Reduced neutralizing antibody response to SARS-CoV-2 vaccine booster dose in people living with HIV with severe immunosuppression.

The aim of this study was to assess the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among people living with HIV (PLWH) with severe immunosuppression, after a booster dose. The design was a case-control study nested in a prospective cohort of PLWH. All patients with CD4 cell count <200 cells/mm3 who had received additional dose of messenger RNA (mRNA) COVID-19 vaccine, after a standard immunization scheme were included. Control group: patients age- and sex-matched, with CD4 ≥ 200 cells/mm3 , in the ratio of 2:1. Antibody response to a booster dose (anti-S levels 33.8 ≥ BAU/mL) and neutralizing activity against SARS-CoV-2 B.1, B.1.617.2, and Omicron BA.1, BA.2, and BA.5 strains were assessed after the booster shot. Fifty-four PLWH were included, 18 with CD4 counts < 200 cells/mm3 . Fifty-one (94%) showed response to a booster dose. Response was less frequent in PLWH with CD4 < 200 cells/mm3 than in those with CD4 counts ≥ 200 cells/mm3 (15 [83%] vs. 36 [100%], p = 0.033). In the multivariate analysis, CD4 counts ≥ 200 cells/mm3 [incidence rate ratio (IRR) = 18.1 (95% confidence interval [CI]: 16.8-19.5), p < 0.001] was associated with a higher probability of showing antibody response. Neutralization activity against SARS-CoV-2 B.1, B.1.617, BA.1, and BA.2 strains was significantly inferior among individuals with CD4 counts < 200 cells/mm3 . In conclusion, among PLWH with CD4 counts < 200 cells/mm3 , the immune response elicited by mRNA additional vaccine dose is reduced.

Severe immunosuppression is related to poorer immunogenicity to SARS-CoV-2 vaccines among people living with HIV.

OBJECTIVES: The aim of this study was to assess the immunogenicity of SARS-CoV-2 available vaccines among people living with HIV (PLWH) after a complete vaccination scheme, and determine predictors of seroconversion. METHODS: This multicentre prospective cohort study included 420 PLWH who had received a standard immunization, either with mRNA or adenoviral-vectored COVID-19 vaccines. Antibody response was evaluated within 1 to 2 months after the last dose of the vaccine with a quantitative determination of antitrimeric spike protein-specific IgG antibodies and IgG neutralizing antibodies. RESULTS: Overall, 384 of 420 PLWH (91%) showed antibody response to vaccination. Seroconversion was observed in 308 of 326 individuals with cluster of differentiation 4 (CD4) counts ≥350 cells/mm3 (95%), 55 of 61 PLWH with 200 to 349 cells/mm3 (90%), and 21 of 33 PLWH with CD4 counts <200 cells/mm3 (64%; p < 0.001). The median log10 IgG neutralization levels were 2.4 IU/mL (Q1-Q3, 1.0-3.1) among PLWH with CD4 counts <200 cells/mm3, 3.1 IU/mL (Q1-Q3, 2.8-3.4) for the 200 to 349 cells/mm3 group, and 3.1 IU/mL (Q1-Q3, 2.7-3.4) for PLWH with CD4 counts ≥350 cells/mm3 (p = 0.016). In the multivariate analysis, CD4 counts ≥350 cells/mm3 (OR: 7.10; 95% CI, 1.91-26.46; p = 0.004) and receiving mRNA-vectored COVID-19 vaccines (OR: 8.19; 95% CI, 3.24-20.70; p ≤ 0.001) were independently associated with a higher probability of response to vaccination. DISCUSSION: HIV-related immunosuppression impairs the antibody response to SARS-CoV-2 vaccines. Specific vaccination schemes should be urgently tailored in this setting, particularly in patients with CD4 cell counts <200 cells/µL. Adenoviral-vectored vaccines should be avoided in PLWH whenever possible.

Poor increase on HAV vaccination coverage among people living with HIV after an immunization-based intervention

