ABSTRACT
Introduction: COVID-19 patients with non-resolving ARDS may benefit from treatment with high-dose steroids (HDS), because of a presumed persistent systemic and alveolar hyperinflammation. At ICU admission, it is unknown which patients require HDS. Obtaining insights in their inflammatory state by using biomarkers and determining their association with the effect of HDS could support decisionmaking. The goal of this study is to compare the patient characteristics and biomarker profiles at ICU admission of the patients that received HDS to the patients who did not. Method(s): This was a retrospective cohort study including COVID-19 patients admitted to the ICU of the Erasmus MC between 2020 and 2022. The primary intervention was treatment with HDS, defined as 1000 mg methylprednisolone or > 40 mg prednisolone for three consecutive days. We compared demographics, comorbidities, biomarkers and mortality between patients treated with HDS and without. Logistic regression multivariate analyses was used to analyze which biomarkers were associated with initiation of HDS. Result(s): We included 151 patients, of which 48 were treated with HDS at a median of 6 days after ICU admission (Table 1). There were no significant differences in demographics and comorbidities. Patients treated with HDS had a significantly longer ICU length of stay (p < 0.001) and higher hospital mortality rate (p < 0.001). LDH (p = 0.02) and ferritin (p = 0.05) levels on admission were significantly higher in patients treated with HDS, whereas their CRP was significantly lower (p = 0.02). In multivariate regression analysis, these were not independently associated with the initiation of HDS. Conclusion(s): At ICU admission, demographics and comorbidities did not differ between patients treated with HDS and without. There were no factors associated with the initiation of HDS in COVID-19 patients in the ICU. Further studies on the association between the inflammatory state, mortality, and the effect of HDS are required to understand which patients may benefit from HDS.
ABSTRACT
Background: Vaccines can be less immunogenic in people living with HIV (PLWH). So far, the immune response after SARS-CoV-2 vaccination of PLWH is not well-established. Methods: A prospective cohort study in 22 HIV treatment centres in the Netherlands examined the immunogenicity of SARS-CoV-2 vaccines in PLWH. Included were adult PLWH without prior COVID-19 infection, invited by the national vaccination programme to receive the BNT162b2, mRNA-1273, ChAdOx1-S or Ad26.COV2.S vaccine. Data from HIV-negative healthy controls were acquired from 2 concurrent prospective vaccination trials. The primary endpoint was the anti-SARS-CoV-2 IgG response (Liaison Trimeric Spike IgG in BAU/ml) measured 4-6 weeks after vaccination with one of the 2 mRNA vaccines in PLWH versus controls. Secondary endpoints included antibody response according to sex, CD4+ T-cell count, and vaccine reactogenicity. Results: Between February 14th and September 7th 2021, 1269 PLWH were enrolled and complete results were available for 1148 PLWH as well as for 440 healthy controls. 879 of the PLWH were vaccinated with BNT162b2 while 100, 150 and 19 had received mRNA-1273, ChAdOx1-S and 19 Ad26.COV2.S respectively. Their median age was 53 years [IQR 44-60], 85.5% was male, the median CD4+ T-cell count was 710/μ L [IQR 520-913]. 99% was on cART with HIV-RNA <50 copies/ml in 97.7%. The control group consisted of 440 healthy people;247 vaccinated with mRNA-1273, 94 with BNT162b2, 26 with ChAdOx1-S and 73 with Ad26.COV2.S. Their median age was 43 [IQR 33-53] and 28.6% was male. PLWH had a significantly lower anti-SARS-CoV-2 RBD IgG response compared to controls (mean value of 2171 BAU/mL (95% CI 1888-2453) versus 3586 BAU/ml (95% CI 3250-3922, p<0.001)). In the multivariable analysis, being HIV positive, age >65 years, being male and having received a non-mRNA vaccination were all independently associated with a lower antibody concentration (p<0.01 for all). In the PLWH vaccinated with BNT162b2 or mRNA-1273, mean antibody levels were significantly lower in those with a CD4+ T-cell counts <250/μ L (1617 BAU/mL, 95% CI 828-2407) compared to CD4 ≥250/μ L (2486 BAU/ml 95% CI 2149-2824, p=0.002). Reactogenicity occurred in 55 and 50% after the first and second vaccination respectively and were generally mild without vaccine-related SAE. Conclusion: After vaccination with BNT162b2 or mRNA-1273, Anti-Spike IgG levels were lower in PLWH compared to healthy controls. In PLWH, a CD4+ T cell count <250/μ L was associated with lower antibody concentration.