Kinetics of humoral immune response over 17 months of COVID-19 pandemic in a large cohort of healthcare workers in Spain: the ProHEpiC-19 study.

BACKGROUND: Understanding the immune response to the SARS-CoV-2 virus is critical for efficient monitoring and control strategies. The ProHEpic-19 cohort provides a fine-grained description of the kinetics of antibodies after SARS-CoV-2 infection with an exceptional resolution over 17 months. METHODS: We established a cohort of 769 healthcare workers including healthy and infected with SARS-CoV-2 in northern Barcelona to determine the kinetics of the IgM against the nucleocapsid (N) and the IgG against the N and spike (S) of SARS-CoV-2 in infected healthcare workers. The study period was from 5 May 2020 to 11 November 2021.We used non-linear mixed models to investigate the kinetics of IgG and IgM measured at nine time points over 17 months from the date of diagnosis. The model included factors of time, gender, and disease severity (asymptomatic, mild-moderate, severe-critical) to assess their effects and their interactions. FINDINGS: 474 of the 769 participants (61.6%) became infected with SARS-CoV-2. Significant effects of gender and disease severity were found for the levels of all three antibodies. Median IgM(N) levels were already below the positivity threshold in patients with asymptomatic and mild-moderate disease at day 270 after the diagnosis, while IgG(N and S) levels remained positive at least until days 450 and 270, respectively. Kinetic modelling showed a general rise in both IgM(N) and IgG(N) levels up to day 30, followed by a decay with a rate depending on disease severity. IgG(S) levels remained relatively constant from day 15 over time. INTERPRETATION: IgM(N) and IgG(N, S) SARS-CoV-2 antibodies showed a heterogeneous kinetics over the 17 months. Only the IgG(S) showed a stable increase, and the levels and the kinetics of antibodies varied according to disease severity. The kinetics of IgM and IgG observed over a year also varied by clinical spectrum can be very useful for public health policies around vaccination criteria in adult population. FUNDING: Regional Ministry of Health of the Generalitat de Catalunya (Call COVID19-PoC SLT16_04; NCT04885478).

Follow up of the Humoral Response in Healthcare Workers after the Administration of Two Dose of the Anti SARS-CoV-2 Vaccines-Effectiveness in Delta Variant Breakthrough Infections.

The implementation of vaccination among healthcare workers (HCWs) allowed the management of the pandemic in a manner that differed from that in the first waves. It has been demonstrated that the mRNA vaccines elicit good humoral responses but that there are still breakthrough infections. In summer 2021, a fifth wave emerged, despite the good coverage of HCWs in Spain. We aimed to study the SARS-CoV-2 IgG antibody levels as a marker to predict the possibility of Delta variant infections after vaccination after a seroepidemiological campaign. Of the 5000 participants, a total of 4902 (98.04%) showed a positive result in the serological anti-S test and only 98 (1.96%) were negative. Among the 4368 fully vaccinated participants, only in five cases was the serology negative. Of the total number of participants that received antibody results during the study, 162 were PCR positive in the subsequent two months. Among these, 151 were fully vaccinated (two doses). Significant differences between antibody BAU/mL levels were found between PCR positive and non-PCR positive participants (p < 0.01). The median of BAU/mL was higher in those vaccinated patients with no infection (1260 BAU/mL; 465−2080) versus infected patients (661 BAU/mL; 361−2080). These data support the idea that vaccines play an important role in the control of the pandemic, especially among HCWs at the time of the Delta variant circulation. More studies with other variants of concern must be performed in order to establish a correlation between the levels of IgG and the new infections.

Seroprevalence of SARS-CoV-2 IgG specific antibodies among healthcare workers in the Northern Metropolitan Area of Barcelona, Spain, after the first pandemic wave.

BACKGROUND: The rapid spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) around the world has caused a global pandemic, infecting millions of individuals, with an unprecedented impact in health care systems worldwide. Healthcare workers are one of the risk groups that need to be well protected, due to their strategic role in patient management, presently and in prevention of healthcare needs for future outbreaks. Here, we present the results of the first SARS-CoV-2 seroprevalence study in the Northern Metropolitan Area of Barcelona, Spain. METHODS: IgG SARS-CoV-2 antibodies were analyzed in serum samples from 7563 healthcare workers of the Northern Metropolitan Area of Barcelona. Samples were collected after the first pandemic wave (from May 4th to May 22nd, 2020) and were analyzed by automated chemiluminescence assays. All samples were tested for IgG anti-S1/S2. Participant samples with negative or equivocal results but with analytical signals above the limit of detection and/or previously confirmed COVID-19 diagnosis were also tested for IgG anti-Nucleocapsid. RESULTS: A total of 779 of 7563 (10.3%) healthcare workers were positive for anti-SARS-CoV-2 IgG (specific for either S1/S2 or N antigens). No significant differences were observed between those working at primary care or at the reference hospital. Interestingly, among 341 participants with a confirmed COVID-19 diagnosis, 36 (10.55%) tested negative for SARS-CoV-2 IgG (both S1/S2 and recombinant N antigen). CONCLUSION: Seroprevalence of anti-SARS-CoV-2 IgG in the healthcare workers of the North Metropolitan Area of Barcelona was higher than in the general population in the same geographical area. Safety measures have to be stressed in order to protect these essential workers from future pandemic waves.