Objectives To assess HAV serologic and vaccination status among people who live with HIV (PLWH), and to evaluate the impact of a vaccination-based strategy on HAV-negative patients in Seville, Spain. Methods Study with two time-overlapping phases: (i) cross-sectional study of HAV immunity prevalence among PLWH followed at a Spanish hospital between August 2019 and March 2020. (ii) Patients seronegative for HAV, reliably unvaccinated were included in a before-and-after quasi-experimental study, with an intervention focused on HAV vaccination according to national recommendations in force. Results Six hundred and fifty-six patients were included, of which 111 [17%, 95% confidence interval (95% CI) 14–20%] were seronegative for HAV. Of these, 48 [43% (95% CI, 34–53%)] individuals were MSM. The absence of HAV immunity was attributed in 69 [62% (95% CI, 52–71%)] patients to non-referral to vaccination, followed by lack of achievement of a correct vaccination scheme [n=26;23% (95% CI, 16–32%)]. After the program implementation, 96 [15% (95% CI, 12–18%)] individuals were seronegative (17% vs. 15%, p=0.256), of whom 42 [41% (95% CI, 32–51%)] were MSM. The absence of immunity after the intervention was mainly attributed to: adherence failure in 23 [24.0% (95% CI, 15.8–33.7%)] patients, on-course immunization scheme in 34 [33% (95% CI, 24–43%)] individuals and pending appointment at the vaccine delivery unit in 20 [20.8% (95% CI, 13.2–30.3%)] patients. Conclusions A sizeable proportion of PLWH remains susceptible for HAV infection in future outbreaks. A program based on referral to the vaccine delivery unit yields poor results, largely due to program adherence failures. New strategies are needed to increase HAV vaccination coverage. Resumen Objetivos Evaluar la prevalencia de inmunidad frente al VHA en personas que viven con VIH así como el impacto de una intervención basada en la vacunación de pacientes seronegativos frente al VHA. Métodos Estudio con dos fases solapadas en el tiempo: 1) transversal de prevalencia de inmunidad frente al VHA en personas que viven con VIH seguidas en un hospital de tercer nivel, entre agosto de 2019 y el inicio de las medidas nacionales de contención de la epidemia por SARS-CoV-2, marzo de 2020. 2) Cuasiexperimental, con una intervención centrada en la vacunación frente a VHA de pacientes seronegativos, en la unidad responsable de esta. Resultados Ciento once (17%, [95% IC, 14-20%]) de los 656 pacientes incluidos eran seronegativos frente al VHA. Las principales causas de la ausencia de inmunidad fueron: 69 (62% [95% IC, 52-71%]) individuos no derivados a la unidad responsable de la vacunación;26 pacientes (23% [95% CI, 16-32%]) no completaron el esquema vacunal. Tras la intervención, 96 (15% [95% IC, 12-18%]) pacientes continuaron siendo seronegativos frente al VHA (comparada con la prevalencia basal, p=0,256), 42 (18% [95% IC, 13-23%]) eran HSH. Las principales causas de la ausencia de inmunidad fueron: 26 (23% [95% IC, 15-32%]) individuos presentaron fallos de adherencia al circuito vacunal;34 (33% [95% IC, 24-43%]) pacientes habían recibido una sola dosis;22 (22% [95% IC, 14-31%]) seguían sin una primera valoración por parte de la unidad responsable de la vacunación. Conclusiones Una proporción considerable de personas que viven con VIH, particularmente HSH, sigue siendo susceptible a la infección por VHA. La derivación sistemática a la unidad responsable de la vacunación se traduce en modestos incrementos de la prevalencia de inmunidad. Son necesarias nuevas estrategias para aumentar la cobertura vacunal.

Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study.

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis.

Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. METHODS: We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany (n = 135), Spain (n = 133), Switzerland (n = 20) and the United States (n = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID-19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). FINDINGS: We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted p-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. INTERPRETATION: HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2. FUNDING: Funded by Roche Sequencing Solutions, Inc.

Incidence of and factors associated with SARS-CoV-2 infection among people living with HIV in Southern Spain after one year of pandemic.

Whether people living with HIV (PLWH) are at greater risk of acquiring SARS-CoV-2 infection is currently unknown. Prospective serologic studies may allow seroincidence analyses, where all infections are accurately identified. Because of this, we evaluated the incidence of associated factors with and the clinical outcome of SARS-CoV-2 infection in PLWH in Southern Spain. This prospective cohort study included PLWH from a Tertiary University Hospital in Southern Spain. Patients were enrolled in the study if (1) they had attended as outpatients our Unit from 1 August 2019 to 8 February 2020 and (2) had two subsequent evaluations from 9 February 2020 to 4 March 2021. SARS-CoV-2 infections were diagnosed by PCR, antigen detection or serology. Seven hundred and nine PLWH were included in the study. Of them, 55 [7.8%, 95% confidence interval (95% CI) 5.9%-9.9%] patients developed SARS-CoV-2 infection. Between 18 May and 29 November 2020, the rate of seroconversion was 5.3% (95% CI: 3.1%-9.0%) for the general population in the area of Seville and 2.3% (95% CI: 1.3%-2.6%) for PLWH in this study (p = .001). After multivariable analysis, adjusted by age, sex, and risk factors for HIV infection, active tobacco use and CDC stage, active tobacco smoking was the only factor independently associated with lower risk of SARS-Cov-2 infection [Incidence rate ratio: 0.29 (95% CI 0.16-0.55) p < .001]. In conclusion, the incidence of SARS-CoV-2 infection among PLWH in Southern Spain during the ongoing pandemic was lower than that reported for the general population in the same area.

