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Background: Kidney transplant recipients (KTRs) generate lower antibody responses to messenger RNA (mRNA)‐based severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination, yet precise mechanisms for this poor response remain uncertain. One potential contributor is suboptimal spike antigen (sAg) translation and expression owing to transplant immunosuppression, which might lead to insufficient exposure to develop humoral and/or cellular immune responses. Methods: Within a single‐arm clinical trial, 65 KTRs underwent ultrasensitive plasma sAg testing before, and 3 and 14 days after, the third mRNA vaccine doses. Anti‐SARS‐CoV‐2 spike antibodies (anti‐receptor binding domain [anti‐RBD]) were serially measured at 14 and 30 days post‐vaccination. Associations between sAg detection and clinical factors were assessed. Day 30 anti‐RBD titer was compared among those with versus without sAg expression using Wilcoxon rank sum testing. Results: Overall, 16 (25%) KTRs were sAg positive (sAg+) after vaccination, peaking at day 3. Clinical and laboratory factors were broadly similar in sAg(+) versus sAg(‐) KTRs. sAg(+) status was significantly negatively associated with day 30 anti‐RBD response, with median (interquartile range) 10.8 (<0.4–338.3) U/mL if sAg(+) versus 709 (10.5–2309.5) U/mL if sAg(‐) (i.e., 66‐fold lower; p =.01). Conclusion: Inadequate plasma sAg does not likely drive poor antibody responses in KTRs, rather sAg detection implies insufficient immune response to rapidly clear vaccine antigen from blood. Other downstream mechanisms such as sAg trafficking and presentation should be explored. [ABSTRACT FROM AUTHOR]

Background: Adolescent solid organ transplant recipients (aSOTRs) who received three doses of the COVID‐19 mRNA vaccine experience high seroconversion rates and antibody persistence for up to 3 months. Long‐term antibody durability beyond this timeframe following three doses of the SARS‐CoV‐2 mRNA vaccine remains unknown. We describe antibody responses 6 months following the third vaccine dose (D3) of the BNT162b2 mRNA vaccination among aSOTRs. Methods: Participants in a multi‐center, observational cohort who received the third dose of the vaccine were analyzed for antibodies to the SARS‐CoV‐2 spike protein receptor‐binding domain (Roche Elecsys anti‐SARS‐CoV‐2‐S positive: ≥0.8, maximum: >2500 U/mL). Samples were collected at 1‐, 3‐, and 6‐months post‐D3. Participants were surveyed at each timepoint and at 12‐months post‐D3. Results: All 34 participants had positive anti‐RBD antibody titers 6 months post‐D3. Variations in titers occurred between 3 and 6 months post‐D3, with 8/28 (29%) having decreased antibody levels at 6 months compared to 3 months and 2/28 (7%) reporting increased titers at 6 months. The remaining 18/28 (64%) had unchanged antibody titers compared to 3‐month post‐D3 levels. A total of 4/34 (12%) reported breakthrough infection within 6 months and 3/32 (9%) reported infection after 6–12 months following the third dose of the SARS‐CoV‐2 mRNA vaccine. Conclusions: The results suggest that antibody durability persists up to 6 months following three doses of the SARS‐CoV‐2 mRNA in aSOTRs. Demography and transplant characteristics did not differ for those who experienced antibody weaning. Breakthrough infections did occur, reflecting immune‐evasive nature of novel variants such as Omicron. [ABSTRACT FROM AUTHOR]

This article discusses a study conducted on vaccinated solid organ transplant recipients (SOTRs) with COVID-19 to evaluate the accuracy of anti-N antibody testing for prior SARS-CoV-2 infection. The study found that the sensitivity of anti-N testing for prior infection was relatively poor at 55% and only marginally increased with time since diagnosis. Certain organ and immunosuppressive characteristics, such as the use of mTOR inhibitors, were associated with a higher rate of anti-N positivity. The study concludes that a negative clinical anti-N test is not sufficient to rule out prior SARS-CoV-2 infection in SOTRs, particularly among more immunosuppressed groups and those who experienced milder disease. [Extracted from the article]

