ABSTRACT
Asymptomatic subjects account for 25 to 45% of SARS-CoV-2 infections, and in particular, subjects on mild immunosuppressive therapy may have symptoms masked and could spread virus for an extended period of time. To determine the cumulative incidence of symptomatic and asymptomatic SARS-CoV-2 infections and associated risk factors, we conducted a prospective clinical and serological survey in a cohort of 278 liver transplant recipients (LTRs) from Central Italy. Three different serology tests were performed every 4 months in 259 LTRs between April 2020 and April 2021: one based on raw extract of whole SARS-CoV-2 virus and two on specific viral antigens (nucleoprotein and receptor binding domain) to detect specific IgG, IgM and IgA. Hundred fifteen LTRs who reported symptoms or close contact with a SARS-CoV-2-positive subject, or had a positive serological result underwent molecular testing by standard screening procedures (RT-PCR on naso-pharyngeal swab). Thirty-one past or active SARS-CoV-2 infections were identified: 14 had positive molecular test (64% symptomatic), and 17 had positive serology only (18% symptomatic). SARS-CoV-2 infection was not statistically related to gender, age, obesity, diabetes, renal impairment, type of anti-rejection therapy or time from transplant. Asymptomatic SARS-CoV-2 cases (61.3%) were more frequent in males and in those with glomerular filtrate rate >50 ml/min. Overall, the addition of repeated serology to standard diagnostic molecular protocols increased detection of SARS-CoV-2 infection from 5.1% to 10.9%. Anti-SARS-CoV-2 seroprevalence among our LTRs (11.2%) is comparable to the general population of Central Italy, considered a medium-impact area. Only one asymptomatic subject (6%) was found to carry SARS-CoV-2 in respiratory tract at the time of serological diagnosis.Copyright © 2021 The Authors
ABSTRACT
Background: In Italy in September 2021, administration of a booster shot (BS) of COVID-19 vaccine was approved for PLWH with advanced disease (current CD4 count<200 cell/mm3 and/or previous AIDS). The aim of this analysis was to investigate the degree of immunogenicity after BS by current CD4 count. Methods: In PLWH attending INMI Spallanzani Hospital in Rome, Italy and receiving a BS of BNT162b2 or mRNA-1273 >28 days after a complete mRNA vaccination cycle, immunogenicity was assessed at time of BS (T0) and at day 15 (T1) by anti-RBD CLIA, microneutralization assay [MNA90] and IFNγ production. Participants were stratified by CD4 count at T0 (severe immunodeficiency, SID: <200/mm3;minor immunodeficiency, MID: 200-500/mm3;no immunodeficiency, NID: >500/mm3). Immune response was defined: anti-RBD >7.1 BAU/mL, MNA90 titres >1:10 and IFNγ >12 pg/mL. A paired t-test was used to test overall changes (log2 scale) over T0-T1. ANOVA and truncated regression models were used to compare change in titers from T0 to T1, association between current CD4 count and the lack of immune response was determined by fitting a multivariable logistic regression adjusted for age, time from HIV diagnosis, CD4 nadir, cancer and HIV-RNA a T0. Results: We included 216 PLWH on ART (n=76 SID, n=96 MID, n=44 NID): median age 54 yrs (IQR 47-59), median CD4 nadir 45 cell/mm3 (20-122), 93% HIV-RNA <50 c/mL, 7yrs (3-12) since HIV diagnosis and 5yrs (2-8) since AIDS if diagnosed. Participants received BS after a median of 142 (132-156) days from second dose. Response rate was 95.5% in SID, 100% in MID, 100% in NID for anti-RBD (p=0.02);86.3%, 97.9% and 98.7% for nAbs (p=0.002), and 70%, 95.6% and 97.2% for IFNγ (p<0.0001). Overall we observed a significant increase of BS immunogenicity [anti RBD: mean Log2 4.5 (SD 1.9),p<0.0001;nAbs: 3.7 (2.2),p<0.0001;IFNγ: 0.77 (2.9),p=0.0003]. However, there was no evidence for a difference in mean change of humoral immunogenicity, anti-RBD, nAbs and IFNγ changes by CD4 count groups (Figure 1 A-C). A current CD4 count <200 cell/mm3 was not associated with the risk of failing to elicit neutralizing and cell-mediated response by logistic regression (Figure1D). Conclusion: A mRNA BS strongly boosted humoral response in PLWH with advanced disease, regardless of CD4 count at the time of booster. Although clinical implications of the observed immunological response remain uncertain, our data support the usefulness of BS in PLWH with immune dysregulation.
