Persistent Immunity against SARS-CoV-2 in Individuals with Oncohematological Diseases Who Underwent Autologous or Allogeneic Stem Cell Transplantation after Vaccination.

The high morbimortality due to SARS-CoV-2 infection in oncohematological diseases (OHD) and hematopoietic stem cell transplant (HSCT) recipients in the pre-vaccine era has made vaccination a priority in this group. After HSCT, the immune responses against common vaccines such as tetanus, varicella, rubella, and polio may be lost. However, the loss of immunity developed by COVID-19 vaccination after HSCT has not been completely defined. In this study, both humoral and cellular immunity against SARS-CoV-2 were analyzed in 29 individuals with OHD who were vaccinated before receiving allogeneic (n = 11) or autologous (n = 18) HSCT. All participants had low but protective levels of neutralizing IgGs against SARS-CoV-2 after HSCT despite B-cell lymphopenia and immaturity. Although antibody-dependent cellular cytotoxicity was impaired, direct cellular cytotoxicity was similar to healthy donors in participants with autologous-HSCT, in contrast to individuals with allogeneic-HSCT, which severely deteriorated. No significant changes were observed in the immune response before and after HSCT. During follow-up, all reported post-HSCT SARS-CoV-2 infections were mild. This data emphasizes that COVID-19 vaccination is effective, necessary, and safe for individuals with OHD and also supports the persistence of some degree of immune protection after HSCT, at least in the short term, when patients cannot yet be revaccinated.

COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study

Simple Summary There are contradictory data about coronavirus disease (COVID-19) in patients with hematological malignancies. In this population-based study we evaluated severity and survival of unvaccinated patients with hematological malignancies (HM) and COVID-19 in the Madrid region, Spain, between early February 2020 and February 2021. Also, a comparison was made with non-cancer patients from the SEMI-COVID registry and post COVID-19 conditions were evaluated. Overall, 30-day mortality was 32.7%, with higher mortality among certain groups of patients (aged ≥ 60 years, presence of ≥ 3 comorbidities, diagnosis of AML/ALL, treatment with conventional chemotherapy within 30 days of COVID-19 diagnosis, recipients of systemic corticosteroids as COVID-19 therapy). Mortality rates were similar between earlier and later phases of the pandemic, not paralleling the reduction of mortality in non-cancer patients. Up to 27.3% patients had a post COVID-19 condition. These findings will be useful to understand COVID-19 morbidity and mortality in unvaccinated patients diagnosed with HM. Abstract Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February–June 2020;n = 769 (66%)) and later (July 2020–February 2021;n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11–0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77;2.01–3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34;0.22–0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12;0.81–1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.

COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study.

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February-June 2020; n = 769 (66%)) and later (July 2020-February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11-0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01-3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22-0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81-1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.

The impact of the Coronavirus disease 2019 on hospitalizations for coronary artery revascularization: results from California State Inpatient Database.

BACKGROUND: Coronavirus disease 2019 (COVID-19) outbreak has negatively impacted routine cardiovascular care. In this study, we assessed the impact of COVID-19 pandemic on percutaneous coronary artery intervention (PCI) and coronary artery bypass grafting (CABG) hospitalizations and outcomes using a large database. METHODS: The current study was a retrospective analysis of California State Inpatient Database (SID) during March-December of 2019 and 2020. All adult hospitalizations for coronary artery revascularization were included for the analysis. ICD-10-CM diagnosis and procedure codes were used for identifying hospitalizations and procedures. The primary outcome was inhospital mortality, and secondary outcomes were hospital length of stay, stroke, acute kidney injury, and mechanical ventilation. Propensity score match analysis was done to compare adverse clinical outcomes. RESULTS: PCI hospitalizations (relative decrease, 15.0%, P for trend <0.001) and CABG hospitalizations (relative decrease, 16.4%, P for trend <0.001) decreased from 2019 to 2020, while viral pneumonia hospitalizations increased (relative increase, 1751.6%, P for trend <0.001). Monthly PCI and CABG hospitalization showed decreasing trends from January 2019 to December 2020. Propensity score match analysis showed that the odds of inhospital mortality (OR, 1.12; 95% CI, 1.01-1.24), acute kidney injury (OR, 1.12; 95% CI, 1.06-1.17), and ARDS (OR, 1.89; 95% CI, 1.18-3.01) were higher among patients who received PCI in 2020. CONCLUSION: Results of our study indicate that initiatives such as encouraging patients to receive treatments and controlling the spread of COVID-19 should be instituted to improve PCI and CABG hospitalizations.

One-year breakthrough SARS-CoV-2 infection and correlates of protection in fully vaccinated hematological patients.

