The Effects of COVID-19 in Kidney Transplantation: Evidence From Tissue Pathology.

BACKGROUND: The biological effects of SARS-CoV-2 infection in transplanted kidneys are uncertain with little pathological information. METHODS: This single-center, prospective observational study evaluated kidney transplant biopsies from recipients of deceased donors with COVID-19, current recipients contracting SARS-CoV-2 Omicron variant in 2022, against prior BK virus (BKV) infection and uninfected (without SARS-CoV-2 or BKV) samples, as respective positive and negative comparators (n = 503 samples). RESULTS: We demonstrated nonvirus tubular injury in implanted tissue from infected donors and prevalent recipients with mild acute COVID-19 and acute kidney injury, excluding direct viral infection as a cause of kidney damage. COVID particles were absent in 4116 ultrastructural images of 295 renal tubules from 4 patients with acute COVID-19. No viral cytopathic effect, viral allograft nephropathy, or SARS-CoV-2 RNA was detected in acute tissues, nor in 128 sequential samples from infected donors or recipients with COVID-19. Following recipient COVID-19 (mean 16.8 ±â€…12.0 wk post-infection), the biopsy-prevalence of rejection was 33.0% (n = 100 biopsies) versus 13.4% for contemporaneous uninfected controls (n = 337; P < 0.001). Prior COVID-19 was an independent risk factor for incident rejection using multivariable generalized estimating equation adjusted for competing risks (odds ratio, 2.195; 95% confidence interval, 1.189-4.052; P = 0.012). Landmark and matched-pair analyses confirmed an association of SARS-CoV-2 with subsequent transplant rejection, with a similar pattern following BKV infection. CONCLUSIONS: Transplantation from COVID-19+ deceased donors yielded good recipient outcomes without evidence of viral tissue transmission. Acute kidney injury during COVID-19 was mediated by archetypical tubular injury and infection correlated with an increased risk of subsequent rejection.

Clostridioides difficile Infection: Clinical Practice and Health Outcomes in 6 Large Tertiary Hospitals in Eastern Australia.

Background: Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality in both healthcare and community settings. We aimed to define the predisposing factors, risks for severe disease, and mortality determinants of CDI in eastern Australia over a 1-year period. Methods: This is an observational retrospective study of CDI in hospitalized patients aged ≥18 years in 6 tertiary institutions from 1 January 2016 to 31 December 2016. Patients were identified through laboratory databases and medical records of participating institutions. Clinical, imaging, and laboratory data were input into an electronic database hosted at a central site. Results: A total of 578 patients (578 CDI episodes) were included. Median age was 65 (range, 18-99) years and 48.2% were male. Hospital-onset CDI occurred in 64.0%. Recent antimicrobial use (41.9%) and proton pump inhibitor use (35.8%) were common. Significant risk factors for severe CDI were age <65 years (P < .001), malignancy within the last 5 years (P < .001), and surgery within the previous 30 days (P < .001). Significant risk factors for first recurrence included severe CDI (P = .03) and inflammatory bowel disease (P = .04). Metronidazole was the most common regimen for first episodes of CDI with 65.2% being concordant with Australian treatment guidelines overall. Determinants for death at 60 days included age ≥65 years (P = .01), severe CDI (P < .001), and antibiotic use within the prior 30 days (P = .02). Of those who received metronidazole as first-line therapy, 10.1% died in the 60-day follow-up period, compared to 9.8% of those who received vancomycin (P = .86). Conclusions: Patients who experience CDI are vulnerable and require early diagnosis, clinical surveillance, and effective therapy to prevent complications and improve outcomes.

Improved Neutralisation of the SARS-CoV-2 Omicron Variant following a Booster Dose of Pfizer-BioNTech (BNT162b2) COVID-19 Vaccine.

