The humoral response to COVID-19 vaccinations can predict the booster effect on health care workers-toward personalized vaccinations?

BACKGROUND: Waning immunity after the coronavirus disease 2019 (COVID-19) vaccinations creates the constant need of boosters. Predicting individual responses to booster vaccines can help in its timely administration. We hypothesized that the humoral response to the first two doses of the BNT162b2 vaccine can predict the response to the booster vaccine. METHODS: A prospective cohort of hospital health care workers (HCW) that received three doses of the BNT162b2 vaccine. Participants completed serological tests at 1 and 6 months after the second vaccine dose and 1 month after the third. We analyzed predictive factors of antibody levels after the booster using multivariate regression analyses. RESULTS: From 289 eligible HCW, 89 (31%) completed the follow-up. Mean age was 48 (±10) and 46 (52%) had daily interaction with patients. The mean (±standard deviation) antibody level 1 month after the second vaccine was 223 (±59) AU/ml, and 31 (35%) had a rapid antibody decline (>50%) in 6 months. Low antibody levels 1 month after the second vaccine and a rapid antibody decline were independent predictors of low antibody levels after the booster vaccine. CONCLUSIONS: The characteristics of the humoral response to COVID-19 vaccinations show promise in predicting the humoral response to the booster vaccines.

Dialysis modality, humoral response to vaccine, and SARS-CoV-2 infection risk: Comparative prospective evaluation.

BACKGROUND: COVID-19 vaccinations have a central role in decreasing severe SARS-CoV-2 disease complications. This study investigated the long-term humoral immune response to BNT162b2 vaccine among hemodialysis (HD) versus peritoneal dialysis (PD) patients, and their relative risk for COVID-19 infection. METHODS: This prospective, observational study included maintenance HD and PD patients who had received at least two BNT162b2 vaccine doses. Levels of antibodies targeting SARS-CoV-2 spike protein were measured 6 and 12 months after the first vaccine dose, and 2-3 weeks after the third and fourth vaccine doses. Patients were divided according to dialysis modality (HD or PD). Humoral response was evaluated at different time points among different vaccine regimens (two vs. three vs. four doses of vaccine). An adjusted multivariate model was used to assess cumulative risk for SARS-CoV-2 infection. RESULTS: Eighty-seven HD and 36 PD patients were included. Among them, 106 (86%) received at least three vaccine doses. Both HD and PD patients demonstrated marked increases in humoral response 2-3 weeks after the third dose (mean anti-S antibody increased from 452 ± 501 AU/mL to 19,556 ± 14,949 AU/mL, p < 0.001). By 6 months after the third dose, antibody titers had declined significantly (mean anti-S antibody 9841 ± 10,493 AU/mL, p < 0.001). HD patients had higher risk for SARS-CoV-2 infection than PD patients (OR 4.4 [95% CI 1.4-13.6], p = 0.006). In multivariate analysis, the most important predictor for SARS-CoV-2 infection was dialysis modality. CONCLUSION: This study found a high antibody response rate after the third and fourth doses of BNT162b2 vaccine among dialysis patients. Hemodialysis as dialysis modality is an important predictor of COVID-19 infection, despite similar humoral responses to vaccine in peritoneal dialysis.

Transbronchial Cryobiopsy Is Superior to Forceps Biopsy for Diagnosing both Fibrotic and Non-Fibrotic Interstitial Lung Diseases.

