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3.
Annals of the Rheumatic Diseases ; 81:1676-1677, 2022.
Article in English | EMBASE | ID: covidwho-2008969

ABSTRACT

Background: Patients with rheumatic diseases are at an increased risk for community infections (1,2). There still exists lack of data regarding SARS-CoV-2 vaccines' efficacy in vulnerable collectives with a compromised immune system, either due to a chronic pathology or to therapies targeting an autoimmune disease (3). Objectives: To evaluate neutralizing antibodies (nAB) to SARS-CoV-2 vaccine after 3 to 5 months from administration in Systemic Lupus Erythematosus (SLE) patients, as a surrogate of sustained-immunological response. Methods: This cross-sectional study compared nAB titre of 39 SLE patients and 37 Healthy individuals with no previous SARS-CoV-2 infection, who had all received two doses of a mRNA SARS-CoV-2 vaccine within the last 3 to 6 months. SLE patients included 10 Not-treated subjects, 10 patients with Hydroxychloroquine (First-Line), 10 subjects with immunosuppressive drugs (Second-Line) and 9 patients under biological treatment (Third-Line). Glucocorticoids were permitted in all patient groups. Neutralization assay were used to determine nAB titre according previously validated protocol (4). Results: Neutralizing antibody titres were assessed for a total of 76 serum samples from 39 (51%) Lupus patients and 37 (49%) healthy Controls. Healthy individuals showed the highest levels of nAB (1638.0 titre median), which were like not treated SLE subjects (1361.5 titre median). Treated patients presented substantially lower nAB titres compared to Healthy subjects: a 73% decrease for First-Line patients (p-value = 0.0135), 56% for patients received a Second-Line treatment (p-value = 0.2218) and 72% for Third-Line treated patients (p-value = 0.0104). A multivariate analysis pointed to Glucocorticoids as the most associated factor with declining nAB levels (75% decrease, p-value = 0.0037), and the one explaining, to a large extent, the lower acquired response in treated SLE patients. Furthermore, a significant reduction in nAB titres was observed for patients treated with Rituximab compared to Healthy subjects (89% decrease, p-value= 0.0008) (Figure 1). Conclusion: Medium-term response of SLE patients to SARS-CoV-2 vaccination, as measured by the titre of nABs, may be compromised by Glucocorticoids and Rituximab users. This reduced response likely translates into a higher probability of COVID-19 infection These fndings might help to inform recommendations in vaccination protocols for SLE patients.

4.
Annals of the Rheumatic Diseases ; 81:1465-1466, 2022.
Article in English | EMBASE | ID: covidwho-2008962

ABSTRACT

Background: Interstitial lung disease (ILD) in connective tissue diseases (CTD) is an important cause of morbidity and mortalitiy. Objectives: To evaluate ILD in CTD (systemic sclerosis, myositis, Sjögren syndrome, rheumatoid arthritis, mixed connective tissue disease), sarcoidosis and interstitial pneumonia with autoimmune features and its progression in 12 months evaluated through high resolution computed tomography (HRCT) and pulmonary function test (PFT). Methods: A retrospective single tertiary center cohort study in CTD-ILD outpatients seen between 2012 and 2021. Clinical, serological data, PFT and HRCT results were collected. ILD patterns were classifed into: usual interstitial pneumonia (UIP), inconsistent UIP, nonspecifc interstitial pneumonia (NSIP), fbrosing NSIP, organizing pneumonia, interstitial lymphoid pneumonia and associated to sarcoidosis. Progression of ILD was defned as:->10% decline in FVC in PFT.->15% decline in DLCO in PFT.-Progression of fbrosis in HRCT. IBM SPSS v23 was used for statistical analysis. Results: 51 patients were collected. Baseline characteristics are shown in Table 1. Figure 1 shows ILD progression in 1 year. During follow up, 1 patient with sarcoidosis died of COVID19 bilateral pneumonia. Conclusion: In our series most patients were middle aged women. Anti-Ro antibodies and smoking status (former or current) were common among patients. Common clinical features were Raynaud (45%), skin affection (45%) and arthritis (40%). 47% of the patients expressed dyspnea at ILD diagnosis. 29,4% were treated with MP pulses, 23,5% with rituximab, 31,4% with mycofenolate mophetil. Fibrosing pattern in HRCT (UIP and fb-NSIP) was the most prevalent. 20% of the patients had progressive fbrosis under PFT criteria and 18% under HCRT. More studies of ILD-CTD are necessary to identify factors for progression and response to treatment and throw out more conclusions of prediction and prognosis of disease.

