Immunogenicity of SARS-CoV-2 vaccines in patients with multiple myeloma: a systematic review and meta-analysis.

Patients with multiple myeloma (MM) have a diminished immune response to coronavirus disease 2019 (COVID-19) vaccines. Risk factors for an impaired immune response are yet to be determined. We aimed to summarize the COVID-19 vaccine immunogenicity and to identify factors that influence the humoral immune response in patients with MM. Two reviewers independently conducted a literature search in MEDLINE, Embase, ISI Web of Science, Cochrane library, and Clinicaltrials.gov from existence until 24 May 24 2022. (PROSPERO: CRD42021277005). A total of 15 studies were included in the systematic review and 5 were included in the meta-analysis. The average rate (range) of positive functional T-lymphocyte response was 44.2% (34.2%-48.5%) after 2 doses of messenger RNA (mRNA) COVID-19 vaccines. The average antispike antibody response rates (range) were 42.7% (20.8%-88.5%) and 78.2% (55.8%-94.2%) after 1 and 2 doses of mRNA COVID-19 vaccines, respectively. The average neutralizing antibody response rates (range) were 25% (1 study) and 62.7% (53.3%-68.6%) after 1 and 2 doses of mRNA COVID-19 vaccines, respectively. Patients with high-risk cytogenetics or receiving anti-CD38 therapy were less likely to have a humoral immune response with pooled odds ratios of 0.36 (95% confidence interval [95% CI], 0.18, 0.69), I2 = 0% and 0.42 (95% CI, 0.22, 0.79), I2 = 14%, respectively. Patients who were not on active MM treatment were more likely to respond with pooled odds ratio of 2.42 (95% CI, 1.10, 5.33), I2 = 7%. Patients with MM had low rates of humoral and cellular immune responses to the mRNA COVID-19 vaccines. Further studies are needed to determine the optimal doses of vaccines and evaluate the use of monoclonal antibodies for pre-exposure prophylaxis in this population.

Effectiveness of Casirivimab-Imdevimab Monoclonal Antibody Treatment Among High-Risk Patients With Severe Acute Respiratory Syndrome Coronavirus 2 B.1.617.2 (Delta Variant) Infection.

Background: Real-world data on the effectiveness of neutralizing casirivimab-imdevimab monoclonal antibody (Cas-Imd mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among high-risk patients may inform the response to future SARS-CoV-2 variants. Methods: This study covers an observational retrospective data analysis in Banner Health Care System sites, mainly in Arizona. During the study period, the prevalence of SARS-CoV-2 Delta variant was between 95% and 100%. Of 29 635 patients who tested positive for coronavirus disease 2019 (COVID-19) between 1 August 2021 and 30 October 2021, in the Banner Health Care System, the study cohort was split into 4213 adult patients who received Cas-Imd mAb (1200 mg) treatment compared to a PS-matched 4213 untreated patients. The primary outcomes were the incidence of all-cause hospitalization, intensive care unit (ICU) admission, and mortality within 30 days of Cas-Imd mAb administration or Delta variant infection. Results: Compared to the PS-matched untreated cohort, the Cas-Imd mAb cohort had significantly lower all-cause hospitalization (4.2% vs 17.6%; difference in percentages, -13.4 [95% confidence interval {CI}, -14.7 to -12.0]; P < .001), ICU admission (0.3% vs 2.8%; difference, -2.4 [95% CI, -3.0 to -1.9]; P < .001), and mortality (0.2% vs 2.0%; difference, -1.8 [95% CI, -2.3 to -1.3]; P < .001) within 30 days. The Cas-Imd mAb treatment was associated with lower rate of hospitalization (hazard ratio [HR], 0.22 [95% CI, .19-.26]; P < .001) and mortality (HR, 0.11 [95% CI, .06-.21]; P < .001). Conclusions: Cas-Imd mAb treatment was associated with a lower hospitalization rate, ICU admission, and mortality within 30 days among patients infected with the SARS-CoV-2 Delta variant.

EFFECTIVENESS OF CASIRIVIMAB-IMDEVIMAB MONOCLONAL ANTIBODY TREATMENT AMONG HIGH-RISK PATIENTS WITH SARS-CoV-2 B.1.617.2 (COVID-19 DELTA VARIANT) INFECTION

