risk factors associated with severe disease. RESULT: Of the 36 patients included in the study, 28 (77%) were males and 8 (23%) were females. Median age was 67 years (min-max: 53-81 years). Six patients (17%) had a diagnosis of small cell LC, whereas 30 patients (83%) had a diagnosis of non-small cell LC. The most common symptoms were fever (n= 28, 77%), coughing and myalgia (n= 21, 58%) and dyspnea (n= 18, 50%). The most common radiological finding was ground glass opacity (GGO) (n= 30), of which 13 was bilateral and 17 was unilateral in distribution. Nearly 30% (n= 11) of LC patients with COVID-19 developed severe disease, 5% (n= 2) of the 36 patients were admitted to intensive care unit and all of these patients eventually expired. LC patients with COVID-19 and patchy consolidation on computed tomography of thorax (Th CT) on admission had a higher risk of developing severe disease in univariate (HR 2.41, 95%CI: 1.4- 4.4, p= 0.04) and multivariate Cox regression analysis (HR 0.48, 95%CI: 0.24-0.97, p= 0.03). CONCLUSIONS: Clinical characteristics, laboratory and radiographic findings were similar in LC patients with COVID-19 when compared with the general population, LC patients have a higher mortality rate than the general population, with a 5% mortality rate in our series. Our findings suggest that LC may be a risk factor associated with the prognosis of COVID-19 patients.

An unusual course of SARS-CoV-2 infection: Challenging diagnosis of Guillain-Barré Syndrome.

COVID-19, caused by severe acute respiratory syndrome coronavirus-2, typically presents with respiratory symptoms and fever, but still a variety of clinical presentations have been reported. In this study, it was aimed to report a case of COVID-19 with an atypical presentation and an atypical course. As well, the recovery phase was complicated with GBS and consequently cytomegalovirus infection. It should be kept in mind that patients with COVID-19 severe disease need to be followed for neurological and other complications which may arise during the course of critical illness.

Pattern of systemic antibiotic use and potential drug interactions: Evaluations through a point prevalence study in Ankara University Hospitals.

Background/aim: Most of the hospitalized patients are on a number of drugs for comorbidities and/or to prevent nosocomial infections. This necessitates a careful consideration of drug interactions not only to avoid possible toxicities but also to reach the highest efficiency with drug treatment. We aimed to investigate drug interactions related to systemic antibiotic use and compare three different databases to check for drug interactions while characterizing the main differences between medical and surgical departments. Materials and methods: This point prevalence study covered data on 927 orders for patients hospitalized between June 3 and 10, 2018 in Ankara University Hospitals. Systemic antibiotic use and related drug interactions were documented using UptoDate, Drugs, and Medscape and comparisons between the departments of medical and surgical sciences were made. Results: The number of orders, or the number of drugs or antibiotics per order were not different between the medical and surgical sciences departments. A total of 1335 antibiotic-related drug interactions of all levels were reported by one, two, or all three databases. UptoDate reported all common and major interactions. Pantoprazole was the most commonly prescribed drug and appeared in 63% of all orders. Among 75 different molecules, ceftriaxone and meropenem were the two most prescribed antibiotics by the surgical and medical departments, respectively. Conclusion: A dramatic variance existed amongst antibiotics prescribed by different departments. This indicated the requirement for a centralized role of an infectious diseases specialist. Especially for the hospitalized patient, prophylactic coverage with at least one antibiotic brought about a number of drug interactions. A precise evaluation of orders in terms of drug interactions by a clinical pharmacist (currently none on duty) will reduce possible drug-related hazards.

