Neutralising antibodies (NAbs) against SARS-CoV-2 in BNT162b2 vaccine recipients with a history of advanced HIV infection: cPass as a simpler alternative to gold-standard tests

Background: Established SARS-CoV-2 NAb tests are labor-intensive. We prospectively measured NAbs vs Wuhan-1 and Omicron BA.2 using the novel GenScript cPass assay and examined correlations with responses measured by gold-standard plaque reduction neutralisation test (PRNT) (Cotugno, Ruggiero et al. Cell Rep 2021) and with anti-Spike IgG quantified by Roche Elecsys. Given the paucity of data, we selected BNT162b2 vaccine recipients with a history of advanced HIV infection (prior AIDS-defining conditions and/or nadir CD4 <200 cells). Method(s): In Mar 2021-Apr 2022, 55 PWH received 2 vaccine doses median 3 weeks apart [IQR 3-3] and a 3rd dose 27 weeks later [23-31]. Plasma samples (n=147) were stored immediately before dose-1 (T0), median 4 weeks [3-5] after dose-2 (T1) and median 13 weeks [9-19] after dose-3 (T2) for batch testing. Result(s): Participants' characteristics: 74% male, 85% white, all on ART, 82% HIV-RNA <50 cps/ml;median age 55 years, ART duration 7 years, nadir CD4 83 cells [36-211], current CD4 440 cells [270-710], CD4:CD8 ratio 0.6 [0.4-1.0];73% had a history of advanced HIV infection;15% received a COVID-19 diagnosis during the study. At T0, T1 and T2, proportions with quantifiable anti-S IgG (>0.8 U/ml) were 11/49 (22%), 50/54 (93%) and 43/43 (100%), respectively;their median anti-S IgG titres were 30 [15-124], 15949 [596-3389] and 8527 [3146-17190] U/ml. Proportions showing Wuhan-1 neutralisation by cPass were 6/50 (12%), 45/53 (85%) and 40/43 (93%), with median neutralisations of 67% [47-70], 97% [91-98] and 98% [98-98] and corresponding NAb titres of 1332 [792-1436], 5354 [3529-6187] and 6242 [5765-6766] U/ml. At T2, 25/28 (89%) showed BA.2 neutralisation by cPass (median 83% [68-93];NAb titre 7836 [3172-12173] U/ml) (Fig 1A). Two participants lacking NAbs at T2 had a history of advanced HIV infection. cPass data were highly correlated with anti-S IgG titres (rho 0.82;p<0.0001) and with PRNT data for both Wuhan-1 (n=27, Fig 1B) and Omicron BA.2 (n=28, Fig 1C). Conclusion(s): cPAss offers a simple methodology for measuring SARS-CoV-2 NAbs. Despite prior advanced HIV infection, neutralising activity improved with successive vaccinations and most participants showed NAbs against both Wuhan-1 and Omicron BA.2 after 3 vaccine doses. (Figure Presented).

