Positive Antigen Research Articles

Association between the Expression Patterns of Hepatitis B Surface Antigen and Hepatitis B Core Antigen with Clinicopathological Parameters and Antiviral Therapy in Liver Biopsies Obtained from Chronically Infected Hepatitis B Positive Omani Patients

Background: Hepatitis B virus (HBV) infection is considered a major global health problem. The main objectives of the current study is to determine the patterns of expression of the hepatitis B surface antigen (HBsAg) and HBV core antigen (HBcAg) in liver tissue samples obtained from hepatitis B virus-infected Omani patients and to associate between the pattern of the expression of HBsAg and HBcAg with the other clinical parameters and anti-viral therapy. Methods : The expression patterns of HBsAg and HBV core antigen HBcAg were determined by immunohistochemistry (IHC), in 58 formalin-fixed paraffin-embedded liver tissue biopsies obtained from chronic hepatitis B Omani patients. The association between positivity for HBV antigens with gender, age group, histological appearances, and antiviral therapy was determined. Results: IHC-positive staining of HBsAg was demonstrated in 28 patients (48.3%) patients, of whom 4 (6.9%) also showed HBcAg expression. The expression pattern of HBsAg was predominantly cytoplasmic and was seen in 25 (89.3%) of patients, whereas expression of HBcAg was nuclear in 3 (75%) of patients. HBsAg and HBcAg IHC positivity were more common among males than females and among those aged 39–58 years (P = 0.130 and 0.569, respectively). The presence of lymphocytic infiltration in the majority of liver biopsies examined in the present study indicates that the liver damage could be attributed to immunologically mediated events, especially because HBV is a non-cytopathogenic virus. No significant statistical association was found between positivity for HBsAg/HBcAg by IHC and antiviral treatment. Conclusions: Determination of the expression patterns of HBV antigens in liver biopsies obtained from chronic hepatitis B Omani patients and the association between these expression patterns with other clinical histopathological parameters and anti-viral therapy, will contribute greatly to a better understanding of the pathogenesis of HBV in this unique cohort group of infected individuals.

Acurateţea testelor neinvazive la copii pentru precizia diagnosticului de infecţie cu Helicobacter pylori

Helicobacter pylori infection is aquired in childhood, af­fects more than half of the world population and is as­so­cia­ted with chronic gastritis. The majority of the in­fec­ted children are asymptomatic. The most frequently used tests for the detection of Helicobacter pylori are ¹³C urea breath test and stool antigen test. Objective. In this stu­dy, we evaluated the accuracy and the utility of the ¹³C urea breath test and Helicobacter pylori stool antigen test in young children. We performed a prospective ob­ser­­va­­tio­nal study of 52 symptomatic children, mostly with uninvestigated dyspepsia suggestive for an or­ga­nic di­sease. The ¹³C urea breath test was used as gold stan­dard method for the diagnosis of Helicobacter py­lo­ri in­fec­tion. Forty-two of the 52 studied children had a po­si­tive ¹³C urea breath test, respectively 21 of 42 Heli­co­bac­ter pylori infected children presented a positive rapid stool antigen test for Helicobacter pylori. Our study did not reveal a strong agreement between Helicobacter py­lo­ri rapid stool antigen test and ¹³C urea breath test. The management of Helicobacter pylori infection in chil­dren remains a problem in clinical practice, therefore test­ing for Helicobacter pylori infection has become a very important part of the diagnostic process. Another mul­ti­cen­ter study from our country is recommended.

Prevalence of bovine viral diarrhea virus from Korean native cattle farms in Jeju

Bovine viral diarrhea virus (BVDV) is an RNA virus belonging to Pestivirus in the family Flaviviridae. BVDV has economic significance for the livestock industry because of its association with acute disease, fetal loss, and birth of persistently infected (PI) animals. This study aimed to investigate the BVDV infection rates in Korean native cattle farms in Jeju for further planning of a BVDV control program in the Jeju Province. BVDV antibodies and antigens were tested in 15,842 sera collected from 302 Korean native cattle herds between January 2014 and June 2017 using enzyme-linked immunosorbent assay (ELISA). Viral antigen was detected by reverse transcription-polymerase chain reaction from 60 sera that were antigen ELISA-positive. BVDV antibodies were found in 90.7% (274/302) herds and 61.1% (9,678/15,842) cows. BVDV antigens were found in 13.2% (40/302) herds and 0.4% (61/15,842) cows. The oldest animal group (> 8 years) exhibited the highest sero-positive rates (91%), while the youngest animal group (< 1 years) had the highest antigen positivity rates (0.52%). Of the 60 antigen-positive sera, BVDV types 1 and 2 were found in 36 and 12 sera, respectively. Additionally, six animals were considered to be PI as BVDV was continually detected in annual examination.