5.
Gut ; 71:A36, 2022.
Article in English | EMBASE | ID: covidwho-2005346

ABSTRACT

Introduction Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. Methods Faecal and serum samples were prospectively collected from patients with IBD established on infliximab therapy (for >12 weeks) who were undergoing vaccination against SARS-CoV-2. The Roche Elecsys Anti-SARS-CoV-2 spike (S) and nucleocapsid (N) immunoassays were used to measure antibody responses following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Seroconversion was defined by a cut-off anti-S concentration of 15 U/ml, which correlated with 20% viral neutralization;anti-S antibody concentration of < 380 U/ml was indicative of poor response to vaccination. Patients with serological evidence of prior SARS-CoV-2 infection were excluded from the analysis. Faecal calprotectin measurement, 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-performance liquid chromatography mass spectrometry (UPLC-MS) were performed on faecal samples. Results Forty-five infliximab-treated patients were recruited (median age 40 [range 19-67];32 Crohn's disease, 13 ulcerative colitis;28 with concomitant immunomodulator therapy;six with prior infection). 14 patients (35%) had seroconverted after one dose of vaccine and 37 (95%) seroconverted after two doses. 18 patients (46%) had a poor response after two doses of vaccine. There was no association between faecal calprotectin and vaccine response (p=0.41). No differences between satisfactory and poor vaccine responders were noted in alpha or beta diversity of the gut microbiota. The faecal metabolome of satisfactory responders was enriched in the microbial metabolite trimethylamine (q=0.03). Trends were noted linking the short chain fatty acid butyrate with satisfactory response (P=0.01) and succinate with poor response (P=0.06). No significant differences in primary or secondary bile acids were found to associate with vaccine response. The butyrate-producing genus Roseburia was positively correlated with faecal butyrate abundance (q=0.03). Conclusions Our data suggest an association between gut microbiota function and variable serological response to vaccination against SARS-CoV-2 in immunocompromised patients. Microbial metabolites including trimethylamine and butyrate may be important in mitigating anti-TNF-induced attenuation of the immune response.

6.
Gastroenterology ; 162(7):S-652, 2022.
Article in English | EMBASE | ID: covidwho-1967353

ABSTRACT

Introduction: Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. Methods: Faecal and serum samples were prospectively collected from patients with IBD established on infliximab therapy (for >12 weeks) who were undergoing vaccination against SARS-CoV-2. The Roche Elecsys Anti-SARS-CoV-2 spike (S) and nucleocapsid (N) immunoassays were used to measure antibody responses following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Seroconversion was defined by a cut-off anti-S concentration of 15 U/ml, which correlated with 20% viral neutralization;anti-S antibody concentration of < 380 U/ml was indicative of poor response to vaccination. Patients with serological evidence of prior SARS-CoV-2 infection were excluded from the analysis. Faecal calprotectin measurement, 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-performance liquid chromatography mass spectrometry (UPLC-MS) were performed on faecal samples. Results: Forty-five infliximab-treated patients were recruited (median age 40 [range 19-67];32 Crohn's disease, 13 ulcerative colitis;28 with concomitant immunomodulator therapy;six with prior infection). 14 patients (35%) had seroconverted after one dose of vaccine and 37 (95%) seroconverted after two doses. 18 patients (46%) had a poor response after two doses of vaccine. There was no association between faecal calprotectin and vaccine response (p=0.41). No differences between satisfactory and poor vaccine responders were noted in alpha or beta diversity of the gut microbiota. The faecal metabolome of satisfactory responders was enriched in the microbial metabolite trimethylamine (q=0.03). Trends were noted linking the short chain fatty acid butyrate with satisfactory response (P=0.01) and succinate with poor response (P=0.06). No significant differences in primary or secondary bile acids were found to associate with vaccine response. The butyrate-producing genus Roseburia was positively correlated with faecal butyrate abundance (q=0.03). Conclusion: Our data suggest an association between gut microbiota function and variable serological response to vaccination against SARS-CoV-2 in immunocompromised patients. Microbial metabolites including trimethylamine and butyrate may be important in mitigating anti-TNF-induced attenuation of the immune response.