The long-term clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has been little explored. A prospective multicenter registry-based cohort study conducted from December 2020 to July 2022 by the Spanish Transplant and Cell Therapy group, was used to analyze the relationship of antibody response over time after full vaccination (at 3-6 weeks, 3, 6 and 12 months) (2 doses) and of booster doses with breakthrough SARS-CoV-2 infection in 1551 patients with hematological disorders. At a median follow-up of 388 days after complete immunization, 266 out of 1551 (17%) developed breakthrough SARS-CoV-2 infection at median of 86 days (range 7-391) after full vaccination. The cumulative incidence was 18% [95% confidence interval (C.I.), 16-20%]. Multivariate analysis identified higher incidence in chronic lymphocytic leukemia patients (29%) and with the use of corticosteroids (24.5%), whereas female sex (15.5%) and more than 1 year after last therapy (14%) were associated with a lower incidence (p < 0.05 for all comparisons). Median antibody titers at different time points were significantly lower in breakthrough cases than in non-cases. A serological titer cut-off of 250 BAU/mL was predictive of breakthrough infection and its severity. SARS-CoV-2 infection-related mortality was encouragingly low (1.9%) in our series. Our study describes the incidence of and risk factors for COVID-19 breakthrough infections during the initial vaccination and booster doses in the 2021 to mid-2022 period. The level of antibody titers at any time after 2-dose vaccination is strongly linked with protection against both breakthrough infection and severe disease, even with the Omicron SARS-CoV-2 variant.

Association between mortality and cardiovascular diseases in the vulnerable Mexican population: A cross-sectional retrospective study of the COVID-19 pandemic

Cardiovascular diseases (CVDs) continue to be the leading cause of death worldwide. Over the past couple of years and with the surge of the COVID-19 pandemic, mortality from CVDs has been slightly overshadowed by those due to COVID-19, although it was during the peak of the pandemic. In the present study, patients with CVDs (CVDs;n = 41,883) were analyzed to determine which comorbidities had the largest impact on overall patient mortality due to their association with both diseases (n = 3,637). Obesity, hypertension, and diabetes worsen health in patients diagnosed positive for COVID-19. Hence, they were included in the overview of all patients with CVD. Our findings showed that 1,697 deaths were attributable to diabetes (p < 0.001) and 987 deaths to obesity (p < 0.001). Lastly, 2,499 deaths were attributable to hypertension (p < 0.001). Using logistic regression modeling, we found that diabetes (OR: 1.744, p < 0.001) and hypertension (OR: 2.179, p < 0.001) significantly affected the mortality rate of patients. Hence, having a CVD diagnosis, with hypertension and/or diabetes, seems to increase the likelihood of complications, leading to death in patients diagnosed positive for COVID-19.

Strong Humoral but Not Cellular Immune Responses against SARS-CoV-2 in Individuals with Oncohematological Disease Who Were Treated with Rituximab before Receiving a Vaccine Booster.

The humoral immune response developed after receiving the full vaccination schedule against COVID-19 is impaired in individuals who received anti-CD20 therapy 6-9 months before vaccination. However, there is little information about the cellular immune responses elicited in these individuals. In this study, we analyzed the humoral and cellular immune responses in 18 individuals with hematological disease who received the last dose of rituximab 13.8 months (IQR 9.4-19) before the booster dose. One month after receiving the booster dose, the seroconversion rate in the rituximab-treated cohort increased from 83.3% to 88.9% and titers of specific IgGs against SARS-CoV-2 increased 1.53-fold (p = 0.0098), while the levels of neutralizing antibodies increased 3.03-fold (p = 0.0381). However, the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) from rituximab-treated individuals remained unchanged, and both antibody-dependent cellular cytotoxicity (ADCC) and direct cellular cytotoxicity (CDD) were reduced 1.7-fold (p = 0.0047) and 2.0-fold (p = 0.0086), respectively, in comparison with healthy donors. Breakthrough infections rate was higher in our cohort of rituximab-treated individuals (33.33%), although most of the infected patients (83.4%) developed a mild form of COVID-19. In conclusion, our findings confirm a benefit in the humoral, but not in the cellular, immune response in rituximab-treated individuals after receiving a booster dose of an mRNA-based vaccine against COVID-19.

Hospital Outcomes Among COVID-19 Hospitalizations With Myocarditis from the California State Inpatient Database.

Many case reports have indicated that myocarditis could be a prognostic factor for predicting morbidity and mortality among patients with COVID-19. In this study, using a large database we examined the association between myocarditis among COVID-19 hospitalizations and in-hospital mortality and other adverse hospital outcomes. The present study was a retrospective analysis of data collected in the California State Inpatient Database during 2020. All hospitalizations for COVID-19 were included in the analysis and grouped into those with and without myocarditis. The outcomes were in-hospital mortality, cardiac arrest, cardiogenic shock, mechanical ventilation, and acute respiratory distress syndrome. Propensity score matching, followed by conditional logistic regression, was performed to find the association between myocarditis and outcomes. Among 164,417 COVID-19 hospitalizations, 578 (0.4%) were with myocarditis. After propensity score matching, the rate of in-hospital mortality was significantly higher among COVID-19 hospitalizations with myocarditis (30.0% vs 17.5%, p <0.001). Survival analysis with log-rank test showed that 30-day survival rates were significantly lower among those with myocarditis (39.5% vs 46.3%, p <0.001). Conditional logistic regression analysis showed that the odds of cardiac arrest (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.16 to 3.14), cardiogenic shock (OR 4.13, 95% CI 2.14 to 7.99), mechanical ventilation (OR 3.30, 95% CI 2.47 to 4.41), and acute respiratory distress syndrome (OR 2.49, 95% CI 1.70 to 3.66) were significantly higher among those with myocarditis. Myocarditis was associated with greater rates of in-hospital mortality and adverse hospital outcomes among patients with COVID-19, and early suspicion is important for prompt diagnosis and management.