BACKGROUND Real-world data on the effectiveness of neutralizing Casirivimab-Imdevimab monoclonal antibody (Cas-Imd mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among high-risk patients may inform the response to future SARS-CoV-2 variants. METHODS This study covers an observational retrospective data analysis in Banner Health Care System sites, mainly in Arizona. During the study period, the prevalence of SARS-CoV-2 Delta variant was between 95% and 100%. Out of 29,635 patients who tested positive for COVID-19 between 8/1/2021 and 10/30/2021, in Banner Health Care System, the study cohort was split into 4213 adult patients who received Cas-Imd mAb (1200 mg) treatment compared to a propensity-matched 4213 untreated patients. The primary outcomes were the incidence of all-cause hospitalization, intensive care unit (ICU) admission, and mortality within 30 days of Cas-Imd mAb administration or COVID-19 Delta variant infection. RESULTS Compared to the propensity matched untreated cohort, the Cas-Imd mAb cohort had significantly lower all-cause hospitalization (4.2% vs 17.6%;difference in percentages and 95% confidence interval [CI] -13.4 [-14,7, -12.0], P <.001), ICU admission (0.3% vs 2.8%;difference and CI -2.4 [-3.0, -1.9], P <.001), and mortality (0.2% vs 2.0%;difference and CI -1.8 [-2.3, -1.3], P <.001) within 30 days. The Cas-Imd mAb treatment was associated with lower rate of hospitalization (hazard ratio [HR], 0.22;95% CI, 0.19-0.26; P <.001) and mortality (HR, 0.11;95% CI, 0.06-0.21; P<.001). CONCLUSIONS Cas-Imd mAb treatment was associated with a lower hospitalization rate, ICU admission, and mortality within 30 days among patients infected with COVID-19 Delta variant.

Immunogenicity and Risk Factors Associated With Poor Humoral Immune Response of SARS-CoV-2 Vaccines in Recipients of Solid Organ Transplant: A Systematic Review and Meta-Analysis.

Importance: Recipients of solid organ transplant (SOT) experience decreased immunogenicity after COVID-19 vaccination. Objective: To summarize current evidence on vaccine responses and identify risk factors for diminished humoral immune response in recipients of SOT. Data Sources: A literature search was conducted from existence of database through December 15, 2021, using MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov. Study Selection: Studies reporting humoral immune response of the COVID-19 vaccines in recipients of SOT were reviewed. Data Extraction and Synthesis: Two reviewers independently extracted data from each eligible study. Descriptive statistics and a random-effects model were used. This report was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data were analyzed from December 2021 to February 2022. Main Outcomes and Measures: The total numbers of positive immune responses and percentage across each vaccine platform were recorded. Pooled odds ratios (pORs) with 95% CIs were used to calculate the pooled effect estimates of risk factors for poor antibody response. Results: A total of 83 studies were included for the systematic review, and 29 studies were included in the meta-analysis, representing 11 713 recipients of SOT. The weighted mean (range) of total positive humoral response for antispike antibodies after receipt of mRNA COVID-19 vaccine was 10.4% (0%-37.9%) for 1 dose, 44.9% (0%-79.1%) for 2 doses, and 63.1% (49.1%-69.1%) for 3 doses. In 2 studies, 50% of recipients of SOT with no or minimal antibody response after 3 doses of mRNA COVID-19 vaccine mounted an antibody response after a fourth dose. Among the factors associated with poor antibody response were older age (mean [SE] age difference between responders and nonresponders, 3.94 [1.1] years), deceased donor status (pOR, 0.66 [95% CI, 0.53-0.83]; I2 = 0%), antimetabolite use (pOR, 0.21 [95% CI, 0.14-0.29]; I2 = 70%), recent rituximab exposure (pOR, 0.21 [95% CI, 0.07-0.61]; I2 = 0%), and recent antithymocyte globulin exposure (pOR, 0.32 [95% CI, 0.15-0.71]; I2 = 0%). Conclusions and Relevance: In this systematic review and meta-analysis, the rates of positive antibody response in solid organ transplant recipients remained low despite multiple doses of mRNA vaccines. These findings suggest that more efforts are needed to modulate the risk factors associated with reduced humoral responses and to study monoclonal antibody prophylaxis among recipients of SOT who are at high risk of diminished humoral response.

Coronavirus Disease 2019-Associated Pulmonary Aspergillosis in Mechanically Ventilated Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) occurs in critically ill patients with COVID-19. Risks and outcomes remain poorly understood. METHODS: A retrospective cohort study of mechanically ventilated adult patients with COVID-19 admitted to 5 Johns Hopkins hospitals was conducted between March and August 2020. CAPA was defined using composite clinical criteria. Fine and Gray competing risks regression was used to analyze clinical outcomes and, multilevel mixed-effects ordinal logistic regression was used to compare longitudinal disease severity scores. RESULTS: In the cohort of 396 people, 39 met criteria for CAPA. Patients with CAPA were more likely than those without CAPA to have underlying pulmonary vascular disease (41% vs 21.6%, respectively; P = .01), liver disease (35.9% vs 18.2%; P = .02), coagulopathy (51.3% vs 33.1%; P = .03), solid tumors (25.6% vs 10.9%; P = .02), multiple myeloma (5.1% vs 0.3%; P = .03), and corticosteroid exposure during the index admission (66.7% vs 42.6%; P = .005), and had lower body mass indexes (median, 26.6 vs 29.9 [calculated as weight in kilograms divided by height in meters squared]; P = .04). Patients with CAPA had worse outcomes, as measured by ordinal severity of disease scores, requiring longer time to improvement (adjusted odds ratio, 1.081.091.1; P < .001), and advancing in severity almost twice as quickly (subhazard ratio, 1.31.82.5; P < .001). They were intubated twice as long as those without CAPA (subhazard ratio, 0.40.50.6; P < .001) and had longer hospital stays (median [interquartile range], 41.1 [20.5-72.4) vs 18.5 [10.7-31.8] days; P < .001). CONCLUSION: CAPA is associated with poor outcomes. Attention to preventive measures (screening and/or prophylaxis) is warranted in people with high risk of CAPA.

