Background
The relationship of host immune response and viral replication with health outcomes in patients with COVID-19 remains to be defined. We aimed to characterize the medium and long-term ...clinical, virological, and serological outcomes after hospitalization for COVID-19, and to identify predictors of long-COVID.
Methods
Prospective, longitudinal study conducted in COVID-19 patients confirmed by RT-PCR. Serial blood and nasopharyngeal samples (NPS) were obtained for measuring SARS-CoV-2 RNA and S-IgG/N-IgG antibodies during hospital stay, and at 1, 2, and 6 months post-discharge. Genome sequencing was performed where appropriate. Patients filled out a COVID-19 symptom questionnaire (CSQ) at 2-month and 6-month visits, and those with highest scores were characterized.
Results
Of 146 patients (60% male, median age 64 years) followed-up, 20.6% required hospital readmission and 5.5% died. At 2 months and 6 months, 9.6% and 7.8% patients, respectively, reported moderate/severe persistent symptoms. SARS-CoV-2 RT-PCR was positive in NPS in 11.8% (median Ct = 38) and 3% (median Ct = 36) patients at 2 months and 6 months, respectively, but no reinfections were demonstrated. Antibody titers gradually waned, with seroreversion occurring at 6 months in 27 (27.6%) patients for N-IgG and in 6 (6%) for S-IgG. Adjusted 2-month predictors of the highest CSQ scores (OR 95%CI) were lower peak S-IgG (0.80 0.66–0.94) and higher WHO severity score (2.57 1.20–5.86); 6-month predictors were lower peak S-IgG (0.89 0.79–0.99) and female sex (2.41 1.20–4.82); no association was found with prolonged viral RNA shedding.
Conclusions
Long-COVID is associated with weak anti-SARS-CoV-2 antibody response, severity of illness, and female gender. Late clinical events and persistent symptoms in the medium and long term occur in a significant proportion of patients hospitalized for COVID-19.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
The pathophysiology of long-COVID remains unknown, and information is particularly limited for symptoms of very long duration. We aimed to assess the serological, T-cell immune responses ...and ANA titers of patients with long-COVID-19 syndrome of 1-year duration.
Methods
Prospective, longitudinal study of hospitalized COVID-19 patients followed-up for 12 months. Sequential blood samples and COVID-19 symptom questionnaires (CSQ) were obtained, and humoral and cellular immune responses, antinuclear antibodies (ANA) and inflammation biomarkers were analyzed.
Results
Of 154 patients discharged from hospital, 72 non-vaccinated with available CSQ in all visits were included. Of them, 14 (19.4%) reported persistent symptoms both at 6-months and 12-months, mainly asthenia (15.3%), myalgia (13.9%), and difficulty concentrating/memory loss (13.9%). Symptomatic patients were more frequently women, smokers, showed higher WHO severity score, and a trend to higher ICU admission. In the adjusted analysis, long-COVID syndrome was associated with lower frequency of detectable neutralizing antibodies (adjusted hazard ratio aHR 0.98; 95% confidence interval CI, 0.97-0.99) and lower SARS-CoV-2-S1/S2 titers (aHR 95%CI 0.14 0.03–0.65). T-cell immune response measured with a SARS-CoV-2-interferon-γ release assay was not different between groups. There was a higher frequency of positive ANA titers (≥160) in symptomatic patients (57.1% vs 29.3%, p=0.04), that was attenuated after adjustment aHR 95% CI 3.37 0.84-13.57, p=0.087. Levels of C-reactive protein and D-dimer were higher during follow-up in symptomatic patients, but with no differences at 12 months.
Conclusion
Patients with 1-year duration long-COVID-19 syndrome exhibit a distinct immunologic phenotype that includes a poorer SARS-CoV-2 antibody response, low-degree chronic inflammation that tends to mitigate, and autoimmunity.
The virological and immunological effects of the immunomodulatory drugs used for COVID-19 remain unknown. We evaluated the impact of interleukin (IL)-6 blockade with tocilizumab on SARS-CoV-2 viral ...kinetics and the antibody response in patients with COVID-19.
Prospective cohort study in patients admitted with COVID-19. Serial nasopharyngeal and plasma samples were measured for SARS-CoV-2 RNA and S-IgG/N-IgG titers, respectively.