Anti-spike antibody (Ab) assays were authorized to determine prior exposure to SARS-CoV-2 and have since been adopted by some clinicians to measure humoral response to vaccination and estimate vulnerability to infection.[[1]] As such, many commercial assays currently in use for clinical and research purposes have not undergone validation in the setting of high antibody concentrations which may be achieved through repeat antigen exposure or monoclonal antibody (mAb) therapies.[3] This is noteworthy because immunoassays used in other settings have been observed to return imprecise or artifactually low quantitative results due to a "hook" or prozone effect in undiluted samples at their upper limits of quantification, that is, in the setting of very high binding antibody titers.[4] We sought to determine whether a hook effect occurs in a semi-quantitative binding assay (Roche-Elecsys anti-SARS-CoV-2 S) which is widely used by medical providers and researchers, given potential clinical implications, particularly for vulnerable populations such as solid organ transplant recipients (SOTRs). Participants in the clinical trial were SOTRs with known poor response to vaccination, and developed lower peak Ab titers, therefore, the reported hook effect proportion may be an underestimate as compared to the general vaccinated SOTR population. Letter to the editor: "hook" (prozone) effect in sars-cov-2 anti-spike binding antibody levels following vaccination, infection, or monoclonal antibody in solid organ transplant recipients. [Extracted from the article]

Background: Tixagevimab and Cilgavimab (T + C) is authorized for pre‐exposure prophylaxis (PrEP) against Coronavirus Disease 2019 (COVID‐19) in solid organ transplant recipients (SOTRs), yet patient‐reported outcomes after injection are not well described. Furthermore, changes in risk tolerance after T + C PrEP have not been reported, of interest given uncertain activity against emerging Omicron sublineages. Methods: Within a national prospective observational study, SOTRs who reported receiving T + C were surveyed for 3 months to ascertain: (1) local and systemic reactogenicity, (2) severe adverse events with focus on cardiovascular and alloimmune complications, and (3) breakthrough COVID‐19, contextualized through (4) changes in attitudes regarding COVID‐19 risk and behaviors. Results: At 7 days postinjection, the most common reactions were mild fatigue (29%), headache (20%), and pain at injection sites (18%). Severe adverse events were uncommon; over 3 months of follow‐up, 4/392 (1%) reported acute rejection and one (.3%) reported a myocardial infarction. Breakthrough COVID‐19 occurred in 9%, 16–129 days after receiving full dose (300/300 mg) T + C, including two non‐ICU hospitalizations. Most surveyed SOTRs (65%) felt T + C PrEP was likely to reduce their COVID‐19 risk, and 70% reported increased willingness to engage in social activities such as visiting friends. However, few felt safe to return to in‐person work (20%) or cease public mask‐wearing (15%). Conclusions: In this prospective study of patient‐reported outcomes, T + C was well tolerated with few serious events. Several COVID‐19 breakthroughs were reported, notable as most SOTRs reported changes in risk tolerance after T + C. These results aid counseling of SOTRs regarding real‐world safety and effectiveness of T + C. [ABSTRACT FROM AUTHOR]

In this national longitudinal study of incident COVID-19 among unvaccinated adults during the Omicron wave, only 12% of those who entered the wave with anti-RBD antibodies reported a test-confirmed COVID-19 infection, compared to 35% of those without antibodies prior to the Omicron wave. We recently reported that 99% of unvaccinated US adults who had a test-confirmed SARS-CoV-2 infection had detectable anti-receptor-binding domain (anti-RBD) antibodies up to 20 months after their positive COVID-19 test [2]. GLO:0IU/01dec22:joim13555-fig-0001.jpg PHOTO (COLOR): 1 Distribution of self-reported COVID-19 infections after December 1, 2021 among unvaccinated US adults, stratified by pre-Omicron wave anti-receptor-binding domain (anti-RBD) antibody level. gl Having antibodies was 67% effective against reporting test-confirmed COVID-19 (35% vs. 12%, I p i < 0.001). [Extracted from the article]