Evaluation of extensively drug-resistant gram-negative bacteremia among solid-organ transplant recipients: a multicenter study

Background/aim: The aim of this study is to evaluate the distribution, sources, clinical features, and mortality rates of bacteremia due to evaluation of extensively drug-resistant (XDR) gram negative among solid-organ transplant (SOT) recipients. Materials and methods: A retrospective study of SOT recipients with bacteremia due to XDR gram-negative pathogens in 11 centers between 2016 and 2018 was conducted. Patients' records were evaluated. Results: Of 171 bacteremia that occurred in 164 SOT recipients, 93 (56.7%) were liver, 46 (28%) kidney, 14 (8.5%) heart, and 11 (6.7%) lung recipients. Bacteremia episodes were recorded in the first year in 63.7% of the patients (n = 109), early-onset bacteremia was recorded in 45% (n = 77) of the episodes. In multivariate analysis, catheter-associated bacteremia was an independent risk factor for 7-day mortality (p = 0.037), and early-onset bacteremia was found as an independent risk factor for 30-day mortality (p = 0.017). Conclusion: Difficult-to-treat infections due to XDR bacteria in SOT recipients shadow the success of transplantation. Central venous catheters seem to be the main risk factor. Judicious use of medical devices is of pivotal importance.

The Efficacy of Glecaprevir/Pibrentasvir in Chronic Hepatitis C Patients and the Impact of the COVID-19 Pandemic: Multicenter Real-Life Data.

Objective: This study aimed to demonstrate the real-life efficacy and safety of glecaprevir /pibrentasvir in the treatment of chronic hepatitis C, as well as to identify the problems caused by the COVID-19 pandemic in the follow-up and treatment of patients. Materials and Methods: The study was conducted retrospectively with the participation of researchers from universities or training and research hospitals. It included patients with chronic hepatitis C who were over 18 years of age, treatment-naïve or treatment-experienced, had detectable HCV RNA and were receiving glecaprevir/pibrentasvir treatment. Results: Only 188 of the 385 patients who participated in the study came to the follow-up visit 12 weeks after treatment, and all of them had a sustained virological response. It was thought that a significant portion of the 177 patients who did not come to the follow-up visit at 12 weeks after treatment refrained from coming to the hospital due to the COVID-19 pandemic. None of the patients who attended the follow-up visits required treatment discontinuation due to adverse events. Conclusion: Glecaprevir/pibrentasvir is a highly effective and relatively safe drug in the treatment of chronic hepatitis C. The COVID-19 pandemic has negatively affected the follow-up and treatment processes of patients. New measures are needed for the follow-up and treatment of patients with chronic hepatitis C during pandemics.

Recovery from Respiratory Failure in Patients with Coronavirus Disease 2019.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) can cause hypoxic respiratory failure; long-term oxygen therapy (LTOT) duration is unknown. MATERIAL AND METHODS: The aim was to investigate which patients would need LTOT after COVID-19 pneumonia. This single-center, prospective study was conducted at the Ankara University Faculty of Medicine, Department of Chest Diseases, between May 2021 and December 2021. The 70 patients hospitalized for COVID-19 pneumonia and discharged with LTOT due to hypoxemic respiratory failure were included. Patients were divided into 2 groups as group I (LTOT requirement <3 months) and group II (LTOT requirement continued ≥3 months). RESULTS: The mean age was 64.4 ± 13.5 years, and 44 (62.9%) of them were male. The most frequently encountered comorbidities were cardiovascular disease (57.1%) and lung disease (22.9%). While PaO2 levels increased in both groups during the follow-up period, this increment was significantly higher in group I (PaO2: 66.6 ± 9.9 mm Hg, P < .001). The factors affecting the LTOT requirement were evaluated using binary logistic regression. On multivariate analyses of lymphocytes, ferritin, C-reactive protein, PaO2, SaO2, subpleural reticulation, and number of lobes affected (≥3 lobes), the SaO2 level and presence of subpleural reticulation were significantly different between the 2 groups [odds ratio (OR) (95% CI): 0.853 (0.749-0.971), P = .016] and [OR (95% CI): 0.171 (0.042-0.733), P = .017], respectively. CONCLUSION: A significant proportion of patients who develop respiratory failure due to COVID-19 recover within the first 3 months. Factors determining the LTOT requirement for more than 3 months were SaO2 and the presence of subpleural reticulation.

Dark Side of the COVID-19 Pandemic; 'Long COVID'.

