Delayed antigen-specific CD4+ T cell induction correlates with impaired immune responses to SARS-COV-2 mRNA vaccination in the elderly

Despite the clinical efficacy of coronavirus disease 2019 mRNA vaccines, the elderly demonstrate lower IgG levels and neutralizing titers and a higher risk of severe diseases. CD4+ T cells play a central role in regulating antigen-specific antibody and CD8+ T-cell responses; however, because their composition and functionality change significantly with age, relationships between age-associated defects in T cells and the immunogenicity of or reactogenicity to mRNA vaccines are unclear. Using a vaccine cohort (n = 216), we found that the elderly (aged [≥]65 years) showed delayed induction and early contraction of vaccine-specific CD4+ T cells, and that the compromised C-X-C motif chemokine receptor 3+ circulating T follicular helper cell response after the first dose was associated with the lower IgG levels. Additionally, the elderly experienced significantly fewer systemic adverse effects (AEs) after the second dose, with those exhibiting few AEs showing lower cytokine+ CD4+ T cells after the first dose and lower antibody levels after the second dose. Furthermore, T helper 1 cells in the elderly expressed higher levels of programmed cell death protein-1, a negative regulator of the T-cell response, which was associated with less production of vaccine-specific CD4+ T cells and impaired CD8+ T-cell expansion. Thus, efficient induction of vaccine-specific effector/memory CD4+ T cells after the first dose may trigger robust cytokine production after the second dose, leading to effective vaccine responses and higher systemic reactogenicity. These results suggested that an enhanced CD4+ T-cell response after the first dose is key to improved vaccination efficacy in the elderly. One Sentence SummaryWe compared immunogenicity and reactogenicity to COVID-19 mRNA vaccine in 107 adults (aged <65 years) and 109 elderly (aged [≥]65) individuals.

Large-scale cross-sectional seroepidemiologic study of COVID-19 in Japan: Acquisition of herd immunity and the vaccines' efficacy

BackgroundThe COVID-19 pandemic situation has been changing drastically worldwide due to the continuous appearance of SARS-CoV-2 variants and the roll-out of mass vaccination. Periodic cross-sectional studies during the surge of COVID-19 cases is essential to elucidate the pandemic situation. MethodsSera of 1,000 individuals who underwent a health check-up in Hyogo Prefecture Health Promotion Association clinics in Japan were collected in August and December 2021. Antibodies against SARS-CoV-2 N and S antigens were detected in the sera by an electrochemiluminescence immunoassay (ECLIA) and an enzyme-linked immunosorbent assay (ELISA), respectively. The seras neutralization activities for the conventional SARS-CoV-2 (D614G), Delta, and Omicron variants were measured. ResultsThe seropositive rates for the antibody against N antigen were 2.1% and 3.9% in August and December 2021 respectively, demonstrating a Delta variant endemic during that time; the actual infection rate was approximately twofold higher than the rate estimated based on the polymerase chain reaction (PCR)-based diagnosis. The anti-S seropositive rate was 38.7% in August and it reached 90.8% in December, in concordance with the vaccination rate in Japan. In the December cohort, 78.7% of the sera showed neutralizing activity against the Delta variant, whereas that against the Omicron was much lower at 36.6%. ConclusionsThese analyses revealed that herd immunity against SARS-CoV-2 including the Delta variant was established in December 2021, leading to convergence of the variants. The low neutralizing activity against the Omicron variant suggests the need for the further promotion of the prompt three-dose vaccination to overcome this variants imminent 6th wave in Japan. SummarySeroepidemiologic study of COVID-19 on December 2021 in Japan showed neutralizing antibodies for Delta were 78.7%, indicating the acquisition of herd immunity by mass vaccination leading to convergence while those for Omicron were only 36.6%, indicating need of booster vaccination.

Large-scale seroepidemiologic surveillance of COVID-19 - Cross-sectional study in Hyogo prefecture of Japan in August, 2021

The situation of the COVID-19 pandemic in Japan is drastically changing in the 2nd year, 2021, due to the appearance of SARS-CoV-2 variants of concern and the roll-out of mass vaccination. In addition to PCR diagnosis, periodic seroepidemiologic surveillance is important to analyze the epidemic situation. In this study, we analyzed the rate of seropositivity for the SARS-CoV-2 N and S antigens in Hyogo prefecture, Japan in August 2021. Sera collected from people who received a health check-up in a clinic of the Hyogo Prefecture Health Promotion Association were subjected to analysis of reactivity to the SARS-CoV-2 N and S antigens by electrochemiluminescence immunoassay (ECLIA) and enzyme-linked immunosorbent assay (ELISA), respectively. For a total 1,000 sera, the positive rates to N and S antigens were 2.1% and 38.7%, respectively. The infectious rate estimated by serological analysis based on the presence of the anti-N antibody was 2.5-fold higher than the value reported based on PCR-based analysis, and it increased five-fold compared to the rate determined by our previous seroepidemiologic study in October, 2020. The anti-S positive rate was almost consistent with the vaccination rate in this area. The observed high anti-S antibody level in the seropositive population may indicate that the mass vaccination in Japan is being performed smoothly at this time point, although the infectious rate has also increased.