Fewer than 45% of solid organ transplant recipients (SOTRs) mount a detectable antispike antibody level after two doses of mRNA SARS-CoV-2 vaccination (D2).1 Various vaccination strategies, including mixing platforms, have been proposed, but there is no consensus on the optimal vaccination sequence to improve immunogenicity.2,3 Although using similar technology, the mRNA-1273 vaccine has been associated with higher peak antibody responses than the use of BNT162b2 in immunosuppressed populations, potentially related to a higher vaccine antigen dose.3,4 We therefore studied whether the use of mRNA-1273 versus BNT162b2 as a third primary vaccine dose (D3) might generate a more robust antibody response in SOTR who remained seronegative after two doses of BNT162b2. Improved humoral immunogenicity with mRNA-1273 versus BNT162b2 as third vaccine dose among solid organ transplant recipients seronegative after two BNT162b2 doses METHODS From our national observational study, approved by the Johns Hopkins Institutional Review Board (IRB00248540),4 we included adult SOTRs who tested seronegative after two doses of BNT162b2 and received either a D3-BNT162b2 or D3-mRNA-1273. [Extracted from the article]

Solid organ transplant recipients (SOTRs) have reduced immunogenicity to SARS-CoV-2 vaccines and are at increased risk of severe COVID-19 when compared to the general population.[1] Previously, a fourth dose (D4) of SARS-CoV-2 vaccine has shown improved antibody responses in SOTRs, but given the decreasing titers seen by 6 months post-dose 2 and 3, immune responses achieved after D4 could decrease in a similar fashion.[[2]] This study assesses the durability and kinetics of vaccine-induced antibody responses in SOTRs post-D4 and evaluates these responses in the context of the Omicron variant, which requires higher levels of antibody to neutralize. In this study of antibody responses after a fourth dose of SARS-CoV-2 vaccine in SOTRs with 6 months of follow up, 61% demonstrated antibody titers associated in prior studies with potential SARS-CoV-2 Omicron variant neutralization at 3 months. 3 c 5/18 SOTRs with low titers and 8/39 SOTRs with high titers were unable to provide titers at 3-months post-D4. [Extracted from the article]

Objective: To evaluate disease flare and postvaccination reactions (reactogenicity) in patients with rheumatic and musculoskeletal diseases (RMDs) following 2‐dose SARS–CoV‐2 messenger RNA (mRNA) vaccination. Methods: RMD patients (n = 1,377) who received 2‐dose SARS–CoV‐2 mRNA vaccination between December 16, 2020 and April 15, 2021 completed questionnaires detailing local and systemic reactions experienced within 7 days of each vaccine dose (dose 1 and dose 2), and 1 month after dose 2, detailing any flares of RMD. Associations between demographic/clinical characteristics and flares requiring treatment were evaluated using modified Poisson regression. Results: Among the patients, 11% reported flares requiring treatment; there were no reports of severe flares. Flares were associated with prior SARS–CoV‐2 infection (incidence rate ratio [IRR] 2.09, P = 0.02), flares in the 6 months preceding vaccination (IRR 2.36, P < 0.001), and the use of combination immunomodulatory therapy (IRR 1.95, P < 0.001). The most frequently reported local and systemic reactions included injection site pain (87% after dose 1, 86% after dose 2) and fatigue (60% after dose 1, 80% after dose 2). Reactogenicity increased after dose 2, particularly for systemic reactions. No allergic reactions or SARS–CoV‐2 diagnoses were reported. Conclusion: Flares of underlying RMD following SARS–CoV‐2 vaccination were uncommon. There were no reports of severe flares. Local and systemic reactions typically did not interfere with daily activity. These early safety data can help address vaccine hesitancy in RMD patients. [ABSTRACT FROM AUTHOR]

Antibody response to a third dose of SARS-CoV-2 vaccine in heart and lung transplant recipients Morbidity and mortality from SARS-CoV-2 infection in heart (HT) and lung transplant (LT) recipients are high, especially for LT recipients, despite vaccination.[1] Despite severe COVID-19 outcomes, HT/LT recipients represent <10% of solid organ transplant recipients (SOTRs) included in cohort studies evaluating two and three dose regimens.[2] There is now strong evidence to support that SOTRs in a greater immunosuppressed state (common among HT/LT recipients) are at increased risk for persistent seronegative state post-D3.[[3]] Therefore, we evaluated antispike antibody responses before and after a third vaccine dose (D3) in HT/LT recipients to quantify post-D3 antibody responses. Effect of Mycophenolate mofetil dosing on antibody response to SARS-CoV-2 vaccination in heart and lung transplant recipients. [Extracted from the article]

