Immunoglobulins in COVID-19 pneumonia: from the acute phase to the recovery phase.

BACKGROUND: COVID-19 pneumonia causes hyperinflammatory response that culminates in acute respiratory syndrome (ARDS) related to increased multiorgan dysfunction and mortality risk. Antiviral-neutralizing immunoglobulins production reflect the host humoral status and illness severity, and thus, immunoglobulin (Ig) circulating levels could be evidence of COVID-19 prognosis. METHODS: The relationship among circulating immunoglobulins (IgA, IgG, IgM) and COVID-19 pneumonia was evaluated using clinical information and blood samples in a COVID-19 cohort composed by 320 individuals recruited during the acute phase and followed up to 4 to 8 weeks (n = 252) from the Spanish first to fourth waves. RESULTS: COVID-19 pneumonia development depended on baseline Ig concentrations. Circulating IgA levels together with clinical features at acute phase was highly associated with COVID-19 pneumonia development. IgM was positively correlated with obesity (ρb = 0.156, P = 0.020), dyslipemia (ρb = 0.140, P = 0.029), COPD (ρb = 0.133, P = 0.037), cancer (ρb = 0.173, P = 0.007) and hypertension (ρb = 0.148, P = 0.020). Ig concentrations at recovery phase were related to COVID-19 treatments. CONCLUSIONS: Our results provide valuable information on the dynamics of immunoglobulins upon SARS-CoV-2 infection or other similar viruses.

Mitochondrial dysfunction, lipids metabolism, and amino acid biosynthesis are key pathways for COVID-19 recovery.

The metabolic alterations caused by SARS-CoV-2 infection reflect disease progression. To analyze molecules involved in these metabolic changes, a multiomics study was performed using plasma from 103 patients with different degrees of COVID-19 severity during the evolution of the infection. With the increased severity of COVID-19, changes in circulating proteomic, metabolomic, and lipidomic profiles increased. Notably, the group of severe and critical patients with high HRG and ChoE (20:3) and low alpha-ketoglutaric acid levels had a high chance of unfavorable disease evolution (AUC = 0.925). Consequently, patients with the worst prognosis presented alterations in the TCA cycle (mitochondrial dysfunction), lipid metabolism, amino acid biosynthesis, and coagulation. Our findings increase knowledge regarding how SARS-CoV-2 infection affects different metabolic pathways and help in understanding the future consequences of COVID-19 to identify potential therapeutic targets.

Fucosylated N-glycans as early biomarkers of COVID-19 severity.

Background: The pathological mechanisms of SARS-CoV-2 in humans remain unclear and the unpredictability of COVID-19 progression may be attributed to the absence of biomarkers that contribute to the prognosis of this disease. Therefore, the discovery of biomarkers is needed for reliable risk stratification and to identify patients who are more likely to progress to a critical stage. Methods: Aiming to identify new biomarkers we analysed N-glycan traits in plasma from 196 patients with COVID-19. Samples were classified into three groups according to their severity (mild, severe and critical) and obtained at diagnosis (baseline) and at 4 weeks of follow-up (postdiagnosis), to evaluate their behaviour through disease progression. N-glycans were released with PNGase F and labelled with Rapifluor-MS, followed by their analysis by LC-MS/MS. The Simglycan structural identification tool and Glycostore database were employed to predict the structure of glycans. Results: We determined that plasma from SARS-CoV-2-infected patients display different N-glycosylation profiles depending on the disease severity. Specifically, levels of fucosylation and galactosylation decreased with increasing severity and Fuc1Hex5HexNAc5 was identified as the most suitable biomarker to stratify patients at diagnosis and distinguish mild from critical outcomes. Conclusion: In this study we explored the global plasma glycosignature, reflecting the inflammatory state of the organs during the infectious disease. Our findings show the promising potential of glycans as biomarkers of COVID-19 severity.

Evaluation of five immunoassays and one lateral flow immunochromatography for anti-SARS-CoV-2 antibodies detection.