CPC12 Coinheritance of BRCA2 and CYLD germline pathogenic variants associated with targetable metastatic malignant cylindroma

Abstract CYLD cutaneous syndrome (CCS) presents during puberty with the development of hair follicle tumours, including cylindromas, spiradenomas or trichoepitheliomas, and is associated with pathogenic variants in the tumour suppressor gene CYLD. Germline pathogenic variants of BRCA2 are associated with an increased risk of breast, ovarian, pancreatic and prostate cancer. Coinheritance of pathogenic variants in both genes has not been previously reported, and here, we present a 29-year-old man with metastatic malignant cylindroma, where knowledge of the germline variants has targetable therapeutic implications. The proband presented with cylindromas on his scalp from the age of 8 years, inherited from his mother who had CCS. The proband’s father and paternal grandmother both had early-onset breast cancer. The proband’s 33-year-old sister had been diagnosed with breast cancer and CCS; genetic testing revealed germline pathogenic variants in both BRCA2 and CYLD. Aged 28 years, the proband presented with a growing, ulcerated cylindroma on the scalp. Histology revealed a biphasic neoplasm, showing malignant cylindroma with high-grade features arising within a pre-existing benign cylindroma. The malignant epithelioid component of the tumour showed brisk mitotic activity (25 mitoses per mm2) and large infiltrative nests with central comedo-type necrosis. Immunohistochemistry showed positivity for epithelial membrane antigen, CK7, p63 and patches of CK5/6, whereas carcinoembryonic antigen, S100 and human melanoma black-45 were negative. Several weeks after excision of the malignant scalp cylindroma, a lump presented on the left side of the patient’s neck; biopsy revealed histology consistent with the malignant scalp cylindroma. Radiological imaging revealed metastatic deposits of malignant cylindroma in the right axilla, both lungs and the brain. Genetic testing of the proband revealed germline pathogenic variants in both BRCA2 and CYLD, as seen in his sister. The patient received radiotherapy for the tumour in his neck, with partial resolution of symptoms and gamma-knife ablation of brain metastases. DNA extracted from the patient’s tumour was analysed using a high-resolution single-nucleotide polymorphism array, which demonstrated loss of heterozygosity including the BRCA2 and CYLD loci. The germline and somatic pathogenic variants in this patient support the use of unlicensed therapeutics that target BRCA deficiency, such as poly-ADP ribose polymerase inhibitors, which have not previously been used to treat malignant cylindroma. This case emphasizes the importance of recognizing coinheritance of tumour suppressor genes in rare genetic conditions, as this can provide novel management options and improve patient outcomes.

The Omicron Variant Reinfection Risk among Individuals with a Previous SARS-CoV-2 Infection within One Year in Shanghai, China: A Cross-Sectional Study.

Reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants due to immune escape is challenging for the global response to the pandemic. We estimated the Omicron reinfection prevalence among people who had a previous SARS-CoV-2 infection in Shanghai, China. We conducted a telephone survey in December 2022 with those who had previously been infected with Omicron between March and May 2022. Information on their demographics, coronavirus disease 2019 (COVID-19) testing, and vaccination history was collected. The overall and subgroup reinfection rates were estimated and compared. Among the 1981 respondents who were infected between March and May 2022, 260 had positive nucleic acid or rapid antigen tests in December 2022, with an estimated reinfection rate of 13.1% (95% confidence interval [95% CI]: 11.6-14.6). The reinfection rate for those who had a booster vaccination was 11.4% (95% CI: 9.2-13.7), which was significantly lower than that for those with an incomplete vaccination series (15.2%, 95% CI: 12.3-18.1) (adjusted odds ratio [aOR]: 0.579; 95% CI: 0.412-0.813). Reinfection with the Omicron variant was lower among individuals with a previous SARS-CoV-2 infection and those who had a booster vaccination, suggesting that hybrid immunity may offer protection against reinfection with Omicron sublineages.

A diagnostic quandary: Rotavirus vaccine associated diarrhea

The patient is an otherwise healthy two-month-old boy who received the recommended vaccinations for his age group, which included the rotavirus pentavalent vaccine (RV5; RotaTeq) at his two-month well child visit. Three days later, he developed prolonged non-bloody diarrhea and was found to have persistently positive rotavirus antigen in his stool. Subsequent workup revealed mild defects in his functional T-cell immunocompetence. Genetic testing was obtained through the Invitae panel and was negative for hereditary forms of primary immunodeficiencies. The rotavirus antigen was found to have cleared from his stool around four months after receiving the RV5. Unfortunately, the source of the rotavirus infection was unable to be determined. The caregivers had misconceptions about the vaccine and the child’s immune system function which led to refusal of any further vaccinations. Healthcare providers should strive to develop honest and respectful relationships with parents to have thoughtful dialogues regarding vaccine safety and efficacy.