BACKGROUND: Interstitial lung disease (ILD) evaluation often requires lung biopsy for definite diagnosis. In recent years, transbronchial cryobiopsy (TBCB) emerged as a procedure with higher diagnostic yield than transbronchial forceps biopsy (TBFB), especially for fibrotic ILDs. Nonetheless, studies comparing these modalities in non-fibrotic ILDs and for specific ILD diagnoses are scarce. OBJECTIVES: The aim of this study was to evaluate the diagnostic yield and safety of TBCB and TBFB in patients with fibrotic and non-fibrotic ILDs. METHOD: An observational retrospective multicenter study including patients with ILD diagnosis by multidisciplinary discussion that underwent TBCB or TBFB between 2017 and 2021. Chest CT scans were reviewed by a chest radiologist. Biopsy specimens were categorized as diagnostic (with specific histological pattern), nondiagnostic, or without lung parenchyma. Nondiagnostic samples were reassessed by a second lung pathologist. TBCB and TBFB diagnostic yields were analyzed by multivariate regression. Procedural complications were evaluated as well. RESULTS: 276 patients were included, 116 (42%) underwent TBCB and 160 (58%) TBFB. Fibrotic ILDs were present in 148 patients (54%). TBCB diagnostic yield was 78% and TBFB 48% (adjusted odds ratio [AOR] 4.2, 95% CI: 2.4-7.6, p < 0.01). The diagnostic yield of TBCB was higher than TBFB among patients with fibrotic ILD (AOR 3.8, p < 0.01), non-fibrotic ILD (AOR 5.8, p < 0.01), and across most ILD diagnoses. TBCB was associated with higher risk for significant bleeding (10% vs. 3%, p < 0.01), but similar risk for pneumothorax. CONCLUSIONS: Diagnostic yield of TBCB was superior to that of TBFB for both fibrotic and non-fibrotic ILDs, and across most diagnoses.

Intra-Cranial Arterial Calcifications in Hemodialysis Patients.

Background and objectives: Vascular calcification is an integral part of atherosclerosis and has been reported to be an independent risk factor for cardiovascular diSsease. Intra Cranial Arterial Calcifications (ICAC) in maintenance hemodialysis (MHD) is highly prevalent. Materials and Methods: The aim of this retrospective study was to assess the predictors and outcomes of ICAC in MHD patients compared to a control group without kidney disease. A blinded neuroradiologist graded ICAC in brain imaging (computerized tomography) of MHD patients. Age- and sex-matched patients with normal kidney function served as the control group. Results: A total of 280 patients were included in the cohort; 140 of them were MHD patients with a mean ICAC score of 2.3 ± 0.2 versus a mean ICAC score of 1.4 ± 0.2 in the control group (p < 0.01). More than 90% of hemodialysis patients in our study had some degree of ICAC. Lower albumin and higher phosphorus and CRP levels were associated with increased ICACs. The multivariate analysis model for predictors of 1-year mortality demonstrated an increased odds ratio for mortality as the ICAC score increased. Conclusions: ICAC is very prevalent among MHD patients and results not simply from passive deposition of calcium and phosphate but rather from complex and active processes involving inflammation and structural changes in blood vessels. ICAC independently predicted all-cause mortality and may help with risk stratification of this high-risk population.

The Clinical Significance of LDL-Cholesterol on the Outcomes of Hemodialysis Patients with Acute Coronary Syndrome.

Background and objectives: Dyslipidemia is one of the most important modifiable risk factors in the pathogenesis of cardiovascular disease in the general population, but its importance in the hemodialysis (HD) population is uncertain. Materials and Methods: This retrospective cohort study includes HD patients hospitalized due to acute coronary syndrome (ACS) in the period 2015-2020 with lipid profile data during ACS. A control group with preserved kidney function was matched. Risk factors for 30-day and 1-year mortality were assessed. Results: Among 349 patients included in the analysis, 246 were HD-dependent ("HD group"). HD group patients had higher prevalence of diabetes, hypertension, and heart disease than the control group. At ACS hospitalization, lipid profile and chronic statin treatment were comparable between groups. Odds ratios for 30-day mortality in HD vs. control group was 5.2 (95% CI 1.8-15; p = 0.002) and for 1-year, 3.4 (95% CI 1.9-6.1; p <0.001). LDL and LDL < 70 did not change 30-day and 1-year mortality rates in the HD group (p = 0.995, 0.823, respectively). However, survival after ACS in HD patients correlated positively with nutritional parameters such as serum albumin (r = 0.368, p < 0.001) and total cholesterol (r = 0.185, p < 0.001), and inversely with the inflammatory markers C-reactive protein (CRP; r = -0.348, p < 0.001) and neutrophils-to-lymphocytes ratio (NLR; r = -0.181, p = 0.019). Multivariate analysis demonstrated that heart failure was the only significant predictor of 1-year mortality (OR 2.8, p = 0.002). LDL < 70 mg/dL at ACS hospitalization did not predict 1-year mortality in the HD group. Conclusions: Despite comparable lipid profiles and statin treatment before and after ACS hospitalization, mortality rates were significantly higher among HD group. While malnutrition-inflammation markers were associated with survival of dialysis patients after ACS, LDL cholesterol was not. Thus, our study results emphasize that better nutritional status and less inflammation are associated with improved survival among HD patients.