INTRODUCTION: In order to deal with the current pandemic caused by the novel SARS-CoV-2 coronavirus several serological immunoassays have been recently developed with the objective of being used as a complementary diagnostic tool and to support the RT-PCR technique currently considered the "gold-standard" method. However, these new assays need to be evaluated and validated. The purpose of this study was to assess the performance of five immunoassays (two ELISA and three CLIA assays) and one rapid immunochromatographic test for the detection of anti-SARS-CoV-2 antibodies. METHODS: Five semiquantitative immunoassays (MENARINI®, PALEX®, VIRCLIA®, ROCHE® and SIEMENS®) and one lateral flow rapid test (WONDFO®) were performed. A total of 124 samples were studied. Case serum samples (n=78) were obtained from COVID-19 patients confirmed by real-time RT-PCR/epidemiological-clinical-radiological criteria, and control non-SARS-CoV-2 samples (n=46) belonged to healthy healthcare workers involved in a seroprevalence study. RESULTS: Overall, the tests showed sensitivities around 70-90% and specificities greater than 95%, including the immunochromatographic test. In addition, we observed very good agreements among them, being better for the detection of IgG than for IgM antibodies (Cohen's kappa index of 0.95 for VIRCLIA® IgG with ROCHE®), as well as good diagnostic power of the tests as determined by the ROC curves. CONCLUSIONS: This study demonstrates the proper performance of the different immunoassays in order to be applied in the clinical practice as support in the diagnostic approach and in the development of vaccines and seroepidemiological studies of COVID-19.

Lipoprotein Profile in Immunological Non-Responders PLHIV after Antiretroviral Therapy Initiation.

Nuclear magnetic resonance (NMR)-based advanced lipoprotein tests have demonstrated that LDL and HDL particle numbers (LDL-P and HDL-P) are more powerful cardiovascular (CV) risk biomarkers than conventional cholesterol markers. Of interest, in people living with HIV (PLHIV), predictors of preclinical atherosclerosis and vascular dysfunction may be associated with impaired immune function. We previously stated that immunological non-responders (INR) were at higher CV risk than immunological responders (IR) before starting antiretroviral therapy (ART). Using Liposcale® tests, we characterized the lipoprotein profile from the same cohort of PLHIV at month 12 and month 36 after starting ART, intending to explore what happened with these indicators of CV risk during viral suppression. ART initiation dissipates the differences in lipoprotein-based CV risk markers between INR and IR, and only an increase in the number of HDL-P was found in INR + IR when compared to controls (p = 0.047). Interestingly, CD4+ T-cell counts negatively correlated with medium HDL-P concentrations at month 12 in all individuals (ρ = -0.335, p = 0.003). Longitudinal analyses showed an important increase in LDL-P and HDL-P at month 36 when compared to baseline values in both IR and INR. A proper balance between a proatherogenic and atherogenic environment may be related to the reconstitution of CD4+ T-cell count in PLHIV.

Susceptibility and risk of SARS-COV-2 infection among middle-aged and older adults in Tarragona area, Spain.

Objective: To analyse susceptibility/risk of suffering COVID-19 among adults with distinct underlying medical conditions. Methods: Population-based cohort study involving 79,083 individuals ≥50 years old in Tarragona (Southern Catalonia, Spain). Baseline cohort characteristics (demographic, pre-existing comorbidities, chronic medications and vaccinations history) were established at study start (01/03/2020) and primary outcome was laboratory-confirmed COVID-19 occurred among cohort members throughout 01/03/2020-30/06/2020. Risk of suffering COVID-19 was evaluated by Cox regression, estimating multivariable hazard ratios (HRs) adjusted for age/sex and pre-existing comorbidities. Results: Across study period, 536 laboratory-confirmed COVID-19 cases were observed (mean incidence: 39.5 cases per 100,000 persons-week). In multivariable-analysis, increasing age/years (HR: 1.01; 95% CI: 1.00-1.02), nursing-home (HR: 20.19; 95% CI: 15.98-25.51), neurological disease (HR: 1.35; 95% CI: 1.03-1.77), taking diuretics (HR: 1.39; 95% CI: 1.10-1.75), antiplatelet (HR: 1.36; 95% CI: 1.05-1.76) and benzodiazepines (HR: 1.24; 95% CI: 1.00-1.53) increased risk; conversely, taking angiotensin-converting-enzyme inhibitors (HR: 0.78; 95% CI: 0.61-1.00), angiotensin-receptor-blockers (HR: 0.70; 95%CI: 0.51-0.96) and statins (HR: 0.75; 95% CI: 0.58-0.96) were associated with reduced risk. Among community-dwelling individuals, pre-existing cancer, renal and cardiac disease appeared also related with an increased risk, whereas influenza vaccination was associated with reduced risk. Conclusion: In a setting with relatively low incidence of COVID-19 across the first wave of pandemic period, increasing age, nursing-home residence and multiple comorbidities appear predisposing for COVID-19 among middle-aged/older adults. Conversely, statins, angiotensin-receptor blockers/inhibitors and influenza vaccination were related with decreased risk.

