ABSTRACT
ObjectivesThere is scarce information as to the durability of immune responses elicited by the Comirnaty(R) COVID-19 vaccine in nursing home residents. Here, we assessed SARS-CoV-2-Spike (S)-targeted antibody and functional T cell responses at around 6 months after complete vaccination. MethodsThe sample comprised 46 residents (34 females; age, 60-100 years), of whom 10 had COVID-19 prior to vaccination. Baseline (median of 17.5 days after vaccination) and follow-up (median, 195 days) plasma specimens were available for quantitation of SARS-CoV-2-S antibodies and enumeration of SARS-CoV-2-S-reactive IFN-{gamma} CD4+ and CD8+ T cells by flow cytometry. ResultsIn total, 44/45 participants had detectable SARS-CoV-2-S antibodies at follow-up. Overall, antibody levels were found to decrease (median, 4.8 fold). Antibodies waning was more frequent (P<0.001) in SARS-CoV-2 naive (29/35) than in recovered (1/10) residents. SARS-CoV-2-S IFN-{gamma} CD8+ T cells were detected in 33/46 and 24/46 at baseline and follow-up, respectively. The figures for CD4+ T cell counterparts were 12/46 and 30/46. Detectable SARS-CoV-2 IFN-{gamma} CD8+ and CD4+ T cell responses at follow-up were more common in recovered (8/10 and 7/10, respectively) than in naive residents (9/36 and 25/36, respectively). For those with detectable responses at both time points, SARS-CoV-2-S IFN-{gamma} CD8+ T cell frequencies decreased significantly (P=0.001) over time whereas the opposite (P=0.01) was observed in CD4+ T cells. ConclusionAlmost all residents displayed detectable SARS-CoV-2-S-reactive antibodies and T cell responses, respectively, by around 6 months after complete vaccination with Comirnaty(R) COVID-19 vaccine, albeit generally waning in magnitude over time.
ABSTRACT
ObjectivesThe immunogenicity of the BNT162b2 COVID-19 vaccine is understudied in elderly people with comorbidities. We assessed SARS-CoV-2-S-targeted antibody and T cell responses following full vaccination in nursing home residents (NHR). MethodsWe recruited 60 NHR (44 female; median age, 87.5 years), of whom 10 had previously had COVID-19, and 18 healthy controls (15 female; median age, 48.5 years). Pre- and post-vaccination blood specimens were available for quantitation of total antibodies binding RBD and enumeration of SARS-CoV-2-S-reactive IFN-{gamma} CD4+ and CD8+ T cells by flow cytometry. ResultsThe seroconversion rate in presumably SARS-CoV-2 naive NHR (95.3%), either with or without comorbidities, was similar to controls (94.4%). A robust booster effect was documented in NHR with prior COVID-19. Plasma antibody levels were higher in convalescent NHR than in individuals across the other two groups. A large percentage of NHR had SARS-CoV-2 S-reactive IFN-{gamma} CD8+ and/or CD4+ T cells at baseline, in contrast to healthy controls. Either CD8+ and/or CD4+ T-cell responses were documented in all control subjects after vaccination. Contrariwise, the percentage of NHR exhibiting detectable SARS-CoV-2 IFN-{gamma} CD8+ or CD4+ T-cell responses (or both), irrespective of their baseline SARS-CoV-2 infection status, dropped consistently after vaccination. Overall, SARS-CoV-2 IFN-{gamma} CD8+ and CD4+ T-cell responses in NHR decreased in post-vaccination specimens. ConclusionThe BNT162b2 COVID-19 vaccine elicits robust SARS-CoV-2-S antibody responses in NHR. Nevertheless, the frequency and magnitude of detectable SARS-CoV-2 IFN-{gamma} T-cell responses after vaccination was lower in NHR compared to controls.
