SARS-CoV-2 vaccine response and rate of breakthrough infection in patients with hematological disorders.

BACKGROUND: The clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has not yet been established. PATIENTS AND METHODS: A prospective multicenter registry-based cohort study conducted from December 2020 to December 2021 by the Spanish transplant and cell therapy group was used to analyze the relationship of antibody response at 3-6 weeks after full vaccination (2 doses) with breakthrough SARS-CoV-2 infection in 1394 patients with hematological disorders. RESULTS: At a median follow-up of 165 days after complete immunization, 37 out of 1394 (2.6%) developed breakthrough SARS-CoV-2 infection at median of 77 days (range 7-195) after full vaccination. The incidence rate was 6.39 per 100 persons-year. Most patients were asymptomatic (19/37, 51.4%), whereas only 19% developed pneumonia. The mortality rate was 8%. Lack of detectable antibodies at 3-6 weeks after full vaccination was the only variable associated with breakthrough infection in multivariate logistic regression analysis (Odds Ratio 2.35, 95% confidence interval 1.2-4.6, p = 0.012). Median antibody titers were lower in cases than in non-cases [1.83 binding antibody units (BAU)/mL (range 0-4854.93) vs 730.81 BAU/mL (range 0-56,800), respectively (p = 0.007)]. We identified 250 BAU/mL as a cutoff above which incidence and severity of the infection were significantly lower. CONCLUSIONS: Our study highlights the benefit of developing an antibody response in these highly immunosuppressed patients. Level of antibody titers at 3 to 6 weeks after 2-dose vaccination links with protection against both breakthrough infection and severe disease for non-Omicron SARS-CoV-2 variants.

SMART-LAMP: A Smartphone-Operated Handheld Device for Real-Time Colorimetric Point-of-Care Diagnosis of Infectious Diseases via Loop-Mediated Isothermal Amplification.

Nucleic acid amplification diagnostics offer outstanding features of sensitivity and specificity. However, they still lack speed and robustness, require extensive infrastructure, and are neither affordable nor user-friendly. Thus, they have not been extensively applied in point-of-care diagnostics, particularly in low-resource settings. In this work, we have combined the loop-mediated isothermal amplification (LAMP) technology with a handheld portable device (SMART-LAMP) developed to perform real-time isothermal nucleic acid amplification reactions, based on simple colorimetric measurements, all of which are Bluetooth-controlled by a dedicated smartphone app. We have validated its diagnostic utility regarding different infectious diseases, including Schistosomiasis, Strongyloidiasis, and COVID-19, and analyzed clinical samples from suspected COVID-19 patients. Finally, we have proved that the combination of long-term stabilized LAMP master mixes, stored and transported at room temperature with our developed SMART-LAMP device, provides an improvement towards true point-of-care diagnosis of infectious diseases in settings with limited infrastructure. Our proposal could be easily adapted to the diagnosis of other infectious diseases.

How Has the Aspergillosis Case Fatality Rate Changed over the Last Two Decades in Spain?

(1) Background: Aspergillus produces high morbidity and mortality, especially in at-risk populations. In Spain, the evolution of mortality in recent years due to this fungus is not well established. The aim of this study was to estimate the case fatality rate of aspergillosis in inpatients from 1997 to 2017 in Spain. (2) Methodology: A retrospective descriptive study was conducted with records of inpatients admitted to the National Health System with a diagnosis of aspergillosis. (3) Principal findings: Of 32,960 aspergillosis inpatients, 24.5% of deaths were registered, and 71% of the patients who died were men. The percentage of deaths increased progressively with age. The case fatality rate progressively decreased over the period, from 25.4 and 27.8% in 1997-1998 to values of 20.6 and 20.8% in 2016 and 2017. Influenza and pneumonia occurrence/association significantly increased case fatality rates in all cases. (4) Conclusions: Our study shows that lethality significantly decreased in the last two decades despite the increase in cases. This highlights the fact that patients with solid and/or hematological cancer do not have a much higher mortality rate than the group of patients with pneumonia or influenza alone, these two factors being the ones that cause the highest CFRs. We also need studies that analyze the causes of mortality to decrease it and studies that evaluate the impact of COVID-19.

Detection of SARS-CoV-2 RNA in Urine by RT-LAMP: A Very Rare Finding.

Detection of SARS-CoV-2 is routinely performed in naso/oropharyngeal swabs samples from patients via RT-qPCR. The RT-LAMP technology has also been used for viral RNA detection in respiratory specimens with both high sensitivity and specificity. Recently, we developed a novel RT-LAMP test for SARS-CoV-2 RNA detection in nasopharyngeal swab specimens (named, N15-RT-LAMP) that can be performed as a single-tube colorimetric method, in a real-time platform, and as dry-LAMP. To date, there has been very little success in detecting SARS-CoV-2 RNA in urine by RT-qPCR, and the information regarding urine viral excretion is still scarce and not comprehensive. Here, we tested our N15-RT-LAMP on the urine of 300 patients admitted to the Hospital of Salamanca, Spain with clinical suspicion of COVID-19, who had a nasopharyngeal swab RT-qPCR-positive (n = 100), negative (n = 100), and positive with disease recovery (n = 100) result. The positive group was also tested by RT-qPCR for comparison to N15-RT-LAMP. Only a 4% positivity rate was found in the positive group via colorimetric N15-RT-LAMP and 2% via RT-qPCR. Our results are consistent with those obtained in other studies that the presence of SARS-CoV-2 RNA in urine is a very rare finding. The absence of SARS-CoV-2 RNA in urine in the recovered patients might suggest that the urinary route is very rarely used for viral particle clearance.