#5721 HEPATITIS B VIRUS REACTIVATION IN KIDNEY TRANSPLANT RECIPIENTS TREATED WITH BELATACEPT

Abstract Background and Aims Hepatitis B virus (HBV) reactivation in kidney transplant recipients may be associated with liver failure and graft loss, especially in anti-HBc antibody (HBcAb)-positive HBs antigen (HBsAg)-negative patients. Belatacept, a selective costimulation blocker, has been used in kidney transplantation for some time and has been associated with reactivation of other viruses as BK or CMV. However, there are few data on HBV reactivation among kidney recipients treated with belatacept. Method We performed a retrospective study in two French kidney transplantation centres including all transplant recipients receiving belatacept. Among HBcAb-positive patients, we analyzed HBV reactivation rate, outcomes and risks factors. Results 135 patients treated with belatacept were included, and 32 were HBcAb-positive. Seven patients reactivated HBV (21.9% of HBcAb-positive patients), including 5 HBsAg-negative patients (16.7%); reactivation occurred 54.8 (± 70.9) months after transplantation. There was no significant difference in survival between patients that reactivated HBV and patients that did not: 5-year patient survival of 100% (28.6; 100) and 83.4% (67.6; 100), respectively (p = 0.363) and 5-year graft survival of 100% (28.6; 100) and 79.8% (61.7; 100), respectively (p = 0.335). No factor, including HBsAb positivity and antiviral prophylaxis, was statistically associated with the risk of HBV reactivation. Conclusion Compared to the few studies that exist in this area, the HBV reactivation rate was high in patients treated with belatacept in our study. Our findings suggest that systematic antiviral prophylaxis for anti-HBc antibody (HBcAb)-positive HBs antigen (HBsAg)-negative patients should be considered and that there should be close monitoring of HBV serology and viral load in these patients to detect early HBV reactivation.

SECONDARILY INFECTED CYSTIC LESION: MICROSCOPIC MISCHARACTERIZATION MIMICKING SPINDLE CELL LESION

A 27-year-old man sought health care, complaining of discomfort and drainage of purulent secretion in the retromolar region of the mandible. Clinical examination revealed a slight volume increase of the left buccal bone plate, effacement of vestibule fundus, drainage of white/yellow content from gingival sulcus of tooth 37, and moderate painful symptoms on palpation. Radiographic examination revealed a well-delimited, multiloculated, radiolucent image, extending from the periapical region of tooth 37 to the middle portion of the mandible ramus. Diagnostic hypotheses were keratocyst and ameloblastoma. Aspiration puncture revealed reddish content. An incisional biopsy was performed, and the lesion was decompressed with a drain. Histopathological evaluation reported a lesion compatible with fusocellular injury of uncertain nature. Immunohistochemical evaluation showed positive CD34 (QBEnd10), Vimetine (VIM3B4), and low Ki67 antigen (KiS5) expression. A 3-month follow-up showed bone neoformation in the entire extension of the lesion. The final diagnosis was a secondarily infected cystic lesion. A 27-year-old man sought health care, complaining of discomfort and drainage of purulent secretion in the retromolar region of the mandible. Clinical examination revealed a slight volume increase of the left buccal bone plate, effacement of vestibule fundus, drainage of white/yellow content from gingival sulcus of tooth 37, and moderate painful symptoms on palpation. Radiographic examination revealed a well-delimited, multiloculated, radiolucent image, extending from the periapical region of tooth 37 to the middle portion of the mandible ramus. Diagnostic hypotheses were keratocyst and ameloblastoma. Aspiration puncture revealed reddish content. An incisional biopsy was performed, and the lesion was decompressed with a drain. Histopathological evaluation reported a lesion compatible with fusocellular injury of uncertain nature. Immunohistochemical evaluation showed positive CD34 (QBEnd10), Vimetine (VIM3B4), and low Ki67 antigen (KiS5) expression. A 3-month follow-up showed bone neoformation in the entire extension of the lesion. The final diagnosis was a secondarily infected cystic lesion.

