8 research outputs found
Anti-chemokine antibodies after SARS-CoV-2 infection correlate with favorable disease course.
Infection by SARS-CoV-2 leads to diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse COVID-19 outcomes. Instead, we discovered that antibodies against specific chemokines are omnipresent after COVID-19, associated with favorable disease, and predictive of lack of long COVID symptoms at one year post infection. Anti-chemokine antibodies are present also in HIV-1 and autoimmune disorders, but they target different chemokines than those in COVID-19. Finally, monoclonal antibodies derived from COVID- 19 convalescents that bind to the chemokine N-loop impair cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising anti-chemokine antibodies associated with favorable COVID-19 may be beneficial by modulating the inflammatory response and thus bear therapeutic potential.
One-Sentence Summary
Naturally arising anti-chemokine antibodies associate with favorable COVID-19 and are predictive of lack of long COVID
Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein
Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2´ site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization and, like fp.006 and hr2.016, protects mice expressing human ACE2 against infection when present as bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae, including SARS-CoV-2 variants
Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course
Infection with severe acute respiratory syndrome coronavirus 2 associates with diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse coronavirus disease 2019 (COVID-19) outcomes. Here we discovered that antibodies against specific chemokines were omnipresent post-COVID-19, were associated with favorable disease outcome and negatively correlated with the development of long COVID at 1 yr post-infection. Chemokine antibodies were also present in HIV-1 infection and autoimmune disorders, but they targeted different chemokines compared with COVID-19. Monoclonal antibodies derived from COVID-19 convalescents that bound to the chemokine N-loop impaired cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising chemokine antibodies may modulate the inflammatory response and thus bear therapeutic potential
Laparoscopic and robot-assisted continent urinary diversions (Mitrofanoff and Yang-Monti conduits) in a consecutive series of 15 adult patients: The Saint Augustin technique
Feasibility of robotic double Yang-Monti ileal conduit with bladder augmentation: Surgical technique
False positive dipstick for urinary blood in childhood
BACKGROUND: In view of the obvious practical advantages, the most common test for hematuria is currently a reagent strip. METHODS: A standardized microscopic examination of the sediment was performed in 20 asymptomatic children referred for evaluation of chronic isolated microhematuria detected by means of a reagent strip. RESULTS: In 6 of the 20 children the microscopic examination failed to confirm the result of the dipstick test. CONCLUSIONS: Confirmation for the presence of hematuria by microscopy is the most important step in children with a positive dipstick for urinary blood
Long-term oncologic outcome of an initial series of laparoscopic radical prostatectomy for clinically localized prostate cancer after a median follow-up of 10 years
INTRODUCTION: When laparoscopic radical prostatectomy (LRP) was introduced as a novel treatment option for prostate cancer, it had to compete with the established open techniques. The short- and intermediate-term oncologic and functional outcomes were encouraging and comparable to those with retropubic radical prostatectomy. However, the long-term oncologic safety for LRP has yet to be fully elucidated. We evaluated the long-term oncologic outcomes of an initial series of patients who had undergone LRP.
PATIENTS AND METHODS: An initial unselected and consecutive series of 100 patients who had undergone LRP for clinically localized prostate cancer from 1999 to 2001 was identified. The pre-, intra-, and postoperative data were collected. Biochemical recurrence (BCR) was defined as a prostate-specific antigen (PSA) value of ≥ 0.2 ng/mL. The outcome measures were cancer control (CC), BCR-free survival (BCRFS), cancer-specific survival (CSS), and overall survival (OS).
RESULTS: The mean patient age was 64 ± 7 years, and the mean preoperative PSA level was 9.6 ± 8.3 ng/mL. Of the 100 patients, 79 (79%) had stage pT2 and 15 (15%) had stage pT3 disease. Positive surgical margins were found in 25 patients (25%; 16.4% for pT2 and 40% for pT3). The median follow-up time was 126 months (range, 60-176 months). The 5-year CC rate was 82%. The estimated 10-year BCRFS was 83% and 80% for patients with stage pT2 and pT3 tumors, respectively. The median time to BCR was 52 months (range, 6-144 months). The estimated 10-year CSS and OS was 98% and 93%, respectively.
CONCLUSION: Our long-term follow-up data from an initial unselected patient cohort have indicated that LRP offers excellent long-term oncologic control for patients with localized prostate cancer
Anti-chemokine antibodies after SARS-CoV-2 infection correlate with favorable disease course
Infection by SARS-CoV-2 leads to diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse COVID-19 outcomes. Instead, we discovered that antibodies against specific chemokines are omnipresent after COVID-19, associated with favorable disease, and predictive of lack of long COVID symptoms at one year post infection. Anti-chemokine antibodies are present also in HIV-1 and autoimmune disorders, but they target different chemokines than those in COVID-19. Finally, monoclonal antibodies derived from COVID- 19 convalescents that bind to the chemokine N-loop impair cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising anti-chemokine antibodies associated with favorable COVID-19 may be beneficial by modulating the inflammatory response and thus bear therapeutic potential.
One-sentence summary: Naturally arising anti-chemokine antibodies associate with favorable COVID-19 and are predictive of lack of long COVID