HOW HIV MODULATES the SAFETY and IMMUNOGENICITY of the BNT162b2 COVID-19 VACCINE

Background: The pivotal BNT162b2 trials included only ∼60 vaccine recipients, all with well controlled HIV, and there is a need to gather more information on vaccine safety and immunogenicity in diverse populations. This prospective study evaluated solicited and unsolicited adverse events (AEs) and anti-S and anti-NC serological profiles in a diverse cohort of people with HIV undergoing BNT162b2 vaccination (2 doses 3 weeks apart). Methods: Participants completed structured questionnaires modelled on the BNT162b2 trials (FDA submission, Nov 2020) to report solicited and unsolicited AEs in the 7 days after each vaccine dose, indicating severity and duration. Serum samples collected prior to dose-1 (T0) and 3-6 weeks after dose-2 (T1) underwent qualitative anti-NC and quantitative anti-S testing by Elecsys®. Factors associated with T1 anti-S titres were explored in linear regression models including all available parameters. Results: Overall, 259 adults received dose-1 (26% female, 77% white, 44% MSM, 44% history of advanced disease, 31% ≥1 comorbidity, 10% HIV RNA >50 cps/ml [median 122 cps], 7% prior COVID-19 diagnosis, 15% anti-NC positive;median age 48 years, ART duration 7 years, nadir/current CD4 count 225/708 cells/mm3, CD4:CD8 ratio 0.8);257 received dose-2. Local AEs were more common after dose-1 than dose-2 (70% vs. 62%, p=0.015), whereas systemic AEs increased with dose-2 (50% vs 60%;p=0.006) (Fig 1a-c);22% experienced moderate-severe systemic AEs after dose-2. Unsolicited AEs (mainly nausea and light-headedness) were reported by 7% after dose-1 and 9% after dose-2. Among 206 participants with T1 samples, 205 (99%) had measurable anti-S (>0.8 U/ml). Anti-S levels were significantly lower at CD4 counts <200 cells/mm3 (Fig 1d). In adjusted regression analyses, factors associated with anti-S titres comprised anti-NC positivity (fold-change 7.39;95% CI 3.92-13.91;p<0.01), HIV viraemia (FC 0.24;0.11-0.50;p<0.01), reporting moderate-severe systemic AEs after dose-2 (FC 1.77;1.03-3.04;p=0.04) and either the CD4 count (FC 1.01;1.00-1.01;p=0.04) or CD4:CD8 ratio (FC 1.05;1.00-1.10;p=0.05). Conclusion: In this cohort with HIV, AE patterns after vaccination were similar to those seen in the pivotal BNT162b2 trials and most AEs were mild and short-lived. Whilst prior exposure to SARS-CoV-2 predicted higher anti-S responses, CD4 counts <200 cells/mm3 and low-level viraemia predicted reduced anti-S responses, thus identifying a subset potentially vulnerable to reduced vaccine efficacy.

Low testosterone levels and high estradiol to testosterone ratio are associated with hyperinflammatory state and mortality in hospitalized men with COVID-19.

OBJECTIVE: Evidence supports a sex disparity in clinical outcomes of COVID-19 patients, with men exhibiting higher mortality rates compared to women. We aimed to test the correlation between serum levels of sex hormones [total testosterone, estradiol (E2), estradiol to testosterone (E2/T) ratio, progesterone), prolactin and 25-hydroxyvitamin D [25(OH)D] and markers of inflammation, coagulation and sepsis at admission in hospitalized men with COVID-19. PATIENTS AND METHODS: We conducted an exploratory retrospective study including symptomatic men with confirmed SARS-CoV-2 infection who were consecutively admitted to our Institution between April 1 and May 31, 2020. RESULTS: Patients were divided into survivors (n=20) and non-survivors (n=39). As compared to survivors, non-survivors showed significantly higher median neutrophil-to-lymphocyte ratio (NLR) values, D-dimer and procalcitonin (PCT) levels, along with significantly lower median 25(OH)D levels and total testosterone levels. Non-survivors exhibited significantly higher median values of E2/T ratio (a marker of aromatase activity). Spearman's correlation analysis revealed that total testosterone levels were significantly and inversely correlated with NLR, high-sensitivity C-reactive protein (hsCRP), interleukin-6, D-dimer and PCT. Conversely, E2/T ratio values were significantly and positively correlated with the aforementioned markers and with white blood cell (WBC) count. In a multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, body mass index, hypertension and cardiovascular disease, diabetes mellitus and malignancy), total testosterone levels were significantly and inversely associated with risk of COVID-19-related in-hospital mortality. CONCLUSIONS: Low total testosterone levels and elevated E2/T ratio values at admission are associated with hyperinflammatory state in hospitalized men with COVID-19. Low total testosterone levels at admission represent an independent risk factor for in-hospital mortality in such patients. Therefore, total testosterone and E2/T ratio may serve as prognostic markers of disease severity in this population.

Subjective neurological symptoms frequently occur in patients with SARS-CoV2 infection. (Special Issue: Immunopsychiatry of COVID-19 pandemic.)

Objective: Coronavirus disease 2019 (COVID-19) represents a novel pneumonia leading to severe acute respiratory syndrome (SARS). Recent studies documented that SARS-Coronavirus2 (SARS-CoV2), responsible for COVID-19, can affect the nervous system. The aim of the present observational study was to prospectively assess subjective neurological symptoms (sNS) in patients with SARS-CoV2 infection.