GRAd-COV2 vaccine provides potent and durable humoral and cellular immunity to SARS-CoV-2 in randomized placebo-controlled phase 2 trial.

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccine portfolios. GRAd-COV2 is a gorilla adenovirus-based COVID-19 vaccine candidate encoding prefusion-stabilized spike. The safety and immunogenicity of GRAd-COV2 is evaluated in a dose- and regimen-finding phase 2 trial (COVITAR study, ClinicalTrials.gov: NCT04791423) whereby 917 eligible participants are randomized to receive a single intramuscular GRAd-COV2 administration followed by placebo, or two vaccine injections, or two doses of placebo, spaced over 3 weeks. Here, we report that GRAd-COV2 is well tolerated and induces robust immune responses after a single immunization; a second administration increases binding and neutralizing antibody titers. Potent, variant of concern (VOC) cross-reactive spike-specific T cell response peaks after the first dose and is characterized by high frequencies of CD8s. T cells maintain immediate effector functions and high proliferative potential over time. Thus, GRAd vector is a valuable platform for genetic vaccine development, especially when robust CD8 response is needed.

Humoral and T-cell mediated response after administration of mRNA vaccine BNT162b2 in frail populations

Patients with frailty are considered to be at greater risk to get severe infection from SARS-CoV-2. One of the most effective strategies is vaccination. In our study we evaluated both the humoral immune response elicited by the vaccination at different time points, and the T-cell response in terms of interferon (IFN)-γ production in frail patients and healthy donors. Fifty-seven patients (31 patients undergoing hemodialysis and 26 HIV positive subjects) and 39 healthcare workers were enrolled. All participants received two doses of the mRNA vaccine BNT162b2. Healthcare workers showed a significantly higher antibody titer than patients twenty-one days after the first dose (p<0.001). From the same time point we observed for both groups a decay of the antibody levels with a steeper slope of decline in the patients group. Regarding T-cell response the only significant difference between non-reactive and reactive subjects was found in median antibody levels, higher in the responders group than in non-responders. The healthcare workers seem to better respond to the vaccination in terms of antibodies production;the lack of T-cell response in about 50% of the participants seems to suggest that in our study population both humoral and cell-mediated response decline over time remarking the importance of the booster doses, particularly for frail patients.

The Effect of SARS-CoV-2 Vaccination on B-Cell Phenotype in Systemic Sclerosis Patients.

OBJECTIVE: to assess the influence of SARS-CoV-2 mRNA vaccine on B-cell phenotypes in systemic sclerosis (SSc). METHODS: peripheral blood B-cell subpopulations were evaluated before (t1) and 3 months (t3) after the second dose of vaccine in 28 SSc patients. Peripheral blood B-cell subpopulations were evaluated in 21 healthy controls (HCs) only at t1. Anti-spike IgG levels were evaluated at t3 in both cohorts. RESULTS: SSc patients presented higher naive, double-negative, and CD21low B cells compared to HCs. IgM-memory and switched-memory B cells were lower in SSc patients than HCs. No differences in anti-spike IgG levels after vaccination were observed between SSc patients and HCs. Anti-spike IgG levels after vaccination were lower in SSc patients with increased CD21low B cells at baseline compared to SSc patients with normal CD21low B cells. A positive correlation was found between IgG levels and naive B cells. A negative linear correlation was shown between IgG levels and IgM-memory, switched-memory, double-negative, and CD21low B cells. CONCLUSIONS: SARS-CoV-2 mRNA vaccine response is normal in SSc patients not undergoing immunosuppressive therapy. The normal number of naive B cells is a positive marker of antibody response. The increased percentage of CD21low B cells represents a negative marker of antibody response.