Humoral Response to Pfizer BNT162b2 Vaccine Booster in Maintenance Hemodialysis Patients.

INTRODUCTION: Coronavirus disease is associated with increased morbidity and mortality in maintenance hemodialysis (MHD) patients. Recent breakthrough infection in vaccinated people has led some authorities to recommend a booster dose for patients fully vaccinated 5-8 months ago. We aimed to assess the humoral response of MHD patients following a booster dose with the BNT162b2 vaccine. METHODS: The study included 102 MHD patients vaccinated with 2 doses of the BNT162b2 (Pfizer-BioNTech) vaccine. A third dose (booster) was recommended to all MHD patients in our center and was given to those who opted to receive it, resulting in a booster group and a control group that did not receive the booster. Previous exposure was excluded by testing for the presence of the anti-nucleocapsid antibody (SARS-CoV-2) or positive PCR. We assessed the humoral response before and after the booster dose. RESULTS: Of 66 patients in the booster group, 65 patients (98.5%) developed a positive antibody response, from 472.7 ± 749.5 to 16,336.8 ± 15,397.3, as compared to a sustained decrease in the control group (695.7 ± 642.7 to 383.6 ± 298.6), p < 0.0001. No significant adverse effects were reported. Prior antibody titers were positively correlated to IgG levels following the booster dose. There was a significant association between malnutrition-inflammation markers and the humoral response. CONCLUSIONS: Almost all MHD patients developed a substantial humoral response following the booster dose, which was significantly higher than levels reported for MHD patients following administration of 2 doses alone. Further studies and observations are needed to determine the exact timing and dosing schedule.

Humoral Response and SARS-CoV-2 Infection Risk following the Third and Fourth Doses of the BNT162b2 Vaccine in Dialysis Patients.

The optimal SARS-CoV-2 vaccination schedule in dialysis patients and the potential need for a fourth vaccine dose are debatable. We prospectively assessed the humoral responses to three and four doses of BNT162b2 among dialysis patients. The study included 106 dialysis patients; 60 (56.6%) and 46 (43.4%) received 3 and 4 vaccine doses, respectively. Anti-spike (anti-S) antibody titers significantly increased after the third vaccine dose, followed by a decline, yet still remained higher than all previous measurements. The fourth vaccine dose led to another profound rise in anti-S titers. The absolute increase following the fourth dose correlated with response to the third dose. Infection risk however was similar between patients vaccinated with three or four doses.

Disease severity and renal outcomes of patients with chronic kidney disease infected with COVID-19.

