Mycobacterium manresensis induces trained immunity in vitro.

The COVID-19 pandemic posed a global health crisis, with new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants weakening vaccine-driven protection. Trained immunity could help tackle COVID-19 disease. Our objective was to analyze whether heat-killed Mycobacterium manresensis (hkMm), an environmental mycobacterium, induces trained immunity and confers protection against SARS-CoV-2 infection. To this end, THP-1 cells and primary monocytes were trained with hkMm. The increased secretion of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1ß, and IL-10, metabolic activity, and changes in epigenetic marks suggested hkMm-induced trained immunity in vitro. Healthcare workers at risk of SARS-CoV-2 infection were enrolled into the MANRECOVID19 clinical trial (NCT04452773) and were administered Nyaditum resae (NR, containing hkMm) or placebo. No significant differences in monocyte inflammatory responses or the incidence of SARS-CoV-2 infection were found between the groups, although NR modified the profile of circulating immune cell populations. Our results show that M. manresensis induces trained immunity in vitro but not in vivo when orally administered as NR daily for 14 days.

Determinants of Anti-S Immune Response at 9 Months after COVID-19 Vaccination in a Multicentric European Cohort of Healthcare Workers-ORCHESTRA Project.

Background: The persistence of antibody levels after COVID-19 vaccination has public health relevance. We analyzed the determinants of quantitative serology at 9 months after vaccination in a multicenter cohort. Methods: We analyzed data on anti-SARS-CoV-2 spike antibody levels at 9 months from the first dose of vaccinated HCW from eight centers in Italy, Germany, Spain, Romania and Slovakia. Serological levels were log-transformed to account for the skewness of the distribution and normalized by dividing them by center-specific standard errors. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of one standard deviation of log antibody level and the corresponding 95% confidence interval (CI), and combined them in random-effects meta-analyses. Finally, we conducted a trend analysis of 1 to 7 months' serology within one cohort. Results: We included 20,216 HCW with up to two vaccine doses and showed that high antibody levels were associated with female sex (p = 0.01), age (RR = 0.87, 95% CI = 0.86-0.88 per 10-year increase), 10-day increase in time since last vaccine (RR = 0.97, 95% CI 0.97-0.98), previous infection (3.03, 95% CI = 2.92-3.13), two vaccine doses (RR = 1.22, 95% CI = 1.09-1.36), use of Spikevax (OR = 1.51, 95% CI = 1.39-1.64), Vaxzevria (OR = 0.57, 95% CI = 0.44-0.73) or heterologous vaccination (OR = 1.33, 95% CI = 1.12-1.57), compared to Comirnaty. The trend in the Bologna cohort, based on 3979 measurements, showed a decrease in mean standardized antibody level from 8.17 to 7.06 (1-7 months, p for trend 0.005). Conclusions: Our findings corroborate current knowledge on the determinants of COVID-19 vaccine-induced immunity and declining trend with time.

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).

Neurocognitive Profile of the Post-COVID Condition in Adults in Catalonia-A Mixed Method Prospective Cohort and Nested Case-Control Study: Study Protocol.

The diagnosis of the post-COVID condition is usually achieved by excluding other diseases; however, cognitive changes are often found in the post-COVID disorder. Therefore, monitoring and treating the recovery from the post-COVID condition is necessary to establish biomarkers to guide the diagnosis of symptoms, including cognitive impairment. Our study employs a prospected cohort and nested case-control design with mixed methods, including statistical analyses, interviews, and focus groups. Our main aim is to identify biomarkers (functional and structural neural changes, inflammatory and immune status, vascular and vestibular signs and symptoms) easily applied in primary care to detect cognitive changes in post-COVID cases. The results will open up a new line of research to inform diagnostic and therapeutic decisions with special considerations for cognitive impairment in the post-COVID condition.

Evaluation of a support system for health professionals confined by COVID-19.