ABSTRACT
Background: Few data are available about comparison of different monoclonal antibodies (MAbs) for COVID-19 in the real-world setting. We aim to compare effectiveness of bamlanivimab/etesevimab (BAM/ETE) versus (vs) casirivimab/imdevimab (CAS/IMD) and to estimate predictors of hospitalization/death. Methods: Observational analysis of all consecutive outpatients (pts) with mild/moderate COVID-19 enrolled within the AIFA access program in a single center in Rome, from March to October, 2021. At first baseline (BL) visit, RT-PCR from nasopharyngeal swab with cycle thereshold (CT) measurement and viral sequencing was performed. Pts received intravenous BAM/ETE (700/1400 mg) or CAS/IMD (1200/1200 mg) and were followed through day 30. Primary endpoint was hospitalization/death due to severe COVID-19 by day 30. Average treatment effect (ATE) in the multiplicative scale of the odds was the chosen estimand to compare the two treatments, adjusted for age, obesity, time from onset to infusion, median C-reactive protein (CRP), vaccination, variant of concern (VOC) and BL-CT. Predictors of clinical failure were explored by two different models of multivariable logistic regression. Results: 242 pts receiving BAM/ETE (n=76) or CAS/IMD (n=166) were included (male 54%;median age 65 yrs;median SpO2 97%;diabetes 12%;hypertension 40%;CVD 17%;COPD 26%;autoimmune diseases 12%;immunodeficiency 18%). Median time from symptoms onset to infusion was 4 days (IQR 3-6). No differences were observed between the two MAbs for BL characteristics except for BMI>35 (BAM/ETE 24%, CAS/IMD 12%), CRP (BAM/ETE 1.8, CAS/IMD 1.2), vaccination (BAM/ETE 26%, CAS/IMD 46%) and distribution of VOC (Alpha 46% BAM/ETE vs 22% CAS/IMD;Gamma 20% vs 7%;Delta 5% vs 55%). Proportion of patients with COVID-related hospitalization/death by day 30 was 12/76 (15.8%) for BAM/ETE and 6/166 (3.6%) for CAS/IMD. Estimate of causal effect of BAM/ETE exposure compared to CAS/IMD on primary end point by ATE is reported in Table 1a. Factors associated with an increased risk of clinical failure by fitting multivariable logistic regression were BMI >35 and P1/Gamma VOC;higher BL-CT was associated with a reduced risk (Table 1b-1c). Conclusion: In a real-life setting, receiving BAM/ETE was associated with a 4-fold higher risk of COVID-19 progression to hospitalization/death than CAS/IMD. SARS-CoV-2 P.1/Gamma, but not B.1617.2/Delta VOC, obesity and higher BL viral load also predicted an increased risk of clinical worsening.