#2955 THE IMPACT OF SARS-COV-2 INFECTION ON LONG-TERM RENAL FUNCTION IN PATIENTS WITH GLOMERULAR DISEASES

Abstract Background and Aims We sought to evaluate the long-term effects of SARS-CoV-2 infection on renal function in patients with glomerular diseases. Method A total of 451 patients with biopsy-proven glomerular disease and at least 12 months of follow-up after COVID-19 pandemic onset were included in the study. A SARS-CoV-2 infection was diagnosed based on a positive RT-PCR and/or antigen test. Multivariate Cox proportional hazards regression analysis was performed to identify the independent predictors of a composite endpoint (≥30% decline in eGFR, ESRD). In addition, a multivariate linear regression analysis was developed to identify the impact of SARS-CoV-2 infection on eGFR decline at 12 months after pandemic onset. Results Since 26th February 2020, when the first case of SARS-CoV-2 infection was diagnosed in Romania, 23.1% of patients had a SARS-CoV-2 infection during a follow-up period of 2.5 y (0.8-2.6). The most frequent glomerular disease was IgA nephropathy (22.6%), followed by lupus nephritis (11.5%) and membranous nephropathy (9.5%). 71.8% of the study cohort received various regimens of immunosuppression. Patients with SARS-CoV-2 infection were younger and more likely to have received immunosuppressive therapy compared to patients without infection, but the renal function at baseline was similar between the study groups (eGFR, 52±31.2 vs 52.1±29.3 ml/min, respectively; p = 0.78). 17.6% of patients reached the composite endpoint, while 12.3% progressed to ESRD. Those with SARS-CoV-2 infection were more likely to reach the composite endpoint compared to those without infection [prevalence of composite endpoint, 26.7% vs. 14.8%, p = 0.006; OR, 2.1 (95%CI, 1.23-3.58), p = 0.006) (Figure 1). Similarly, there was a significant decline of eGFR in the first year of follow-up between the two study groups [-2.24 (-24.8; 20.9) vs. +2.31 (-16.8; 27.5) ml/min, respectively, p = 0.004]. In multivariate Cox proportional hazards regression analysis, the independent predictors of the composite endpoint were baseline eGFR (HR, 0.94; 95%CI, 0.92-0.95, p<0.001), the occurrence of SARS-CoV-2 infection (HR, 1.91; 1.16-3.12, p = 0.01) and male gender (HR, 1.64; 95%CI, 1.01-2.66, p = 0.04). When taking into account the severity of SARS-CoV-2 infection, a severe infection was the most important predictor of the composite endpoint (HR, 2.1; 95%CI, 1.02-4.29, p = 0.04) (Figure 2). The results remained consistent when restricting the analysis to ESRD as an endpoint. When taking into account the eGFR slope at 12 months after COVID-19 pandemic onset as the outcome variable in multivariate linear regression analysis, the SARS-CoV-2 infection occurrence independently determined a reduction of eGFR by 4.62 ml/min/1.73m2 (β coefficient, -4.62; 95%CI, -7.74 to -1.5, p = 0.004). Conclusion There is a significant impact of SARS-CoV-2 infection on long-term renal function in patients with glomerular diseases, while those with severe infection had a greater decline of eGFR and a worse renal survival.

Viral emissions into the air and environment after SARS-CoV-2 human challenge: a phase 1, open label, first-in-human study

Effectively implementing strategies to curb SARS-CoV-2 transmission requires understanding who is contagious and when. Although viral load on upper respiratory swabs has commonly been used to infer contagiousness, measuring viral emissions might be more accurate to indicate the chance of onward transmission and identify likely routes. We aimed to correlate viral emissions, viral load in the upper respiratory tract, and symptoms, longitudinally, in participants who were experimentally infected with SARS-CoV-2. In this phase 1, open label, first-in-human SARS-CoV-2 experimental infection study at quarantine unit at the Royal Free London NHS Foundation Trust, London, UK, healthy adults aged 18-30 years who were unvaccinated for SARS-CoV-2, not previously known to have been infected with SARS-CoV-2, and seronegative at screening were recruited. Participants were inoculated with 10 50% tissue culture infectious dose of pre-alpha wild-type SARS-CoV-2 (Asp614Gly) by intranasal drops and remained in individual negative pressure rooms for a minimum of 14 days. Nose and throat swabs were collected daily. Emissions were collected daily from the air (using a Coriolis μ air sampler and directly into facemasks) and the surrounding environment (via surface and hand swabs). All samples were collected by researchers, and tested by using PCR, plaque assay, or lateral flow antigen test. Symptom scores were collected using self-reported symptom diaries three times daily. The study is registered with ClinicalTrials.gov, NCT04865237. Between March 6 and July 8, 2021, 36 participants (ten female and 26 male) were recruited and 18 (53%) of 34 participants became infected, resulting in protracted high viral loads in the nose and throat following a short incubation period, with mild-to-moderate symptoms. Two participants were excluded from the per-protocol analysis owing to seroconversion between screening and inoculation, identified post hoc. Viral RNA was detected in 63 (25%) of 252 Coriolis air samples from 16 participants, 109 (43%) of 252 mask samples from 17 participants, 67 (27%) of 252 hand swabs from 16 participants, and 371 (29%) of 1260 surface swabs from 18 participants. Viable SARS-CoV-2 was collected from breath captured in 16 masks and from 13 surfaces, including four small frequently touched surfaces and nine larger surfaces where airborne virus could deposit. Viral emissions correlated more strongly with viral load in nasal swabs than throat swabs. Two individuals emitted 86% of airborne virus, and the majority of airborne virus collected was released on 3 days. Individuals who reported the highest total symptom scores were not those who emitted most virus. Very few emissions occurred before the first reported symptom (7%) and hardly any before the first positive lateral flow antigen test (2%). After controlled experimental inoculation, the timing, extent, and routes of viral emissions was heterogeneous. We observed that a minority of participants were high airborne virus emitters, giving support to the notion of superspreading individuals or events. Our data implicates the nose as the most important source of emissions. Frequent self-testing coupled with isolation upon awareness of first symptoms could reduce onward transmissions. UK Vaccine Taskforce of the Department for Business, Energy and Industrial Strategy of Her Majesty's Government.

COVID-19-associated pulmonary aspergillosis (CAPA): identification of Aspergillus species and determination of antifungal susceptibility profiles.

