COVID-19 cases from the first local outbreak of SARS-CoV-2 B.1.1.7 variant in China presented more serious clinical features: a prospective, comparative cohort study

BackgroundThe SARS-CoV-2 B.1.1.7 variant which was first identified in the United Kingdom (U.K.) has increased sharply in numbers worldwide and was reported to be more contagious. On January 17, 2021, a COVID-19 clustered outbreak caused by B.1.1.7 variant occurred in a community in Daxing District, Beijing, China. Three weeks prior, another non-variant (lineage B.1.470) COVID-19 outbreak occurred in Shunyi District, Beijing. This study aimed to investigate the clinical features of B.1.1.7 variant infection. MethodsA prospective cohort study was conducted on COVID-19 cases admitted to Ditan hospital since January 2020. Data of 74 COVID-19 cases from two independent COVID-19 outbreaks in Beijing were extracted as study subjects from a Cloud Database established in Ditan hospital, which included 41 Shunyi cases (Shunyi B.1.470 group) and 33 Daxing cases (Daxing B.1.1.7 group) that have been hospitalized since December 25, 2020 and January 17, 2021, respectively. We conducted a comparison of the clinical characteristics, RT-qPCR results and genomic features between the two groups. FindingsCases from Daxing B.1.1.7 group (15 [45.5%] male; median age, 39 years [range, 30.5, 62.5]) and cases from Shunyi B.1.470 group (25 [61.0%] male; median age, 31 years [range, 27.5, 41.0]) had a statistically significant difference in median age (P =0.014). Seven clinical indicators of Daxing B.1.1.7 group were significantly higher than Shunyi B.1.470 group including patients having fever over 38{degrees}C (14/33 [46.43%] in Daxing B.1.1.7 group vs. 9/41 (21.95%) in Shunyi B.1.470 group [P = 0 .015]), C-reactive protein ([CRP, mg/L], 4.30 [2.45, 12.1] vs. 1.80, [0.85, 4.95], [P = 0.005]), Serum amyloid A ([SAA, mg/L], 21.50 [12.50, 50.70] vs. 12.00 [5.20, 26.95], [P = 0.003]), Creatine Kinase ([CK, U/L]), 110.50 [53.15,152.40] vs. 70.40 [54.35,103.05], [P = 0.040]), D-dimer ([DD, mg/L], 0.31 [0.20, 0.48] vs. 0.24 [0.17,0.31], [P = 0.038]), CD4+ T lymphocyte ([CD4+ T, mg/L], [P = 0.003]), and Ground-glass opacity (GGO) in lung (15/33 [45.45%] vs. 5/41 [12.20%], [P =0.001]). After adjusting for the age factor, B.1.1.7 variant infection was the risk factor for CRP (P = 0.045, Odds ratio [OR] 2.791, CI [1.025, 0.8610]), SAA (0.011, 5.031, [1.459, 17.354]), CK (0.034, 4.34, [0.05, 0.91]), CD4+ T (0.029, 3.31, [1.13, 9.71]), and GGO (0.005, 5.418, [1.656, 17.729]) of patients. The median Ct value of RT-qPCR tests of the N-gene target in the Daxing B.1.1.7 group was significantly lower than the Shunyi B.1.470 group (P=0.036). The phylogenetic analysis showed that only 2 amino acid mutations in spike protein were detected in B.1.470 strains while B.1.1.7 strains had 3 deletions and 7 mutations. InterpretationClinical features including a more serious inflammatory response, pneumonia and a possible higher viral load were detected in the cases infected with B.1.1.7 SARS-CoV-2 variant. It could therefore be inferred that the B.1.1.7 variant may have increased pathogenicity. FundingThe study was funded by the National Key Research and Development Program (grant nos.2020YFC0846200 and 2020YFC0848300) and National Natural Science Foundation of China (grant no. 82072295).

Adsorptive separation of hemoglobin by molecularly imprinted chitosan beads.

