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.

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.

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.

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.

An indirect effect of COVID-19 pandemic: Increased pediatric perforated appendicitis rate due to delayed admission.

Objectives: Appendicitis is a common surgical emergency among children. The coronavirus pandemic affected the system of hospitals more than any other field, and great amount of people were concerned about visiting the hospitals for any reason. In this study, it was aimed to evaluate the profile of appendicitis by emphasizing perforated and acute appendicitis in the pandemic period and to compare the rates with previous three years. Material and Methods: Charts of the children who underwent laparoscopic appendectomy due to appendicitis between March 11-September 30 between 2017-2020 were retrospectively analyzed in terms of demographic data, duration of symptoms, duration between hospital admission and surgery, radiologic imaging and perioperative outcomes. Results: This study includes 467 children who underwent laparoscopic appendectomy. There were 97 procedures in 2020, 111 in 2019, 146 in 2018 and 113 in 2017. Multiple comparison tests revealed that age did not show difference; but onset of symptoms in admission (p= 0.004), hospitalization time before surgery (p <0.001), total hospitalization time (p <0.001) showed statistically significant difference between years. Pairwise comparisons showed that these parameters were increased in 2020 compared to other years. Perforated appendicitis rate was significantly increased in 2020 when compared to previous years. Conclusion: Although there is no direct relation between appendicitis and COVID-19 infection in the current knowledge, perforated appendicitis was found to be increased in children during the COVID pandemic. Reason of the higher rate of perforated appendicitis may be multifactorial; however, the pandemic appears to have a role in increased morbidity in children with appendicitis indirectly due to delay of hospital admissions.

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.

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.

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.

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.

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.

Heart transplant recipient survivor from COVID-19: The first case of Turkey.

Any highly infectious and rapidly spreading disease is a primary concern for immunocompromised solid organ transplant recipients. The number of data about the spectrum of clinical illness, the treatment modalities, and the outcomes of COVID-19 in this vulnerable population is scant and still remains empirical. Herein, we report the first COVID-19 case of a heart transplant recipient in Turkey who presented with fever, postnasal discharge, and myalgias for two days. The possibility of lung involvement was ruled out by thoracic computed tomography. Despite stable vital signs, we reduced the intensity of immunosuppressive therapy and maintained home self-isolation promptly. We also commenced a five-day course of hydroxychloroquine 200 mg q12h initially. After confirmation of real-time reverse-transcriptase-polymerasechain- reaction testing of the nasopharyngeal swab positive for COVID-19, the patient was hospitalized. After a loading dose of favipiravir 1,600 mg b.i.d., the patient received a five-day course of favipiravir 600 mg q12h. He was discharged with cure after 23 days of hospital isolation and treatment. In conclusion, treatment process can be affected by the daily electrocardiography, hand-held portable echocardiography, myocardial injury markers, and pulse oximeter for selfmonitoring in the follow-up of previous heart transplant recipients suffering from COVID-19. The lack of treatment protocols in the solid organ transplant recipients with COVID-19 infection and the controversies about the protective effect of immunosuppression invite a global and update discussion.