In late November 2021, the World Health Organization declared the SARS-CoV-2 lineage B.1.1.529 the fifth variant of concern, Omicron. This variant has acquired over 30 mutations in the spike protein (with 15 in the receptor-binding domain), raising concerns that Omicron could evade naturally acquired and vaccine-derived immunity. We utilized an authentic virus, multicycle neutralisation assay to demonstrate that sera collected one, three, and six months post-two doses of Pfizer-BioNTech BNT162b2 had a limited ability to neutralise SARS-CoV-2. However, four weeks after a third dose, neutralising antibody titres were boosted. Despite this increase, neutralising antibody titres were reduced fourfold for Omicron compared to lineage A.2.2 SARS-CoV-2.

Proposed delay for safe surgery after COVID-19.

BACKGROUND: Long-term effects after COVID-19 may affect surgical safety. This study aimed to evaluate the literature and produce evidence-based guidance regarding the period of delay necessary for adequate recovery of patients following COVID-19 infection before undergoing surgery. METHODS: A rapid review was combined with advice from a working group of 10 clinical experts across Australia and New Zealand. MEDLINE, medRxiv and grey literature were searched to 4 October 2020. The level of evidence was stratified according to the National Health and Medical Research Council evidence hierarchy. RESULTS: A total of 1020 records were identified, from which 20 studies (12 peer-reviewed) were included. None were randomized trials. The studies comprised one case-control study (level III-2 evidence), one prospective cohort study (level III-2) and 18 case-series studies (level IV). Follow-up periods containing observable clinical characteristics ranged from 3 to 16 weeks. New or excessive fatigue and breathlessness were the most frequently reported symptoms. SARS-CoV-2 may impact the immune system for multiple months after laboratory confirmation of infection. For patients with past COVID-19 undergoing elective curative surgery for cancer, risks of pulmonary complications and mortality may be lowest at 4 weeks or later after a positive swab. CONCLUSION: After laboratory confirmation of SARS-CoV-2 infection, minor surgery should be delayed for at least 4 weeks and major surgery for 8-12 weeks, if patient outcome is not compromised. Comprehensive preoperative and ongoing assessment must be carried out to ensure optimal clinical decision-making.

Screening and testing for COVID-19 before surgery.

BACKGROUND: Preoperative screening for coronavirus disease 2019 (COVID-19) aims to preserve surgical safety for both patients and surgical teams. This rapid review provides an evaluation of current evidence with input from clinical experts to produce guidance for screening for active COVID-19 in a low prevalence setting. METHODS: An initial search of PubMed (until 6 May 2020) was combined with targeted searches of both PubMed and Google Scholar until 1 July 2020. Findings were streamlined for clinical relevance through the advice of an expert working group that included seven senior surgeons and a senior medical virologist. RESULTS: Patient history should be examined for potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hyposmia and hypogeusia may present as early symptoms of COVID-19, and can potentially discriminate from other influenza-like illnesses. Reverse transcription-polymerase chain reaction is the gold standard diagnostic test to confirm SARS-CoV-2 infection, and although sensitivity can be improved with repeated testing, the decision to retest should incorporate clinical history and the local supply of diagnostic resources. At present, routine serological testing has little utility for diagnosing acute infection. To appropriately conduct preoperative testing, the temporal dynamics of SARS-CoV-2 must be considered. Relative to other thoracic imaging modalities, computed tomography has the greatest utility for characterizing pulmonary involvement in COVID-19 patients who have been diagnosed by reverse transcription-polymerase chain reaction. CONCLUSION: Through a rapid review of the literature and advice from a clinical expert working group, evidence-based recommendations have been produced for the preoperative screening of surgical patients with suspected COVID-19.

Deep Sequencing of Urine Specimens Detects Two BK Polyomavirus Genotypes in a Hematopoietic Stem Cell Transplant Recipient.

BK polyomavirus (BKPyV) is an important pathogen in transplant recipients. We report four draft BKPyV genomes, three of BKPyV genotype I (subtype I-b2) (AUS-105, AUS-106, and AUS-108) and one of genotype II (AUS-107). These draft genomes were identified in longitudinal urine samples collected from a single hematopoietic stem cell transplant recipient.