Objective: Besides its morbidity and mortality all over the world, SARS-CoV-2 infection maintains its importance with prolonged symptoms after acute disease. The post-infectious period including a heterogeneous group of symptoms is named 'long COVID'. This study aimed to describe persisting symptoms three months after COVID-19 and risk factors associated with 'long COVID'. Materials and Methods: This cross-sectional retrospective study included COVID-19 patients diagnosed with SARS-CoV-2 PCR positivity in the first 18 months of the COVID-19 pandemic, between March 2020 and September 2021. We conducted a survey in 2022 to inquire about the participants' symptoms that lasted three months or more after their own COVID-19 period. All patients were employees of one of the biggest national banks in Turkey. Participants answered a total of 31 questions over the phone. The presence of one or more symptoms persisting ≥3 months was defined as 'long COVID'. The risk factors associated with 'long COVID' were determined. Results: A total of 1301 patients were included in our study. The median age of patients was 40 (22-57), and 558 (42.9%) were women. 257 (19.8%) patients had 'long COVID' symptoms. The most prevalent symptoms were myalgia (14.3%), arthralgia (14.1%), and back pain (13.8%). Female gender ( p=0.000, OR=2.19 [95% CI=1.655-2.904]) and diabetes mellitus ( p=0.016, OR=2.43 [95% CI=1.177-5.017]) were found as independent risk factors for 'long COVID' by multivariant logistic regression analysis. Conclusion: Female gender and diabetes mellitus are risk factors for 'long COVID'. Detecting patients with a high risk for developing 'long COVID' is crucial for their management during the COVID and post-COVID periods.

Clinical evaluation of DIAGNOVIR SARS-CoV-2 ultra-rapid antigen test performance compared to PCR-based testing.

Coronavirus Disease-19 (COVID-19) is a highly contagious infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The development of rapid antigen tests has contributed to easing the burden on healthcare and lifting restrictions by detecting infected individuals to help prevent further transmission of the virus. We developed a state-of-art rapid antigen testing system, named DIAGNOVIR, based on immune-fluorescence analysis, which can process and give the results in a minute. In our study, we assessed the performance of the DIAGNOVIR and compared the results with those of the qRT-PCR test. Our results demonstrated that the sensitivity and specificity of the DIAGNOVIR were 94% and 99.2%, respectively, with a 100% sensitivity and 96.97% specificity, among asymptomatic patients. In addition, DIAGNOVIR can detect SARS­CoV­2 with 100% sensitivity up to 5 days after symptom onset. We observed that the DIAGNOVIR Rapid Antigen Test's limit of detection (LoD) was not significantly affected by the SARS­CoV­2 variants including Wuhan, alpha (B1.1.7), beta (B.1.351), delta (B.1.617.2) and omicron (B.1.1.529) variants, and LoD was calculated as 8 × 102, 6.81 × 101.5, 3.2 × 101.5, 1 × 103, and 1 × 103.5 TCID50/mL, respectively. Our results indicated that DIAGNOVIR can detect all SARS-CoV-2 variants in just seconds with higher sensitivity and specificity lower testing costs and decreased turnover time.

BNT162b2 or CoronaVac as the Third Dose against Omicron: Neutralizing Antibody Responses among Transplant Recipients Who Had Received Two Doses of CoronaVac.

We evaluated neutralizing antibodies against the Omicron variant and Anti-Spike IgG response in solid organ (SOT) or hematopoietic stem cell (HSTC) recipients after a third dose of BNT162b2 (BNT) or CoronaVac (CV) following two doses of CV. In total, 95 participants underwent SOT (n = 62; 44 liver, 18 kidney) or HSCT (n = 27; 5 allogeneic, 22 autologous) were included from five centers in Turkey. The median time between third doses and serum sampling was 154 days (range between 15 to 381). The vaccine-induced antibody responses of both neutralizing antibodies and Anti-Spike IgGs were assessed by plaque neutralizing assay and immunoassay, respectively. Neutralizing antibody and Anti-Spike IgG levels were significantly higher in transplant patients receiving BNT compared to those receiving CV (Geometric mean (GMT):26.76 vs. 10.89; p = 0.03 and 2116 Au/mL vs. 172.1 Au/mL; p < 0.001). Solid organ transplantation recipients, particularly liver transplant recipients, showed lower antibody levels than HSCT recipients. Thus, among HSCT recipients, the GMT after BNT was 91.29 and it was 15.81 in the SOT group (p < 0.001). In SOT, antibody levels after BNT in kidney transplantation recipients were significantly higher than those in liver transplantation recipients (GMT: 48.32 vs. 11.72) (p < 0.001). Moreover, the neutralizing antibody levels after CV were very low (GMT: 10.81) in kidney transplantation recipients and below the detection limit (<10) in liver transplant recipients. This study highlights the superiority of BNT responses against Omicron as a third dose among transplant recipients after two doses of CV. The lack of neutralizing antibodies against Omicron after CV in liver transplant recipients should be taken into consideration, particularly in countries where inactivated vaccines are available in addition to mRNA vaccines.