7.
Topics in Antiviral Medicine ; 30(1 SUPPL):101-102, 2022.
Article in English | EMBASE | ID: covidwho-1880960

ABSTRACT

Background: Understanding the determinants of long-term immune responses to SARS-CoV-2 and the concurrent impact of vaccination and emerging variants of concern will guide optimal strategies to achieve global protection against the COVID-19 pandemic. Methods: A prospective cohort of 332 COVID 19 patients was followed beyond one year. Plasma neutralizing activity was evaluated using HIV-based reporter pseudoviruses expressing different SARS-CoV-2 spikes and was longitudinally analyzed using mixed-effects models. Results: Long-term neutralizing activity was stable beyond one year after infection in mild/asymptomatic and hospitalized participants. However, longitudinal models suggest that hospitalized individuals generate both short-and long-lived memory B cells, while responses of non-hospitalized were dominated by long-lived B cells. In both groups, vaccination boosted responses to natural infection. In unvaccinated participants, viral variants, mainly beta, reduced the efficacy of long-term (>300 days from infection) neutralization. Importantly, despite showing higher neutralization titers, hospitalized patients showed lower cross-neutralization of beta variant compared to non-hospitalized. Multivariate analysis identified severity of primary infection as the factor that independently determines both the magnitude and the inferior cross-neutralization activity of long-term neutralizing responses. Conclusion: Neutralizing response induced by SARS-CoV-2 is heterogeneous in magnitude but stable beyond one year after infection. Vaccination boosts these long-lasting natural neutralizing responses and should help counteract the resistance to neutralization of variants of concern such as the beta variant. Severity of primary infection determines higher magnitude but poorer quality of long-term neutralizing responses.

8.
Topics in Antiviral Medicine ; 30(1 SUPPL):181-182, 2022.
Article in English | EMBASE | ID: covidwho-1880616

ABSTRACT

Background: SARS-CoV-2 is spread via airborne transmission. Mouthwashes containing virucidal compounds can help reduce viral spread. Here we show that cetylpyridinium chloride (CPC), a quaternary ammonium present in many oral mouthwashes, reduces SARS-CoV-2 infectivity by disrupting viral membranes both in vitro and in vivo. Methods: We tested the capacity of CPC-containing mouthwashes to inhibit SARS-CoV-2 entry into target cells by using a luciferase-based assay with a reporter lentivirus pseudotyped with the SARS-CoV-2 spike protein. The replication-competent SARS-CoV-2 B.1.1.7 and D614G variants were also assayed. Viral envelope disruption by CPC's virucidal effect was measured by dynamic light-scattering analyses (DSL). We confirmed these results by modifying an ELISA that detects the SARS-CoV-2 nucleocapsid (NC), which was used in the absence of its own lysis buffer. The effect of CPC in the saliva of individuals with CoVID-19 was assessed in a double-blind, placebo-controlled, randomized clinical trial. SARS-CoV-2 positive patients were randomized to gargle either water or 0.07% CPC mouthwash. The study outcomes were the SARS-CoV-2 log10 viral RNA load by RT-PCR and the NC protein levels by ELISA, both in saliva at 1h and 3h post-intervention. Results: CPC-containing mouthwashes inhibited SARS-CoV-2 viral fusion in vitro in a dose-dependent manner and decreased more than a 1000 times the viral TCID50 in target cells, regardless of the variant tested. The ELISA and the DSL analyses pointed to the effective disruption of the integrity of viral membranes after treatment with CPC. The clinical study performed with 105 patients showed no significant differences in viral RNA load at 1h and 3h post-treatment in saliva between placebo and CPC-treated groups. However, the levels of SARS-CoV-2 NC protein of lysed viruses were significantly higher in the CPC group at 1h and 3h post-intervention. Conclusion: CPC decreased more than a 1000 times the infectivity of SARS-CoV-2 in vitro and was effective against different SARS-CoV-2 variants. In CoVID-19 patients, the use of a 0.07% CPC mouthwash correlated with a statistically significant increase of NC protein levels in saliva, indicating enhanced disruption of viral particles. CPC-containing mouth rinses can represent a cost-effective measure to reduce SARS-CoV-2 infectivity in saliva, aiding to reduce viral transmission from infected individuals regardless of the variants they are infected with.