Rapid and accurate detection of novel coronavirus SARS-CoV-2 using CRISPR-Cas3

Novel coronavirus SARS-CoV-2 outbreaks have rapidly spread to multiple countries, highlighting the urgent necessity for fast, sensitive, and specific diagnostic tools for virus surveillance. Here, the previously unknown collateral single-stranded DNA cleavage we observed with type I CRISPR-Cas3 highlights its potential for development as a Cas3-mediated rapid (within 40 min), low-cost, instrument-free detection method for SARS-CoV-2. This Cas3-based assay is comparable with Cas12- and real-time reverse-transcriptase PCR-based assays in its speed and sensitivity, but offers greater specificity for single-base-pair discrimination while negating the need for highly trained operators. These findings support the use of CRISPR diagnostics for point-of-care testing in patients with suspected SARS-CoV-2 infections.

Comparison of 12 molecular detection assays for SARS-CoV-2

Molecular testing for SARS-CoV-2 is the mainstay for accurate diagnosis of the infection, but the diagnostic performances of available assays have not been defined. We compared 12 molecular diagnostic assays, including 8 commercial kits using 155 respiratory samples (65 nasopharyngeal swabs, 45 oropharyngeal swabs, and 45 sputum) collected at 2 Japanese hospitals. Sixty-eight samples were positive for more than one assay and one genetic locus and were defined as true positive samples. All the assays showed a specificity of 100% (95% confidence interval, 95.8 to 100). The N2 assay kit of the US Centers for Disease Control and Prevention (CDC) and the N2 assay of the Japanese National Institute of Infectious Disease (NIID) were the most sensitive assays with 100% sensitivity (95% confidence interval, 94.7 to 100), followed by the CDC N1 kit, E assay by Corman, and NIID N2 assay multiplex with internal control reactions. These assays are reliable as first-line molecular assays in laboratories when combined with appropriate internal control reactions.

Descending Aortic Replacement for Pseudoaneurysm Following Total Arch Replacement with Proximal Endoclamping Using an Occlusion Balloon / 日本心臓血管外科学会雑誌

An 83-year-old man who had undergone aortic arch repair using the elephant trunk technique in addition to abdominal aorta repair required surgical intervention for a pseudoaneurysm at the distal anastomosis of the aortic arch graft. Due to marked adhesion around the aneurysm, aortic cross-clamping was not feasible. Thus, under femoro-femoral partial bypass, the arch prosthesis was endoclamped using an aortic occlusion balloon inserted through the left femoral artery into the aortic arch graft and through the elephant trunk, guided by fluoroscopy and transesophageal echocardiography. This allowed descending aorta replacement with minimal bleeding. His postoperative course was uneventful. This technique enabled safe and bloodless clamping of the proximal portion of the aortic arch graft.

A Case of Concomitant Surgery for Funnel Chest and Ventricular Septal Defect / 日本心臓血管外科学会雑誌

A 10-year-old girl with heart murmur immediately after birth was found to have a ventricular septal defect (VSD). Although she had been followed up for an insignificant shunt, funnel chest became apparent and was referred to our hostpital at the age of 10. She was 133 cm in height, 25.7 kg in weight with a body surface area of 0.99 m². The VSD was the muscular outflow type with a Qp/Qs of 1.1, defect of 2.5 mm in diameter, and pulmonary artery pressure of 24/10/15 mmHg. Pectus excavatum was apparent with a CT index of 2.99. The preceding surgery for one was likely to interfere with the subsequent surgery for the other. Therefore we decided on concomitant surgery for both. Under median sternotomy, cardiopulmonary bypass was established and the VSD was closed with a patch. After the pericardium was sutured and closed, a tape was carefully passed through the chest wall under the guidance of direct vision and digital palpation. A metal bar was inserted guided by the tape, reversed with a rotator, appropriately shaped with a hand bender, and was fixed to the chest wall with the stabilizer bars at both ends. The sternum was sutured with 1-0 polyester sutures and two sternum pins made of particulate hydroxyapatite and poly-L lactide. The postoperative course was uneventful. After 2 years, the excavatum was adequately corrected and the bar was successfully removed under general anesthesia. Although the comorbidity of VSD and funnel chest is rare, concomitant surgery for both can be safely carried out and may be considered as an option for treatment.