Objetivo: Analizar incidencia y riesgo/susceptibilidad de sufrir la COVID-19 en adultos según distintas condiciones médicas preexistentes. Métodos: Cohorte de base poblacional que incluyó 79.083 personas ≥50 años en Tarragona. Características basales de la cohorte (edad/sexo, comorbilidades, medicaciones crónicas) se establecieron a 01-03-2020 y se registraron todos los casos de COVID-19 confirmada ocurridos en miembros de la cohorte hasta el 30-06-2020. Para estimación de riesgos se realizó regresión de Cox, con cálculo de hazard ratio (HR) ajustados por edad, sexo y comorbilidad. Resultados: Se observaron 536 casos confirmados de COVID-19 (incidencia media: 39,5 casos por 100.000 personas-semana). En análisis multivariante, edad/años (HR: 1,01; IC el 95%: 1,00-1,02; p = 0,050), estar institucionalizado/residencia (HR: 20,19; IC 95%: 15,98-25,51; p<0,001), enfermedad neurológica (HR: 1,35; IC el 95%: 1,03-1,77), diuréticos (HR: 1,39; IC 95%: 1,10-1,75), antiagregantes plaquetarios (HR: 1,36; IC 95%: 1,05-1,76) y benzodiacepinas (HR: 1,24; IC 95%: 1,00-1,53) se asociaron con un riesgo aumentado de la COVID-19 analizando la totalidad de la cohorte; contrariamente, medicación IECA (HR: 0,78; IC el 95%: 0,61-1,00), ARA-II (HR: 0,70; IC el 95%: 0,51-0,96) y estatinas (HR: 0,75; IC el 95%: 0,58-0,96) se asociaron con menor riesgo. Entre personas no institucionalizadas, cáncer, nefropatía y cardiopatía se asociaron con mayor riesgo y vacunación antigripal con menor riesgo. Conclusión: En un área con relativamente baja incidencia de COVID-19, edad, institucionalización y múltiples comorbilidades aumentaron el riesgo/susceptibilidad de sufrir la COVID-19. Contrariamente, estatinas, inhibidores del sistema renina-angiotensina y vacunación antigripal se asociaron con menor riesgo.

Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control.

Long-term elite controllers (LTECs) are a fascinating small subset of HIV individuals with viral and immunological HIV control in the long term that have been designated as models of an HIV functional cure. However, data on the LTEC phenotype are still scarce, and hence, the metabolomics and lipidomics signatures in the LTEC-extreme phenotype, LTECs with more than 10 years of viral and immunological HIV control, could be pivotal to finding the keys for functional HIV remission. Metabolomics and lipidomics analyses were performed using high-resolution mass spectrometry (ultra-high-performance liquid chromatography-electrospray ionization-quadrupole time of flight [UHPLC-(ESI) qTOF] in plasma samples of 13 patients defined as LTEC-extreme, a group of 20 LTECs that lost viral and/or immunological control during the follow-up study (LTEC-losing) and 9 EC patients with short-term viral and immunological control (less than 5 years; no-LTEC patients). Long-term viral and immunological HIV-1 control was found to be strongly associated with elevated tricarboxylic acid (TCA) cycle function. Interestingly, of the nine metabolites identified in the TCA cycle, α-ketoglutaric acid (p = 0.004), a metabolite implicated in the activation of the mTOR complex, a modulator of HIV latency and regulator of several biological processes, was found to be a key metabolite in the persistent control. On the other hand, a lipidomics panel combining 45 lipid species showed an optimal percentage of separation and an ability to differentiate LTEC-extreme from LTEC-losing, revealing that an elevated lipidomics plasma profile could be a predictive factor for the reignition of viral replication in LTEC individuals.

Resistin and IL-15 as Predictors of Invasive Mechanical Ventilation in COVID-19 Pneumonia Irrespective of the Presence of Obesity and Metabolic Syndrome.