9.
Topics in Antiviral Medicine ; 30(1 SUPPL):379-380, 2022.
Article in English | EMBASE | ID: covidwho-1880551

ABSTRACT

Background: Routine medical care was drastically affected by the overwhelming irruption of COVID-19 pandemic. We comprehensively assessed the impact of the COVID-19 pandemic on the prevention and care for HIV and other sexually transmitted infections at a large reference hospital providing preventive and clinical services for HIV infection and other sexually transmitted infections. Methods: We retrospectively compared clinical and laboratory data from March to December 2020 (first ten months of the SARS-CoV-2 epidemics in Spain) vs. the same period 2019 in the setting of Hospital Clínic of Barcelona which provides preventive and clinical services for HIV infection and other sexually transmitted infections for the region of Catalonia and is the largest of its kind in Spain. Monthly clinical data on HIV pre-exposure and post-exposure prophylaxis users and on adults with HIV infection were retrieved from the administrative hospital database. Monthly tests for HIV, hepatitis B and C, Treponema pallidum, Neisseria gonorrhoeae, and Chlamydia trachomatis, and plasma lipids and glucose were recovered from the laboratory database. De novo HIV, hepatitis B, or hepatitis C diagnosis were considered whenever a person had a first known positive laboratory test. Results: There were less (28% reduction) but more advanced (mean [SD] CD4 cell counts per mm3 at HIV diagnosis 305 [167] vs. 370 [170], P<0.001;26 (18%) persons had AIDS-defining conditions at HIV diagnosis vs. 20 (10%), P=0.03) HIV cases and more gonorrhea (39% increase, P<0.001) and chlamydia (37% increase, P<0.001) infections in 2020 vs. 2019. In people with HIV, rates of viral load above the level of detection remained stable (11% vs 11%, P=0.147) despite less scheduled visits (25% reduction, P<0.001). However, they had less antiretroviral prescription changes (10% reduction, P=0.018), worse plasma lipids (mean total cholesterol 190 vs 185 mg/dL, P<0.001;mean LDL cholesterol 114 vs 110 mg/dL, P<0.001;mean triglycerides 136 vs 125 mg/dL, P<0.001;mean HDL cholesterol 47 vs 48 mg/dL, P=0.006), and an excess of mortality (29 deaths vs 11, 264% increase, P=0.006) due in great part to COVID-19 (n=11) but also to other non-COVID-19 causes. Conclusion: In the setting of a large Spanish reference hospital, SARS-CoV-2 epidemics was associated with an increase of some prevalent sexually transmitted infections, with less but more advanced de novo HIV infections, and with worse non-virologic healthcare outcomes and higher mortality in people living with HIV.

