Post-Acute Sequelae of Sars-Cov-2 Infection in Solid Organ Transplant Recipients

Purpose: Post-acute sequelae of SARS-CoV-2 infection (PASC) is an increasingly recognized phenomenon manifested by long lasting cognitive, mental, and physical symptoms. We aimed to estimate the prevalence of PASC symptoms in solid organ transplant recipients (SOTRs) in the short (1- 6 months) and long-term (> 6 months) periods after SARS-CoV-2 infection. We also compared the prevalence of these symptoms between those with SARS-CoV-2 infection requiring hospitalization and those not requiring hospitalization. Method(s): We surveyed 111 SOTRs with self-reported SARS-CoV-2 infection diagnosed more than 4 weeks prior to survey administration. The survey consisted of 7 validated questionnaires ("Quick Dementia Rating System (QDRS)", "Patient Health Questionnaire (PHQ9)", "Generalized Anxiety Disorder 7 (GAD-7)", "Impact of Events Scale (IES-6)", "EuroQol- 5 Dimension (EQ-5D)", "PROMIS global physical health scale (GHS) "and "Breathlessness, Cough and Sputum Scale (BCSS)"). Result(s): Of the 111 survey participants, 32 (33%) had been hospitalized and 35 (36%) had SARS-CoV-2 infection >6 months ago. Median (IQR) age was 58 years (46, 65). Median time from SARS-CoV-2 diagnosis was 167 days (138, 221). Cognitive impairment, anxiety, depression, insomnia, feeling of trauma, fatigue, pain, breathing problems, cough, abnormal smell, abnormal taste, and diarrhea were reported by 40%, 23%, 36%, 55%, 53%, 41%, 19%, 33%, 33%, 21%, 22%, and 32% of patients respectively. Hospitalized patients had poorer scores in cognition (QDRS survey score of 2 versus 0.75, p=0.048) (Figure 1), quality of life (EQ-5D survey score of 2 versus 1, p=0.043), physical health (PROMIS GHS survey score of 10 versus 11, p=0.013), respiratory status (BCSS survey score of 1 versus 0, p=0.056), and pain (Pain score of 3 versus 0, p 0.006). Among patients who had SARS-CoV-2 infection >6 months ago, abnormal breathing, cough, abnormal smell, abnormal taste, and diarrhea continued to be reported by 31%, 31%, 29%, 32%, and 32% of patients respectively. Conclusion(s): After SARS-CoV-2 infection, SOTRs had a high prevalence of PASC symptoms. Some of the symptoms are more severe in patients who had required hospitalization and persist beyond 6 months. Further studies are needed to understand the long term sequalae of SARS-CoV-2 infection in SOTRs and to develop an evidence-based multidisciplinary approach for caring for these patients beyond the acute phase. (Table Presented).

Solid organ transplant recipient attitudes towards a SARS-CoV-2 vaccine

Purpose: An effective and widely-accepted SARS-CoV-2 vaccine could protect the community and vulnerable populations. We investigated the attitudes of solid organ transplant recipients (SOTRs) towards a SARS-CoV-2 vaccine and identified potential barriers to vaccination. Methods: We conducted a national survey of SOTRs between November 11 - December 2, 2020 through the network and social media platforms of the National Kidney Foundation. We studied 3 major domains: a) attitudes towards a vaccine, b) impact of the pandemic on daily life, and c) impact on mental health. Results: Among 1308 SOTRs, 783 (59.9%) were female and 1035 (79.1%) were White. Respondents were evenly distributed throughout the US and were largely college graduates (829, 63.4%) and married (830, 63.5%). Half (647, 49.5%) of SOTRs would be either unsure or unwilling to receive a SARS-CoV-2 vaccine once available (Table 1). Major concerns included side effects (537, 85.2%), lack of rigor in vaccine development (439, 69.7%), and incompatibility with organ transplant (482, 75.4%). However, 1135 (86.8%) SOTRs would be willing to receive a vaccine if recommended by a transplant provider. A small fraction (161 12.3%) were in self-isolation and severe anxiety related to the COVID-19 pandemic remained low (25, 1.9%). There were no significant differences in vaccine attitudes after the announcement of 94.5% efficacy in the mRNA-1273 vaccine (Moderna, Inc.). Conclusions: Transplant recipients expressed large amounts of skepticism in a potential SARS-CoV-2 vaccine, even after announcements of high vaccine efficacy. However, transplant providers may be the defining influence in vaccine acceptance due to the trust vested in them.

Safety of SARS-CoV-2 mrna vaccines in solid organ transplant recipients

Purpose: The safety of SARS-CoV-2 mRNA vaccines in solid organ transplant recipients (SOTRs) remains unknown. We investigated adverse events in SOTRs who received these mRNA vaccines. Methods: We studied SOTRs between 12/16/2020 - 2/10/2021 who received at least one dose of a vaccine. Vaccine reactogenicity within one week following the first or second dose was self-reported via an interactive, online platform. Results: A total of 790 SOTRs received either the Pfizer/BioNTech (49%) or Moderna (51%) vaccine. Most participants have, thus far, received only one dose, but 211 (27%) received both doses. The median (IQR) age was 58 (43-68), with 57% female, 90% White, and 81% college educated. Organs transplanted include kidney (56%), liver (20%), and heart (16%), with a median (IQR) of 6 (3-13) years since transplantation. There were no reports of new COVID-19 infection, acute rejection, anaphylaxis requiring epinephrine, or new neurological conditions such as Guillain- Barré or Bell's palsy. Overall, moderate to severe local and systemic adverse reactions remained low (Figure 1). Comparison between the first and second dose showed that moderate to severe systemic adverse reactions, while uncommon, were higher after the second dose, including fatigue (22% vs 12%, p<0.001), headache (14% vs. 8%, p<0.01), chills (6% vs. 2%, p<0.01), and fever (3% vs. 1%, p<0.001)(Table 1). Conclusions: In our observational cohort, there were no reports of new COVID-19 infection, acute rejection, anaphylaxis requiring epinephrine, or new neurological conditions following SARS-CoV-2 mRNA vaccination. While uncommon, moderate to severe systemic adverse reactions were higher after the second dose. Thus far, there are no large safety concerns for SARS-CoV-2 mRNA vaccines in SOTRs.