SARS-CoV-2-reactive antibody detection after SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: Prospective survey from the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group.

This is a multicenter prospective observational study that included a large cohort (n = 397) of allogeneic (allo-HSCT; (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3-6 weeks after complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from February 1, 2021, to July 20, 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of the recipients (93%) were vaccinated more than 1 year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia < 1 × 109 /ml (odds ratio [OR] 0.33, 95% confidence interval [95% CI] 0.16-0.69, p = .003), active graft versus host disease (GvHD; OR 0.51, 95% CI 0.27-0.98, p = .04) and vaccination within the first year of transplant (OR 0.3, 95% CI 0.15-0.9, p = .04) associated with lower antibody detection whereas. In ASCT, non-Hodgkin's lymphoma (NHL; OR 0.09, 95% CI 0.02-0.44, p = .003) and active corticosteroid therapy (OR 0.2, 95% CI 0.02-0.87, p = .03) were associated with lower detection rate. We report an encouraging rate of SARS-CoV-2-reactive antibodies detection in these severe immunocompromised patients. Lymphopenia, GvHD, the timing of vaccine, and NHL and corticosteroids therapy should be considered in allo-HSCT and ASCT, respectively, to identify candidates for SARS-CoV-2 antibodies monitoring.

Influence of the drugs used in migrant patients with severe acute respiratory syndrome coronavirus 2 and the development of symptomatic strongyloidiasis.

BACKGROUND: The use of dexamethasone in patients infected with Strongyloides stercoralis can cause severe complications. It is necessary to investigate the relationship between coronavirus disease 2019 (COVID-19) and strongyloidiasis infection. METHODS: A retrospective, longitudinal, descriptive study was undertaken to review all patients admitted with a diagnosis of COVID-19 infection at the Complejo Asistencial Universitario de Salamanca, Spain, during 1 March-31 December 2020. RESULTS: A total of 2567 patients received a diagnosis of COVID-19. Eighty-six patients from endemic areas were included. Seven patients had strongyloidiasis. Five patients were female. The mean age (±SD) was 39 (±10.8) y. Six patients were Latin-American and only one patient was from Africa. Six patients had previous symptoms compatible with strongyloidiasis infections. Only three patients received dexamethasone (6 mg once daily) for 10 d. In all cases, the clinical courses of the patients were satisfactory. No patient died or was admitted to the ICU. CONCLUSIONS: Screening programmes using serological techniques should be implemented in COVID-19 patients to prevent strongyloidiasis. Our study suggested that drugs used against COVID-19 in patients with strongyloidiasis did not affect the evolution of the disease. However, more studies are necessary to elucidate the role of dexamethasone in COVID-19 patients infected with Strongyloides.

Seroprevalence of SARS-CoV-2 Antibodies and Factors Associated with Seropositivity at the University of Salamanca: The DIANCUSAL Study.

BACKGROUND: Systematic screening for antibodies against SARS-CoV-2 is a crucial tool for surveillance of the COVID-19 pandemic. The University of Salamanca (USAL) in Spain designed a project called "DIANCUSAL" (Diagnosis of New Coronavirus, COVID-19, in University of Salamanca) to measure antibodies against SARS-CoV-2 among its ~34,000 students and academic staff, as the influence of the university community in the spread of the SARS-CoV-2 pandemic in the city of Salamanca and neighboring towns hosting USAL campuses could be substantial. OBJECTIVE: The aim of this study was to estimate the prevalence of SARS-CoV-2 antibodies among USAL students, professors and staff and to evaluate the demographic, academic, clinical and lifestyle and behavioral factors related to seropositivity. METHODOLOGY: The DIANCUSAL study is an ongoing university population-based cross-sectional study, with the work described herein conducted from July-October 2020. All USAL students, professors and staff were invited to complete an anonymized questionnaire. Seroprevalence of anti-SARS-CoV-2 antibodies was detected and quantified by using chemiluminescent assays for IgG and IgM. PRINCIPAL FINDINGS: A total of 8197 (24.71%) participants were included. The mean age was 31.4 (14.5 SD) years, and 66.0% of the participants were female. The seroprevalence was 8.25% overall and was highest for students from the education campus (12.5%) and professors from the biomedical campus (12.6%), with significant differences among faculties (p = 0.006). Based on the questionnaire, loss of smell and fever were the symptoms most strongly associated with seropositivity, and 22.6% of seropositive participants were asymptomatic. Social distancing was the most effective hygiene measure (p = 0.0007). There were significant differences in seroprevalence between participants with and without household exposure to SARS-CoV-2 (p = 0.0000), but not between students who lived in private homes and those who lived in dormitories. IgG antibodies decreased over time in the participants with confirmed self-reported COVID-19 diagnoses. CONCLUSIONS: The analysis revealed an overall 8.25% seroprevalence at the end of October 2020, with a higher seroprevalence in students than in staff. Thus, there is no need for tailored measures for the USAL community as the official average seroprevalence in the area was similar (7.8% at 22 June and 12.4 at 15 November of 2020). Instead, USAL members should comply with public health measures.