The cytokine signature present in COVID-19 could provide information on the pathogenic mechanisms of the disease and could identify possible prognostic biomarkers and possible therapeutic targets. In this longitudinal work, we studied the clinical and biochemical parameters and circulating cytokine levels of 146 patients at the time of admission for COVID-19 and 4-6 weeks later. The main objective of this study was to determine whether basal cytokines could be early prognostic biomarkers of COVID-19, and also to analyze the impact of comorbidities, such as obesity or metabolic syndrome (MS), in the cytokine profile. The levels of most inflammatory cytokines were elevated on admission in relation to the level that was reached 4-6 weeks later, except for IL-1ß, which was lower on admission; these levels were irrespective of the presence of obesity or MS since the cytokine storm masks these inflammatory processes. Among the cytokines analyzed, those that correlated with a worse prognosis of COVID-19 were resistin, IL-6, IL-8, IL-15, MCP-1 and TNF-α. Specifically, resistin and IL-15 are the best early predictors of requiring invasive ventilation. Therefore, resistin and IL-15 should be included in the personalized treatment decision algorithm of patients with COVID-19.

Adipokines as New Biomarkers of Immune Recovery: Apelin Receptor, RBP4 and ZAG Are Related to CD4+ T-Cell Reconstitution in PLHIV on Suppressive Antiretroviral Therapy.

A significant proportion of people living with HIV (PLHIV) who successfully achieve virological suppression fail to recover CD4+ T-cell counts. Since adipose tissue has been discovered as a key immune organ, this study aimed to assess the role of adipokines in the HIV immunodiscordant response. This is a multicenter prospective study including 221 PLHIV starting the first antiretroviral therapy (ART) and classified according to baseline CD4+ T-cell counts/µL (controls > 200 cells/µL and cases ≤ 200 cells/µL). Immune failure recovery was considered when cases did not reach more than 250 CD4+ T cells/µL at 144 weeks (immunological nonresponders, INR). Circulating adipokine concentrations were longitudinally measured using enzyme-linked immunosorbent assays. At baseline, apelin receptor (APLNR) and zinc-alpha-2-glycoprotein (ZAG) concentrations were significantly lower in INRs than in immunological responders (p = 0.043 and p = 0.034), and they remained lower during all ART follow-up visits (p = 0.044 and p = 0.028 for APLNR, p = 0.038 and p = 0.010 for ZAG, at 48 and 144 weeks, respectively). ZAG levels positively correlated with retinol-binding protein 4 (RBP4) levels (p < 0.01), and low circulating RBP4 concentrations were related to a low CD4+ T-cell gain (p = 0.018 and p = 0.039 at 48 and 144 weeks, respectively). Multiple regression adjusted for clinical variables and adipokine concentrations confirmed both low APLNR and RBP4 as independent predictors for CD4+ T cells at 144 weeks (p < 0.001). In conclusion, low APLNR and RBP4 concentrations were associated with poor immune recovery in treated PLHIV and could be considered predictive biomarkers of a discordant immunological response.

Susceptibility and risk of SARS-COV-2 infection among middle-aged and older adults in Tarragona area, Spain.

OBJECTIVE: To analyse susceptibility/risk of suffering COVID-19 among adults with distinct underlying medical conditions. METHODS: Population-based cohort study involving 79,083 individuals ≥50 years old in Tarragona (Southern Catalonia, Spain). Baseline cohort characteristics (demographic, pre-existing comorbidities, chronic medications and vaccinations history) were established at study start (01/03/2020) and primary outcome was laboratory-confirmed COVID-19 occurred among cohort members throughout 01/03/2020-30/06/2020. Risk of suffering COVID-19 was evaluated by Cox regression, estimating multivariable hazard ratios (HRs) adjusted for age/sex and pre-existing comorbidities. RESULTS: Across study period, 536 laboratory-confirmed COVID-19 cases were observed (mean incidence: 39.5 cases per 100,000 persons-week). In multivariable-analysis, increasing age/years (HR: 1.01; 95% CI: 1.00-1.02), nursing-home (HR: 20.19; 95% CI: 15.98-25.51), neurological disease (HR: 1.35; 95% CI: 1.03-1.77), taking diuretics (HR: 1.39; 95% CI: 1.10-1.75), antiplatelet (HR: 1.36; 95% CI: 1.05-1.76) and benzodiazepines (HR: 1.24; 95% CI: 1.00-1.53) increased risk; conversely, taking angiotensin-converting-enzyme inhibitors (HR: 0.78; 95% CI: 0.61-1.00), angiotensin-receptor-blockers (HR: 0.70; 95%CI: 0.51-0.96) and statins (HR: 0.75; 95% CI: 0.58-0.96) were associated with reduced risk. Among community-dwelling individuals, pre-existing cancer, renal and cardiac disease appeared also related with an increased risk, whereas influenza vaccination was associated with reduced risk. CONCLUSION: In a setting with relatively low incidence of COVID-19 across the first wave of pandemic period, increasing age, nursing-home residence and multiple comorbidities appear predisposing for COVID-19 among middle-aged/older adults. Conversely, statins, angiotensin-receptor blockers/inhibitors and influenza vaccination were related with decreased risk.

