SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study

Background

Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood.

Objectives

COVID-19 in patients with antibody deficiency (COV-AD) is a multi-site UK study that aims to determine the immune response to SARS-CoV-2 infection and vaccination in patients with primary or secondary antibody deficiency, a population that suffers from severe and recurrent infection and does not respond well to vaccination.

Methods

Individuals on immunoglobulin replacement therapy or with an IgG less than 4 g/L receiving antibiotic prophylaxis were recruited from April 2021. Serological and cellular responses were determined using ELISA, live-virus neutralisation and interferon gamma release assays. SARS-CoV-2 infection and clearance were determined by PCR from serial nasopharyngeal swabs.

Results

A total of 5.6% (n?=?320) of the cohort reported prior SARS-CoV-2 infection, but only 0.3% remained PCR positive on study entry. Seropositivity, following two doses of SARS-CoV-2 vaccination, was 54.8% (n?=?168) compared with 100% of healthy controls (n?=?205). The magnitude of the antibody response and its neutralising capacity were both significantly reduced compared to controls. Participants vaccinated with the Pfizer/BioNTech vaccine were more likely to be seropositive (65.7% vs. 48.0%, p?=?0.03) and have higher antibody levels compared with the AstraZeneca vaccine (IgGAM ratio 3.73 vs. 2.39, p?=?0.0003). T cell responses post vaccination was demonstrable in 46.2% of participants and were associated with better antibody responses but there was no difference between the two vaccines. Eleven vaccine-breakthrough infections have occurred to date, 10 of them in recipients of the AstraZeneca vaccine.

Conclusion

SARS-CoV-2 vaccines demonstrate reduced immunogenicity in patients with antibody deficiency with evidence of vaccine breakthrough infection.

     

Clinical and Economic Outcomes for Patients with Health Care-Associated Staphylococcus aureus Pneumonia

While the increasing importance of methicillin-resistant Staphylococcus aureus (MRSA) as a pathogen in health care-associated S. aureus pneumonia has been documented widely, information on the clinical and economic consequences of such infections is limited. We retrospectively identified all patients admitted to a large U.S. urban teaching hospital between January 2005 and May 2008 with pneumonia and positive blood or respiratory cultures for S. aureus within 48 h of admission. Among these patients, those with suspected health care-associated pneumonia (HCAP) were identified using established criteria (e.g., recent hospitalization, admission from nursing home, or hemodialysis). Subjects were designated as having methicillin-resistant (MRSA) or methicillin-susceptible (MSSA) HCAP, based on initial S. aureus isolates. Initial therapy was designated “appropriate” versus “inappropriate” based on the expected susceptibility of the organism to the regimen received. We identified 142 patients with evidence of S. aureus HCAP. Their mean (standard deviation [SD]) age was 64.5 (17) years. Eighty-seven patients (61%) had initial cultures that were positive for MRSA. Most (∼90%) patients received appropriate initial antibiotic therapy (86% for MRSA versus 91% for MSSA; P = 0.783). There were no significant differences between MRSA and MSSA HCAP patients in mortality (29% versus 20%, respectively), surgery for pneumonia (22% versus 20%), receipt of mechanical ventilation (60% versus 58%), or admission to the intensive care unit (79% versus 76%). Mean (SD) total charges per admission were universally high ($98,170 [$94,707] for MRSA versus $104,121 [$91,314]) for MSSA [P = 0.712]). Almost two-thirds of patients admitted to hospital with S. aureus HCAP have evidence of MRSA infection. S. aureus HCAP, irrespective of MRSA versus MSSA status, is associated with significant mortality and high health care costs, despite appropriate initial antibiotic therapy.Traditionally, infections have been categorized as either community associated or nosocomial in origin. The theory supporting this dichotomy arose from observations that pathogens causing these two types of infections were distinct. However, with the spread of health care delivery beyond the confines of acute-care hospitals, patients increasingly may present to emergency departments (ED) with infections caused by organisms such as methicillin-resistant Staphylococcus aureus (MRSA). This trend has led to the evolution of the concept of health care-associated infection (HCAI). Recent studies have validated the concept of HCAI for a number of types of infection, ranging from endocarditis to pneumonia (1, 4, 10, 12). Many such reports, however, have provided scant microbiologic information and have focused more on distinctions in patient types and risk factors for resistant infection. The situation regarding limited microbiologic data is particularly acute with respect to S. aureus. Although Fridkin and colleagues, in an assessment of the national burden of MRSA, underscored the growing prevalence of this pathogen in health care-associated pneumonia (HCAP) (3), they presented little information regarding outcomes of such infections.S. aureus in general—and MRSA in particular—remains a growing challenge for both hospitals and physicians. Good infection prevention practices necessitate isolation precautions for patients with MRSA, which has made early identification of these persons a time-sensitive endeavor. Beyond infection prevention issues, which may complicate the care of patients at risk for MRSA HCAP, patients with HCAP due to either methicillin-sensitive S. aureus (MSSA) or MRSA may consume substantial resources. Further complicating management of HCAP due to S. aureus is the shift in strain types and antimicrobial resistance implicated in pneumonia (3). The USA300 strain of MRSA, for example, may produce significant toxins and may not respond well to anti-MRSA antimicrobials that are routinely employed (11). Because of these issues, physicians require data regarding the microbiology, epidemiology, and outcomes associated with HCAP due to S. aureus (both MSSA and MRSA).To address these issues, we conducted a retrospective observational study of patients in a large urban hospital with HCAP due to culture-proven S. aureus. Our aims were to describe outcomes and resource utilization among patients with S. aureus HCAP and to understand possible differences between patients with MSSA versus MRSA pneumonia. We also sought to examine differences in outcomes and resource utilization as a function of pathogen susceptibility to vancomycin and the specific strain type involved.(Preliminary findings from this study were presented at the 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy [ICAAC]-Infectious Diseases Society of America [IDSA] 46th Annual Meeting and the 2008 annual meeting of the American College of Chest Physicians [ACCP] [1a, 10a, 11a].)     