138 patients with confirmed infection were included; 76 (55%) underwent IL-6 blockade. Median initial SOFA (p = 0•016) and SARS-CoV-2 viral load (p<0•001, Mann-Whitney-Wilcoxon test) were significantly higher among anti-IL-6 users. Patients under IL-6 blockade showed delayed viral clearance in the Kaplan-Meier curves (HR 0•35 95%CI 0•15–0•81, log-rank p = 0•014), but an adjusted propensity score matching model did not demonstrate a significant relationship of IL-6 blockade with viral clearance (HR 1•63 0•35–7•7). Cox regression showed an inverse association between SARS-CoV-2 RNA clearance and the initial viral load (HR 0•35 0•11–0•89). Patients under the IL-6 blocker showed shorter median time to seropositivity, higher peak antibody titers, and higher cumulative proportion of seropositivity in the Kaplan Meier curves (HR 3•1 1•9–5 for S-IgG; and HR 3•0 1•9–4•9 for N-IgG; log-rank p<0•001 for both). However, no significant differences between groups were found in either S-IgG (HR 1•56 0•41–6•0) nor N-IgG (HR 0•96 0•26–3•5) responses in an adjusted propensity score analysis.
Our results suggest that in patients infected with SARS-CoV-2, IL-6 blockade does not impair the viral specific antibody responses. Although a delayed viral clearance was observed, it was driven by a higher initial viral load. The study supports the safety of this therapy in patients with COVID-19.
Instituto de salud Carlos III (Spain).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Human immunodeficiency virus type 1 RNA levels were longitudinally evaluated in 211 rectal and 152 seminal samples from 12 virologically suppressed participants switching to monthly long-acting ...cabotegravir plus rilpivirine or continuing with daily dolutegravir-abacavir-lamivudine. Maintenance of viral suppression in rectal and seminal compartments was comparable, and blips occurred with similar frequency with both treatment regimens.
NCT02938520.
Abstract
Background
We evaluated a standardized interferon-γ (IFN-γ) release assay (IGRA) for detection of T-cell immune response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ...infection or vaccination.
Methods
This prospective study included patients with coronavirus disease 2019 (COVID-19) with different severity of illness and follow-up (FU), vaccinated subjects, and healthy unvaccinated persons. SARS-CoV-2 T-cell response was measured using a specific quantitative IGRA in whole blood (Euroimmun, Germany) and TrimericS-IgG and neutralizing antibodies with validated serological platforms. Positivity of reverse transcription–polymerase chain reaction or vaccination was considered as the reference standard.
Results
A total of 239 individuals were included (152 convalescent, 54 vaccinated, and 33 uninfected unvaccinated). Overall sensitivity, specificity, and positive- and negative-predictive values (95% confidence interval) of the IGRA were 81.1% (74.9–86%), 90.9% (74.5–97.6%), 98.2% (94.5–99.5%), and 43.5% (31.8–55.9%), respectively. All vaccinated SARS-CoV-2-naive subjects had positive IGRA at 3 months. In convalescent subjects the magnitude of IFN-γ responses and IGRA accuracy varied according to disease severity and duration of FU, with the best performance in patients with severe COVID-19 at 3 months and the worst in those with mild disease at 12 months. The greatest contribution of IGRA to serological tests was observed in patients with mild disease and long-term FU (incremental difference, 30.4%).
Conclusions
The IGRA was a reliable method of quantifying T-cell response after SARS-COV-2 infection or vaccination. In convalescent patients, the sensitivity is largely dependent on disease severity and time since primary infection. The assay is more likely to add clinical value to serology in patients with mild infections.
Excessive interleukin-6 signaling is a key factor contributing to the cytokine release syndrome implicated in clinical manifestations of COVID-19. Preliminary results suggest that tocilizumab, a ...humanized monoclonal anti-interleukin-6 receptor antibody, may be beneficial in severely ill patients, but no data are available on earlier stages of disease. An anticipated blockade of interleukin-6 might hypothetically prevent the catastrophic consequences of the overt cytokine storm. We evaluated early-given tocilizumab in patients hospitalized with COVID-19, and identified outcome predictors. Consecutive patients with initial Sequential-Organ-Failure-Assessment (SOFA) score < 3 fulfilling pre-defined criteria were treated with tocilizumab. Serial plasma biomarkers and nasopharyngeal swabs were collected. Of 193 patients admitted with COVID-19, 64 met the inclusion criteria. After tocilizumab, 49 (76.6%) had an early favorable response. Adjusted predictors of response were gender, SOFA score, neutrophil/lymphocyte ratio, Charlson comorbidity index and systolic blood pressure. At week-4, 56.1% of responders and 30% of non-responders had cleared the SARS-CoV-2 from nasopharynx. Temporal profiles of interleukin-6, C-reactive protein, neutrophil/lymphocyte ratio, NT-ProBNP, D-dimer, and cardiac-troponin-I differed according to tocilizumab response and discriminated final in-hospital outcome. No deaths or disease recurrences were observed. Preemptive therapy with tocilizumab was safe and associated with favorable outcomes in most patients. Biological and clinical markers predicted outcomes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Durability of the humoral immune response to SARS-CoV-2 has yet to be defined. We longitudinally evaluated during a 12-month period the antibody responses to SARS-CoV-2, and analysed predictors of ...antibody titres decline and seroreversion.