Antibody response to BNT162b2 SARS-CoV-2 mRNA vaccine in adult patients with systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) patients are at risk for a severe disease course during SARS-CoV-2 infection either due to comorbidities or immunosuppression. The availability of SARS-CoV-2 vaccines is crucial for the prevention of this hard-to-treat illness. The aim of this study is to assess the humoral response after mRNA vaccination against SARS-CoV-2 in SSc patients. METHOD: Seropositivity rate and serum IgG levels were evaluated 1 month (t1) and 3 months (t3) after the second dose of vaccine in a cohort of SSc patients and healthy controls (HC). Differences were made with Student's or Mann-Whitney's t-test and with the chi-square or Fisher exact test. Logistic regression model including immunosuppressive treatments (corticosteroids, CCS; mycophenolate mofetil, MMF; methotrexate, MTX; rituximab, RTX) was built to assess the predictivity for seropositivity. RESULTS: The seropositivity rate was similar in 78 SSc patients compared to 35 HC at t1 but lower at t3. SSc patients had lower serum IgG levels than HC at t1 but not at t3. SSc patients treated with immunosuppressive therapy showed both a lower seropositive rate (t1, 90.3% vs 100%; t3, 87.1% vs 97.9%; p < 0.05) and serum IgG levels than untreated patients both at t1 [851 BAU/ml (IQR 294-1950) vs 1930 BAU/ml (IQR 1420-3020); p < 0.001] and t3 [266 BAU/ml (IQR 91.7-597) vs 706 BAU/ml (IQR 455-1330); p < 0.001]. In logistic regression analysis, only MTX was significant [OR 39.912 (95% CI 1.772-898.728); p < 0.05]. CONCLUSIONS: SSc patients treated with MTX had a lower serological response to mRNA vaccine, and even low doses of CCS can adversely affect antibody titer and vaccination response. Key Points • SSc patients are able to produce vaccine-induced antibodies after mRNA vaccination. • In SSc patients, clinical characteristics of disease did not influence seropositivity rate. • In SSc patients, even low doses of CCS can adversely affect antibody titer and vaccination response. • In SSc patients, MTX treatment is mainly associated with reduced seropositivity and lower serum IgG levels.

Long-Term Subjective and Objective Assessment of Smell and Taste in COVID-19.

Among the first clinical symptoms of the SARS-CoV-2 infection is olfactory-gustatory deficit; this continues for weeks and, in some cases, can be persistent. We prospectively evaluated 162 patients affected by COVID-19 using a visual analogue scale (VAS) for nasal and olfactory-gustatory symptoms. Patients were checked after 7, 14, 21, 28, 90, and 180 days. A total of 118 patients (72.8%) reported an olfactory VAS < 7 at baseline (group B), and 44 (27.2%) reported anosmia (VAS ≥ 7) (group A) and underwent the Brief Smell Identification Test (B-SIT) and Burghart Taste Strips (BTS) to quantify the deficit objectively and repeated the tests to confirm the sense recovery. Group A patients showed B-SIT anosmia and hyposmia in 44.2% and 55.8% of cases, respectively. A total of 88.6% of group A patients reported ageusia with VAS ≥ 7, and BTS confirmed 81.8% of ageusia and 18.2% of hypogeusia. VAS smell recovery was recorded starting from 14 days, with normalization at 28 days. The 28-day B-SIT score showed normosmia in 90.6% of group A patients. The mean time for full recovery (VAS = 0) was shorter in group B (22.9 days) than in group A (31.9 days). Chemosensory deficit is frequently the first symptom in patients with COVID-19, and, in most cases, recovery occurs after four weeks.

Clinical management of patients with primary immunodeficiencies during the COVID-19 pandemic.

Introduction: Patients affected by Inborn Errors of Immunity (IEI) represent a potential group-at-risk in the current COVID-19 pandemic. Studies on large and small cohorts of IEI reported a huge variability clinical manifestations associated to SARS-Cov-2, ranging from asymptomatic, mild, moderate/severe to death. A great impulse to improve remote assistance programs and to switch to home-based treatment to reduce mobility and face to face contacts has been implemented.Areas covered: The authors completed a comprehensive review of the literature by searching the PubMed database for studies on large and small cohorts and case reports of IEI patients with COVID-19, with the aim to provide useful information for their clinical management during the COVID-19 pandemic.Expert opinion: Surprisingly, a low number of IEI patients affected by SARS-Cov-2 were reported with a risk to die for COVID-19 overlapping that of the general population. The low number might be explained by the choice of most physicians to inform early in the pandemic about safety measures, to switch most of the IEI patients to home therapy and to remote assistance. The guidelines issued by the scientific societies and periodically updated, represent the best tool for the clinical management of IEI patients.