Among the co-infectious agents in COVID-19 patients, Aspergillus species cause invasive pulmonary aspergillosis (IPA). IPA is difficult to diagnose and is associated with high morbidity and mortality. This study is aimed at identifying Aspergillus spp. from sputum and tracheal aspirate (TA) samples of COVID-19 patients and at determining their antifungal susceptibility profiles. A total of 50 patients with COVID-19 hospitalized in their intensive care units (ICU) were included in the study. Identification of Aspergillus isolates was performed by phenotypic and molecular methods. ECMM/ISHAM consensus criteria were used for IPA case definitions. The antifungal susceptibility profiles of isolates were determined by the microdilution method. Aspergillus spp. was detected in 35 (70%) of the clinical samples. Among the Aspergillus spp., 20 (57.1%) A. fumigatus, six (17.1%) A. flavus, four (11.4%) A. niger, three (8.6%) A. terreus, and two (5.7%) A. welwitschiae were identified. In general, Aspergillus isolates were susceptible to the tested antifungal agents. In the study, nine patients were diagnosed with possible IPA, 11 patients were diagnosed with probable IPA, and 15 patients were diagnosed with Aspergillus colonization according to the used algorithms. Serum galactomannan antigen positivity was found in 11 of the patients diagnosed with IPA. Our results provide data on the incidence of IPA, identification of Aspergillus spp., and its susceptibility profiles in critically ill COVID-19 patients. Prospective studies are needed for a faster diagnosis or antifungal prophylaxis to manage the poor prognosis of IPA and reduce the risk of mortality.

Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial

Post-COVID-19 condition (also known as long COVID) is an emerging chronic illness potentially affecting millions of people. We aimed to evaluate whether outpatient COVID-19 treatment with metformin, ivermectin, or fluvoxamine soon after SARS-CoV-2 infection could reduce the risk of long COVID. We conducted a decentralised, randomised, quadruple-blind, parallel-group, phase 3 trial (COVID-OUT) at six sites in the USA. We included adults aged 30-85 years with overweight or obesity who had COVID-19 symptoms for fewer than 7 days and a documented SARS-CoV-2 positive PCR or antigen test within 3 days before enrolment. Participants were randomly assigned via 2 × 3 parallel factorial randomisation (1:1:1:1:1:1) to receive metformin plus ivermectin, metformin plus fluvoxamine, metformin plus placebo, ivermectin plus placebo, fluvoxamine plus placebo, or placebo plus placebo. Participants, investigators, care providers, and outcomes assessors were masked to study group assignment. The primary outcome was severe COVID-19 by day 14, and those data have been published previously. Because the trial was delivered remotely nationwide, the a priori primary sample was a modified intention-to-treat sample, meaning that participants who did not receive any dose of study treatment were excluded. Long COVID diagnosis by a medical provider was a prespecified, long-term secondary outcome. This trial is complete and is registered with ClinicalTrials.gov, NCT04510194. Between Dec 30, 2020, and Jan 28, 2022, 6602 people were assessed for eligibility and 1431 were enrolled and randomly assigned. Of 1323 participants who received a dose of study treatment and were included in the modified intention-to-treat population, 1126 consented for long-term follow-up and completed at least one survey after the assessment for long COVID at day 180 (564 received metformin and 562 received matched placebo; a subset of participants in the metformin vs placebo trial were also randomly assigned to receive ivermectin or fluvoxamine). 1074 (95%) of 1126 participants completed at least 9 months of follow-up. 632 (56·1%) of 1126 participants were female and 494 (43·9%) were male; 44 (7·0%) of 632 women were pregnant. The median age was 45 years (IQR 37-54) and median BMI was 29·8 kg/m2 (IQR 27·0-34·2). Overall, 93 (8·3%) of 1126 participants reported receipt of a long COVID diagnosis by day 300. The cumulative incidence of long COVID by day 300 was 6·3% (95% CI 4·2-8·2) in participants who received metformin and 10·4% (7·8-12·9) in those who received identical metformin placebo (hazard ratio [HR] 0·59, 95% CI 0·39-0·89; p=0·012). The metformin beneficial effect was consistent across prespecified subgroups. When metformin was started within 3 days of symptom onset, the HR was 0·37 (95% CI 0·15-0·95). There was no effect on cumulative incidence of long COVID with ivermectin (HR 0·99, 95% CI 0·59-1·64) or fluvoxamine (1·36, 0·78-2·34) compared with placebo. Outpatient treatment with metformin reduced long COVID incidence by about 41%, with an absolute reduction of 4·1%, compared with placebo. Metformin has clinical benefits when used as outpatient treatment for COVID-19 and is globally available, low-cost, and safe. Parsemus Foundation; Rainwater Charitable Foundation; Fast Grants; UnitedHealth Group Foundation; National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health; and National Center for Advancing Translational Sciences.

Optimal allocation of scarce PCR tests during the COVID-19 pandemic.