Prevalence of Early Chronic Kidney Disease and Main Associated Factors in Spanish Population: Populational Study.

The aim of this study was to determine the prevalence of early chronic kidney disease (EKD) (stages 1 and 2) and the factors associated. This was a populational study including individuals from 18-75 years randomly selected from 18 Primary Healthcare centers in the area of Barcelonès Nord and Maresme (Catalunya, Spain). Variables: anamnesis, physical examination, blood pressure, and analysis. EKD was defined with by a glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 and albumin/creatinine ratio (ACR) ≥17 mg/g in men and ≥25 mg/g in women confirmed with two determinations. 2871 individuals: 43% men, mean age 55 years (19-75), 32.2% obese, 50.5% abdominal obesity, 21.1% hypertensive, and 10.6% diabetic. Prevalence of EKD: With one determination 157 individuals (5.5%), 110 men (9%) and 47 women (2.8%); with two determinations 109 individuals (3.8%), 85 men (7%), and 24 women (1.5%). Factors independently associated with the multivariate logistic regression model: Man (OR 3.35), blood pressure ≥ 135/85 mmHg (OR 2.29), BMI ≥ 30 kg/m2 (OR 2.48), glycemia ≥ 100 mg/dL (OR 1.73), smoker (OR 1.67) and age (OR 1.04). The prevalence varies if the diagnosis is established based on one or two analytical determinations, overestimated if only one determination is made and depends on the value chosen to define urine albumin excretion.

Urinary levels of regenerating protein Iα do not differentiate celiac patients and healthy subjects.

Celiac disease is an autoimmune disorder induced by gluten in genetically predisposed people. The discovery of new biomarkers may help in the diagnosis and follow-up of celiac patients. Regenerating islet-derived 1 alpha (REGIα)--a biomarker related to tissue regeneration--is increased in serum at the onset of the disease, decreasing after gluten-free diet (GFD). As REGIα is a 18 kDa soluble glycoprotein, it may be detected in urine samples, increasing in celiac patients. We have determined REGIα levels by ELISA. No differences were found among patients (onset or after GFD) and controls and no correlation exists among REGIα in sera and urine.

Pretransplant inflammation: a risk factor for delayed graft function?

BACKGROUND: Inflammation plays an important role in the pathogenesis of ischemic acute kidney injury (IAKI). In this study, we hypothesize that transplant recipients with pretransplant inflammation may have a greater chance of developing delayed graft function (DGF), an example of IAKI. PATIENTS AND METHODS: We analyzed 178 patients who had undergone their first transplant using cadaveric donors. Blood samples were extracted from transplant recipients prior to transplantation. C-reactive protein (CRP) (nephelometry); interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) (automatized enzyme chemiluminescence immunometric assay); and pregnancy-associated plasma protein A (PAPP-A) (enzyme-linked immunosorbent assay) were determined using the pretransplant blood samples. The risk factors analyzed included cold ischemia, type and time of dialysis, donor and recipient age and HLA compatibility. RESULTS: Sixty-one patients (34.3%) developed DGF. Pretransplant TNF-alpha (9.31 +/- 2.57 vs. 10.56 +/- 3.82 pg/mL; p=0.039) and PAPP-A (1.25 +/- 0.74 vs. 1.90 +/- 1.56 mU/L; p=0.002) were significantly elevated in the group of patients with DGF. Univariate analysis showed that PAPP-A, TNF-alpha, cold ischemia, type of dialysis (hemodialysis) and donor age were associated with DGF. Multivariate analysis showed that PAPP-A (p=0.006), cold ischemia (p=0.009) and type of dialysis (p=0.046) were independent risk factors for DGF. CONCLUSIONS: Pretransplant inflammation (TNF-alpha, PAPP-A) in transplant recipients could be a risk factor for the development of DGF.