Higher rates of cefiderocol resistance among NDM producing Klebsiella bloodstream isolates applying EUCAST over CLSI breakpoints.

BACKGROUND: Cefiderocol is generally active against carbapenem-resistant Klebsiella spp. (CRK) with higher MICs against metallo-beta-lactamase producers. There is a variation in cefiderocol interpretive criteria determined by EUCAST and CLSI. Our objective was to test CRK isolates against cefiderocol and compare cefiderocol susceptibilities using EUCAST and CLSI interpretive criteria. METHODS: A unique collection (n = 254) of mainly OXA-48-like- or NDM-producing CRK bloodstream isolates were tested against cefiderocol with disc diffusion (Mast Diagnostics, UK). Beta-lactam resistance genes and multilocus sequence types were identified using bioinformatics analyses on complete bacterial genomes. RESULTS: Median cefiderocol inhibition zone diameter was 24 mm (interquartile range [IQR] 24-26 mm) for all isolates and 18 mm (IQR 15-21 mm) for NDM producers. We observed significant variability between cefiderocol susceptibilities using EUCAST and CLSI breakpoints, such that 26% and 2% of all isolates, and 81% and 12% of the NDM producers were resistant to cefiderocol using EUCAST and CLSI interpretive criteria, respectively. CONCLUSIONS: Cefiderocol resistance rates among NDM producers are high using EUCAST criteria. Breakpoint variability may have significant implications on patient outcomes. Until more clinical outcome data are available, we suggest using EUCAST interpretive criteria for cefiderocol susceptibility testing.

Cytomegalovirus infection in patients with glomerular diseases treated with cyclophosphamide: a single-center prospective study.

PURPOSE: Cytomegalovirus infection is an important complication in immunocompromised patients. As few studies have shown that cyclophosphamide treatment is a risk factor for cytomegalovirus infection in patients with glomerulonephritis, we aimed to describe the frequency and risk factors of cytomegalovirus infection in glomerulonephritis patients treated with cyclophosphamide. METHODS: We prospectively recruited 43 cytomegalovirus seropositive patients with glomerulonephritis treated with cyclophosphamide. We screened all patients for viral DNA monthly during treatment. Patients were compared for age, sex, glomerular pathology, renal function and clinical status regarding development of cytomegalovirus infection before and after the treatment. RESULTS: Cytomegalovirus infection was detected in 10 (23.3%) patients, most commonly within the first 2 months of cyclophosphamide treatment. All patients recovered without any cytomegalovirus-related complications. Patients with cytomegalovirus infection had higher serum creatinine (4.2 ± 3.2 vs. 1.9 ± 1.8 mg/dl, p = 0.006) and lower estimated glomerular filtration rate (29 ± 11 vs. 65 ± 8 ml/min/1.73 m2, p = 0.016) at diagnosis compared with cytomegalovirus infection non-occurred patients. In addition, number of patients presented with rapidly progressive glomerulonephritis were higher in cytomegalovirus infection group (80.0% vs. 27.3%, p = 0.007). Moreover, cytomegalovirus infection was associated with prolonged hospital stay (54 ± 7 vs. 29 ± 6 days, p = 0.027). CONCLUSION: Cytomegalovirus infection is a common complication in glomerulonephritis patients treated with cyclophosphamide in this prospective study. Routine monitoring and prophylaxis should be considered for these high-risk patients.

SARS-CoV-2 Infection may be Prevented with Cytochrome Inhibitors: Cobicistat and Ritonavir.