During the coronavirus disease (COVID-19) pandemic, Germany and various other countries experienced a shortage of polymerase chain reaction (PCR) laboratory tests due to the highly transmissible SARS-CoV-2 Omicron variant that drove an unprecedented surge of infections. This study developed a mathematical model that optimizes diagnostic capacity with lab-based PCR testing. A mathematical model was constructed to determine the value of PCR testing in relation to the pre-test probability of COVID-19. Furthermore, the model derives the lower and upper bounds for the threshold pre-test probability of the designated priority group. The model was applied in a German setting using the PCR test-positivity rate at the beginning of February 2022. The value function of PCR testing is bell-shaped with respect to the pre-test probability, reaching a maximum at a pre-test probability of 0.5. Based on a PCR test-positivity rate of 0.3 and assuming that at least two thirds of the tested population have a pre-test probability below, lower and higher pre-test probability thresholds are ≥ 0.1 and 0.7, respectively. Therefore, individuals who have a 25% likelihood of testing positive because they exhibit symptoms should be a higher priority for PCR testing. Furthermore, a positive rapid antigen test in asymptomatic individuals with no known exposure to COVID-19 should be confirmed using PCR. Yet, symptomatic individuals with a positive RAT should be excluded from PCR testing. A mathematical model that allows for the optimal allocation of scarce PCR tests during the COVID-19 pandemic was developed.

Possibilities of Discriminant Analysis in the Differential Diagnosis of Chronic Aspergillosis and Nonmicotic Lung Lesions

Objective: to improve the efficiency of differential diagnosis of chronic pulmonary aspergillosis (СPA) based on the assessment of its probability using a discriminant mathematical model. Material and methods. The prospective study included 74 patients with CPA (57% women, median age 53 years) meeting the ERS/ESCMID criteria (2016). The control group consisted of 35 patients with lung diseases without CPA. Clinical and anamnestic data, the results of computed tomography (CT), laboratory and instrumental methods of research were analysed. By means of stepwise discriminant analysis, the model was created in order to differentiate compared groups. Results. The main forms of CPA were simple solitary aspergilloma (n = 30, 40%) and cavitary CPA (n = 21, 28%). On CT scans, in patients with CPA pulmonary emphysema (n = 50, 74%; 95% CI 63–83), bronchiectasis (n = 42, 56%; 95% CI 44–67), pleura thickening (n = 40, 56%; 95% CI 42–65) were detected with a high frequency. The sensitivity and specificity of typical for CPA air sickle symptom were 66.2% and 74.29%, respectively. The diagnostic informativeness of laboratory methods was characterized by high specificity (85–100%), however, it had sensitivity 40–60%. A discriminant model was worked up. It included five variables: mycological confirmation of the diagnosis (р < 0.001), air sickle symptom on CT (p = 0.03), ground glass opacity sympton on CT (p = 0.017), accompanying rheumatological diseases (p = 0,031), positive Aspergillus antigen in bronchoalveolar lavage (p = 0.036). The resulting model of differential diagnosis is statistically significant (F = (5.102) = 27.291; p < 0.001). Conclusion. CT-patterns of CPA include typical (air sickle symptom) and nonspecific (pleura thickening, emphysema, bronchiectasis) changes. Separately taken laboratory indicators and CT-symptoms are not always the determining criteria for diagnosis; an integrated approach is required to make a diagnosis. The proposed model improves the accuracy of differential diagnosis between CPA and nonmycotic lung diseases: increases sensitivity to 82.43%, specificity to 94.28% in comparison with separately analyzed laboratory data and typical CT-pattern of air sickle symptom. As a whole this model allows to classify the CPA and nonmycotic lung disease in 86,23% of cases.

Predicting omicron pneumonia severity and outcome: a single-center study in Hangzhou, China.

In December 2022, there was a large Omicron epidemic in Hangzhou, China. Many people were diagnosed with Omicron pneumonia with variable symptom severity and outcome. Computed tomography (CT) imaging has been proven to be an important tool for COVID-19 pneumonia screening and quantification. We hypothesized that CT-based machine learning algorithms can predict disease severity and outcome in Omicron pneumonia, and we compared its performance with the pneumonia severity index (PSI)-related clinical and biological features. Our study included 238 patients with the Omicron variant who have been admitted to our hospital in China from 15 December 2022 to 16 January 2023 (the first wave after the dynamic zero-COVID strategy stopped). All patients had a positive real-time polymerase chain reaction (PCR) or lateral flow antigen test for SARS-CoV-2 after vaccination and no previous SARS-CoV-2 infections. We recorded patient baseline information pertaining to demographics, comorbid conditions, vital signs, and available laboratory data. All CT images were processed with a commercial artificial intelligence (AI) algorithm to obtain the volume and percentage of consolidation and infiltration related to Omicron pneumonia. The support vector machine (SVM) model was used to predict the disease severity and outcome. The receiver operating characteristic (ROC) area under the curve (AUC) of the machine learning classifier using PSI-related features was 0.85 (accuracy = 87.40%, p < 0.001) for predicting severity while that using CT-based features was only 0.70 (accuracy = 76.47%, p = 0.014). If combined, the AUC was not increased, showing 0.84 (accuracy = 84.03%, p < 0.001). Trained on outcome prediction, the classifier reached the AUC of 0.85 using PSI-related features (accuracy = 85.29%, p < 0.001), which was higher than using CT-based features (AUC = 0.67, accuracy = 75.21%, p < 0.001). If combined, the integrated model showed a slightly higher AUC of 0.86 (accuracy = 86.13%, p < 0.001). Oxygen saturation, IL-6, and CT infiltration showed great importance in both predicting severity and outcome. Our study provided a comprehensive analysis and comparison between baseline chest CT and clinical assessment in disease severity and outcome prediction in Omicron pneumonia. The predictive model accurately predicts the severity and outcome of Omicron infection. Oxygen saturation, IL-6, and infiltration in chest CT were found to be important biomarkers. This approach has the potential to provide frontline physicians with an objective tool to manage Omicron patients more effectively in time-sensitive, stressful, and potentially resource-constrained environments.