Prognostic Value of Procalcitonin and C-Reactive Protein in 1608 Critically Ill Patients with Severe Influenza Pneumonia.

Background: Procalcitonin (PCT) and C-Reactive protein (CRP) are well-established sepsis biomarkers. The association of baseline PCT levels and mortality in pneumonia remains unclear, and we still do not know whether biomarkers levels could be related to the causative microorganism (GPC, GNB). The objective of this study is to address these issues. Methods: a retrospective observational cohort study was conducted in 184 Spanish ICUs (2009-2018). Results: 1608 patients with severe influenza pneumonia with PCT and CRP available levels on admission were included, 1186 with primary viral pneumonia (PVP) and 422 with bacterial Co-infection (BC). Those with BC presented higher PCT levels (4.25 [0.6-19.5] versus 0.6 [0.2-2.3]ng/mL) and CRP (36.7 [20.23-118] versus 28.05 [13.3-109]mg/dL) as compared to PVP (p < 0.001). Deceased patients had higher PCT (ng/mL) when compared with survivors, in PVP (0.82 [0.3-2.8]) versus 0.53 [0.19-2.1], p = 0.001) and BC (6.9 [0.93-28.5] versus 3.8 [0.5-17.37], p = 0.039). However, no significant association with mortality was observed in the multivariate analysis. The PCT levels (ng/mL) were significantly higher in polymicrobial infection (8.4) and GPC (6.9) when compared with GNB (1.2) and Aspergillus (1.7). The AUC-ROC of PCT for GPC was 0.67 and 0.32 for GNB. The AUROC of CRP was 0.56 for GPC and 0.39 for GNB. Conclusions: a single PCT/CRP value at ICU admission was not associated with mortality in severe influenza pneumonia. None of the biomarkers have enough discriminatory power to be used for predicting the causative microorganism of the co-infection.

Evaluation of five immunoassays and one lateral flow immunochromatography for anti-SARS-CoV-2 antibodies detection.

INTRODUCTION: In order to deal with the current pandemic caused by the novel SARS-CoV-2 coronavirus several serological immunoassays have been recently developed with the objective of being used as a complementary diagnostic tool and to support the RT-PCR technique currently considered the "gold-standard" method. However, these new assays need to be evaluated and validated. The purpose of this study was to assess the performance of five immunoassays (two ELISA and three CLIA assays) and one rapid immunochromatographic test for the detection of anti-SARS-CoV-2 antibodies. METHODS: Five semiquantitative immunoassays (MENARINI®, PALEX®, VIRCLIA®, ROCHE® and SIEMENS®) and one lateral flow rapid test (WONDFO®) were performed. A total of 124 samples were studied. Case serum samples (n=78) were obtained from COVID-19 patients confirmed by real-time RT-PCR/epidemiological-clinical-radiological criteria, and control non-SARS-CoV-2 samples (n=46) belonged to healthy healthcare workers involved in a seroprevalence study. RESULTS: Overall, the tests showed sensitivities around 70-90% and specificities greater than 95%, including the immunochromatographic test. In addition, we observed very good agreements among them, being better for the detection of IgG than for IgM antibodies (Cohen's kappa index of 0.95 for VIRCLIA® IgG with ROCHE®), as well as good diagnostic power of the tests as determined by the ROC curves. CONCLUSIONS: This study demonstrates the proper performance of the different immunoassays in order to be applied in the clinical practice as support in the diagnostic approach and in the development of vaccines and seroepidemiological studies of COVID-19.

Influence of prior comorbidities and chronic medications use on the risk of COVID-19 in adults: a population-based cohort study in Tarragona, Spain.