A simply hemoglobin (Hb) molecularly imprinted polymer (MIP) was prepared using Hb as the imprinted molecule, acrylamide as the functional monomer and cross-linked chitosan beads as the supporting matrix. The MIP was achieved by entrapment of the selective soft polyacrylamide gel in the pores of the cross-linked chitosan beads by letting acrylamide monomer and the protein diffuse into the pores of chitosan beads before starting the polymerization. The chitosan beads were freed from the surrounding polyacrylamide gel by washing. The Langmuir and Freundlich adsorption models were applied to describe the equilibrium isotherms. Langmuir analysis showed that an equal class of adsorption was formed in the MIP and the adsorption equilibrium constant and the maximum adsorption capacity were evaluated. The MIP has much higher adsorption capacity for Hb than the non-imprinted polymer with the same chemical composition, and the MIP also has a higher selectivity for the imprinted molecule. The MIP can be reused in an easy way and the reproduction coefficient was approximately 100% at low concentration.

[Genetic analysis of facioscapulohumeral muscular dystrophy (FSHD)].

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscular disorder which is characterized by progressive weakness and atrophy of the facial, shoulder-girdle and upper arm muscles, and occasional subsequent pelvic-girdle and lower limb involvement. The gene responsible for FSHD has been localized to chromosome 4q35-qter, although a few 4q-unlinked families are known. To examine FSHD-associated DNA rearrangements in the Japanese population, we performed Southern blot analysis of the genomic DNA, using the p13E-11 and pFR-1 probes. Most of the Japanese FSHD patients (> 95%) had specific smaller (< 28 kb) EcoRI fragments which cosegregated with the disease. Restriction enzyme maps of the polymorphic EcoRI fragment detected by the probes have revealed that the disease occurs due to a deletion of the integral numbers of the 3.3kb KpnI tandemly repeated fragments (D4Z4) which contain homeobox-like sequences. Indeed, we cloned and characterized the FSHD-associated EcoRI fragments (the shortest fragment identified to date: 10kb) from two severely affected patients (unrelated). The 10kb fragment were identical and contained only one 3.3kb KpnI repeat unit. Although we still do not know whether truncation deletion of the D4Z4 region could produce FSHD directly or indirectly (position effect), we now beginning to understand FSHD. In the next step, FSHD gene products (mRNA and protein) responsible for the disease should be investigated.

Superficial necrolytic dermatitis (necrolytic migratory erythema) in dogs.

Twenty-two dogs with superficial necrolytic dermatitis were evaluated prospectively, twenty-one of which had characteristic crusting lesions of the paw pads. Histologically, epidermal lesions included parakeratosis and laminar intracellular edema. The plasma amino acid concentrations of eight dogs were markedly depressed. Nine dogs had terminal diabetes mellitus. These clinical and morphologic findings were strikingly similar to those of necrolytic migratory erythema in human beings, the most common cause of which is hyperglucagonemia due to islet cell tumor of the pancreas. No pancreatic tumors were found in these dogs; plasma glucagon concentrations in the five dogs tested were normal. The serum alkaline phosphatase concentrations were elevated in all dogs. Severe vacuolar hepatopathy, suggesting metabolically or hormonally induced hepatic dysfunction, was found in 21 dogs at necropsy or by biopsy; one dog had ultrasonographic abnormalities of the liver. Histopathologically, severe vacuolar alteration resulted in parenchymal collapse and nodular regeneration, which grossly mimicked cirrhosis. Although the definitive metabolic stimulus was not discovered for the cutaneous and hepatic lesions, the similarity of the cutaneous and biochemical features of canine superficial necrolytic dermatitis to human necrolytic migratory erythema warrants further investigation into possible underlying pancreatic hormonal dysfunction.

Clinical evaluation of etretinate for the treatment of canine solar-induced squamous cell carcinoma and preneoplastic lesions.