The risk for celiac disease after Covid-19 infection

BackgroundCeliac disease (CD) is an autoimmune disease leading to gastrointestinal symptoms and mineral deficiencies. The pathogenetic mechanisms, besides the clear HLA association, are elusive. Among environmental factors infections have been proposed. Covid-19 infection results in a systemic inflammatory response that often also involves the gastrointestinal tract. The aim of the present study was to investigate whether Covid-19 infection could increase the risk for CD.Patients and methodsAll patients, both children and adults, in the county Skåne (1.4 million citizens) in southern Sweden with newly diagnosed biopsy- or serology-verified CD or a positive tissue transglutaminase antibody test (tTG-ab) during 2016–2021 were identified from registries at the Departments of Pathology and Immunology, respectively. Patients with a positive Covid-19 PCR or antigen test in 2020 and 2021 were identified from the Public Health Agency of Sweden.ResultsDuring the Covid-19 pandemic (March 2020 – December 2021), there were 201 050 cases of Covid-19 and 568 patients with biopsy- or serology-verified CD or a first-time positive tTG-ab tests, of which 35 patients had been infected with Covid-19 before CD. The incidence of verified CD and tTG-ab positivity was lower in comparison to before the pandemic (May 2018 – February 2020; 22.5 vs. 25.5 cases per 100 000 person-years, respectively, incidence rate difference (IRD) -3.0, 95% CI -5.7 – -0.3, p = 0.028). The incidence of verified CD and tTG-ab positivity in patients with and without prior Covid-19 infection was 21.1 and 22.4 cases per 100 000 person-years, respectively (IRD − 1.3, 95% CI -8.5–5.9, p = 0.75).ConclusionsOur results indicate that Covid-19 is not a risk factor for CD development. While gastrointestinal infections seem to be an important part of the CD pathogenesis, respiratory infections probably are of less relevance.

Outcomes Following Extracorporeal Membrane Oxygenation for Severe COVID-19 in Pregnancy or Post Partum

Existing reports of pregnant patients with COVID-19 disease who require extracorporeal membrane oxygenation (ECMO) are limited, with variable outcomes noted for the maternal-fetal dyad. To examine maternal and perinatal outcomes associated with ECMO used for COVID-19 with respiratory failure during pregnancy. This retrospective multicenter cohort study examined pregnant and postpartum patients who required ECMO for COVID-19 respiratory failure at 25 hospitals across the US. Eligible patients included individuals who received care at one of the study sites, were diagnosed with SARS-CoV-2 infection during pregnancy or up to 6 weeks post partum by positive nucleic acid or antigen test, and for whom ECMO was initiated for respiratory failure from March 1, 2020, to October 1, 2022. ECMO in the setting of COVID-19 respiratory failure. The primary outcome was maternal mortality. Secondary outcomes included serious maternal morbidity, obstetrical outcomes, and neonatal outcomes. Outcomes were compared by timing of infection during pregnancy or post partum, timing of ECMO initiation during pregnancy or post partum, and periods of circulation of SARS-CoV-2 variants. From March 1, 2020, to October 1, 2022, 100 pregnant or postpartum individuals were started on ECMO (29 [29.0%] Hispanic, 25 [25.0%] non-Hispanic Black, 34 [34.0%] non-Hispanic White; mean [SD] age: 31.1 [5.5] years), including 47 (47.0%) during pregnancy, 21 (21.0%) within 24 hours post partum, and 32 (32.0%) between 24 hours and 6 weeks post partum; 79 (79.0%) had obesity, 61 (61.0%) had public or no insurance, and 67 (67.0%) did not have an immunocompromising condition. The median (IQR) ECMO run was 20 (9-49) days. There were 16 maternal deaths (16.0%; 95% CI, 8.2%-23.8%) in the study cohort, and 76 patients (76.0%; 95% CI, 58.9%-93.1%) had 1 or more serious maternal morbidity events. The largest serious maternal morbidity was venous thromboembolism and occurred in 39 patients (39.0%), which was similar across ECMO timing (40.4% pregnant [19 of 47] vs 38.1% [8 of 21] immediately postpartum vs 37.5% postpartum [12 of 32]; P > .99). In this multicenter US cohort study of pregnant and postpartum patients who required ECMO for COVID-19-associated respiratory failure, most survived but experienced a high frequency of serious maternal morbidity.