OBJECTIVE: To investigate possible relationships between pre-existing medical conditions (including common comorbidities and chronic medications) and risk for suffering COVID-19 disease in middle-aged and older adults. DESIGN: Population-based retrospective cohort study. SETTING: Twelve primary care centres (PCCs) in Tarragona (Spain). PARTICIPANTS: 79 083 people (77 676 community-dwelling and 1407 nursing-home residents), who were all individuals aged >50 years affiliated to the 12 participating PCCs. OUTCOMES: Baseline cohort characteristics (age, sex, vaccinations, comorbidities and chronic medications) were established at study start (1st. March 2020) and primary outcome was time to COVID-19 confirmed by PCR among cohort members throughout the epidemic period (from 1st. March 2020 to 23rd. May 2020). Risk for suffering COVID-19 was evaluated by Cox regression, estimating multivariable HRs adjusted for age, sex, comorbidities and medications use. RESULTS: During the study period, 2324 cohort members were PCR-tested, with 1944 negative and 380 positive results, which means an incidence of 480.5 PCR-confirmed COVID-19 cases per 100 000 persons-period. Assessing the total study cohort, only age (HR 1.02; 95% CI 1.01 to 1.03; p=0.002), nursing-home residence (HR 21.83; 95% CI 16.66 to 28.61; p<0.001) and receiving diuretics (HR 1.35; 95% CI 1.04 to 1.76; p=0.026) appeared independently associated with increased risk. Smoking (HR 0.62; 95% CI 0.41 to 0.93; p=0.022), ACE inhibitors (HR 0.68; 95% CI 0.47 to 0.99; p=0.046) and antihistamine (HR 0.47; 95% CI 0.22 to 1.01; p=0.052) were associated with a lower risk. Among community-dwelling individuals, cancer (HR 1.52; 95% CI 1.03 to 2.24; p=0.035), chronic respiratory disease (HR 1.82; 95% CI 1.08 to 3.07; p=0.025) and cardiac disease (HR 1.53; 95% CI 1.06 to 2.19; p=0.021) emerged to be also associated with an increased risk. Receiving ACE inhibitors (HR 0.66; 95% CI 0.44 to 0.99; p=0.046) and influenza vaccination (HR 0.63; 95% CI 0.44 to 0.91; p=0.012) was associated with decreased risk. CONCLUSION: Age, nursing-home residence and multiple comorbidities appear predisposing for COVID-19. Conversely, receiving ACE inhibitors, antihistamine and influenza vaccination could be protective, which should be closely investigated in further studies specifically focused on these concerns.

Use of distinct anti-hypertensive drugs and risk for COVID-19 among hypertensive people: A population-based cohort study in Southern Catalonia, Spain.

The use of some anti-hypertensive drugs in the current COVID-19 pandemic has become controversial. This study investigated possible relationships between anti-hypertensive medications use and COVID-19 infection risk in the ambulatory hypertensive population. This is a population-based retrospective cohort study involving 34 936 hypertensive adults >50 years in Tarragona (Southern Catalonia, Spain) who were retrospectively followed through pandemic period (from 01/03/2020 to 30/04/2020). Two data sets including demographic/clinical characteristics (comorbidities and cardiovascular medications use) and laboratory PCR codes for COVID-19 were linked to construct an anonymized research database. Cox regression was used to calculate multivariable hazard ratios (HRs) and estimate the risk of suffering COVID-19 infection. Across study period, 205 PCR-confirmed COVID-19 cases were observed, which means an overall incidence of 586.8 cases per 100 000 persons-period. In multivariable analyses, only age (HR: 1.03; 95% CI: 1.02-1.05; P < .001) and nursing home residence (HR: 19.60; 95% CI: 13.80-27.84; P < .001) appeared significantly associated with increased risk of COVID-19. Considering anti-hypertensive drugs, receiving diuretics (HR: 1.22; 95% CI: 0.90-1.67; P = .205), calcium channel blockers (HR: 1.29; 95%CI: 0.91-1.82; P = .148), beta-blockers (HR: 0.97; 95% CI: 0.68-1.37; P = .844), and angiotensin-converting enzyme inhibitors (HR: 0.83; 95% CI: 0.61-1.13; P = .238) did not significantly alter the risk of PCR-confirmed COVID-19, whereas receiving angiotensin II receptor blockers was associated with an almost statistically significant reduction risk (HR: 0.67; 95% CI: 0.44-1.01; P = .054). In conclusion, our data support that receiving renin-angiotensin-aldosterone system inhibitors does not predispose for suffering COVID-19 infection in ambulatory hypertensive people. Conversely, receiving angiotensin II receptor blockers could be related with a reduced risk.