New advances in the management of cytomegalovirus in allogeneic haemopoietic stem cell transplantation.

Cytomegalovirus (CMV) viraemia continues to be a frequent complication in the post-haemopoietic stem cell transplantation period despite a low incidence of CMV end-organ disease. Several significant advances in the understanding and management of CMV infection have occurred in the last few years including improved diagnostics, monitoring of CMV immunity, availability of novel anti-CMV drugs, and emerging use of immunotherapies including CMV-specific T-cell infusions. In addition to reviewing these advances we also explore some of the more practical prescribing issues of the older and newer CMV drugs including cost, toxicity and drug interactions to help clinicians navigate this new era of CMV management.

Viral exanthems.

PURPOSE OF REVIEW: Determining the viral cause of a rash presents significant diagnostic challenges. We review contemporary literature on viral exanthems and suggest a structured approach to aid diagnosis. RECENT FINDINGS: Strains responsible for, and the clinical presentation of, enteroviral infections have diverged from classic descriptions. The causative relationship between antibiotic administration and rash in Epstein-Barr virus infection has been recently questioned. Major measles virus outbreaks have recently occurred in Europe and the USA. The largest Ebola virus outbreak in West Africa has resulted in importation of the virus to other countries and secondary local transmission. Autochthonous transmission of Chikungunya virus has occurred in nonendemic areas, including Europe, the Caribbean and Americas. Zika virus has re-emerged in the Pacific with local transmission from imported cases. Climate change, global warming and spillover of zoonotic viruses are contributing to the emergence and spread of viral diseases. SUMMARY: Important clues to the diagnosis of viral exanthems include their distribution and morphology, geographic location and potential exposure to vector-borne or blood-borne viruses. Diagnosis is commonly made via serology, nucleic acid tests or, rarely, viral culture. Skin biopsy is not usually required. In general, viral exanthems are self-limiting and treatment is supportive.

Viral respiratory infections among Hajj pilgrims in 2013.

Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged in the Arabian Gulf region, with its epicentre in Saudi Arabia, the host of the 'Hajj' which is the world's the largest mass gathering. Transmission of MERS-CoV at such an event could lead to its rapid worldwide dissemination. Therefore, we studied the frequency of viruses causing influenza-like illnesses (ILI) among participants in a randomised controlled trial at the Hajj 2013. We recruited 1038 pilgrims from Saudi Arabia, Australia and Qatar during the first day of Hajj and followed them closely for four days. A nasal swab was collected from each pilgrim who developed ILI. Respiratory viruses were detected using multiplex RT-PCR. ILI occurred in 112/1038 (11%) pilgrims. Their mean age was 35 years, 49 (44%) were male and 35 (31%) had received the influenza vaccine pre-Hajj. Forty two (38%) pilgrims had laboratory-confirmed viral infections; 28 (25%) rhinovirus, 5 (4%) influenza A, 2 (2%) adenovirus, 2 (2%) human coronavirus OC43/229E, 2 (2%) parainfluenza virus 3, 1 (1%) parainfluenza virus 1, and 2 (2%) dual infections. No MERS-CoV was detected in any sample. Rhinovirus was the commonest cause of ILI among Hajj pilgrims in 2013. Infection control and appropriate vaccination are necessary to prevent transmission of respiratory viruses at Hajj and other mass gatherings.

Tests for latent tuberculosis in people with ESRD: a systematic review.

