Key Points Question What are the humoral immune response rates and risk factors associated with diminished response after COVID-19 vaccination in recipients of solid organ transplant? Findings In this systematic review and meta-analysis of 29 studies and 11 713 recipients of solid organ transplant, seroconversion rates increased with progressively increased numbers of mRNA COVID-19 vaccine doses. Older age, recent transplantation, deceased donor status, active use of antimetabolites, and recent exposure to antithymocyte globulin or rituximab were risk factors associated with diminished humoral immune response after receiving 2 doses of mRNA vaccines. Meaning These findings suggest that more efforts are needed to modulate the risk factors associated with reduced humoral responses among recipients of solid organ transplant.

Background. Respiratory syncytial virus (RSV) infection in lung transplant recipients (LTRs) causes mortality rates of 10%–20% despite antiviral therapy. Ribavirin (RBV) has been used to treat RSV-infected LTRs with limited data. Methods. A retrospective study including all LTRs at Duke Hospital during January 2013–May 2017 with positive RSV polymerase chain reaction respiratory specimens was performed. Results. Fifty-six of 70 patients in the oral RBV group and 29 of 32 in the inhaled RBV group had symptomatic RSV infection. One patient receiving oral RBV had to prematurely stop drug due to significant nausea and vomiting. While unadjusted all-cause 1-year mortality was significantly higher in the inhaled RBV group (24.1% versus 7.1% [oral RBV], P = 0.03), adjusted hazard ratio (HR) for death and oral RBV use (compared to inhaled RBV), accounting for oxygen requirement and need for mechanical ventilation, showed the HR for death and oral RBV use was 0.38 ([0.10, 1.46], P = 0.38). The HR for death in patients with supplemental oxygen >2 L/min at diagnosis was 6.18 ([1.33, 26.83], P = 0.02). Kaplan-Meier curves showed patients with forced expiratory volume in 1 second decline ≥5% and ≥10% at 90 days post-RSV infection had a higher 1-year mortality (P = 0.004 and P = 0.001, respectively). Conclusions. Oral and inhaled RBV appear to be well tolerated in LTRs, and our data support the use of oral RBV as a safe alternative to inhaled ribavirin in LTRs. Oxygen requirement >2 L/min at diagnosis and forced expiratory volume in 1 second decline ≥5% postinfection may be markers for increased mortality.

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.

Nintedanib and pirfenidone are anti-fibrotic medications that slow IPF progression. There have been concerns about the potential of these medications to impair wound healing following surgery. These concerns have led to variable approaches to the management of the medications in patients listed for lung transplantation. It is unknown whether continuing anti-fibrotic medications until the time of transplant increases the risks of intra-operative and post-transplant complications. This study assessed whether the duration of time between discontinuation of anti-fibrotic therapy for IPF and lung transplantation impacts rates of intra-operative and post-transplant complications. Methods: We performed a multi-centered, observational study to explore these questions. Subjects' historical data collected in the medical record were utilized. All patients with IPF who underwent transplantation and were being treated with nintedanib or pirfenidone continuously for at least 90 days at the time of their listing eligibility were included. Subjects were grouped by the time period between their anti-fibrotic discontinuation and transplant dates. Group 1 were those that stopped the medication prior to transplant within 5 half-lives of their anti-fibrotic medication (i.e. 2 days or less for nintedanib, and 1 day or less for pirfenidone); group 2 stopped between 5 anti-fibrotic half-lives and 28 days; and group 3 stopped > 28 days before their transplant. Rates of major clinical events and complications during and after transplant across the 2 anti-fibrotic medications and 3 medication discontinuation groups were analyzed. Results: 235 patients were included in the analysis, 86 of whom were taking nintedanib at the time of listing eligibility, 149 taking pirfenidone. Most patients (nintedanib 58/86, 67%; pirfenidone 102/149, 68%) continued anti-fibrotic therapy beyond being listed and were categorized into group 1. Time to initial post-operative extubation, primary graft dysfunction rates, final chest tube removal day, and ICU length of stay appeared similar across the 6 groups. Anastomotic dehiscences, while rare (3%), were only seen in group 1 patients for both medications. Sternal breakdown/dehiscences occurred in 5 patients (2%), all of whom were in pirfenidone group 1. Conclusion: While most outcomes appeared similar across the 2 anti-fibrotic medications and 3 medication discontinuation groups, airway and sternal dehiscence events were only recorded in patients that discontinued anti-fibrotic therapy within 5 medication half-lives prior to their transplant.

BackgroundRespiratory syncytial virus (RSV) infections in lung transplant recipients (LTRs) have been associated with bronchiolitis obliterans syndrome (BOS). However, limited data exists regarding the association of RSV with other types of rejection.MethodsThis retrospective study of all RSV-infected LTRs at Duke University from January 2013 to May 2017 examined acute cellular rejection (ACR), acute antibody mediated rejection (AMR), new human leukocyte antigen (HLA) detection, new donor-specific antigen (DSA) detection, new BOS development and BOS progression at 1 year after RSV infection. Early and late RSV was defined as infection occurring ≤ or >180 days post lung transplant, respectively. Logistic regression was performed to adjust risk of rejection.ResultsOf 114 RSV-infected LTRs, 20 and 94 had early and late infection respectively. The cohort differs regarding underlying prior BOS, site of infection and RBV treatment (see table). Overall 1-year ACR after RSV infection was 44.7% (75% vs. 38.3% in early and late groups, respectively). Patients with early RSV infection had significantly higher rate of new HLA and DSA detection (see table). After adjusting by infection site and RBV exposure, the odd ratios (OR) for new HLA detection for patients with early RSV was 5.4 [1.4, 20.7]. Both oral and inhaled RBV did not decrease the OR for ACR after adjusting for infection and timing of RSV infection after lung transplantation.ConclusionOur data showed RSV infection was associated with very high rates of ACR in both early and later RSV groups. Patients with early RSV had higher rates of new HLA and DSA detection.Early RSV N = 20 (%)Late RSV N = 94 (%) P-valueUnderlying BOS prior to RSV infection024 (25.5)0.01Site of infection0.03Upper tract3 (15)41 (43.6)Lower tract9 (45)36 (38.3)Asymptomatic8 (40)17 (18.1)Treatment<0.001Oral RBV4 (20)66 (70.2)Inhaled RBV10 (50)22 (23.4)Supportive care6 (30)6 (6.4)Concomitant IVIG3 (15)18 (19.4)0.65RejectionsACR15 (75)36 (38.3)0.03Median episodes of ACR within 1 year after RSV infection (range)1 (1–5)1 (1–3)0.38AMR3 (15)4 (4.3)0.07New detection of:HLA7 (35)10 (10.6)0.005DSA6/7 (85.7)3/10 (30)0.03BOS4/20 (20)19/70(27.1)0.52BOS progression (patients with prior BOS)-9/24 (37.5)-Disclosures R. Miller, scynexis: Investigator, Research support.