Differential antibody production by symptomatology in SARS-CoV-2 convalescent individuals

The association between COVID-19 symptoms and antibody responses against SARS-CoV-2 is poorly characterized. We analyzed antibody levels in individuals with known SARS-CoV-2 infection to identify potential antibody-symptom associations. Convalescent plasma from 216 SARS-CoV-2 RNA+ individuals with symptomatology information were tested for the presence of IgG to the spike S1 subunit (Euroimmun ELISA), IgG to receptor binding domain (RBD, CoronaCHEK rapid test), and for IgG, IgA, and IgM to nucleocapsid (N, Bio-Rad ELISA). Logistic regression was used to estimate the odds of having a COVID-19 symptom from the antibody response, adjusting for sex and age. Cough strongly associated with antibodies against S1 (adjusted odds ratio [aOR]= 5.33; 95% CI from 1.51 to 18.86) and RBD (aOR=4.36; CI 1.49, 12.78). In contrast, sore throat significantly associated with the absence of antibodies to S1 and N (aOR=0.25; CI 0.08, 0.80 and aOR=0.31; 0.11, 0.91). Similarly, lack of symptoms associated with the absence of antibodies to N and RBD (aOR=0.16; CI 0.03, 0.97 and aOR=0.16; CI 0.03, 1.01). Cough appeared to be correlated with a seropositive result, suggesting that SARS-CoV-2 infected individuals exhibiting lower respiratory symptoms generate a robust antibody response. Conversely, those without symptoms or limited to a sore throat while infected with SARS-CoV-2 were likely to lack a detectable antibody response. These findings strongly support the notion that severity of infection correlates with robust antibody response.

A Third Dose of SARS-CoV-2 Vaccine Increases Neutralizing Antibodies Against Variants of Concern in Solid Organ Transplant Recipients

Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses increase anti-spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti-spike IgG, pseudoneutralization (ACE2 blocking), and live-virus neutralization (nAb) against VOCs before and after a third SARS-CoV-2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti-spike IgG assays and focused on thresholds associated with neutralizing activity. A third SARS-CoV-2 vaccine dose increased median anti-spike (1.6-fold) and receptor-binding domain (1.5-fold) IgG, as well as pseudoneutralization against VOCs (2.5-fold versus Delta). However, IgG and neutralization activity were significantly lower than healthy controls (p<0.001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination. Correlation with nAb was seen at anti-spike IgG >4 AU on the clinical assay and >10^4 AU on the research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.

A hemagglutination-based, semi-quantitative test for point-of-care determination of SARS-CoV-2 antibody levels

Serologic, point-of-care tests to detect antibodies against SARS-CoV-2 are an important tool in the COVID-19 pandemic. The majority of current point-of-care antibody tests developed for SARS-CoV-2 rely on lateral flow assays, but these do not offer quantitative information. To address this, we developed a new method of COVID-19 antibody testing employing hemagglutination tested on a dry card, similar to that which is already available for rapid typing of ABO blood groups. A fusion protein linking red blood cells (RBCs) to the receptor-binding domain (RBD) of SARS-CoV-2 spike protein was placed on the card. 200 COVID-19 patient and 200 control plasma samples were reconstituted with O-negative RBCs to form whole blood and added to the dried protein, followed by a stirring step and a tilting step, 3-minute incubation, and a second tilting step. The sensitivity for the hemagglutination test, Euroimmun IgG ELISA test and RBD-based CoronaChek lateral flow assay was 87.0%, 86.5%, and 84.5%, respectively, using samples obtained from recovered COVID-19 individuals. Testing pre-pandemic samples, the hemagglutination test had a specificity of 95.5%, compared to 97.3% and 98.9% for the ELISA and CoronaChek, respectively. A distribution of agglutination strengths was observed in COVID-19 convalescent plasma samples, with the highest agglutination score (4) exhibiting significantly higher neutralizing antibody titers than weak positives (2) (p<0.0001). Strong agglutinations were observed within 1 minute of testing, and this shorter assay time also increased specificity to 98.5%. In conclusion, we developed a novel rapid, point-of-care RBC agglutination test for the detection of SARS-CoV-2 antibodies that can yield semi-quantitative information on neutralizing antibody titer in patients. The five-minute test may find use in determination of serostatus prior to vaccination, post-vaccination surveillance and travel screening.