BACKGROUND: The relative diagnostic accuracy of interferon γ release assays (IGRAs; based on ELISA [enzyme-linked immunosorbent assay] or ELISPOT [enzyme-linked immunosorbent spot], ie, the QuantiFERON and T-SPOT.TB tests, respectively) and the tuberculin skin test (TST) for latent tuberculosis (TB) infection in people with end-stage kidney disease is uncertain and national guidelines for their use are inconsistent. STUDY DESIGN: Systematic review. SELECTION CRITERIA FOR STUDIES: Evaluated performance of tests for latent TB with clinical risk-factor assessment. SETTING & POPULATION: People with end-stage kidney disease (chronic kidney disease stage 5 [eGFR <15] or kidney transplant recipients). No limits on setting. INDEX TESTS: ELISA- or ELISPOT-based IGRAs, TST, assays to detect antimycobacterial antibodies, and flow cytometry-based tests. OUTCOMES: Odds of test positivity with clinical risk factor for latent TB, expressed as ORs and relative ORs (RORs). RESULTS: 47 studies (6,828 participants) were included, but only 30 studies (4,546 participants) contained sufficient data to contribute to meta-analysis. Studies were predominately in the dialysis population (23/30; 3,700 participants) in countries with low to moderate TB prevalence (0.0-50.0 cases/10(5) persons). BCG vaccination rate was variable (2.7%-100.0%). 9 studies compared IGRAs with the TST directly, 17 studies evaluated the TST only, and the other 4 studies evaluated other tests. Compared to a positive TST result, a positive ELISA-based IGRA result was associated more strongly with radiologic evidence of past TB (ROR, 4.29; 95% CI, 1.83-10.3; P = 0.001) and contact with active TB (ROR, 3.36; 95% CI, 1.61-7.01; P = 0.001). Compared to a negative TST result, a negative ELISA-based IGRA result was associated more strongly with BCG vaccination (ROR, 0.30; 95% CI, 0.14-0.63; P = 0.002). There were insufficient data to compare performance of the ELISPOT-based IGRA with the TST or ELISA-based IGRA. LIMITATIONS: 17 of 47 included studies (36.2%) did not contain sufficient data to contribute to meta-analysis. CONCLUSIONS: Compared to the TST, the ELISA-based IGRA was associated more strongly with risk factors for latent TB in end-stage kidney disease.

Viral arthritides.

Viral infections may manifest as acute or chronic arthritis. Joint involvement arises from either direct infection of the joint, through an immunological response directed towards the virus or autoimmunity. Epidemiological clues to the diagnosis include geographic location and exposure to vector-borne, blood-borne or sexually transmitted viruses. Although not always possible, it is important to diagnose the pathogenic virus, usually by serology, nucleic acid tests or rarely, viral culture. In general, viral arthritides are self-limiting and treatment is targeted at symptomatic relief. This article focuses on the causes, clinical features, diagnosis and treatment of viral arthritides.

Pandemic (H1N1) 2009 influenza virus seroconversion rates in HIV-infected individuals.

The impact of pandemic (H1N1) 2009 influenza in HIV-infected individuals is unknown. Determining the prevalence of pandemic influenza in this at-risk group will guide vaccination programs. After the first pandemic wave, the seroprevalence rate of pandemic influenza in HIV-infected individuals in western Sydney, New South Wales, Australia, was 34.2%, similar to the rate observed in the general population. However, true seroprevalence is more accurately determined by seroconversion, defined as a 4-fold or greater rise between preexposure and postexposure antibody levels, which was 14.6% in the present study. Seroconversion rates were independent of CD4 T-lymphocyte count and HIV plasma load. Neither HIV infection, nor severe immunosuppression, was a significant risk factor for pandemic influenza during the first southern hemisphere pandemic wave.

Protein-losing enteropathy and hypogammaglobulinaemia as first manifestations of disseminated histoplasmosis coincident with Nocardia infection.

Disseminated histoplasmosis and nocardiosis typically affect immunocompromised hosts. We report a case of gastrointestinal and adrenal histoplasmosis, presenting as protein-losing enteropathy and hypogammaglobulinaemia, coincident with Nocardia infection, in a HIV-negative patient in whom a specific immunological defect could not be identified. Clinicians in areas of non-endemicity should be vigilant for rare manifestations of histoplasmosis.