Prospective study conducted in a cohort of patients hospitalized for microbiologically-confirmed COVID-19. Blood and nasopharyngeal samples were sequentially obtained during hospital stay and at 1, 2, 6 and 12 months after patients’ discharge for measuring anti-spike (S) and anti-nucleocapsid (N) IgG antibody levels and SARS-CoV-2 RNA, respectively.
80 non-vaccinated patients were analysed. At month 12 after discharge, 73 (91.2%) patients exhibited detectable S-IgG and 35 (43.8%) N-IgG antibody titres. A gradual wane was observed in S-IgG and N-IgG antibody titres. Linear regression showed that S-IgG decline was positively associated with peak antibody titres (coefficient 95% CI 0.059 0.05–0.067, p < 0.001), inversely with WHO severity score (coefficient 95% CI −0.042 -0.079/-0.004, p = 0.033), and there was a trivial positive association with age (coefficient 95% CI 0.002 0–0.005, p = 0.10); N-IgG decline was positively associated with peak antibody titres (coefficient 95% CI 0.091 0.078–0.105, p < 0.001). Logistic regression showed that seroreversion for S-IgG was inversely associated with peak S-IgG (OR 0.19; 95% CI, 0.04-0.45; p = 0.004); seroreversion for N-IgG was inversely associated with peak N-IgG (OR 0.71; 95% 0.53–0.90; p = 0.009) and positively with cycle threshold of RT-PCR (OR 1.14; 95% CI, 1.00–1.33; p = 0.062).
Anti-spike IgG antibodies remain detectable one year after hospitalization for COVID-19. Higher peak antibody titres and disease severity were associated with increased durability of detectable antibodies.
•Postinfection humoral immunity may protect against SARS-CoV-2 reinfection.•Durability of the humoral immune response remains unknown.•Most COVID-19 patients show persistent S-IgG antibodies one year after hospitalization.•Durability of antibody response associated with higher peak titres and disease severity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background The relationship of microbiota composition dynamics and the progression of subclinical atherosclerosis in people with human immunodeficiency virus (PWH) remains unknown. Methods A ...96-week, prospective, longitudinal study was performed in virologically suppressed PWH. Carotid intima-media thickness (cIMT) measurements and stool samples were obtained at baseline and at 48- and 96-week visits. cIMT progression was defined as an increase of >10% and/or detection of new carotid plaque. To profile the gut microbiome, amplification and sequencing of 16S ribosomal RNA (V3–V4 variable regions) were carried out, following the Illumina protocol. Sequencing was performed using the MiSeq platform. Results At the baseline, 48-week, and 96-week visits, 191, 190, and 167 patients, respectively, had fecal samples available for microbiome analysis. Eighty-seven participants (43%) showed atherosclerosis progression, and 54 (26.7%) presented with new carotid plaque. No significant differences were observed in adjusted α-diversity indices between groups, defined by cIMT progression. β-Diversity, determined through principal coordinate analysis, showed that the groups exhibited distinct microbial profiles (P = .03; permutational multivariate analysis of variance). Longitudinal analysis with Analysis of Compositions of Microbiomes with Bias Correction 2, adjusted for traditional cardiovascular risk factors, status as men who have sex with men, and nadir CD4 count, revealed that cIMT progression was consistently associated with Agathobacter and Ruminococcus 2, while nonprogression was consistently associated with Prevotella 7. Conclusions Progression of atherosclerosis in PWH might be associated with distinctive signatures in the gut microbiota.
We conducted a multicentre observational study in people living with HIV (PLHIV) on antiretroviral therapy in Alicante (Spain) from 2019 to 2020 aiming to analyse the prevalence of abuse and assess ...treatment adherence according to this variable. We used the Abuse Assessment Screen tool, the simplified medication adherence questionnaire and the medication possession ratio to assess outcomes.. Of the 161 included PLHIV, 53 (32.9%) had suffered abuse (27 emotional abuse, 6 physical abuse, 3 sexual abuse, 13 emotional and physical abuse, 4 unknown type). Seven (4.3%) had suffered abuse in the last year (5 emotional, 2 physical). Abuse had lasted a median of 48 months (interquartile range 12-81). HIV status was considered as a cause of violence by 9.4% of victims. In the multivariable analysis, only abuse was independently associated with non-adherence adjusted odds ratio (aOR) 3.92; 95% confidence interval (CI) 1.80-8.84; p = 0.0007. Abuse (aOR 6.14; 95% CI 1.63-27.70; p = 0.001) and previous incarceration (aOR 15.08 95% CI 2.71-104.71; p = 0.003) were associated with detectable viral load. In conclusion, the prevalence of abuse is high in PLHIV, hampering adherence and virological success. Abuse screening tools should be incorporated into routine HIV care.
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