Objective: Highly contagious character of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the lack of specific drugs have led many scientists worldwide to re-evaluate the molecules currently in use for other diseases/viruses. Thus, high-throughput screening with docking studies has the rationale to identify potential therapeutics from existing drug molecules. Conflicting results of the studies, including SARS-CoV-2 and human immunodeficiency virus (HIV) coinfected population, suggested a possible preventive effect of antiretroviral regimens they have been receiving. Materials and Methods: Interactions between the widely used antiretroviral molecules, in particular; abacavir, cobicistat, dolutegravir, elvitegravir, emtricitabine, lamivudine, raltegravir, and tenofovir, and the main proteins on SARS-CoV-2 that may be targeted for SARS-CoV-2 infection were analyzed using molecular docking studies. Results: Analysis of the compounds strikingly revealed that not the antiretroviral drugs but cobicistat and ritonavir, the inhibitors of cytochrome P450, had strong interactions with the main protease active site and RNA polymerase on SARS-CoV-2, as well as the active site of angiotensin-converting-enzyme 2, the protein that enables the entry of the virus into human cells. Conclusion: Our results suggest cobicistat and ritonavir may be used to prevent SARS-CoV-2 infection.

Factors associated with progression of depression, anxiety, and stress-related symptoms in outpatients and inpatients with COVID-19: A longitudinal study.

It is known that there is an increase in the frequency of psychiatric disturbances in the acute and post-illness phase of coronavirus disease (COVID-19). Comorbid psychiatric symptoms complicate the management of patients and negatively affect the prognosis, but there is no clear evidence of their progress. We aimed to determine psychiatric comorbidity in inpatients and outpatients with COVID-19 and recognize the factors that predict psychiatric comorbidity. For this purpose, we evaluated patients on the first admission and after 4 weeks. We investigated psychiatric symptoms in outpatients (n = 106) and inpatients (n = 128) diagnosed with COVID-19. In the first 7 days after diagnosis (first phase), sociodemographic and clinic data were collected, a symptom checklist was constructed, and the Hospital Anxiety and Depression Scale (HADS) and the Severity of Acute Stress Symptoms Scale (SASSS) were applied. After 30-35 days following the diagnosis, the SASSS and the HADS were repeated. In the first phase, the frequency of depression and anxiety were 55% and 20% in inpatients, and 39% and 18% in outpatients, respectively. In the second phase, depression scores are significantly decreased in both groups whereas anxiety scores were decreased only in inpatients. The frequencies of patients reporting sleep and attention problems, irritability, and suicide ideas decreased after 1 month. Patients with loss of smell and taste exhibit higher anxiety and depression scores in both stages. Our results revealed that the rate of psychiatric symptoms in COVID-19 patients improves within 1 month. Inpatients have a more significant decrease in both depression and anxiety frequency than do outpatients. The main factor affecting anxiety and depression was the treatment modality. Considering that all patients who were hospitalized were discharged at the end of the first month, this difference may be due to the elimination of the stress caused by hospitalization.

Acute severe hepatitis outbreak in children: A perfect storm. What do we know, and what questions remain?

During the first half of 2022, the World Health Organization reported an outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children, following initial alerts from the United Kingdom (UK) where a cluster of cases was first observed in previously well children aged <6 years. Sporadic cases were then reported across Europe and worldwide, although in most countries incidence did not increase above the expected baseline. There were no consistent epidemiological links between cases, and microbiological investigations ruled out known infectious causes of hepatitis. In this review, we explore the evidence for the role of viral infection, superimposed on a specific host genetic background, as a trigger for liver pathology. This hypothesis is based on a high prevalence of Human Adenovirus (HAdV) 41F in affected children, together with metagenomic evidence of adeno-associated virus (Adeno-associated viruses)-2, which is a putative trigger for an immune-mediated liver injury. Roles for superantigen-mediated pathology have also been explored, with a focus on the potential contribution of SARS-CoV-2 infection. Affected children also had a high frequency of the MHC allele HLA-DRB1*04:01, supporting an immunological predisposition, and may have been vulnerable to viral coinfections due to disruption in normal patterns of exposure and immunity as a result of population lockdowns during the COVID-19 pandemic. We discuss areas of ongoing uncertainty, and highlight the need for ongoing scrutiny to inform clinical and public health interventions for this outbreak and for others that may evolve in future.