10.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-338041

ABSTRACT

Seroconversion panels were collected before and after vaccination with three COVID-19 vaccines: two mRNA vaccines (mRNA-1273 and BNT-162b2) and one adenovirus vector vaccine (Ad26.COV2.S). The panels were tested for antibody activity by chemiluminescent immunoassay, ELISA and one was tested in a pseudovirus neutralization assay. Participants positive for anti-SARS-CoV-2 antibodies before vaccination (18.6%) had a higher response to the first vaccine dose than participants who tested negative. For two-dose vaccines, older participants showed a lower response to the first dose than younger participants. All participants showed positive antibody responses after the second vaccine. For the adenovirus vector vaccine, two participants did not generate antibody responses two weeks and two months after vaccination. Three participants were negative at two weeks but positive at two months. Pseudovirus neutralization showed good correlation with antibody activity (correlation coefficient =0.78, p<0.0001). Antibody responses in participants over 45 years old tended to be less robust.

11.
Managing Sport and Leisure ; 27(1/2):152-156, 2022.
Article in English | CAB Abstracts | ID: covidwho-1769094

ABSTRACT

Indoor cycling has been a trend during the COVID-19 pandemic due to the lockdowns and social distancing measures imposed by most countries. Virtual cycling (eCycling) has grown exponentially, and its popularity among amateur and professional cyclists is shown by the fact that they regularly participate in virtual competitions in which people from all over the world interact via streaming. Although eCycling is derived from a traditional sport and adapted to a virtual platform, its future success once real competitions are reinstated has been seriously questioned. This virtual cycling modality has been openly criticized for the potential differences when competing and that it does not represent the true essence of cycling. These questions and the lack of clear guidelines for its competition suggest that eCycling has to go a long way before being considered a sport. This manuscript aims to present some challenges and opportunities regarding how virtual racing could be sustainable over time once the COVID-19 lockdown is over and demonstrate that eCycling was not just filling a short-term void left by real cycling during this pandemic.

12.
Revista De Transporte Y Territorio ; - (25):1-9, 2021.
Article in Spanish | Web of Science | ID: covidwho-1716471
15.
Annals of the Rheumatic Diseases ; 80(SUPPL 1):1376, 2021.
Article in English | EMBASE | ID: covidwho-1358808

ABSTRACT

Background: This tertiary hospital is the referall centre of 360.000 inhabitants, population with a Covid seroprevalence of 8,4% at final 2020. Since march, we have had a special concern for rheumatologic patients with systemic diseases and under inmunosupressive agents, including disease modifying antirheumatic drugs (DMARDs) and biological therapy (BT). This is why a special protocol for this population was set. It included performance of serology (CLIA test) for patients under BT and PCR and CLIA testing prior to new treatments. PCR testing was also generally performed: if symptomatology consistent with Covid;before hospitalisation;to tight contacts of infected people;and before procedures. Objectives: To evaluate the impact of COVID-19 in our SpA patients in terms of severity of viral infection and its effect on SpA. Methods: Data of 665 SpA patients and confirmed Covid infection seen in our center from March 15th to December 15th was crossed. 3 miscoded patients with rheumatoid arthritis and 2 with non definite CLIA positivity were excluded. Finally 49 patients' clinical records were reviewed. Data regarding epidemiologic features, SpA characteristics, comorbidities, therapy received, clinical activity before and after Covid, and severity of the infection was collected. IBM SPSS v23 was used for statistical analysis. Results: Among 49 SpA patients, 59% were male, mean aged 56,63 years (range 23-79). 62,2% presented at least 1 comorbidity. 65% were psoriatic arthritis. They mostly had longstanding disease (median 10,5 years -range-1-35). Previously 63% had received DMARDs, mainly methotrexate, and 32 % BT. When Covid was diagnosed 37,2% were under DMARDs and 53% under BT (69,2% TNF inhibitors, 26,9% anti-Il 17, 3,9% ustekinumab). At this point, disease activity was controlled in 82% of patients (39% in remission, and 43% in low disease activity state). Only 18% showed moderate activity. Within the 49 patients, 34 were diagnosed by PCR and 15 by CLIA tests. 9 required hospitalisation, of whom 4 developed more severe disease (3 received glucocorticoid pulses and 2 tocilizumab). A woman with PsA under secukinumab presented pneumonia and PE. None required mechanical ventilation. There were no exitus. Due to Covid infection 9 patients (50%) stopped DMARDs treatment, (5 of them hospitalised). 9 patients withdrew BT after Covid diagnosis;60% of the BT-hospitalised, and 28.5% of the BT-non-hospitalised. 1 suffered a flow with severe disease activity after withdrawal of Il-17 inhibitor. Conclusion: Prevalence of SARS cov 2 infection in SpA patients was not greater than in general population. Most were asymptomatic or suffered mild disease. Only 9 were hospitalised. Factors related to hospitalisation seem similar to those of general population, even if statistical significance was not found due to the small sample. BT does not seem to relate to hospitalisation in SpA and we had no deaths to date in them.

