ABSTRACT
The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused the devastating ongoing coronavirus disease-2019 (COVID-19) pandemic which poses a great threat to global public health. The spike (S) polypeptide of SARS-CoV-2 consists of the S1 and S2 subunits and is processed by cellular proteases at the S1/S2 boundary. The inclusion of the 4 amino acids (PRRA) at the S1/S2 boundary forms a furin cleavage site (FCS), 682RRAR{downarrow}S686, distinguishing SARS-CoV-2 from its closest relative, the SARS-CoV. Various deletions surrounding the FCS have been identified in patients. When SARS-CoV-2 propagated in Vero cells, the virus acquired various deletions surrounding the FCS. In the present study, we studied the viral transcriptome in SARS-CoV-2 infected primary human airway epithelia (HAE) cultured at an air-liquid interface (ALI) with an emphasis on the viral genome stability at the S1/S2 boundary using RNA-seq. While we found overall the viral transcriptome is similar to that generated from infected Vero cells, we identified a high percentage of mutated viral genome and transcripts in HAE-ALI. Two highly frequent deletions were found at the S1/S2 boundary of the S gene: one is a deletion of 12 amino acids, 678TNSPRRAR{downarrow}SVAS689, which contains the FCS, another is a deletion of 5 amino acids, 675QTQTN679, which is two amino acids upstream of the FCS. Further studies on the dynamics of the FCS deletions in apically released virions revealed that the selective pressure for the FCS maintains the S gene stability in HAE-ALI but with exceptions, in which the FCS deletions are remained at a high rate. Thus, our study presents evidence for the role of unique properties of human airway epithelia in the dynamics of the FCS region during infection of human airways, which is donor-dependent.
ABSTRACT
<p><b>OBJECTIVE</b>To analyze the clinical risk factors for deep vein thrombosis (DVT) after total hip and knee arthroplasty in Chinese patients who received prophylactic treatment for DVT.</p><p><b>METHODS</b>We evaluated 128 total hip arthroplasty (THA) and total knee arthroplasty (TKA) in 95 patients performed at our center from April 2004 to August 2004, which included 48 THAs in 43 patients and 80 TKAs in 52 patients. There were 27 men and 68 women with a mean age of 59.77 years (range, 23-78 years). All patients had been given low-molecular-weight heparin before operation and for 7-10 days post-operation to prevent DVT. Color Doppler ultrasonography was used to detect DVT of bilateral lower extremities in all patients before operation and at 7-10 days after operation. Nineteen clinical factors were examined preoperation and 7-10 days post-operation in order to analyze their influences on DVT formation after surgery.</p><p><b>RESULTS</b>There were 45 patients who developed DVT after operation. The incidence of DVT in all patients was 47.4% (45/95) and the incidence of proximal DVT was 3.2%. There were more asymptomatic DVT (57.8%, 26/45) than symptomatic ones, and some patients without DVT (14%, 7/50) presented some of the DVT symptoms. Logistic regression analysis demonstrated a definite association of female, obesity (representative by BMI), cement usage and diagnosed RA with DVT with odds ratio of 10.008, 3.094, 8.887, and 0.194 respectively. Other clinical factors had no statistically significant association with DVT.</p><p><b>CONCLUSIONS</b>Female, obesity, and cement usage were the risk factors for DVT after THA and TKA, and diagnosed RA was the protecting factors for DVT after THA and TKA. Other clinical factors such as age, OA, type of implant, monolateral or bilateral operation, duration of anesthesia, surgery and bandage usage for blood control, time for immobilization et al were not the risk factors for DVT.</p>
