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.
ABSTRACT
In hospitalized COVID-19 patients, myocardial injury and echocardiographic abnormalities have been described. The present study investigates cardiac function in COVID-19 patients 6 weeks post-discharge and evaluates its relation to New York Heart Association (NYHA) class. Furthermore cardiac function post-discharge between the first and second wave COVID-19 patients was compared. We evaluated 146 patients at the outpatient clinic of the Leiden University Medical Centre. NYHA class of II or higher was reported by 53% of patients. Transthoracic echocardiography was used to assess cardiac function. Overall, in 27% of patients reduced left ventricular (LV) ejection fraction was observed and in 29% of patients LV global longitudinal strain was impaired (> − 16%). However no differences were observed in these parameters reflecting LV function between the first and second wave patients. Right ventricular (RV) dysfunction as assessed by tricuspid annular systolic planar excursion (< 17 mm) was present in 14% of patients, this was also not different between the first and second wave patients (15% vs. 12%;p = 0.63);similar results were found for RV fraction area change and RV strain. Reduced LV and RV function were not associated with NYHA class. In COVID-19 patients at 6 weeks post-discharge, mild abnormalities in cardiac function were found. However these were not related to NYHA class and there was no difference in cardiac function between the first and second wave patients. Long term symptoms post-COVID might therefore not be explained by mildly abnormal cardiac function.
ABSTRACT
Background: COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been suggested to induce autoimmune phenomena. Multiple studies have reported the presence of autoantibodies in patients with COVID-19. Also the presence of anti-citrullinated protein antibodies (ACPA) and flaring of rheumatoid arthritis (RA) after COVID-19 has been described.[1, 2] Furthermore, in rheumatology clinics patients may present with polyarthritis compatible with RA shortly after SARS-CoV-2 infection. However, it is unclear how often ACPA occur after COVID-19 and whether preceding COVID-19 impacts on disease presentation of RA and phenotype of the ACPA response. Objectives: This study aims to determine the seroprevalence of ACPA after COVID-19 and to investigate the association between preceding COVID-19 infection and disease presentation of new-onset RA, including clinical phenotype and autoantibody response. Methods: To estimate the prevalence of ACPA after COVID-19 we measured ACPA IgG in samples from 61 patients visiting the specialized post-COVID outpatient clinic of the LUMC 5 weeks after hospitalization, using routine tests or in-house ELISA. Furthermore, we identified 5 patients presenting with polyarthritis compatible with RA after SARS-CoV-2 infection. To study the impact of COVID-19 on disease presentation, we examined clinical phenotype, autoantibody isotype positivity and ACPA IgG variable domain (V-domain) glycosylation of these patients and compared these features to regular RA patients. Autoantibody isotypes, including rheumatoid factor (RF) IgM/IgA, anti-CCP2 IgG/ IgM/ IgA and anti-carbamylated protein antibodies (anti-CarP) IgG were measured using in-house ELISA's. The percentage of V-domain glycosylation of purified ACPA IgG was measured with UHPLC. Results: None of the 61 post-COVID patients tested positive for ACPA 5 weeks after hospitalization, except two patients previously diagnosed with ACPA-positive RA. Thus, we could not observe an increase in ACPA-positivity shortly after COVID-19. Of the 5 patients who developed polyarthritis compatible with RA after SARS-CoV-2 infection, the average age was 63.6 years and 2/5 were female. 4/5 patients had been hospitalized due to severe COVID-19. On average, joint complaints started 6.6 weeks after infection, although two patients reported symptoms before infection. 4/5 patients fulfilled the ACR 2010 criteria for RA. Three patients (patient 1, 4, 5) were phenotypically very similar to regular new-onset RA patients. Patient 3 had a history of seronegative RA and had been in DMARD-free remission for 5 years. She flared 6 weeks after SARS-CoV-2 infection. Patient 2 had a remarkably different presentation. He was admitted with a suspected septic polyarthritis or pneumonia with reactive polyarthritis 6 weeks after COVID-19. ACPA level was low positive. The patient died unexpectedly after two days and autopsy revealed dilating myocarditis of unclear underlying cause. No causative pathogen could be identified. Previous studies have shown that RA-patients are most often either seronegative or triple-positive for RF, ACPA and anti-CarP antibodies. Autoantibody measurements on sera of the post-COVID polyarthritis patients revealed a similar pattern (Figure 1A) with two patients being completely seronegative, and three patients positive for a range of autoantibodies. In all post-COVID samples, the percentage of ACPA IgG V-domain glycosylation was significantly increased compared to total IgG (Figure 1B), similar as in regular RA. Conclusion: In conclusion, we found that the seroprevalence of ACPA is not increased post-COVID and that most patients presenting with polyarthritis after COVID-19 resemble regular RA patients, both regarding clinical phenotype and autoantibody characteristics. Although sample size and follow-up was limited, it appears that RA post-COVID may be coincidence rather than connected.
ABSTRACT
BACKGROUND: Short-term follow-up of COVID-19 patients reveals pulmonary dysfunction, myocardial damage and severe psychological distress. Little is known of the burden of these sequelae, and there are no clear recommendations for follow-up of COVID-19 patients.In this multi-disciplinary evaluation, cardiopulmonary function and psychological impairment after hospitalization for COVID-19 are mapped. METHODS: We evaluated patients at our outpatient clinic 6 weeks after discharge. Cardiopulmonary function was measured by echocardiography, 24-hours ECG monitoring and pulmonary function testing. Psychological adjustment was measured using questionnaires and semi-structured clinical interviews. A comparison was made between patients admitted to the general ward and Intensive care unit (ICU), and between patients with a high versus low functional status. FINDINGS: Eighty-one patients were included of whom 34 (41%) had been admitted to the ICU. New York Heart Association class II-III was present in 62% of the patients. Left ventricular function was normal in 78% of patients. ICU patients had a lower diffusion capacity (mean difference 12,5% P = 0.01), lower forced expiratory volume in one second and forced vital capacity (mean difference 14.9%; P<0.001; 15.4%; P<0.001; respectively). Risk of depression, anxiety and PTSD were 17%, 5% and 10% respectively and similar for both ICU and non-ICU patients. INTERPRETATION: Overall, most patients suffered from functional limitations. Dyspnea on exertion was most frequently reported, possibly related to decreased DLCOc. This could be caused by pulmonary fibrosis, which should be investigated in long-term follow-up. In addition, mechanical ventilation, deconditioning, or pulmonary embolism may play an important role.