Mutation and codon bias analysis of the spike protein of Omicron, the recent variant of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is a heavily mutated virus and designated as a variant of concern. To investigate the codon usage pattern of this new variant, we performed mutation and codon bias analysis for Omicron as well as for its sub-lineages BA.1 and BA.2 and compared them with the original SARS-CoV-2 and the Delta variant sequences obtained in this study. Our results indicate that the sub-lineage BA.1 and BA.2 have up to 23 sites of difference on the spike protein, which have minimal impact on function. The Omicron variant and its sub-lineages have similar codon usage patterns and A/U ending codons appear to be preferred over G/C ending codons. The Omicron has a lower degree of codon usage bias in spite of evidence that natural selection, mutation pressure and dinucleotide abundance shape the codon usage bias of Omicron, with natural selection being more significant on BA.2 than the other sub-lineages of Omicron. The codon usage pattern of Omicron variant that we explored provides valid information for a clearer understanding of Omicron and its sub-lineages, which could find application in vaccine development and optimization.

Fast and precise pathogen detection and identification of overlapping infection in patients with CUTI based on metagenomic next-generation sequencing: A case report.

RATIONALE: The gold standard for pathogen detection and identification of complicated urinary tract infection (CUTI) remains quantitative urine culture, however, the diagnostic value of urine culture remains limited due to the time-consuming procedure and low detection rate. Here we report a case of successfully using Metagenomic next-generation sequencing (mNGS) provided fast and precise detection and identification of overlapping infection in patients with CUTI with no similar reports or studies published before to the best of our knowledge. PATIENT CONCERNS: A 70-year-old male was admitted to hospital due to elevated serum creatinine for 2 weeks. DIAGNOSES: Acute exacerbation of chronic renal failure and CUTI were the most critical diagnosis on admission. INTERVENTIONS: Blood purification, bladder irrigation and aggressive anti-infective therapy were administered. But the empirical anti-infection therapy and the adjustment of treatment according to the evidence of urine culture drug sensitivity had no obvious effect. We further carried out urinary PMseq-DNA detection and the results showed overlapping infection with Enterococcus faecium, Enterococcus hirae, Pseudomonas aeruginosa, Pseudomonas denitrificans and Candida albicans. According to the genetic test results, linezolid, meropenem and fluconazole triple anti-infection treatment was given. OUTCOMES: After adjusting the treatment, the infection was basically controlled in 10 days, and even the renal function was significantly improved, dialysis independence was achieved after 3 months. LESSONS: Our case illustrated the potential application of mNGS in detecting pathogenic microorganisms in patients with CUTI especially when overlapping infections are present.

Pneumocystis pneumonia secondary to intensive immunosuppression treatment for anti-GBM disease complicated with IgA nephropathy: A case report and literature review.

RATIONALE: The estimated incidence of anti-glomerular basement membrane (anti-GBM) disease complicated with immunoglobulin A (IgA) nephropathy is minimal, there have only been 15 cases (including this case) reported in the literature, and only 5 (33.33%) of them showed significant improvement in renal function after treatment. Pneumocystis pneumonia is a severe opportunistic pulmonary infection of pneumocystis jiroveci in immunocompromised patients. Here, we report a case of pneumocystis pneumonia secondary to intensive immunosuppression treatment for anti-GBM disease complicated with IgA nephropathy, with no similar reports or studies published before to our knowledge. PATIENT CONCERNS: The patient was admitted to our hospital with a 1-week diagnosis of crescent glomerulonephritis who had been suffered from hematuria and foamy urine for more than 1 month. Before admission, the patient received pulse dose intravenous methylprednisolone and immunosuppression with rituximab, but the renal function and titer of pathogenic antibody did not improve significantly. DIAGNOSIS: Crescentic glomerulonephritis, anti-glomerular basal membrane disease complicated with IgA nephropathy (Type I+II) was pathologically confirmed by renal biopsy. Secondary pneumocystis pneumonia was diagnosed by acute progressive respiratory failure, chest computed tomography and metagenomic next-generation sequencing of transbronchoscopic bronchoalveolar lavage fluid. INTERVENTIONS: The key to successful treatment was to make the pathogenic antibody turn negative quickly by combining pulse dose intravenous methylprednisolone, immunosuppression with rituximab, and plasma exchange therapy. Early identification of pneumocystis pneumonia, accurate etiological identification, and active anti-infective treatment were also crucial. OUTCOMES: The patient was discharged after 16 days of anti-infection with secondary infection controlled and dialysis catheter removed. Up to now, the patient has been followed for a period of 28 weeks, results showed renal function had been repaired even hematuria and proteinuria were basically alleviated. LESSONS: Our case provided experience in the treatment of anti-GBM disease complicated with IgA nephropathy, further proposed the potential therapeutic effects of rituximab, also illustrated low dose hormone combined with tacrolimus can be used as sequential therapy after plasma exchange and intensive immunosuppression. Our research also suggested that resulting in severe immune suppression, a high risk of secondary pneumocystis opportunistic infection should be aware of. metagenomic next-generation sequencing might increase the detection rate of the pathogen.

[Clinical report on treatment of thrombocytopenia with rhIL-11 (Mega) in 10 chronic aplastic anemia patients].

In order to evaluated the curative effect of rhIL-11 (Mega) on thrombocytopenia in chronic aplastic anemia (CAA) patients, ten CAA cases with thrombocytopenia after administration of conventional drugs were selected and subcutaneously injected 0.75 mg Mega per day in 1 - 2 courses of treatment on the basis of conventional therapy. Results showed that platelet counts were obviously increased and the bleeding symptoms were alleviated in all CAA patients after application of Mega for treatment. In conclusion, the rhIL-11 (Mega) could be used as an effective drug for treatment of thrombocytopenia in CAA patients.