INTRODUCTION: While there is evidence of the presence of the coronavirus in the kidneys and resultant acute kidney injury (AKI), information on the effect of chronic kidney disease (CKD) on COVID-19 outcomes and its pathogenesis is currently lacking. METHODS: This retrospective, observational study evaluated the outcomes of all consecutive patients hospitalized during COVID-19 outbreaks in Meir Medical Center. Serum creatinine level was assessed before hospitalization ("baseline serum creatinine") and at admission, as well as minimum and maximum serum creatinine levels during hospitalization. RESULTS: Among 658 patients, 152 had eGFR < 60 ml/min (termed the CKD group), 506 patients served as controls. Patients in the CKD group were older, with higher prevalence of hypertension, diabetes mellitus and atherosclerosis. Disease severity and clinical presentation of CKD group were comparable to that of control group. Odds ratio for AKI was 5.8 (95%CI 3.8-8.7; p < 0.001) in CKD group vs. control group and 3.4 (95%CI 1.1-10.8) for renal replacement therapy (p < 0.026). Among the CKD group, 32.2% died after COVID-19 infection versus 14.8% of the controls (p < 0.001). Mortality increased as CKD stage increased (14.8% in controls, 29.6% in CKD stage 3, and 39.3% in CKD stages 4 and 5, p < 0.001). CONCLUSION: Despite comparable disease severity at presentation, patients with CKD had significantly more AKI events and required more renal replacement therapy during hospitalization than control patients did. Mortality increased as CKD stage increased.

The Diagnostic Yield of Endobronchial Ultrasound Transbronchial Needle Aspiration (EBUS-TBNA) in Respiratory Compromised Patients under General Anesthesia.

BACKGROUND: Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a frequently used method for obtaining tissue samples for the diagnosis of various respiratory conditions, including lung cancer staging. In most cases, EBUS-TBNA is performed under moderate sedation (MS). However, in cases of respiratory compromised patients, if this procedure is performed, it is conducted under general anesthesia (GA). OBJECTIVES: To assess the diagnostic yield of EBUS-TBNA among respiratory compromised patients. METHODS: Data of consecutive patients (n=191) who underwent EBUS-TBNA at our medical center between January 2019 and December 2019 were retrospectively analyzed. Respiratory compromised patients underwent GA and patients without respiratory compromise were mostly moderately sedated (MS). Characteristics, diagnostic yield, and complication rates were compared. RESULTS: Diagnostic yield was similar between the two sedation modes (89% in GA group and 78% in the MS group, P = 0.11). The number of total samples obtained per procedure was significantly higher in the GA vs. the MS group (4.1 ± 2.1 vs. 2.1 ± 1.33, P < 0.01). The overall complication rate was 13% and 20.9% in the GA vs. the MS groups, respectively (P = 0.14), with the most frequent complication being minor bleeding. Interestingly, while the number of brushings, bronchoalveolar lavage, and endobronchial biopsy were similar, the percent of subjects who underwent transbronchial biopsy was significantly higher in the GA group (49% vs. 24.2%, P < 0.01). CONCLUSIONS: EBUS-TBNA performed under GA among respiratory compromised patients is safe and has similar diagnostic yield to that of patients without a respiratory compromise.

The Short- and Long-Term Impact of Pulmonary Rehabilitation in Subjects with Sarcoidosis: A Prospective Study and Review of the Literature.

BACKGROUND: Sarcoidosis is a heterogeneous multisystemic disorder of unknown etiology. Dyspnea and fatigue are two of the most common and debilitating symptoms experienced by subjects with sarcoidosis. There is limited evidence regarding the short- and long-term impact of pulmonary rehabilitation (PR) on exercise capacity and fatigue in these individuals. OBJECTIVE: To evaluate the benefit of PR in subjects with pulmonary sarcoidosis at different severity stages and to review the current literature about PR in sarcoidosis. METHODS: PR included a 12-week training program of a twice-weekly 90-min workouts. Fifty-two subjects with stable pulmonary sarcoidosis were recruited. Maximal exercise capacity, defined as VO2max, was measured using the cardiopulmonary exercise test (CPET). Pulmonary function tests, 6-min walking distance (6MWD), St. George's Respiratory Questionnaire (SGRQ), and the modified Medical Research Council (mMRC) and Hospital Anxiety and Depression Scale (HADS) questionnaires were given before and after PR and following 6 months (follow-up). RESULTS: The PR program significantly increased the VO2max (1.8 ± 2.3 mL/kg/min, p = 0.002), following 12 weeks. mMRC and SGRQ scores were also improved (-0.3 ± 0.8, p = 0.03, and -3.87 ± 10.4, p = 0.03, respectively). The impact of PR on VO2max was more pronounced in subjects with pulmonary parenchymal involvement. The increase in VO2max correlated with initial disease severity (indicated by FEV1/FVC, p = 0.01). Subjects with FEV1/FVC <70% showed greater improvement in 6MWD. 6MWD also improved in those with a transfer coefficient of the lung for CO (KCO) above 80% predicted (p < 0.05). At 6-month follow-up, the VO2max, 6MWD, and SGRQ scores remained stable, thus suggesting lasting effects of PR. CONCLUSION: PR is a promising complementary therapeutic intervention for subjects with sarcoidosis. Further study is needed to validate these findings.