ABSTRACT
Background: Waning of vaccine protection against SARS-CoV-2 infection is currently a concern and durability of specific immunity after vaccination in PLWH is still unknown. The aim of this analysis was to evaluate persistence of immune response to mRNA vaccines in PLWH with advanced disease. Methods: PLWH with a CD4 count ≤200/mm3 and/or previous AIDS, enrolled in a SARS-CoV-2 vaccination program at INMI hospital in Rome, Italy, were evaluated >90 days after 2nd dose of BNT162b2 or mRNA-1273 (time T1). Anti-RBD by CLIA, neutralizing antibody (nAb) titers by microneutralization assay (MNA90) and IFNγ production were assessed and response defined as having anti-RBD >7.1 BAU/mL, nAbs ≥1:10, IFNγ >12 pg/mL. Participants were stratified by CD4 count (severe immunodeficiency, SID, ≤200/mm3;minor immunodeficiency, MID, 201-500/mm3;no immunodeficiency, NID, >500/mm3). Waning of immune response was evaluated in a subgroup of responders for whom two values post 2nd dose were available. Paired t-test was used to test the overall decline. ANOVA and logistic regression analysis controlling for age, viral load, CD4 nadir and cancer were used for comparisons by CD4 groups. Results: 221 pts were included (SID=47;MID=98;NID=76);81% male;median age 55 yrs (IQR 49-60);median time from HIV diagnosis 7 yrs (3-15);74% previous AIDS diagnosis;median CD4 nadir 44/mm3 (16-122). All pts receiving ART, 87% with HIV-RNA<50 cp/mL. After a median of 145 (133-157) days after 2nd dose, a detectable anti-RBD response was still present in 83% of SID, 96% of MID and 98% of NID (P=0.0009);nAbs in 38% of SID, 78% of MID and 88% of NID (P<0.0001);IFNγ in 67% of SID, 90% of MID and 92% of NID (P=0.0002). Magnitude of residual immune response at T1 was significantly lower in SID (Figure 1a). By logistic regression, risk of nAbs undetectability was higher in SID (aOR 5.03;95% CI 1.22-20.81) and in MID (aOR 3.77;11.4-12.48) vs NID, while no evidence for a difference was found for anti-RBD and IFNγ. A significant decline of immune response was observed for all immune parameters [mean log2 (SD):-2.66 (1.08), p<0.001, for anti-RBD;-1.23 (1.26), p<0.001, for nAbs;and-0.51 (2.3), p=0.05, for IFNγ], regardless of CD4 groups (Figure 1b/c). Conclusion: A high proportion of PLWH with advanced disease showed a lack of immune response after a median of 5 months from SARS-CoV-2 mRNA vaccination, suggesting an urgent need for a booster dose. A current CD4 ≤200/mm3 was associated with higher risk of vanishing of neutralizing activity.
ABSTRACT
SARS-CoV-2 serum neutralization assay represents the gold standard for assessing antibody-mediated protection in naturally infected and vaccinated individuals. In the present study, 662 serum samples collected from February 2020 to January 2021 from acute and convalescent COVID-19 patients were tested to determine neutralizing antibody (NAb) titers using a microneutralization test (MNT) for live SARS-CoV-2. Moreover, anti-SARS-CoV-2 IgG, IgA, and IgM directed against different viral antigens were measured by high-throughput automated platforms. We observed higher levels of NAbs in elderly (>60 years old) individuals and in patients presenting acute respiratory distress syndrome. SARS-CoV-2 NAbs develop as soon as five days from symptom onset and, despite a decline after the second month, persist for over 11 months, showing variable dynamics. Through correlation and receiver operating characteristic (ROC) curve analysis, we set up a testing algorithm, suitable for the laboratory workload, by establishing an optimal cutoff value of anti-SARS-CoV-2 IgG for convalescent plasma donors to exclude from MNT samples foreseen to have low/negative NAb titers and ineligible for plasma donation. Overall, MNT, although cumbersome and not suitable for routine testing of large sample sizes, remains the reference tool for the assessment of antibody-mediated immunity after SARS-CoV-2 infection. Smart testing algorithms may optimize the laboratory workflow to monitor antibody-mediated protection in COVID-19 patients, plasma donors, and vaccinated individuals.
ABSTRACT
We report two cases of HIV positive patients with SARS-CoV-2 infection and a recent diagnosis of opportunistic infections of central nervous system (CNS). We investigated the potential impact of coinfection with SARS-CoV-2 on HIV replication in CNS.