Heterologous vaccination has been explored in small populations of solid organ transplant recipients (SOTRs),1-4 yet 38% of participants had persistently suboptimal response indicating potential role for further vaccine doses.1 The US CDC currently recommends immunocompromised adults who received an Ad26.COV2.S prime to receive one additional dose of SARS-CoV-2 mRNA vaccine, either BNT162b2 or mRNA-1273, followed by two mRNA vaccine boosters, although the efficacy of this strategy in immunocompromised persons is not known. A third dose of SARS-CoV-2 vaccine increases neutralizing antibodies against variants of concern in solid organ transplant recipients. Immunogenicity of Ad26.COV2.S prime and two subsequent doses of mRNA SARS-CoV-2 vaccines in solid organ transplant recipients: A case series. [Extracted from the article]

End‐organ cytomegalovirus (CMV) disease can be life threatening to solid organ transplant recipients. Diagnosis is often complicated by variation in amount of CMV DNA in plasma and the need for an invasive procedure to obtain a biopsy of the suspected affected organ, which can delay recognition and treatment. Several inflammatory cytokines are elevated in CMV disease, and the purpose of this study was to determine if they could be used to distinguish solid organ transplant recipients with CMV DNAemia alone from those with possible end‐organ CMV disease. We found that regardless of pre‐transplant CMV serostatus, plasma interleukin (IL)‐18, tumor necrosis factor‐α (TNF‐α), and amount of CMV DNA in plasma were increased in possible end‐organ CMV disease, with elevated IL‐18 associated with increased odds of possible end‐organ CMV disease even after adjusting for amount of CMV DNA. These findings highlight IL‐18 and TNF‐α as potential non‐invasive markers of possible end‐organ CMV disease regardless of transplanted organ or serostatus in solid organ transplant recipients. [ABSTRACT FROM AUTHOR]

In our first survey of transplant centers in March 2020, >75% of kidney and liver programs were either suspended or operating under restrictions. To safely resume transplantation, we must understand the evolving impact of COVID‐19 on transplant recipients and center‐level practices. We therefore conducted a six‐week follow‐up survey May 7‐15, 2020, and linked responses to the COVID‐19 incidence map, with a response rate of 84%. Suspension of live donor transplantation decreased from 72% in March to 30% in May for kidneys and from 68% to 52% for livers. Restrictions/suspension of deceased donor transplantation decreased from 84% to 58% for kidneys and from 73% to 42% for livers. Resuming transplantation at normal capacity was envisioned by 83% of programs by August 2020. Exclusively using local recovery teams for deceased donor procurement was reported by 28%. Respondents reported caring for a total of 1166 COVID‐19–positive transplant recipients; 25% were critically ill. Telemedicine challenges were reported by 81%. There was a lack of consensus regarding management of potential living donors or candidates with SARS‐CoV‐2. Our findings demonstrate persistent heterogeneity in center‐level response to COVID‐19 even as transplant activity resumes, making ongoing national data collection and real‐time analysis critical to inform best practices. [ABSTRACT FROM AUTHOR]

A successful multidisciplinary research center depends on the quality of the science being conducted and the quality of the center's design, culture, infrastructure, and institutional support. In this perspective, we describe our experience building and maintaining a multidisciplinary transplant research center with a large focus on transplant infectious diseases. We identify principles that we believe contributed to our success including: taking inventory, defining culture, creating a multidisciplinary shared leadership model, establishing expertise in a multiple method approach, investing in operations and management, building and sharing resources, and securing institutional support. We share our experience putting these principles into practice and highlight potential roadblocks. [ABSTRACT FROM AUTHOR]

Colletotrichum is an important fungal plant pathogen, yet an uncommon cause of human disease. Herein we report a case of invasive, cutaneous infection in a stem cell transplant recipient due to Colletotrichum species, with accompanying review of the literature. The infection was successfully treated with a combination of liposomal amphotericin B and voriconazole. Multilocus phylogenetic analysis revealed that the distinct isolate belongs to Colletotrichum siamense, a member of the Colletotrichum gloeosporioides species complex not previously described as a human pathogen. Colletotrichum infection remains in the differential for skin lesions in the immune compromised host. [ABSTRACT FROM AUTHOR]