Comparative performance of multiplex salivary and commercially available serologic assays to detect SARS-CoV-2 IgG and neutralization titers

Oral fluid (hereafter saliva) offers a non-invasive sampling method for the detection of SARS-CoV-2 antibodies. However, data comparing performance of salivary tests against commercially-available serologic and neutralizing antibody (nAb) assays are lacking. This study compared the performance of a multiplex salivary SARS-CoV-2 IgG assay targeting antibodies to nucleocapsid (N), receptor binding domain (RBD) and spike (S) antigens to three commercially-available SARS-CoV-2 serology enzyme immunoassays (EIAs) (Ortho Vitros, Euroimmun, and BioRad) and nAb. Paired saliva and plasma samples were collected from 101 eligible COVID-19 convalescent plasma (CCP) donors >14 days since PCR+ confirmed diagnosis. Concordance was evaluated using positive (PPA) and negative (NPA) percent agreement, overall percent agreement (PA), and Cohens kappa coefficient. The range between salivary and plasma EIAs for SARS-CoV-2-specific N was PPA: 54.4-92.1% and NPA: 69.2-91.7%, for RBD was PPA: 89.9-100% and NPA: 50.0-84.6%, and for S was PPA: 50.6-96.6% and NPA: 50.0-100%. Compared to a plasma nAb assay, the multiplex salivary assay PPA ranged from 62.3% (N) and 98.6% (RBD) and NPA ranged from 18.8% (RBD) to 96.9% (S). Combinations of N, RBD, and S and a summary algorithmic index of all three (N/RBD/S) in saliva produced ranges of PPA: 87.6-98.9% and NPA: 50-91.7% with the three EIAs and ranges of PPA: 88.4-98.6% and NPA: 21.9-34.4% with the nAb assay. A multiplex salivary SARS-CoV-2 IgG assay demonstrated comparable performance to three commercially-available plasma EIAs and a nAb assay, and may be a viable alternative to assist in screening CCP donors and monitoring population-based seroprevalence and vaccine antibody response.

Total arch replacement combined with stented elephant trunk implantation for Stanford type A aorticdissection / 中国医师杂志

ObjectiveTo improve the long term outcomes of the surgery for Stafford type A aorticdissection, we performed ascending aorta and total aortic arch replacement combined with transaorticstented graft implantation into the descending aorta for acute type A aortic dissection.MethodsFrom May 2005 to February 2011,36 consecutive patients with acute Stanford type A aorticdissection underwent this procedure.Right axillary artery cannulation was routinely used forcardiopulmonary bypass and selected cerebral perfusion.The stented elephant trunk was implanted through the aortic arch under hypothermic circulatory arrest.The stented elephant trunk was a 10 cm long selfexpandable graft.34 patients were followed up for 2 ～36 months.ResultsCardiopulmonary bypass time was (160 ± 31)min, average cross clamp time was (101 ±26)min, and average selective cerebral perfusion and lower body arrest time was (31 ± 16)min.The in-hospital mortality was 5.5％ (2/36).One patient died of multi-organ failure postoperatively and another died of cerebral infarction 9 day after surgery.No one suffered from spinal cord injury perioperatively.There was no late death during follow up.ConclusionsAscendingaorta and total aortic arch replacement combined with transaortic stented graft implantation into the descending aorta is an effective way in closing the residual false lumen of the descending aorta and might contribute to better long term outcomes of type A aortic dissection.