OBJECTIVE: To evaluate the implementation of a telephone system in a department of Primary Care in Barcelona, Spain, supporting health professionals confined by COVID-19. METHODS: We conducted an observational, descriptive, cross-sectional study with confined professionals, between March 11 and May 31, 2020. We emailed a questionnaire with 18 closed-ended questions and one open-ended question and performed a descriptive analysis of the closed-ended answers and an analysis of the thematic content of the open-ended question. RESULTS: Thirty-nine hundred and ninety-eight professionals evaluated the system overall with a score of 6.54 on a scale of 1 to 10. The evaluation of the format of calls made in the support system had higher scores, while the psychological support unit and the coordination of the different groups had lower scores. The content analysis of the open-ended question provides explanatory arguments for the quantitative results. CONCLUSIONS: The study allowed a valid and reliable evaluation of the implementation of a support system for confined professionals, in addition to recognizing areas for improvement.

Low Levels of Few Micronutrients May Impact COVID-19 Disease Progression: An Observational Study on the First Wave.

We report an observational study performed between March and May 2020 in a Spanish university hospital during the SARS-CoV-2 pandemic. The main objective was to analyse the association between the levels of micronutrients in severe COVID-19 patients and their outcome. Adult patients with a positive polymerase-chain-reaction (PCR) for SARS-CoV-2 in the nasopharyngeal swab or in tracheal aspirate culture in the case of intubation were included. Micronutrient data were obtained from plasma analysis of a standard nutritional assessment performed within the first 24 h of hospital admission. Vitamins A, B6, C and E were analysed with HPLC methods; 25-OH-vitamin D by immunoassay and zinc by colorimetric measurements. One hundred and twenty patients were included. We found that 74.2% patients had low levels of zinc (normal levels >84 µg/dL) with a mean value of 63.5 (SD 13.5); 71.7% patients had low levels of vitamin A (normal levels >0.3 mg/L) with a mean value of 0.17 (SD 0.06); 42.5% patients had low levels of vitamin B6 (normal levels >3.6 ng/mL) with a mean value of 2.2 (SD 0.9); 100% patients had low levels of vitamin C (normal levels >0.4 mg/dL) with a mean value of 0.14 (SD 0.05); 74.3% patients had low values of vitamin D (normal levels >20 ng/mL) with mean value of 11.4 (SD 4.3); but only 5.8% of patients had low levels of vitamin E (normal levels >5 mg/L) with a mean value of 3.95 (SD 0.87). The variables associated with the need for ICU admission were low levels of zinc (standard error 0.566, 95% CI 0.086 to 0.790, p = 0.017), low levels of vitamin A (standard error 0.582, 95% CI 0.061 to 0.594, p = 0.004), age over 65 (standard error 0.018, 95% CI 0.917 to 0.985, p = 0.005) and male gender (standard error 0.458, 95% CI 1.004 to 6.040, p = 0.049). The only variable that was independently associated with the need for orotracheal intubation was low levels of vitamin A (standard error 0.58, 95% CI 0.042 to 0.405, p = 0.000). Conclusions: Low levels of vitamin A and zinc are associated with a greater need for admission to the ICU and orotracheal intubation. Patients older than 65 years had higher mortality. Randomized clinical trials are needed to examine whether micronutrient supplementation could be beneficial as an adjunctive treatment in COVID-19.

Impact of the COVID-19 Pandemic on Burnout in Primary Care Physicians in Catalonia.

BACKGROUND: Recent demands to raise the clinical quality, improve the patient experience, and decrease costs have progressively increased burnout among primary care physicians. This overstretched situation has been greatly aggravated since the onset of the COVID-19 pandemic. The aim of the study is to analyse the prevalence of burnout among primary care physicians and to assess the impact of the COVID-19 pandemic on burnout. METHODS: This was a multicentre longitudinal descriptive study of occupational factors and burnout before and since the start of the COVID-19 pandemic. In order to assess the impact of the pandemic on burnout in primary care physicians, two paired groups of physicians were compared using Wilcoxon's and McNemar's tests. RESULTS: In January 2019, 10% of primary care physicians scored high on all burnout domains. Seven months into the COVID-19 pandemic (October 2020), this percentage increased to 50%. Paired groups analysis showed unprecedented worsening due to the pandemic: emotional exhaustion, which already affected 55% of primary care physicians, jumped to 77%. CONCLUSIONS: Burnout is endemic among primary care physicians. It has been associated with lower patient satisfaction, reduced health outcomes, and increased costs. The COVID-19 pandemic has pushed burnout in primary care professionals to the edge.