ABSTRACT
ObjectivesThere is an imperative need to determine the durability of adaptive immunity to SARS-CoV-2. We enumerated SARS-CoV-2-reactive CD4+ and CD8+ T cells targeting S1 and M proteins and measured RBD-specific serum IgG over a period of 2-6 months after symptoms onset in a cohort of subjects who had recovered from severe clinical forms of COVID-19. MethodsWe recruited 58 patients (38 males and 20 females; median age, 62.5 years), who had been hospitalized with bilateral pneumonia, 60% with one or more comorbidities. IgG antibodies binding to SARS-CoV-2 RBD were measured by ELISA. SARS-CoV-2-reactive CD69+-expressing-IFN{gamma}-producing-CD4+ and CD8+ T cells were enumerated in heparinized whole blood by flow cytometry for ICS. ResultsDetectable SARS-CoV-2-S1/M-reactive CD69+-IFN-{gamma} CD4+ and CD8+ T cells were displayed in 17 (29.3%) and 6 (10.3%) subjects respectively, at a median of 84 days after onset of symptoms (range, 58-191 days). Concurrent comorbidities increased the risk (OR, 3.15; 95% CI, 1.03-9.61; P=0.04) of undetectable T-cell responses in models adjusted for age, sex and hospitalization ward. Twenty-one out of the 35 patients (60%) had detectable RBD-specific serum IgGs at a median of 118 days (range, 60 to 145 days) after symptoms onset. SARS-CoV-2 RBD-specific IgG serum levels were found to drop significantly over time. ConclusionA relatively limited number of subjects who developed severe forms of COVID-19 had detectable SARS-CoV-2-S1/M IFN{gamma} CD4+ and CD8+ T cells at midterm after clinical diagnosis. Our data also indicated that serum levels of RBD-specific IgGs decline over time, becoming undetectable in some patients.
ABSTRACT
There is limited information on SARS-CoV-2 T-cell immune responses in patients with Covid-19. Both CD4+ and CD8+ T cells may be instrumental in the resolution of and protection from SARS-CoV-2 infection. Here, we tested 25 hospitalized patients with either microbiologically documented Covid-19 (n=19) or highly suspected of having the disease (n=6) for the presence of SARS-CoV-2-reactive-CD69+-expressing interferon--producing-(IFN-) CD8+ T cells by a flow-cytometry for intracelular cytokine staining assay. Two sets of overlapping peptides encompassing the SARS-CoV-2 Spike glycoprotein N-terminal 1-643 amino acid sequence and the entire sequence of SARS-CoV-2 M protein were used simultaneously as antigenic stimulus. Ten patients (40%) had detectable responses, displaying frequencies ranging from 0.15 to 2.7% (median of 0.57 cells/L; range, 0.43-9.98 cells/L). The detection rate of SARS-CoV-2-reactive IFN-{gamma} CD8+ T cells in patients admitted to intensive care was comparable (P=0.28) to that in patients hospitalized in other medical wards. No correlation was found between SARS-CoV-2-reactive IFN-{gamma} CD8+ T-cell counts and SARS-CoV-2 S-specific antibody levels. Likewise, no correlation was observed between either SARS-CoV-2-reactive IFN-{gamma} CD8+ T cells or S-specific IgG-antibody titers and blood cell count or levels of inflammatory biomarkers. In summary, in this descriptive, preliminary study we showed that SARS-CoV-2-reactive IFN-{gamma} CD8+ T cells can be detected in a non-negligible percentage of patients with moderate to severe forms of Covid-19. Further studies are warranted to determine whether quantitation of these T-cell subsets may provide prognostic information on the clinical course of Covid-19.
ABSTRACT
OBJECTIVE: To report a case of acute elevation of hepatic enzyme levels as a probable adverse reaction associated with pregabalin. CASE SUMMARY: A 59-year-old man with a history of mantle cell lymphoma developed neuropathic pain and was treated with pregabalin 25 mg daily. Fourteen days after beginning pregabalin therapy, he developed left ankle edema and elevation of liver enzyme levels. Peak values were aspartate transaminase 907 U/L, alanine transaminase 1582 U/L, and γ-glutamyltransferase 510 U/L. Pregabalin was discontinued and hepatic enzyme levels returned gradually (over 4 months) to baseline levels. DISCUSSION: Many medications are commonly associated with liver injury; few cases of pregabalin-associated hepatotoxicity have been documented. A MEDLINE search (1966-November 2010) revealed 2 reports of acute liver injury with the initiation of pregabalin. In our patient, with hemosiderosis after hematopoietic cell transplantation, pregabalin worsened the underlying liver injury. The low pregabalin dosage and the short time to elevation of liver enzyme levels suggest an idiosyncratic reaction. According to the Naranjo probability scale and the Council for International Organizations of Medical Sciences probability scale, this reaction was probably due to pregabalin. CONCLUSIONS: Prescribers should be alert to the possibility of idiosyncratic hepatotoxicity associated with pregabalin use.