Hepatitis B Virus Reactivation in Kidney Transplant Recipients Treated With Belatacept

Hepatitis B virus (HBV) reactivation in kidney transplant recipients has been reported in 3% to 9% of anti-HBc antibody (HBcAb)-positive HBs antigen (HBsAg)-negative patients. It has not been studied in patients receiving belatacept, a selective costimulation blocker. We performed a retrospective study of all transplant recipients receiving belatacept in 2 kidney transplantation centers in France. Among HBcAb-positive patients, we analyzed HBV reactivation rate, outcomes, and risk factors. A total of 135 patients treated with belatacept were included: 32 were HBcAb-positive and 2 were HBsAg-positive. Seven patients reactivated HBV (21.9% of HBcAb-positive patients), including 5 HBsAg-negative patients (16.7% of HBcAb-positive HBsAg-negative patients). Reactivation occurred 54.8 (± 70.9) months after transplantation. One patient presented with severe hepatitis and 1 patient developed cirrhosis. There was no significant difference in survival between patients that reactivated HBV and patients that did not: 5-year patient survival of 100% (28.6; 100) and 83.4% (67.6; 100), respectively (P= 0.363); and 5-year graft survival of 100% (28.6; 100) and 79.8% (61.7; 100), respectively (P= 0.335). No factor, including HBsAb positivity and antiviral prophylaxis, was statistically associated with the risk of HBV reactivation. HBV reactivation rate was high in patients treated with belatacept when compared with previous transplantation studies. HBV reactivation did not impact survival. Further studies are needed to confirm these results. A systematic antiviral prophylaxis for these patients should be considered and evaluated.

Inguinal Lymphadenopathy After Renal Transplantation Leading to the Diagnosis of Prostate Cancer: A Case Report

It is extremely rare for a patient with prostate cancer (PCa) to have palpable lymph nodes at the initial presentation. In fact, only 4 case reports of palpable superficial lymph nodes at the first visit led to the diagnosis of PCa. Moreover, no such cases are reported in kidney transplantation (KT) patients. A 72-year-old man who started hemodialysis due to diabetic nephropathy was referred to our hospital for a KT in 2018. Before the KT, he had a negative screen for cancer, including PCa. The postoperative course was good. He felt a lump in the left inguinal region three years after the KT. A computed tomography scan revealed abdominal and left inguinal lymphadenopathy, which was consistent with a post-transplant lymphoproliferative disorder. However, a biopsy of an inguinal lymph node revealed adenocarcinoma with positive prostate-specific antigen (PSA) staining, suggesting lymph node metastasis of PCa. The blood PSA level was 1674.23 ng/mL. A prostate biopsy was performed, the pathologic diagnosis of which was PCa, with a Gleason score of 10. In conclusion, even though the standardized incidence ratio of PCa is not known to increase in KT patients, PCa should be included in the differential diagnosis, along with the possibility of post-transplant lymphoproliferative disorder. We also suggest the importance of regular screening for malignant tumors after organ transplantation.

Correlates of immunity in SARS-CoV-2 post-vaccine infections in the Prospective Assessment of SARS-CoV-2 Seroconversion (PASS) Study

Abstract Background: We sought to determine pre-infection correlates of immunity against SARS-CoV-2 post-vaccine infections. Methods: Serum and saliva samples from 176 BNT162b2-vaccinated adults in the Prospective Assessment of SARS-CoV-2 Seroconversion study were collected between October and December 2021 and assessed for serum and saliva levels of WT SARS-CoV-2 Spike (S)-specific IgG and IgA antibodies using a microsphere-based multiplex immunoassay. Serum samples were also assessed for neutralization activity against D614G, Delta (617.2), and Omicron BA.1 and BA.1.1 variants using a lentiviral pseudovirus neutralization assay. After the fall visit, participants reported all positive PCR and/or antigen tests for SARS-CoV-2. Duration, severity, and type of symptoms, as well as risk exposures and adherence to precautionary measures, were assessed by questionnaires during the spring 2022 visit. Results: Thirty-two participants (18.2%) had infections between December 7, 2021 and April 1, 2022. Pre-infection anti-S IgG antibody levels and neutralizing titers against BA.1 and BA.1.1 were higher in individuals that did not develop infection (p values 0.0098, 0.0313, and 0.021, respectively). No individuals with an anti-S level greater than 15,000 binding antibody units (BAU/ml) developed a post-vaccine infection. Conclusion: High serum anti-S IgG antibody levels, high neutralization titers against Omicron subvariants, and low home risk scores correlated with protection against post-vaccine infections during the initial Omicron wave. BAU levels greater than 15,000 in the fall of 2021 were associated with complete protection during the initial Omicron wave. This work was supported in whole, or in part, with federal funds from the Defense Health Program (HU00012020067, HU00012020094) and the Immunization Healthcare Branch (HU00012120104) of the Defense Health Agency, United States Department of Defense, and the National Institute of Allergy and Infectious Disease (HU00011920111), under Inter-Agency Agreement Y1-AI-5072.