MiR-608 overexpression in idiopathic pulmonary fibrosis (IPF).

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease that causes scarring of the lungs. The disease is associated with the usual interstitial pneumonia pattern, which was not yet fully recapitulated by an animal model. Therefore, the disease is considered 'human specific'. miRNA-608 is a primate specific miRNA with many potential targets, such CdC42 and Interlukin-6 (IL-6) that were previously implicated in IPF pathology. OBJECTIVE: To test miR-608 expression and its targets in IPF patient samples. METHODS: RNA was extracted from Formalin fixed paraffin embedded tissue sections (N = 18). miRNA-608 and Cdc42 and IL-6 levels were analyzed by qPCR. Acetylcholinesterase (AChE) is another target of miRNA-608. Its' rs17228616 allele has a single-nucleotide polymorphism causing weakened miR-608 interaction (C2098A). Thus, DNA was extracted from whole blood samples from 56 subjects with fibrosing interstitial lung disease and this region was sequenced for assessment of rs17228616 allele polymorphism. RESULTS: miR-608 is significantly overexpressed in IPF samples in comparison with controls (p < 0.05). Cdc42 and IL-6 levels were lower in the IPF patient samples compared with control samples (p < 0.001 and p < 0.05, respectively). The frequency of the rs17228616 minor A-allele was 17/56 (30.4%) with all patients being heterozygous. This result is significant vs. the published Israeli cohort of healthy individuals, which reported 17% prevalence of this allele in healthy control volunteers (p = 0.01, OR = 2.1, CI 95% [1.19-3.9]). CONCLUSION: miR-608 is overexpressed in IPF patients. While the exact mechanism remains to be discovered, it could potentially promote fibrotic disease.

Mucormycosis in lung transplant recipients: A systematic review of the literature and a case series.

BACKGROUND: Mucormycosis is a rare infection in lung transplant recipients (LTR). Our objective was to better define the clinical presentation and optimal management of this frequently lethal infection. METHODS: A systematic review of the literature was performed to identify all published cases of mucormycosis in LTR using PubMed/MEDLINE. These cases were analyzed together with a new case series from our clinic. RESULTS: Literature search yielded 44 articles matching the inclusion criteria, describing 121 cases. Six additional cases were identified from our clinic. Data regarding infection site and outcome were available for a total of 53 patients. The lungs were the most common site of infection (62%), followed by rhinocerebral and disseminated disease. Most cases (78%) developed in the first post-transplant year, with over 40% of them in the first month. Additional risk factors for mucormycosis were identified in over half of the patients. Surgical debridement was uncommon in pulmonary infection (9%). Posaconazole therapy was used in 35% of cases, mostly in combination with amphotericin B. Overall mortality was 32% but varied according to site of infection. CONCLUSION: Mucormycosis in LTRs tends to be an early post-surgical infection, associated with additional risk factors and intensified immunosuppressive states, and most often affects the lungs, where surgical debridement is rarely feasible. Posaconazole as first-line therapy should be further explored.

The Profile of COPD Patients with Prolonged Hospitalizations: A Retrospective Analysis of 200 Hospital Admissions.