Limited immunogenicity of a single dose of SARS-CoV-2 MRNA vaccine in solid organ transplant recipients

Purpose: Given substantial challenges with vaccine allocation and evidence for short-term vaccine efficacy after a single dose of SARS-CoV-2 mRNA vaccines in clinical trials, some have proposed prioritizing first dose administration to reduce COVID-19 morbidity, potentially resulting in delays of second dose administration, or even purposefully withholding second doses for much longer intervals than evaluated in the clinical trials. However, this evidence is largely based off of the early vaccine trials which largely excluded immunocompromised patients. To better understand the immunogenicity of the available SARS-CoV-2 vaccines in immunocompromised individuals, we quantified the humoral response to the first dose of SARS-CoV-2 vaccine in solid organ transplant recipients (SOTRs). Methods: SOTRs who underwent SARS-CoV-2 vaccination were recruited to participate in this study. Participants underwent at-home blood sampling with the TAPIITM Blood Collection Device (7SBio, Medford, MA) or venipuncture. TapIITM samples were tested on the EUROIMMUN enzyme immunoassay (EIA) which tests for IgG to SARS-CoV-2 spike protein. Venipuncture samples were tested on the Roche Elecsys® EIA which tests for antibodies against the receptor binding domain of the SARS-CoV-2 spike protein. Both tests are semi-quantitative and consistent correlates of neutralizing immunity. Results: We studied 279 SOTRs between 12/29/20-2/12/21. None had a prior COVID-19. Median (IQR) age was 51 (40-65) years, 64% were female, 87% were white, and 6% Hispanic/Latino. Median (IQR) time since transplant was 6 (3-13) years;maintenance immunosuppression included tacrolimus (96%), steroids (53%), mycophenolate (74%), azathioprine (9%), sirolimus (4%), everolimus (4%). At a median (IQR) of 20 (15-23) days after the first dose, antibody was detectable in only 16% of participants (binomial exact 95% confidence interval 12-21%). Those not on anti-metabolite maintenance immunosuppression were 5.2 times (95% CI 3.1-8.7, p <0.001) more likely to develop an antibody response. Conclusions: The vast majority of participants did not mount appreciable antibody responses. However, those not on anti-metabolite maintenance immunosuppression were more likely to develop antibody responses. These results contrast dramatically with the robust early immunogenicity observed in mRNA vaccine trials. These findings are an important reminder that any individual with potential immune compromise should not assume they have achieved an immune response to the SARS-CoV-2 vaccine after a first dose.

Development and durability of SARS-CoV-2 antibodies among solid organ transplant recipients

Purpose: The response to SARS-CoV-2 may be blunted in transplant recipients, impacting reinfection risk, treatment selection, and vaccine protocols. We quantified antibody response and durability after COVID-19 in solid organ transplant recipients (SOTRs). Methods: SOTRs with PCR-confirmed COVID-19 were recruited through the EMR August 21-October 15, 2020. Participants underwent at-home blood sampling with the TAPTM Blood Collection Device, Second Edition (7SBio, Medford, MA). Serum samples were screened using Elecsys® anti-SARS-CoV-2 immunoassay (Roche), which uses a recombinant protein representing the nucleocapsid antigen. Confirmatory testing was performed using EUROIMMUN anti-SARS-CoV-2 enzyme-linked immuosorbent assay (ELISA) for semi-quantitative detection of IgG antibodies to spike protein (anti-S1-IgG), a likely correlate of neutralizing immunity. Results: Eighteen SOTRs were studied, for whom COVID-19 occurred at a median of 6 years (IQR 2-9) post-transplant. Median age was 56 years (IQR 42-63);56% were female;33% were Black and 11% were Hispanic. Most participants (89%) had experienced COVID-19 symptoms;72% were hospitalized. Among those hospitalized, 15% were admitted to the ICU and 8% were mechanically ventilated. COVID-19 convalescent plasma (CCP) was administered to 3 kidney and 2 lung recipients. At median 98 days (IQR 55-147) after COVID-19 diagnosis, 78% had reactive screening immunoassays (Table 1). Of the four patients with non-reactive immunoassays, 2 were the lung recipients treated with CCP and 1 was the kidney recipient receiving IVIg. Of those who screened positive, anti-S1-IgG was detectable in 83%. SOTRs who received CCP and/or IVIg were less likely to develop anti-S1- IgG and had lower antibody levels. Conclusions: We found antibody levels suggestive of neutralizing immunity in the majority of participants. However, those who were administered CCP and/or IVIg were less likely to mount a durable immune response. This raises the possibility that exogenous antibody preparations may blunt durable antibody formation. We observed a significant association between more severe disease and higher antibody levels. Seropositivity might decline over time;however, we were unable to distinguish between impaired production or rapid decrement. Our findings are important for individuals with compromised immune systems, whether deliberately for conditions like organ transplantation and cancer, or naturally in the elderly, frail, and autoimmune populations.