Similar incidence of coronavirus disease 2019 (COVID-19) in patients with rheumatic diseases with and without hydroxychloroquine therapy.

BACKGROUND: Hydroxychloroquine is not efficacious as post-exposure prophylaxis against coronavirus disease 2019 (COVID-19). It is not known whether as pre-exposure prophylaxis it may prevent COVID-19. OBJECTIVE: To compare the incidence of COVID-19 in Spanish patients with autoimmune rheumatic diseases treated with and without hydroxychloroquine. PATIENTS AND METHODS: Retrospective electronic record review, from February 27th to June 21st, 2020, of patients with autoimmune inflammatory diseases followed at two academic tertiary care hospitals in Seville, Spain. The cumulative incidence of confirmed COVID-19, by PCR or serology, was compared between patients with and without hydroxychloroquine as part of their treatment of autoimmune inflammatory diseases. RESULTS: Among 722 included patients, 290 (40%) were receiving hydroxychloroquine. During the seventeen-week study period, 10 (3.4% [95% CI: 1.7%-6.7%] cases of COVID-19 were registered among patients with hydroxychloroquine and 13 (3.0% [1.6%-5.1%]) (p = 0.565) in those without hydroxychloroquine. COVID-19 was diagnosed by PCR in four (1.4%, 95% CI 0.38%-3.5%) subject with hydroxychloroquine and six (1.4%, 95% CI 0.5%-3.0%) without hydroxychloroquine (p = 0.697). Three patients on hydroxychloroquine and four patients without hydroxychloroquine were admitted to the hospital, none of them required to be transferred to the intensive care unit and no patient died during the episode. CONCLUSIONS: The incidence and severity of COVID-19 among patients with autoimmune rheumatic diseases with and without hydroxychloroquine was not significantly different.

The Other Side of SARS-CoV-2 Infection: Neurological Sequelae in Patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the globe causing coronavirus disease 2019 (COVID-19). Because it affects the respiratory system, common symptoms are cough and breathing difficulties with fever and fatigue. Also, some cases progress to acute respiratory distress syndrome (ARDS). The acute phase of COVID-19 has been also related to nervous system symptoms, including loss of taste and smell as well as encephalitis and cerebrovascular disorders. However, it remains unclear if neurological complications are due to the direct viral infection of the nervous system, or they appear as a consequence of the immune reaction against the virus in patients who presented pre-existing deficits or had a certain detrimental immune response. Importantly, the medium and long-term consequences of the infection by SARS-CoV-2 in the nervous system remain at present unknown. This review article aims to give an overview of the current neurological symptoms associated with COVID-19, as well as attempting to provide an insight beyond the acute affectation.

High rate of major drug-drug interactions of lopinavir-ritonavir for COVID-19 treatment.

The impact of drug-drug interactions (DDI) between ritonavir-boosted lopinavir (LPV-r) to treat patients with coronavirus disease 2019 (COVID-19) and commonly used drugs in clinical practice is not well-known. Thus, we evaluated the rate and severity of DDI between LPV-r for COVID-19 treatment and concomitant medications. This was a cross-sectional study including all individuals diagnosed of SARS-CoV-2 infection treated with LPV-r and attended at a single center in Southern Spain (March 1st to April 30th, 2020). The frequency [95% confidence interval (95% CI)] of potential and major DDI were calculated. Overall, 469 patients were diagnosed of COVID-19, 125 (27%) of them were prescribed LPV-r. LPV-r had potential DDI with concomitant medications in 97 (78%, 95% CI 69-85%) patients, and in 33 (26%, 95% CI 19-35%) individuals showed major DDI. Twelve (36%) patients with major DDI and 14 (15%) individuals without major DDI died (p = 0.010). After adjustment, only the Charlson index was independently associated with death [adjusted OR (95% CI) for Charlson index ≥ 5: 85 (10-731), p < 0.001]. LPV-r was discontinued due to side effects in 31 (25%) patients. Management by the Infectious Diseases Unit was associated with a lower likelihood of major DDI [adjusted odds ratio (95% CI): 0.14 (0.04-0.53), p = 0.003). In conclusion, a high frequency of DDI between LPV-r for treating COVID-19 and concomitant medications was found, including major DDI. Patients with major DDI showed worse outcomes, but this association was explained by the older age and comorbidities. Patients managed by the Infectious Diseases Unit had lower risk of major DDI.