SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID

Prediction of antigenic determinants and secondary structures of the major AIDS virus proteins

AbstractCriteria for the design of peptide vaccines to prevent AIDS are presented. The best vaccine candidates contain both B and T lymphocyte-defined epitopes in regions conserved in sequence between viral isolates. We propose that attention should focus on proteins specified by the gag and, possibly, pol genes in addition to the env gene envelope glycoproteins being actively studied. The predictions of B- and T-epitopes are refined by consideration of secondary structure prediction and inter-isolate sequence variability to suggest peptides from env, gag and pol that would be the best vaccine candidates

Increase in serum bilirubin levels in obstructive jaundice secondary to pancreatic and periampullary malignancy – implications for timing of resectional surgery and use of biliary drainage

Background. Routine preoperative biliary drainage in cases of jaundice secondary to pancreatobiliary malignancy is associated with a significant risk of complications, failure and stent occlusion. It may be possible to avoid biliary drainage in those patients who are not deeply jaundiced. Aims. To measure presenting serum bilirubin and its rate of increase in patients with malignant obstructive jaundice. To predict the urgency with which surgery should be performed to avoid preoperative biliary drainage. Patients and methods. Prospective data collection for all pancreatic and periampullary malignancies over a period of 18 months was carried out. Serum bilirubin levels before successful drainage were recorded. Rates of increase in bilirubin and the number of days for bilirubin to reach different thresholds were calculated. Results. Of 111 patients, 66 (59%) had resectable disease on imaging investigations. Median serum bilirubin on presentation was 160 µmol/l. Median increase was 13.1 µmol/l/day or approximately 100 µmol/l/week. The predicted number of days for bilirubin levels to reach a variety of thresholds varied significantly. For a patient presenting with a serum bilirubin of 160 µmol/l, the mean number of days for it to rise to 200 µmol/l, 300 µmol/l, 400 µmol/l and 500 µmol/l was 3, 13, 22 and 31 days, respectively. Conclusions. There is a variable window of opportunity in jaundiced patients with pancreatic and periampullary malignancy during which surgery may be performed to avoid biliary drainage procedures, depending on the threshold for operating on the jaundiced patient