16.
J Dent Res ; 100(11): 1265-1272, 2021 10.
Article in English | MEDLINE | ID: covidwho-1318252

ABSTRACT

Oral mouthwashes decrease the infectivity of several respiratory viruses including SARS-CoV-2. However, the precise agents with antiviral activity in these oral rinses and their exact mechanism of action remain unknown. Here we show that cetylpyridinium chloride (CPC), a quaternary ammonium compound in many oral mouthwashes, reduces SARS-CoV-2 infectivity by inhibiting the viral fusion step with target cells after disrupting the integrity of the viral envelope. We also found that CPC-containing mouth rinses decreased more than a thousand times the infectivity of SARS-CoV-2 in vitro, while the corresponding vehicles had no effect. This activity was effective for different SARS-CoV-2 variants, including the B.1.1.7 or Alpha variant originally identified in United Kingdom, and in the presence of sterilized saliva. CPC-containing mouth rinses could therefore represent a cost-effective measure to reduce SARS-CoV-2 infectivity in saliva, aiding to reduce viral transmission from infected individuals regardless of the variants they are infected with.


Subject(s)
COVID-19 , Mouthwashes , Cetylpyridinium/pharmacology , Humans , Mouthwashes/pharmacology , SARS-CoV-2
17.
Topics in Antiviral Medicine ; 29(1):86-87, 2021.
Article in English | EMBASE | ID: covidwho-1250792

ABSTRACT

Background: Understanding the adaptive immune response to SARS-CoV-2, kinetics, persistence and their relationship with the disease severity would be crucial in order to predict recurrences, reinfections and could serve in the design of vaccination strategies. We sought to characterize IgG and neutralizing antibodies (NAbs) against SARS-CoV-2 in patients who were admitted to hospital with COVID-19 disease. Methods: All patients admitted between March-April 2020 with moderate, severe and critical SARS-CoV-2 pneumonia were prospectively studied. Clinical, laboratory data and IgG against SARS-CoV-2 levels were assessed at baseline (upon admission) and months 1, 3 and 6. NAbs were assessed at month 1, 3 and 6. IgG against the SARS-CoV-2 spike (S) protein was measured in serum by chemiluminescence (LIAISON® SARS-CoV-2 S1/S2, DiaSorin) and results were expressed in arbitrary units (AU)/mL. The neutralizing activity of plasma samples was analyzed in a 293T/hACE2 cell infection test using a surrogate viral inhibition assay that uses human immunodeficiency virus type 1 (HIV-1)-based virus expressing SARS-CoV-2 S protein and Luciferase. For neutralization assays, pseudoviruses were incubated with increasing plasma dilutions (range 1/60-1/14,580) in order to obtain the ID50 values. Results: A total of 110 patients who were discharged from hospital were recruited. Median (range) age was 61 (57-71);61.2% were male and most reported comorbidities were hypertension (39.6%), diabetes (24.3%) and obesity (19.8%). Median time from symptoms onset to admission was 9 days (range 7-11). Median (range) IgG levels (AU/mL) at baseline and months 1, 3 and 6 were 48 (28-81), 168 (134-210), 140 (112-171) and 146 (104-206) respectively. No significant differences were observed in median IgG fold change values up to month 6 among severity groups. Median (range) ID50 values for NAbs at months 1, 3 and 6 were 3938 (1958-6407), 4344 (2335-6752) and 424 (124-1022) respectively. NAb titers presented a significant decrease (overall-10.2-fold change from maximal values) without differences among severity groups (Figure 1 a and b). No reinfections occurred. Conclusion: Specific humoral immune response to SARS CoV-2 in patients requiring hospital admission characterizes for a clear peak between 30 and 90 days after admission followed by a significant decline in titer of NAbs by day 180 regardless of disease severity. Longer follow-up may help to determine the longevity of the specific immune response.