[Evaluation of incidence and risk profile for suffering Covid-19 infection by underlying conditions among middle-aged and older adults in Tarragona.] / Evaluación de la incidencia y perfil de riesgo de Covid-19 según comorbilidad previa en adultos ≥50 años del área de Tarragona.

OBJECTIVE: Population-based data on the current Covid-19 pandemic is scarce. This study investigated incidence and risk to suffer Covid-19 by baseline underlying conditions in people ≥50 years in Tarragona region across march-april 2020. METHODS: Population-based retrospective cohort study involving 79,071 adults ≥50 years-old in Tarragona region (Southern Catalonia, Spain). Cohort characteristics (age, sex, residence, vaccinations history and comorbidities) were established at baseline, and Covid-19 cases occurring between 01/03/2020-30/04/2020 were registered. Cox regression analysis calculating Hazard ratios (HRs) adjusted by age, sex and comorbidities was used to estimate risk for Covid-19. RESULTS: Across study period, 1,547 cohort members were PCR tested (22.6% positive) and 367 were presumptive cases without PCR tested. Considering PCR-confirmed Covid-19, incidence (per 100,000 persons-period) was 441 overall (248, 141, 424, 1,303 and 3,135 in 50-59, 60-69, 70-79, 80-89 and ≥90 years-old, respectively; 380 in men and 497 in women; 259 in community-dwelling and 10,571 in nursing-home). By comorbidities, maximum incidence emerged among persons with neurological disease (2,723), atrial fibrillation (1,348), chronic renal failure (1,050), cardiac disease (856), respiratory disease (798) and diabetes (706). Lower incidence appeared in rheumatic diseases (230) and smokers (180). In multivariable analysis focused on community-dwelling individuals (N=77,671), only cardiac disease (HR: 1.47; 95% CI: 1.01-2.15; p=0.045) and respiratory disease (HR: 1.75; 95% CI: 1.00-3.02; p=0.051) were associated with an increased risk, whereas smoking (HR:0.43; 95% CI: 0.25-0.74; p=0.002) and influenza vaccinated (HR: 0.63; 95% CI: 0.43-0.92; p=0.015) appeared associated with a decreased risk. CONCLUSIONS: Apart of increasing age and nursing-home residence, chronic respiratory and cardiac disease appear at increased risk for suffering covid19. This study investigated population-based incidence of Covid-19 infection by underlying conditions among adults ≥50 years in Tarragona (Southern Catalonia, Spain) across two first months pandemic period.

OBJETIVO: Los datos clínico-epidemiológicos de base poblacional durante la actual pandemia de Covid-19 son escasos. Este estudio investigó la incidencia y riesgo de sufrir Covid-19 según condiciones basales subyacentes en la población ≥50 años de Tarragona durante marzo-abril 2020. METODOS: Estudio de cohortes retrospectivo que incluyó a 79.071 personas ≥50 años en el área de Tarragona. Se establecieron características basales de la cohorte (edad, sexo, residencia, vacunaciones y comorbilidades previas), y se registró la ocurrencia de Covid-19 entre 01/03/2020-30/04/2020. Para la estimación de riesgos se realizó regresión de Cox, con cálculo de Hazard ratios (HRs) ajustados por edad, sexo y comorbilidad. RESULTADOS: Se realizaron PCR-tests en 1.547 personas (22,6% positivos) y 367 fueron codificados como presuntos casos sin realizarse PCR-test. Considerando Covid-19 confirmada (PCR positivo), la incidencia (por 100.000 personas-periodo) fue de 441 (248, 141, 424, 1.303 y 3.135 en 50-59, 60-69, 70-79, 80-89 y ≥90 años, respectivamente; 380 en hombres frente a 497 en mujeres; 259 residentes en la comunidad respecto a 10.571 en institucionalizados). Según comorbilidades, las máximas incidencias aparecieron en enfermedad neurológica (2.723), fibrilación auricular (1.348), insuficiencia renal crónica (1.050), cardiopatía (856), enfermedad respiratoria (798) y diabetes (706). Menores incidencias aparecieron en enfermedad reumatológica (230) y fumadores (180). En personas no institucionalizadas (N=77.671), solo la enfermedad cardiaca (HR: 1,47; IC95%: 1,01-2,15; p=0,045) y respiratoria (HR: 1,75; IC95%: 1,00-3,02; p=0,051) se asociaron con incremento del riesgo, mientras que ser fumador (HR: 0,43; IC95%: 0,25-0,74; p=0,002) y vacunación antigripal en otoño previo (HR: 0,63; IC95%: 0,43-0,92; p=0,015) se asociaron con menor riesgo. CONCLUSIONES: Aparte de la edad y la institucionalización, la existencia de enfermedad respiratoria y/o cardiaca crónicas se asocia con una mayor incidencia de Covid-19 en adultos.