Cardiometabolic multimorbidity is associated with a worse Covid-19 prognosis than individual cardiometabolic risk factors: a multicentre retrospective study (CoViDiab II).

BACKGROUND: Cardiometabolic disorders may worsen Covid-19 outcomes. We investigated features and Covid-19 outcomes for patients with or without diabetes, and with or without cardiometabolic multimorbidity. METHODS: We collected and compared data retrospectively from patients hospitalized for Covid-19 with and without diabetes, and with and without cardiometabolic multimorbidity (defined as ≥ two of three risk factors of diabetes, hypertension or dyslipidaemia). Multivariate logistic regression was used to assess the risk of the primary composite outcome (any of mechanical ventilation, admission to an intensive care unit [ICU] or death) in patients with diabetes and in those with cardiometabolic multimorbidity, adjusting for confounders. RESULTS: Of 354 patients enrolled, those with diabetes (n = 81), compared with those without diabetes (n = 273), had characteristics associated with the primary composite outcome that included older age, higher prevalence of hypertension and chronic obstructive pulmonary disease (COPD), higher levels of inflammatory markers and a lower PaO2/FIO2 ratio. The risk of the primary composite outcome in the 277 patients who completed the study as of May 15th, 2020, was higher in those with diabetes (Adjusted Odds Ratio (adjOR) 2.04, 95%CI 1.12-3.73, p = 0.020), hypertension (adjOR 2.31, 95%CI: 1.37-3.92, p = 0.002) and COPD (adjOR 2.67, 95%CI 1.23-5.80, p = 0.013). Patients with cardiometabolic multimorbidity were at higher risk compared to patients with no cardiometabolic conditions (adjOR 3.19 95%CI 1.61-6.34, p = 0.001). The risk for patients with a single cardiometabolic risk factor did not differ with that for patients with no cardiometabolic risk factors (adjOR 1.66, 0.90-3.06, adjp = 0.10). CONCLUSIONS: Patients with diabetes hospitalized for Covid-19 present with high-risk features. They are at increased risk of adverse outcomes, likely because diabetes clusters with other cardiometabolic conditions.

Clinical features of patients with type 2 diabetes with and without Covid-19: A case control study (CoViDiab I).

AIMS: To evaluate whether subjects with diabetes hospitalized for Coronavirus disease-19 (Covid-19) represent a subgroup of patients with high-risk clinical features compared to patients with diabetes without Covid-19. METHODS: In this case-control study 79 patients with type 2 diabetes out of 354 adults hospitalized for Covid-19 and 158 controls with type 2 diabetes but without Covid-19, matched for age and gender, were enrolled. Medical history and concomitant therapies were retrieved from medical charts and compared between cases and controls, controlling for confounders. RESULTS: Fully-adjusted multivariate logistic regression model showed that previous CVD history did not differ between patients with and without Covid-19 (odds ratio 1.40, 95% confidence interval [CI]: 0.59-3.32, p = 0.45). A higher prevalence of chronic obstructive pulmonary disease (COPD) (OR 3.72, 95%CI: 1.42-9.72, p = 0.007) and of chronic kidney disease (CKD) (OR 3.08, 95%CI: 1.18-8.06, p = 0.022) and a lower prevalence of ever smokers (OR 0.30, 95%CI: 0.13-0.67, p = 0.003), of users of lipid lowering agents (OR 0.26, 95%CI: 0.12-0.54, p < 0.001), and of anti-hypertensive drugs (OR 0.39, 95%CI: 0.16-0.93, p = 0.033) were found among cases. CONCLUSIONS: CVD prevalence does not differ between people with diabetes with and without Covid-19 requiring hospitalization. An increased prevalence of COPD and of CKD in Covid-19 patients with type 2 diabetes is suggested. These findings aid to clarify the relationship between underlying conditions and SARS-CoV-2 infection in the high-risk group of patients with diabetes.