18.
Topics in Antiviral Medicine ; 29(1):88, 2021.
Article in English | EMBASE | ID: covidwho-1250606

ABSTRACT

Background: One of the fundamental pillars of SARS-CoV-2 pandemic control and vaccine development is understanding mid-and long-term immunity. Early humoral response has been extensively studied, however data on what recovered individuals are still scarce and the most recent studies are based on few time points over time, which limits the comprehension of the longitudinal pattern of the potential changes. In this study we have evaluated the neutralizing activity and IgG antibody titer against SARS-CoV-2 in mild/ asymptomatic and hospitalized COVID-19 individuals, over a 6-month period. Methods: We have evaluated the kinetics of the humoral immune response in 210 individuals infected by SARS-CoV-2 covering the first and second waves of COVID-19 outbreak in Catalonia (Spain). IgG antibody titer was evaluated with an in-house sandwich ELISA against the S2 subunit, the binding domain receptor (RBD) and the nucleoprotein (NP) and the neutralizing activity was evaluated by a neutralization assay with HIV reporter pseudoviruses expressing SARS-CoV-2 S protein. Statistical analyses were carried out using mixed-effects non-linear and linear models. Results: Most study participants developed a neutralizing humoral response against SARS-CoV-2, however the maximum neutralization titer was 10-fold lower in mild/asymptomatic individuals compared to those with a more severe illness. We observed a slow and progressive decay of neutralizing activity in individuals with mild or asymptomatic disease throughout the 6-month period. In hospitalized individuals, half maximal neutralization activity was achieved on day 10 and showed an initial rapid decline that significantly slowed and remained nearly flat after day 80. Despite this, activity at six months remained higher in hospitalized individuals compared to mild symptomatic participants. On the other hand, we observed that IgG antibody titers against S2, RBD and NP had a more marked fall without showing differences in the decay pattern between individuals with different degree of severity of the disease. Conclusion: Our data suggest that the neutralizing activity remains relatively stable for more than 6 months despite the decline in IgG antibodies, suggesting that the quality of immune response evolves and allows maintaining the neutralizing activity despite the decay in antibody titers. Our results provide a more detailed picture of the behavior of the natural humoral immune response over time that complements the current evidence on mid-term immunity.