Correlates and trend of HIV prevalence among female sex workers attending sexually transmitted disease clinics in Pune, India (1993-2002)

In India, substantial efforts have been made to increase awareness about HIV/AIDS among female sex workers (FSWs). We assessed the impact of awareness regarding safe sex in a cohort of FSWs by studying trends in HIV prevalence, sexually transmitted diseases (STDs), and risk behaviors measured from 1993 to 2002 in Pune, India. A total of 1359 FSWs attending 3 STD clinics were screened for HIV infection, and data on demographics, sexual behaviors, and past and current STDs were obtained. The overall HIV prevalence among FSWs was 54%. Not being married (adjusted odds ratio [AOR] = 1.74, 95% confidence interval [CI]: 1.17 to 2.59), being widowed (AOR = 2.10, 95% CI: 1.16 to 3.80), inconsistent condom use (AOR = 1.60, 95% CI: 1.02 to 2.50), clinical presence of genital ulcer disease (GUD; AOR = 1.66, 95% CI: 1.07 to 2.56), and genital warts (AOR = 4.70, 95% CI: 1.57 to 14.08) were independently associated with HIV infection among FSWs. The prevalence of HIV remained stable over 10 years (46% in 1993 and 50% in 2002; P = 0.80). The prevalence of GUD decreased over time (P < 0.001), whereas that of observed genital discharge remained stable. Reported consistent condom use as well as the proportion of FSWs who refused sexual contact without condoms increased over time (P < 0.001). These data collectively suggest that safe sex interventions have had a positive impact on FSWs in Pune, India.     

Human embryonic stem cells have a unique epigenetic signature

Human embryonic stem (hES) cells originate during an embryonic period of active epigenetic remodeling. DNA methylation patterns are likely to be critical for their self-renewal and pluripotence. We compared the DNA methylation status of 1536 CpG sites (from 371 genes) in 14 independently isolated hES cell lines with five other cell types: 24 cancer cell lines, four adult stem cell populations, four lymphoblastoid cell lines, five normal human tissues, and an embryonal carcinoma cell line. We found that the DNA methylation profile clearly distinguished the hES cells from all of the other cell types. A subset of 49 CpG sites from 40 genes contributed most to the differences among cell types. Another set of 25 sites from 23 genes distinguished hES cells from normal differentiated cells and can be used as biomarkers to monitor differentiation. Our results indicate that hES cells have a unique epigenetic signature that may contribute to their developmental potential.     

