A hybrid individual-based mathematical model to study bladder infections

RB was supported by a fellowship funded by the Medical Research Council, MR/P014704/1, and also acknowledges funding from the Academy of Medical Sciences (London), the Wellcome Trust (London), the UK Government Department of Business, Energy and Industrial Strategy (London), the British Heart Foundation (London), and the Global Challenges Research Fund (Swindon, UK; grant number SBF003\1052). TL gratefully acknowledges support from the Italian Ministry of University and Research (MUR) through the grant Dipartimenti di Eccellenza 2018-2022 (Project no. E11G18000350001) and the PRIN 2020 project (No. 2020JLWP23) Integrated Mathematical Approaches to Socio-Epidemiological Dynamics (CUP: E15F21005420006).Introduction: Bladder infections are common, affecting millions each year, and are often recurrent problems. Methods: We have developed a spatial mathematical framework consisting of a hybrid individual-based model to simulate these infections in order to understand more about the bacterial mechanisms and immune dynamics. We integrate a varying bacterial replication rate and model bacterial shedding as an immune mechanism. Results: We investigate the effect that varying the initial bacterial load has on infection outcome, where we find that higher bacterial burden leads to poorer outcomes, but also find that only a single bacterium is needed to establish infection in some cases. We also simulate an immunocompromised environment, confirming the intuitive result that bacterial spread typically progresses at a higher rate. Conclusions: With future model developments, this framework is capable of providing new clinical insight into bladder infections.Publisher PDFPeer reviewe

Lessons for the clinical nephrologist: recurrence of nephrotic syndrome induced by SARS-CoV-2

Abstract SARS-CoV-2 is characterized by a multiorgan tropism including the kidneys. Recent autopsy series indicated that SARS-CoV-2 can infect both tubular and glomerular cells. Whereas tubular cell infiltration may contribute to acute kidney injury, data on a potential clinical correlative to glomerular affection is rare. We describe the first case of nephrotic syndrome in the context of COVID-19 in a renal transplant recipient. A 35 year old male patient received a kidney allograft for primary focal segmental glomerulosclerosis (FSGS). Three months posttransplant a recurrence of podocytopathy was successfully managed by plasma exchange, ivIG, and a conversion from tacrolimus to belatacept (initial proteinuria > 6 g/l decreased to 169 mg/l). Six weeks later he was tested positive for SARS-CoV-2 and developed a second increase of proteinuria (5.6 g/l). Renal allograft biopsy revealed diffuse podocyte effacement and was positive for SARS-CoV-2 in RNA in-situ hybridation indicating a SARS-CoV-2 associated recurrence of podocytopathy. Noteworthy, nephrotic proteinuria resolved spontaneously after recovering from COVID-19. The present case expands the spectrum of renal involvement in COVID-19 from acute tubular injury to podocytopathy in renal transplant recipients. Thus, it may be wise to test for SARS-CoV-2 prior to initiation of immunosuppression in new onset glomerulopathy during the pandemic

A hybrid individual-based mathematical model to study bladder infections

Introduction: Bladder infections are common, affecting millions each year, and are often recurrent problems. Methods: We have developed a spatial mathematical framework consisting of a hybrid individual-based model to simulate these infections in order to understand more about the bacterial mechanisms and immune dynamics. We integrate a varying bacterial replication rate and model bacterial shedding as an immune mechanism. Results: We investigate the effect that varying the initial bacterial load has on infection outcome, where we find that higher bacterial burden leads to poorer outcomes, but also find that only a single bacterium is needed to establish infection in some cases. We also simulate an immunocompromised environment, confirming the intuitive result that bacterial spread typically progresses at a higher rate. Conclusions: With future model developments, this framework is capable of providing new clinical insight into bladder infections

Detection of SARS-CoV-2 pneumonia: two case reports

Background!#!Developing therapeutic strategies for a SARS-CoV-2 infection is challenging, but first the correct diagnosis has to be made. Unspecific upper and lower respiratory tract symptoms can be misleading; hence, a nasopharyngeal swab test with a real-time reverse-transcription-polymerase chain reaction is of great importance. However, early viral clearing jeopardizes a sound diagnosis of COVID-19.!##!Case presentation!#!We report on two Caucasian patients who had negative pharyngeal swab tests at the onset of SARS-CoV-2 pneumonia. In one patient, the virus was not even detectable in bronchoalveolar lavage despite typical radiomorphologic changes.!##!Conclusions!#!Negative PCR findings in both the pharynx and bronchoalveolar lavage do not exclude COVID-19 pneumonia. Computed tomography is a crucial diagnostic prerequisite in this context

Lessons for the clinical nephrologist: recurrence of nephrotic syndrome induced by SARS-CoV-2

SARS-CoV-2 is characterized by a multiorgan tropism including the kidneys. Recent autopsy series indicated that SARS-CoV-2 can infect both tubular and glomerular cells. Whereas tubular cell infiltration may contribute to acute kidney injury, data on a potential clinical correlative to glomerular affection is rare. We describe the first case of nephrotic syndrome in the context of COVID-19 in a renal transplant recipient. A 35 year old male patient received a kidney allograft for primary focal segmental glomerulosclerosis (FSGS). Three months posttransplant a recurrence of podocytopathy was successfully managed by plasma exchange, ivIG, and a conversion from tacrolimus to belatacept (initial proteinuria > 6 g/l decreased to 169 mg/l). Six weeks later he was tested positive for SARS-CoV-2 and developed a second increase of proteinuria (5.6 g/l). Renal allograft biopsy revealed diffuse podocyte effacement and was positive for SARS-CoV-2 in RNA in-situ hybridation indicating a SARS-CoV-2 associated recurrence of podocytopathy. Noteworthy, nephrotic proteinuria resolved spontaneously after recovering from COVID-19. The present case expands the spectrum of renal involvement in COVID-19 from acute tubular injury to podocytopathy in renal transplant recipients. Thus, it may be wise to test for SARS-CoV-2 prior to initiation of immunosuppression in new onset glomerulopathy during the pandemic