19.
Topics in Antiviral Medicine ; 29(1):90, 2021.
Article in English | EMBASE | ID: covidwho-1250361

ABSTRACT

Background: Many immune studies of SARS-CoV-2 (CoV-2) infection have focused on the generation of virus-specific as a means of protection. However, a small group of CoV-2 infected individuals called Non-seroconverters (NSC), do not generate antibodies but experience a mild or moderate disease course. Identifying mechanism of CoV-2 control in NSC may inform the development of novel therapeutics and vaccines approaches. Methods: We identified eleven CoV-2 NSC (3.6%) from the King-cohort study (PI-20-217). NSC were defined by a positive CoV-2 PCR at the time of diagnosis in the absence of IgG, IgA and IgM in serum and plasma measured by two independent ELISA techniques. For comparison, we identify groups of CoV-2 convalescent (n=15) and low-neutralizers (n=15). We measured T-cell responses to the CoV-2 Spike (S) and Nucleocapsid (NP) recombinant proteins in PBMCs by ELISPOT and flow cytometry. We combined T-cell surface and lineage markers together with PD-1, functional (TNF, IFN-y, and IL-2) and activation induced markers (AIM: CD25, CD137 and OX40). Results: We identified CoV-2 specific CD4+ and CD8+ T-cells against the S and the NP in NSC individuals. All NSC responded to S by production of one or more cytokine in either CD4+ or CD8+ T-cells, and 57% responded to NP. Specific-CD8+ T cells against S in NSC were characterized by IFN-y, and TNF production, and we observed higher levels of TNF production as compared to low neutralizers (p=0.02). No differences were found in IFN-y, IL-2 and TNF production in S-specific CD4+ T cells between groups, nor in NP CD8+ or CD4+ T-cell responses. The levels of CD137/OX40 in CD8+ and CD4+ T cells were significantly lower in NSC in response to S (p=0.006, and p=0.012). Also, lower levels of PD-1 were observed in CD8+ T cells in response to NP in NSC (p=0.017). Conclusion: We provide evidence of SARS-CoV2 cellular immunity in NSC individuals despite the absence of humoral neutralizing responses. CD8+ and CD4+ T cells against the S and NP were present in NSC and characterized by TNF production in CD8+ T-cells in responses to S when compared to low neutralizers. Decreased levels of activation markers were observed in NSCs following S and NP stimulation. We propose a protective role of cellular immunity in NSC potentially driven by preexisting cellular responses.

20.
Topics in Antiviral Medicine ; 29(1):248, 2021.
Article in English | EMBASE | ID: covidwho-1249965

ABSTRACT

Background: Several large cohort studies have shown that adults with HIV (PWH) may have worse COVID-19 outcomes than non-HIV-infected persons. Whether it may be due to a higher frequency of co-morbidities or to a direct HIV effect is currently unclear. Methods: We performed a nation-wide multicenter prospective case-cohort study. Consecutive COVID-19-confirmed PWH (cases) admitted in 39 Spanish centers were matched 1:1 to COVID-19-confirmed non-HIV-infected adults (controls) for center, calendar week, age and gender. The contribution for death of HIV adjusted for co-morbidities was assessed in the whole population, and the contribution of immunological, virological, and antiretroviral factors only in the PWH group. Conditional logistic, random-effects logit and Fine-Gray competing-risks regression models were estimated. Results: From 26/Feb to 21/Sep 2020, 204 cases and 204 controls were included. Median (IQR) age was 54 (47-60) years and 85% were men. Among PWH, 33% had prior AIDS events, current median CD4 cells/mm3 were 521 (IQR 310-756), 14% had CD4<200/mm3, and 90% had HIV suppressed;antiretrovirals were: 17% NNRTI, 23% PI, 70% InSTI, 89% NRTI, 6% TDF, 45% TAF, and 31% ABC. Chronic liver disease (aOR 8.68, 95%CI 1.51-49.97, P=0.0156), cardiovascular disease (aOR 2.09, 95%CI 1.19-3.68, P=0.0103), and obesity (aOR 0.30, 95%CI 0.19-0.49, P<0.0001) significantly differed between cases and controls. Twenty (9.8%) cases and 7 (3.4%) controls died. HIV infection was associated with a higher risk of death after adjustment for chronic liver disease, cardiovascular disease, and obesity (aOR 5.27, 95%CI 1.00-27.72, P=0.0499) and a higher incidence of death (subHR 3.45, 95%CI 1.47-8.11, P=0.0045). Increasing age, hypertension, diabetes, COPD, decreasing haemoglobin and leukocytes, and CKD-EPI eGFR ≤90 mL/min/1.73 m2 were associated with death in cases, while increasing age and neoplasia were associated with death in controls. Only increasing age and COPD in cases and neoplasia in controls remained associated with death in the adjusted logistic regression. Current or nadir CD4 counts and CD4/CD8 ratio, detectable HIV RNA, and specific antiretroviral agents were not associated with death. Conclusion: In this cohort of COVID-19 in-patients, risk of death was higher in PWH than in non-HIV-infected controls. Several co-morbidities through increasing age, but not immunological, virological, or antiretroviral factors, were associated with a higher risk of death in PWH.

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