Expression of ki-67 and intimal hyperplasia of the irradiated human umbilical artery incorporated with nofloxacin and silver grafts / 中国医师杂志

Objective To investigate the expression of ki-67 and the development of the intimal hyperplasia(IH) of the irradiated human umbilical artery incorperated with nofloxacin and silver(IHUAINS) grafts into the carotid arteries of the rabbit. Methods Twenty IHUAINSs were sterilely produced. Thirty rabbit were performed bilateral carotid bypass grafting. The IHUAINS(experimental group)and the left carotid arteries (control group) were implanted in the left and right carotid arteries respectively. Graft patency was checked at the 2nd and 6th week after implantation, and the grafts were studied with standard histological techniques and immunohistochemieal method for meas-urement of intimal thickness and the expression of ki-67. Results The total patency rate of the grafts was 89.6%. Light microscopic exami-nation of the grafts revealed intimal and media proliferation, cellular in-filtration. The endothelial cells covered the vascular lumen. There was no significant difference of the intimal thickness between two groups at the 2nd week after grafting (P>0.05). The intimal thickness of the experimental group was larger than that in control group at the 6th week after implantation without statistical significance (P>0.05). At the same time, immunocytochemical analysis showed that the expression of ki-67 in the experimental group was stronger than that in control group without statistical significance(P>0.05). Conclusion The IH of the IHUAINS was larger than that of the autologous artery, but there is no difference between these two groups. Thus, IHUAINS may be an ideal graft in the field of coronary surgery.

Diagnostic and prognostic values of serum CA125, NSE, CT levels in patients with lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>To explore the clinical and prognostic values of serum carbohydrate antigen (CA125), neuron-specific enolase (NSE), calcitonin (CT) levels in patients with lung cancer before operation.</p><p><b>METHODS</b>Ninety two untreated patients with lung cancer confirmed histologically were studied. Serum CA125, NSE, and CT were detected in 92 lung cancer patients by ELISA before operation. Thirty healthy volunteers were chosen as controls.</p><p><b>RESULTS</b>The sensitivity of CA125, NSE, and CT for the diagnosis of lung cancer were 48.9%, 21.7%, and 7.6% respectively. The level of CA125 in lung cancer patients was significantly higher than that of control (P < 0.05). The level of NSE in patients with small cell lung cancer was significantly higher than that of control (P < 0.01). The level of CT in lung cancer patients was higher than that of control, but without significant difference. The 3-year survival rate of patients with increased serum CA125 level before operation was 44.4% (20/45), whereas that of patients with normal CA125 level was 66.0% (31/47) (P < 0.05). The 3-year survival rate of patients with increased serum NSE and CT levels was 45.0% (9/20) and 42.8% (3/7) respectively, whereas that of patients with normal serum NSE and CT level was 58.3% (42/72) and 56.5% (48/85) respectively. The 3-year survival rate of patients with increased serum NSE or CT level had no significant difference with that of patients with normal level (P > 0.05).</p><p><b>CONCLUSIONS</b>The diagnostic values of CA125, NSE and CT are limited. CA125 can be used as an prognostic parameter in patients with lung cancer after operation.</p>

Occlusion of Atrial Septal Defect via Small Chest Incision:Report of 41 Cases / 中国微创外科杂志

Objective To discuss the surgical outcomes of atrial septal defects(ASD) by closing the ostium secundum via small chest incision.MethodsTotally 41 cases with ASD were treated by occlusion via a small incision(3-4 cm) at the right anterior chest.After cutting the pericardium,the right atrial was sutured with double ring and a special occluding device was inserted to close the ostium.Afterwards,under the guidance of transthoracical or transesophageal echocardiography,the satisfiable position for the occluder was confirmed by repeated testing with the protect string.After that,the right atrial and the occluder were sutured by a needle thread for fixation.ResultsOf the patients,the procedure was successfully completed in 39 cases.The mean operation time was 45 to 95 minutes(mean,60 minutes).The patients were discharged from our hospital in 3 to 6 days.No dislocation of the device or atrial shut was found in 2 to 24 months after the operation.Two patients were converted to open surgery because of failure in the occlusion.ConclusionOcclusion via small chest incision is safe,minimally invasive,and convenient procedure for ASD.