Carbapenemase-producing Pseudomonas aeruginosa in Spain: interregional dissemination of the high-risk clones ST175 and ST244 carrying blaVIM-2, blaVIM-1, blaIMP-8, blaVIM-20 and blaKPC-2.

Carbapenemase-producing (CP) Pseudomonas aeruginosa is rare compared with mutation-driven carbapenem-resistance, but this situation may be changing. A collection of CP P. aeruginosa isolates was characterized in this study. In 2016, 232 unduplicated carbapenem-resistant P. aeruginosa isolates, of which 71 (30.6%) carried carbapenemase genes, were submitted to the Spanish antibiotic reference laboratory and were further analysed by whole-genome sequencing (WGS). Of the 71 CP P. aeruginosa, 39 (54.9%) carried blaVIM-2, 14 (19.7%) blaVIM-1, 8 (11.3%) blaIMP-8, 6 (8.5%) blaVIM-20, 2 (2.8%) blaVIM-2 plus blaKPC-2, one (1.4%) blaIMP-13 and one (1.4%) blaVIM-1 plus blaIMP-18. Four sequence types (ST175, ST244, ST815 and ST155) encompassed 83.1% of the 71 CP P. aeruginosa; ST175 was detected in hospitals from seven provinces. Using core genome multilocus sequence typing (cgMLST), four clusters were detected: Cluster 1 included nine ST815/VIM-2 isolates; Cluster 2 included five ST175/VIM-2 isolates; Cluster 3 included seven ST244 isolates (five VIM-2 and two VIM-2 plus KPC-2); and Cluster 4 included 11 ST175 isolates (seven VIM-2 and four IMP-8). The average number of acquired resistance genes was significantly higher in the blaVIM-1-carying isolates (7.1 ± 0.94) than in the blaVIM-2-carrying isolates (4.5 ± 0.20). CP P. aeruginosa isolates are spreading in Spain, mainly due to the dissemination of high-risk clones such as ST175 and ST244 producing VIM and IMP carbapenemases. Emergence of CP P. aeruginosa is a cause of clinical and epidemiological concern.

Interregional spread in Spain of linezolid-resistant Enterococcus spp. isolates carrying the optrA and poxtA genes.

The emergence of linezolid-resistant Enterococcus spp. (LRE) due to transferable resistance determinants is a matter of concern. To understand the contribution of the plasmid-encoded optrA and poxtA genes to the emergence of LRE, clinical isolates from different Spanish hospitals submitted to the Spanish Reference Laboratory from 2015-2018 were analysed. Linezolid resistance mechanisms were screened in all isolates by PCR and sequencing. Genetic relatedness of Enterococcus spp. carrying optrA and poxtA was studied by PFGE and MLST. Antimicrobial susceptibility was tested by broth microdilution using EUCAST standards. A total of 97 LRE isolates were studied, in 94 (96.9%) of which at least one resistance determinant was detected; 84/97 isolates (86.6%) presented a single resistance mechanism as follows: 45/84 (53.6%) carried the optrA gene, 38/84 (45.2%) carried the G2576T mutation and 1/84 (1.2%) carried the poxtA gene. In addition, 5/97 isolates (5.2%) carried both optrA and the G2576T mutation and 5/97 (5.2%) carried both optrA and poxtA. The optrA gene was more frequent in Enterococcus faecalis (83.6%) than Enterococcus faecium (11.1%) and was mainly associated with community-acquired urinary tract infections. Carriage of the poxtA gene was more frequent in E. faecium (13.9%) than E. faecalis (1.6%). Among the optrA-positive E. faecalis isolates, two main clusters were detected by PFGE. These two clusters belonged to ST585 and ST480 and were distributed throughout 11 and 6 Spanish provinces, respectively. This is the first description of LRE carrying the poxtA gene in Spain, including the co-existence of optrA and poxtA in five isolates.