Morning report for all: a qualitative study of disseminating case conferences via podcasting.

BACKGROUND: Despite its long-established importance, diagnostic reasoning (DR) education has suffered uneven implementation in medical education. The Clinical Problem Solvers (CPSolvers) podcast has emerged as a novel strategy to help teach DR through case conferences with expert diagnosticians and trainees. CPSolvers has 25,000 listeners in 147 countries. The aim of this study was to evaluate the podcast by eliciting the developers' goals of the podcast, then determining to what extent they aligned with the listeners' actual usage habits, features they valued, and perceptions of the podcast. METHODS: We conducted semi-structured interviews with 3 developers and 8 listeners from April-May 2020, followed by qualitative thematic analysis. RESULTS: Three major developer goals with sub-goals resulted: 1. To teach diagnostic reasoning in a case-based format by (1a) teaching schemas, (1b) modeling expert diagnostic reasoning, (1c) teaching clinical knowledge, and (1d) teaching diagnostic reasoning terminology. 2. To change the culture of medicine by (2a) promoting diversity, (2b) modeling humility and promoting psychological safety, and (2c) creating a fun, casual way to learn. 3. To democratize the teaching of diagnostic reasoning by leveraging technology. Listeners' usage habits, valued features, and perceptions overall strongly aligned with all these aspects, except for (1c) clinical knowledge, and (1d) diagnostic reasoning terminology. Listeners identified (1a) schemas, and (2c) promotion of psychological safety as the most valuable features of the podcast. CONCLUSION: CPSolvers has been perceived as a highly effective and novel way to disseminate DR education in the form of case conferences, serving as an alternative to traditional in-person case conferences suspended during COVID-19. CPSolvers combines many known benefits of in-person case conferences with a compassionate and entertaining teaching style, plus advantages of the podcasting medium - democratizing morning report for listeners around the world.

Impact of COVID-19 on Lung Allograft and Clinical Outcomes in Lung Transplant Recipients: A Case-control Study.

BACKGROUND: The impacts of COVID-19 on lung allograft function, rejection, secondary infection, and clinical outcomes in lung transplant recipients (LTRs) remain unknown. METHODS: A 1:2 matched case-control study was performed to evaluate rehospitalization, lung allograft function, and secondary infections up to 90 d after COVID-19 diagnosis (or index dates for controls). RESULTS: Twenty-four LTRs with COVID-19 (cases) and 48 controls were identified. Cases and controls had similar baseline characteristics and lung allograft function. LTRs with COVID-19 had higher incidence of secondary bacterial infection (29.2% versus 6.3%, P = 0.008), readmission (29.2% versus 10.4%, P = 0.04), and for-cause bronchoscopy (33.3% versus 12.5%, P = 0.04) compared with controls. At d 90, mortality in cases versus controls was 8.3% versus 2.1% (P = 0.21), incidence of invasive fungal infections in cases versus controls was 20.8% versus 8.3% (P = 0.13) and forced expiratory volume in 1 s (FEV1) decline ≥10% from baseline occurred in 19% of cases versus 12.2% of controls (P = 0.46). No acute cellular rejection, acute antibody-mediated rejection, or new donor-specific anti-HLA antibodies were observed among cases or controls within 90 d post index date. CONCLUSIONS: We found LTRs with COVID-19 were at risk to develop secondary infections and rehospitalization post COVID-19, compared with controls. While we did not observe post viral acute cellular rejection or antibody-mediated rejection, further studies are needed to understand if LTRs with COVID-19 who did not recover baseline lung function within 90 d have developed chronic lung allograft dysfunction stage progression.

Impact of Coronavirus Disease 2019 on Infectious Diseases Fellows in the United States: Perspectives From the First National Infectious Diseases Fellows Call.

The coronavirus disease 2019 (COVID-19) pandemic has affected many providers, but its impact on Infectious Diseases (ID) fellows in the United States is largely undescribed. In this study, we discuss key issues that emerged from the first national ID Fellows Call with respect to the ID fellow's role during the COVID-19 pandemic, teaching/learning, and research.

Picture of a pandemic: visual aids in the COVID-19 crisis.

As a global crisis, COVID-19 has underscored the challenge of disseminating evidence-based public health recommendations amidst a rapidly evolving, often uncensored information ecosystem-one fueled in part by an unprecedented degree of connected afforded through social media. In this piece, we explore an underdiscussed intersection between the visual arts and public health, focusing on the use of validated infographics and other forms of visual communication to rapidly disseminate accurate public health information during the COVID-19 pandemic. We illustrate our arguments through our own experience in creating a validated infographic for patients, now disseminated through social media and other outlets across the world in nearly 20 translations. Visual communication offers a creative and practical medium to bridge critical health literacy gaps, empower diverse patient communities through evidence-based information and facilitate public health advocacy during this pandemic and the 'new normal' that lies ahead.