BACKGROUND: Tumors of the skin and subcutaneous tissue account for 30% of all canine neoplasms. Canine solar-induced squamous cell carcinoma (SCC) is the most frequently reported canine cutaneous neoplasm. OBJECTIVE: The purpose of this study was to provide preliminary observations on the safety and efficacy of etretinate for the treatment of solar-induced SCC and associated preneoplastic lesions in dogs. METHODS: Etretinate was administered to 10 dogs at 1 mg/kg twice daily for a minimum of 90 days. RESULTS: Clinically, two dogs showed complete resolution of their preneoplastic lesions, three dogs had partial responses, two dogs maintained stable disease, and three dogs showed progression of lesions after 90 days of etretinate administration. Three dogs showed histologic improvement, four dogs showed no changes, and three dogs showed evidence of progressing SCC. Treatment-related biochemical abnormalities included reversible hypertriglyceridemia and transient serum liver enzyme elevations in three dogs. CONCLUSION: These preliminary findings suggest that etretinate, at the dosage administered, may provide therapeutic efficacy for solar-induced preneoplastic lesions in the dog, particularly for those multifocal lesions not easily managed by local methods of therapy.

Homology of mecA gene in methicillin-resistant Staphylococcus haemolyticus and Staphylococcus simulans to that of Staphylococcus aureus.

A penicillin-binding protein of molecular weight 76,000 inducible by beta-lactams was detected in methicillin-resistant Staphylococcus haemolyticus and Staphylococcus simulans. DNA from these strains hybridized to the mecA gene from Staphylococcus aureus; however, the chromosomal HindIII fragments containing the mecA genes were 3.4 kilobases in S. haemolyticus and 4.3 kilobases in S. simulans.

Restriction maps of the regions coding for methicillin and tobramycin resistances on chromosomal DNA in methicillin-resistant staphylococci.

Chromosomal BamHI DNA fragments containing both the mecA gene encoding the penicillin-binding protein responsible for methicillin resistance and the aadD gene encoding 4',4"-adenylyltransferase responsible for tobramycin resistance were cloned from three methicillin- and tobramycin-resistant strains of Staphylococcus aureus and one strain of Staphylococcus epidermidis. Physical maps of the fragments were similar, suggesting their unique origin.

Evolution of an inducible penicillin-target protein in methicillin-resistant Staphylococcus aureus by gene fusion.

A new beta-lactam-inducible penicillin-binding protein (PBP) that has extremely low affinity to penicillin and most other beta-lactam antibiotics has been widely found in highly beta-lactam(methicillin)-resistant Staphylococcus aureus (MRSA). The gene for this protein was sequenced and the nucleotide sequence in its promoter and close upstream area was found to show close similarity with that of staphylococcal penicillinase, while the amino acid sequence over a wide range of the molecule was found to be similar to those of two PBPs of Escherichia coli, the shape-determining protein (PBP 2) and septum-forming one (PBP 3). Probably the MRSA PBP (Mr 76462) evolved by recombination of two genes: an inducible type I penicillinase gene and a PBP gene of a bacterium, causing the formation of a beta-lactam-inducible MRSA PBP.

Molecular cloning of the gene of a penicillin-binding protein supposed to cause high resistance to beta-lactam antibiotics in Staphylococcus aureus.

A novel penicillin-binding protein, PBP-2' (Mr about 75,000), is known to be induced in excessively large amount by most beta-lactam compounds in cells of a clinically isolated strain of Staphylococcus aureus, TK784, that is highly resistant to beta-lactams and also most other antibiotics. This protein has very low affinities to most beta-lactam compounds and has been supposed to be the cause of the resistance of the cells to beta-lactams. A 14-kilobase DNA fragment was isolated from the cells that carried the gene encoding this penicillin-binding protein and also a genetically linked marker that is responsible for the resistance to tobramycin. This DNA was cloned on plasmid pACYC184 and was shown to cause both production of PBP-2' and resistance to tobramycin in Escherichia coli cells. However, the formation of PBP-2' in E. coli was only moderate and was independent of normal inducer beta-lactams. The PBP-2' formed in the E. coli cells showed slow kinetics of binding to beta-lactams similar to that of PBP-2' formed in the original S. aureus cells and gave a similar pattern of peptides to the latter when digested with the proteolytic V8 enzyme of S. aureus.