Two Case Reports of Newly Diagnosed Crohn's Disease after COVID-19 in Pediatric Patients.

Since the coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome-coronavirus-2 virus (SARS-CoV-2), various complications have been reported. Although most COVID-19 cases exhibited flu-like symptoms, COVID-19 may dysregulate the immune response and promote overwhelming levels of inflammation in some patients. Inflammatory bowel disease (IBD) is caused by dysregulated or inappropriate immune responses to environmental factors in a genetically susceptible host, and a SARS-CoV-2 infection may act as a possible cause of IBD. This paper describes two pediatric patients who developed Crohn's disease following a SARS-CoV-2 infection. They were previously healthy before the SARS-CoV-2 infection. On the other hand, they started to develop fever and gastrointestinal symptoms several weeks after recovery from the infection. They were diagnosed with Crohn's disease by imaging and endoscopic studies, and their symptoms improved after treatment with steroids and azathioprine. This paper suggests that a SARS-CoV-2 infection may trigger IBD in predisposed patients.

Mutational spectrum of SARS-CoV-2 during the global pandemic.

Viruses accumulate mutations under the influence of natural selection and host-virus interactions. Through a systematic comparison of 351,525 full viral genome sequences collected during the recent COVID-19 pandemic, we reveal the spectrum of SARS-CoV-2 mutations. Unlike those of other viruses, the mutational spectrum of SARS-CoV-2 exhibits extreme asymmetry, with a much higher rate of C>U than U>C substitutions, as well as a higher rate of G>U than U>G substitutions. This suggests directional genome sequence evolution during transmission. The substantial asymmetry and directionality of the mutational spectrum enable pseudotemporal tracing of SARS-CoV-2 without prior information about the root sequence, collection time, and sampling region. This shows that the viral genome sequences collected in Asia are similar to the original genome sequence. Adjusted estimation of the dN/dS ratio accounting for the asymmetrical mutational spectrum also shows evidence of negative selection on viral genes, consistent with previous reports. Our findings provide deep insights into the mutational processes in SARS-CoV-2 viral infection and advance the understanding of the history and future evolution of the virus.

Three-Dimensional Human Alveolar Stem Cell Culture Models Reveal Infection Response to SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the cause of a present pandemic, infects human lung alveolar type 2 (hAT2) cells. Characterizing pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hAT2 cells limits the study. Here, we develop a feeder-free, long-term, three-dimensional (3D) culture technique for hAT2 cells derived from primary human lung tissue and investigate infection response to SARS-CoV-2. By imaging-based analysis and single-cell transcriptome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and proinflammatory genes in infected hAT2 cells, indicating a robust endogenous innate immune response. Further tracing of viral mutations acquired during transmission identifies full infection of individual cells effectively from a single viral entry. Our study provides deep insights into the pathogenesis of SARS-CoV-2 and the application of defined 3D hAT2 cultures as models for respiratory diseases.