ABSTRACT
Background. mRNA vaccines for coronavirus disease 2019 (COVID-19) illicit strong humoral and cellular responses and have high efficacy for preventing and reducing the risk of severe illness from COVID-19. Since solid organ transplant (SOT) recipients were excluded from the phase 3 trials, the efficacy of the COVID-19 vaccine remains unknown. Understanding the serological responses to COVID vaccines among SOT recipients is essential to better understand vaccine protection for this vulnerable population. Methods. In this prospective cohort study, a subset of SOT recipients who were part of our center's larger antibody study were enrolled prior to receipt of two doses of the BNT162b2 (Pfizer, Inc) vaccine for high resolution immunophenotyping. To date, plasma has been collected for 10 participants on the day of their first dose (baseline), day of their second dose, and 28 days post second dose. 23 healthy participants planning to receive either BNT162b2 or mRNA-1273 (ModernaTX, Inc) were also enrolled, providing plasma at the same timepoints. Ultrasensitive single-molecule array (Simoa) assays were used to detect SARS-CoV-2 Spike (S), S1, receptor-binding domain (RBD) and Nucleocapsid (N) IgG antibodies. Results. Participant demographics and SOT recipient characteristics are summarized in Table 1. Low titers of anti-N IgG at all timepoints indicate no natural infection with COVID-19 during the study (Fig 1A). There were significantly lower magnitudes for anti-S (p< 0.0001), anti-S1 (p< 0.0001), and anti-RBD (p< 0.0001) IgG titers on the day of dose 2 and day 28 post second dose for SOT recipients compared to healthy controls (Fig 1B,C,D). Using the internally validated threshold of anti-S IgG >1.07 based on pre-pandemic controls, only 50% of the SOT sub-cohort responded to vaccine after series completion (Fig 2). There was a positive trend between months from transplant and anti-S IgG titer (Fig 3). Black error bars denote median and 95% CI. The dotted line on panel B denotes an internally validated cutoff of 1.07;anti-S IgG titers greater than 1.07 denote a positive response. SOT recipients further out from transplant tend to have a higher anti-S IgG response. The dotted line denotes an internally validated cutoff, with anti-S IgG titers greater than 1.07 indicating a positive response. Conclusion. SOT recipients had a significantly decreased humoral response to mRNA COVID-19 vaccines compared to the healthy cohort, with those further out from transplant more likely to respond. Further research is needed to evaluate T-cell responses and clinical efficacy to maximize the SARS-CoV-2 vaccine response among SOT recipients.
ABSTRACT
Background: Disorders of serum sodium (SNa) are common in hospitalized patients with COVID-19 and associated with longer length of stay and inpatient mortality. However, the association of SNa with patient-reported outcomes is not clear. Methods: The Brigham and Women's Hospital COVID-19 Registry is a prospective cohort study of consecutive, adult patients admitted with confirmed SARS-CoV-2 infection (n=809). We examined the association of SNa (continuous and tertiles) at admission with: 1) patient symptoms obtained from detailed chart review;and 2) in-hospital mortality using unadjusted and adjusted logistic regression models. Covariates included demographic data and comorbidities. Only index admissions were considered. Results: Mean age was 60 years, 48% were male, and 35% had diabetes. The most frequent symptoms were cough (64%), fever (60%) and shortness of breath (46%). In adjusted models, higher SNa (per mmol/L) was associated with lower odds of GI symptoms (OR 0.96;95%CI 0.93-0.99), higher odds of confusion (OR 1.08;95%CI 1.40-1.13) and higher odds of in-hospital mortality (OR 1.06;95%CI 1.02-1.11). Compared with the lowest tertile, the highest tertile of SNa was associated with a lower odds of GI symptoms and anosmia/ageusia, and higher odds of confusion and in-hospital mortality (Table 1). Conclusions: In this prospective cohort study of hospitalized patients with COVID-19, hypernatremia is associated with higher odds of confusion and in-hospital mortality, but lower risk of GI symptoms and anosmia. The presence of dysnatremia may help identify higher-risk patients with COVID-19 and prompt ascertainment of patient symptoms, both of which may improve patient-centered approaches to care.