Imaging left ventricular tissue mechanics and hemodynamics during supine bicycle exercise using a combined tagging and phase‐contrast MRI pulse sequence

Imaging the left ventricular mechanical and hemodynamic response to the stress of exercise may offer early prognosis in select patients with cardiac disease. Here, we demonstrate the feasibility of obtaining simultaneous measurements of longitudinal strain and transvalvular blood velocity during supine bicycle exercise stress in a wide bore magnetic resonance scanner. Combining information from the two datasets, we observe that although the time to peak strain (33.28 ± 1.86 versus 25.7 ± 2.12 as % of R–R interval) and time to peak mitral inflow velocity (44.37 ± 5.21 versus 35.5 ± 4.19 as % of R–R interval) from R‐wave of the QRS complex occurred earlier during stress, the time from peak strain to peak mitral inflow velocity was not statistically different (16.5 ± 3.23 versus 13.4 ± 3.06). Further, the percentage of longitudinal relaxation at peak mitral inflow velocity was higher during stress (63.5 ± 7.72 versus 84.32 ± 6.24). These results suggest that although diastole is shortened, early diastolic filling efficiency is augmented during exercise stress in normal volunteers in an effort to maintain stroke volume. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Identifying corpus luteum rupture as the culprit for haemoperitoneum

Corpus luteum rupture presenting as acute abdomen is an underdiagnosed condition. Though a self-limiting entity, its differentiation from other causes is essential to prevent unnecessary surgical procedures. The radiologist should be aware of the possibility of a ruptured haemorrhagic ovarian cyst in a female of reproductive age group presenting with pelvic pain and a large amount of haemorrhagic ascites. Imaging characteristically reveals a thick-walled cystic structure in the adnexa with internal echoes, focal discontinuity or irregularity of its wall with haemoperitoneum. While sonography is usually indicative of corpus luteum rupture, cross-sectional imaging (CT/MRI) can be used to confirm the diagnosis.     

Utilizing cystic plate for safe and rapid liver retraction at laparoscopic cholecystectomy: A useful technique

Nowadays, laparoscopic cholecystectomy for gallstone disease is considered not only the gold standard but an essential component of surgical training. In this regard, liver retraction plays an important role during cholecystectomy and also after specimen extraction. We describe a simple technique for liver retraction that achieves rapid, safe and steady exposure of the cystic fossa along with the subhepatic region for tackling any inadvertent bile leaks or bleeding. It is especially useful for diseased livers which are otherwise prone to iatrogenic laceration during haphazard and uncontrolled hepatic manipulation. Nonetheless, it may be easily mastered by surgical trainees, and thus reduce their learning curve.     

Reliability of MDCT in characterizing pulmonary venous drainage, diameter and distance to first bifurcation: an interobserver study

RATIONALE AND OBJECTIVES: To evaluate the interobserver agreement of readers in evaluating pulmonary venous anatomy and in measuring pulmonary vein ostial diameters and distance to first bifurcation. MATERIALS AND METHODS: This study was approved by our institutional review board. Thin-section contrast material-enhanced multidetector computed tomography examinations of the thorax were retrospectively reviewed in 200 consecutive patients (38 females and 162 males), age 24-79 years (mean, 52.8) referred for imaging before radiofrequency ablation therapy for atrial fibrillation. For each patient, pulmonary venous anatomy and drainage patterns including the number of venous ostia was assessed independently by experienced cardiothoracic radiologists. Pulmonary vein ostial diameter and distance to the first bifurcation of the four major pulmonary veins (right inferior and superior, left inferior and superior), the middle lobe pulmonary vein, and any anomalous pulmonary veins (common trunks and accessory veins) were measured independently at a workstation. Interreader assessment of pulmonary venous anatomy was evaluated using the Kappa statistic. Interreader variation in measurements of venous diameter and distant to first bifurcation were estimated by Bland-Altman plots and Pitman's test of difference in variance. RESULTS: Very good to excellent interreader agreement in detection of anomalous pulmonary venous anatomy, middle lobe pulmonary venous drainage, and other thoracic venous anomalies. No significant variation between readers in pulmonary vein ostial diameter measurements for the four major and middle lobe pulmonary veins, or the anomalous pulmonary veins. Significant interreader variability was noted in measurements of the pulmonary vein distance to first bifurcation for the right inferior (P = .017), middle lobe (P = .005), and left inferior (P = .015) pulmonary veins. CONCLUSIONS: There is excellent interobserver agreement when evaluating normal and anomalous pulmonary venous drainage patterns, and when measuring normal or anomalous pulmonary vein diameters. However, measurements of distances to first bifurcation were less reliable across readers.