This study of SARS-CoV-2 mRNA vaccination in 14 persons with HIV (PWH) demonstrated uniformly high anti-SARS-CoV-2 receptor binding domain (RBD) antibody titres after two doses, despite varied titres after a single dose. The majority of vaccine reactions were mild and no adverse events occurred.Conflicts of interest D.L.S. has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, Thermo Fisher Scientific. C.M.D. has the following financial disclosures: research grants from GlaxoSmithKline and Abbvie and served on a grant review committee for Gilead Sciences. The other authors have no conflicts of interest.
Vaccine‐induced SARS‐CoV‐2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS‐CoV‐2 vaccine doses increase anti‐spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti‐spike IgG, pseudoneutralization (ACE2 blocking), and live‐virus neutralization (nAb) against VOCs before and after a third SARS‐CoV‐2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti‐spike IgG assays and focused on thresholds associated with neutralization. A third SARS‐CoV‐2 vaccine dose increased median total anti‐spike (1.6‐fold), pseudoneutralization against VOCs (2.5‐fold vs. Delta), and neutralizing antibodies (1.4‐fold against Delta). However, neutralization activity was significantly lower than healthy controls (p < .001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination compared to 100% for controls. Correlation with nAb was seen at anti‐spike IgG >4 Log10(AU/ml) on the Euroimmun ELISA and >4 Log10(AU/ml) on the MSD research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.
Background: Normally, regulatory T cells (also known as T regulatory cells or Tregs) migrate into inflamed tissues, dampening inflammatory responses and hastening tissue repair (1). Patients with coronavirus disease 2019 (COVID-19) and acute respiratory distress syndrome (ARDS) have protracted hospitalizations characterized by excessive systemic inflammation (cytokine storm) and delayed lung repair, which is partly due to reduced or defective Tregs (2). Objective: To describe outcomes in 2 patients with COVID-19 and ARDS who were treated with Tregs. Case Reports: The first patient was a 69-year-old man with autism who was hospitalized from his nursing home with COVID-19-induced fever and dyspnea 1 week after initial symptom onset. Despite 5 days of receiving hydroxychloroquine and broad-spectrum antimicrobial agents, he progressed to ARDS and received tocilizumab on day 7 and mechanical ventilation beginning on day 8. Renal failure and shock developed, requiring continuous, venovenous hemofiltration and vasopressors. Refractory hypoxemia required prone positioning, neuromuscular paralysis, inhaled nitric oxide, and FIO 2 greater than 70%. We administered compassionate use, cryopreserved, allogeneic Tregs derived from cord blood (CB) and expanded ex vivo (Cellenkos) at 1 × 10 8 cells per dose intravenously on days 13 and 17. By day 17, he had returned to supine positioning, paralytics were withdrawn, inhaled nitric oxide was weaned to zero, FIO 2 was decreased to 50%, vasopressors were withdrawn, and inflammatory markers were reduced (Table 1). He was extubated on day 22. On day 25, he required a tracheostomy. He is currently receiving care in a weaning facility. The second patient was a 47-year-old man who was hospitalized for COVID-19-induced fever and dyspnea 1 week after initial symptom onset. On day 2 of his hospitalization, he received tocilizumab, and hours later, he had increasing lactate levels and required mechanical ventilation and high-dose Disclosures: Disclosures can be viewed at www.acponline.org /authors/icmje/ConflictOfInterestForms.do?msNum=L20-0681.
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