Residual SARS-CoV-2 viral antigens detected in gastrointestinal and hepatic tissues from two recovered COVID-19 patients

Residual SARS-CoV-2 RNA has been detected in stool samples and gastrointestinal tissues during the convalescence phase of COVID-19 infection. This raises concern for persistence of SARS-CoV-2 virus particles and faecal-oral transmissibility in recovered COVID-19 patients. Using multiplex immunohistochemistry, we unexpectedly detected SARS-CoV-2 viral antigens in intestinal and liver tissues, in surgical samples obtained from two patients who recovered from COVID-19. We further validated the presence of virus by RT-PCR and flow cytometry to detect SARS-CoV-2-specific immunity in the tissues. These findings might have important implications in terms of disease management and public health policy regarding transmission of COVID-19 via faecal-oral and iatrogenic routes during the convalescence phase.

SUCCESSFUL MANUFACTURING OF CLINICAL-GRADE SARS-CoV-2 SPECIFIC T CELLS FOR ADOPTIVE CELL THERAPY

BackgroundAdoptive therapy with SARS-CoV-2 specific T cells for COVID-19 has not been reported. The feasibility of rapid clinical-grade manufacturing of virus-specific T cells from convalescent donors has not been demonstrated for this or prior pandemics. MethodsOne unit of whole blood was collected from each convalescent donor following standard blood bank practices. After the plasma was separated and stored separately, the leukocytes were stimulated using overlapping peptides of SARS-CoV-2, covering the immunodominant sequence domains of the S protein and the complete sequence of the N and M proteins. Thereaftesr, functionally reactive cells were enriched overnight using an automated device capturing IFN{gamma}-secreting cells. FindingsFrom 1x109 leukocytes, 0.56 to 1.16x106 IFN{gamma}+ T cells were produced from each of the first two donors. Most of the T cells (64% to 71%) were IFN{gamma}+, with preferential enrichment of CD56+ T cells, effector memory T cells, and effector memory RA+ T cells. TCRV{beta} spectratyping revealed oligoclonal distribution, with over-representation of subfamilies including V{beta}3, V{beta}16 and V{beta}17. With just two donors, the probability that a recipient in the same ethnic group would share at least one donor HLA allele or one haplotype could be as high as >90% and >30%, respectively. InterpretationsThis study is limited by small number of donors and absence of recipient data; however, crucial first proof-of-principle data are provided demonstrating the feasibility of clinical-grade production of SARS-CoV-2 specific T cells for urgent clinical use, conceivably with plasma therapy concurrently. Our data showing that virus-specific T cells can be detected easily after brief stimulation with SARS-CoV-2 specific peptides suggest that a parallel diagnostic assay can be developed alongside serology testing. FundingThe study was funded by a SingHealth Duke-NUS Academic Medicine COVID-19 Rapid Response Research Grant.

Severe infection with H1N1 requiring intensive care--lessons for preparedness programmes

<p><b>INTRODUCTION</b>The influenza pandemic has generated much interest in the press and the medical world. We report our experience with 15 cases of severe novel influenza A H1N1 (2009) infections requiring intensive care. The aim of this review is to improve our preparedness for epidemics and pandemics by studying the most severely affected patients.</p><p><b>CLINICAL PICTURE</b>During the epidemic, hospitals were required to provide data on all confirmed H1N1 cases admitted to an intensive care unit (ICU) to the Ministry of Health. We abstracted information from this dataset for this report. To highlight learning points, we reviewed the case notes of, and report, the fi ve most instructive cases.</p><p><b>TREATMENT</b>There were 15 cases admitted to an ICU from July 4, 2009 to August 30, 2009. Two patients died.</p><p><b>CONCLUSIONS</b>The lessons we wish to share include the following: preparedness should include having intermediate-care facilities that also provide single room isolation and skilled nursing abilities, stringent visitor screening should be implemented and influenza may trigger an acute myocardial infarction in persons with risk factors.</p>

"Future" threat of gram-negative resistance in Singapore

The emergence of multidrug-resistant gram-negative bacteria is challenging the treatment of serious nosocomial infections. This is an international trend that is mirrored in Singapore too. Reports of strains resistant to all currently available agents have surfaced here and possibly have taken root here as well. The direst situation is among the non-fermenters, Pseudomonas aeruginosa and Acinetobacter baumannii. This is followed closely by the Enterobacteriaceae family with their array of extended-spectrum beta-lactamases, AmpC beta-lactamases and carbapenemases. There are also resistance mechanisms such as efflux pumps and porins downregulation that effect resistance against multiple classes of agents. Potentiating these developments is the dwindling "pipeline" of new agents. Hence, there is a real concern that we are running out of options for our patients. Novel antibiotic combinations, enhanced infection control, antibiotic cycling, computer-assisted programmes, and maybe in the distant future, non-antimicrobial agents is all that we have.