BACKGROUND: Patients with severe chronic obstructive pulmonary disease (COPD) experience frequent exacerbations and need to be hospitalized, resulting in an economic and social burden. Although data exist regarding reasons of frequent hospitalizations, there is no data available about the impact on the length of stay (LOS). OBJECTIVES: To characterize the causes of prolonged hospitalizations in COPD patients. METHODS: A retrospective study was conducted of patients who were diagnosed and treated in the pulmonary department for severe COPD exacerbations. All patient demographic data and medical history were collected. Data regarding the disease severity were also collected (including Global Initiative for Obstructive Lung Disease [GOLD] criteria, pulmonologist follow-up, prior hospitalizations, and LOS). RESULTS: The study comprised 200 patients, average age 69.5 ± 10.8 years, 61% males. Of these patients, 89 (45%) were hospitalized for up to 4 days, 111 (55%) for 5 days or more, and 34 (17%) for more than 7 days. Single patients had longer LOS compared with married patients (48% vs. 34%, P = 0.044). Multivariate analysis showed that the number of prior hospital admissions in the last year was a predictor of LOS (P = 0.038, odds ratio [OR] = 0.807, 95% confidence interval [95%CI] = 0.659-0.988), as well as the use of non-invasive respiratory support by bilevel positive airway pressure (BiPAP) during the hospitalization (P = 0.024, OR = 4.662, 95%CI = 1.229-17.681). CONCLUSIONS: Fewer previous hospitalizations due to COPD exacerbations and the need for non-invasive respiratory support by BiPAP were found as predictors of longer LOS.

High Diagnostic Accuracy of Transbronchial Cryobiopsy in Fibrotic Interstitial Lung Diseases Compared to Final Explant Diagnosis.

BACKGROUND: A diagnostic lung biopsy may be required in some cases of fibrotic interstitial lung diseases (ILD). Transbronchial cryobiopsy has been suggested as a possible alternative to surgical lung biopsy. However, previous estimates of its diagnostic yield were not validated compared to the definitive diagnosis in explanted lungs. OBJECTIVES: We aimed to assess the diagnostic accuracy of cryobiopsy in fibrotic ILD patients who subsequently had lung transplantation. METHODS: All 197 patients who underwent lung transplantation at our Center due to fibrotic ILD from January 2010 to May 2018, were screened for the presence of a pre-transplant cryobiopsy. Fourteen patients who underwent cryobiopsy before transplantation were identified. Two expert lung pathologists blindedto the explant diagnoses, independently examined these cryobiopsy specimens to decide if they match guideline criteria for usual interstitial pneumonia (UIP) pattern or an alternative diagnosis. The primary measure was the diagnostic accuracy of cryobiopsy to detect or refute a UIP pattern, as compared to the final explant diagnosis. RESULTS: Median time between cryobiopsy and transplantation was 1.4 years. All 14 cryobiopsy samples contained adequate alveolar tissue. The explant diagnosis of 13/14 patients was UIP. The two pathologists correctly diagnosed or refuted UIP in the cryobiopsy specimen in 12/14 cases (85.7%) and 11/14 cases (78.6%), respectively. The level of diagnostic agreement between pathologists was good (kappa 0.59, p = 0.016). CONCLUSIONS: Compared to the final explant diagnosis, transbronchial cryobiopsy had high diagnostic accuracy and good inter-observer agreement for UIP pattern. These findings support a potential diagnostic role for cryobiopsy in experienced centers.

[THE SYNDROME OF COMBINED PULMONARY FIBROSIS AND EMPHYSEMA - CPFE].

INTRODUCTION: There is an increasing recognition of patients with radiologic features of both pulmonary fibrosis and emphysema. This association has enabled the description of a syndrome termed combined pulmonary fibrosis and emphysema (CPFE) with unique features. Patients are mostly male smokers who suffer from effort dyspnea and hypoxemia, with near-normal spirometric and lung volumes measurements, and abnormalities of gas exchange. On the computerized tomography there is upper-lobe emphysema and lower-lobe interstitial fibrosis. CPFE is frequently complicated by pulmonary hypertension, lung cancer, acute lung injury and coronary artery disease. Mortality is significant, especially in the presence of pulmonary hypertension. In this article we will review the CPFE syndrome.