Collagen Gel Droplet-Embedded Culture Drug Sensitivity Test (CD-DST) for a Leiomyosarcoma Originating in the Inferior Vena Cava / 日本心臓血管外科学会雑誌

The collagen gel droplet-embedded culture drug sensitivity test (CD-DST) identifies effective anticancer drug using resected tumor specimen, enabling tailor-made chemotherapy for a rare tumor. We report a case of the patient with leiomyosarcoma originating in the inferior vena cava, to which CD-DST was applied. This application has not been previously reported to the best of our knowledge. A 61-year-old woman consulted a nearby hospital because of abdominal pain. Computed tomography revealed an inferior vena cava tumor. The tumor was resected with the inferior vena cava, which was reconstructed with a 16 mm ePTFE graft. The tumor was diagnosed as leiomyosarcoma histopathologically. CDDP, VP-16, ADR, and VDS were CD-DST showed the tumor to be sensitive. Her postoperative course has been good without recurrence of tumor for 6 months, and the results of CD-DST may be helpful for chemotherapy strategy in case of recurrence.

Aortic Valve Replacement after Retrosternal Gastric Tube Reconstruction for Esophageal Cancer / 日本心臓血管外科学会雑誌

We present a case of aortic valve replacement after retrosternal gastric tube reconstruction for esophageal cancer. A 84-year-old man with a history of esophageal resection with retrosternal reconstruction by gastric tube for esophageal cancer required aortic valve replacement for aortic stenosis. The aortic valve was approached through an 8-cm right parasternal incision over the third and fourth costal cartilages. Cardiopulmonary bypass was initiated through cannulas in the ascending aorta and the right atrium and the aortic valve was replaced with a bioprosthetic valve. The postoperative course was uneventful. In the literature, there are only 7 reports on such cases so far, in which aortic valve relplacement was performed through left thoracotomy, right parasternal approach or median sternotomy. We recommend the right parasternal approach in cases of aortic valve replacement in patients with retrosternal gastric tube, because it does not only avoids injury of gastric tube, but also offers an excellent operative view.

Validity of Emergency Thoracic Aortic Surgery in Octogenarians / 日本心臓血管外科学会雑誌

Between January 1994 and October 2004, 87 patients underwent emergency thoracic aortic surgery. Of these, 11 patients were more than 80 years old (O-group) and 76 were less than 80 years old (Y-group). A total of 58 patients (6 in O-group and 52 in Y-group) were treated for acute type-A aortic dissection, 5 (0 in O-group and 5 in Y-group) for acute type-B aortic dissection and 21 (4 in O-group and 17 in Y-group) for the involved rupture of a thoracic aortic aneurysm. The operative procedures consisted of the replacement of either the ascending, or the ascending and transverse aorta in 71 patients (8 in O-group and 63 in Y-group), and the replacement of the distal descending aorta in 15 patients (3 in O-group and 12 in Y-group). The operative mortality rates were 27.2% (3 patients) and 19.7% (15 patients) in the O- and Y-groups, respectively, with no significant difference between the groups. The rate of early complications, including circulatory failure, respiratory failure and cerebral infarction, did not statistically differ between the 2 groups. The overall 2-year survival rates of the patients who survived the operation were 83.3% in the O-group and 95.1% in the Y-group. Moreorer, 75% of the patients (6 of 8) who survived the surgery regained normal activities of daily life after the surgery, at a level similar to before the surgery. The present data indicates that emergency thoracic aortic surgery can be justified in selected in octogenarian patients.

Aneurysmectomy of Mid-Ventricular Obstructive Hypertrophic Cardiomyopathy with an Apical Ventricular Aneurysm / 日本心臓血管外科学会雑誌

A typical feature of mid-ventricular obstructive hypertrophic cardiomyopathy (MVO-HCM), is obvious hypertrophy of the mid-ventricular muscle and ventricle with transformation into the shape of an hourglass. We report a 60-year-old woman who had been given a diagnosis of apical type hypertrophic cardiomyopathy 12 years previously, but it changed to MVO-HCM with apical left ventricular aneurysm. We considered the impending rupture of the aneurysm because its wall was thin and pericardial effusion was detected by UCG (ultrasonic cardiograph). Urgent surgery was performed consisting of ventricular aneurysmectomy and patch reconstruction. After the surgery, a pseudoaneurysm was found in cardiac apex, so we performed surgery again. A residual shunt in the trabeculation caused the pseudoaneurysm, but its origin was not clear. She has been fine for 18 months without complications such as recurrence of aneurysm, ventricular arrhythmia or left ventricular dysfunction since the last surgery.