Early Cellular and Humoral Responses Developed in Oncohematological Patients after Vaccination with One Dose against COVID-19.

Individuals with oncohematological diseases (OHD) may develop an impaired immune response against vaccines due to the characteristics of the disease or to its treatment. Humoral response against SARS-CoV-2 has been described to be suboptimal in these patients, but the quality and efficiency of the cellular immune response has not been yet completely characterized. In this study, we analyzed the early humoral and cellular immune responses in individuals with different OHD after receiving one dose of an authorized vaccine against SARS-CoV-2. Humoral response, determined by antibodies titers and neutralizing capacity, was overall impaired in individuals with OHD, except for the cohort of chronic myeloid leukemia (CML), which showed higher levels of specific IgGs than healthy donors. Conversely, the specific direct cytotoxic cellular immunity response (DCC) against SARS-CoV-2, appeared to be enhanced, especially in individuals with CML and chronic lymphocytic leukemia (CLL). This increased cellular immune response, developed earlier than in healthy donors, showed a modest cytotoxic activity that was compensated by significantly increased numbers, likely due to the disease or its treatment. The analysis of the immune response through subsequent vaccine doses will help establish the real efficacy of COVID-19 vaccines in individuals with OHD.

Strong Cellular Immune Response, but Not Humoral, against SARS-CoV-2 in Oncohematological Patients with Autologous Stem Cell Transplantation after Natural Infection.

Oncohematological patients show a low immune response against SARS-CoV-2, both to natural infection and after vaccination. Most studies are focused on the analysis of the humoral response; therefore, the information available about the cellular immune response is limited. In this study, we analyzed the humoral and cellular immune responses in nine individuals who received chemotherapy for their oncohematological diseases, as well as consolidation with autologous stem cell transplantation (ASCT), after being naturally infected with SARS-CoV-2. All individuals had asymptomatic or mild COVID-19 and were not vaccinated against SARS-CoV-2. These results were compared with matched healthy individuals who also had mild COVID-19. The humoral response against SARS-CoV-2 was not detected in 6 of 9 oncohematological individuals prior to ASCT. The levels of antibodies and their neutralization capacity decreased after ASCT. Conversely, an enhanced cytotoxic activity against SARS-CoV-2-infected cells was observed after chemotherapy plus ASCT, mostly based on high levels of NK, NKT, and CD8+TCRγδ+ cell populations that were able to produce IFNγ and TNFα. These results highlight the importance of performing analyses not only to evaluate the levels of IgGs against SARS-CoV-2, but also to determine the quality of the cellular immune response developed during the immune reconstitution after ASCT.

Predicting the Entrepreneurial Behaviour of Starting Up a New Company: A Regional Study Using PLS-SEM and Data from the Global Entrepreneurship Monitor

It is essential to understand the variables that explain and predict the behaviour of starting up a new company in a regional context. This study aims to analyse the theoretical basis and predictive potential of the Global Entrepreneurship Monitor (GEM) data, considering the concerns and suggestions of other authors. In addition to an extensive literature review, a PLS-SEM methodology and data on variables and countries from the latest GEM report are used in this study. The results show that GEM reports have a sufficient theoretical foundation for quality studies in this field. In addition, a valid and reliable causal model is designed that includes all personal and contextual GEM variables. The hypotheses of the proposed model are based on the existing causal relationships in the literature, using GEM data in its formulation. The model is comprehensive and practical because it significantly predicts entrepreneurial behaviour, particularly entrepreneurial intention and action. The usefulness of this study is high, both for researchers, practitioners and institutions wishing to understand better and further promote entrepreneurial behaviour at a regional (country) level.

Parent's Perspective towards Child COVID-19 Vaccination: An Online Cross-Sectional Study in Mexico.

COVID-19 vaccination programs continue in child populations. Thus, parents' attitude towards COVID-19 vaccination of their children is crucial for these strategies to succeed. The present study derives from the application of an online COVID-19 Vaccine Acceptance & Hesitancy Questionnaire (COV-AHQ) in which we measure parent's hesitancy towards children's vaccination (section 4 of the COV-AHQ) and other significant factors. A logistic regression analysis with backward stepwise method was used to quantify the associations between factors and parent's hesitancy. According to the correlation analysis, the most representative factors predicting vaccine hesitancy/acceptance were positive attitude towards vaccination, parents believing that the COVID-19 vaccine will enhance the economic situation of the country, parents actively researching information, having the willingness to obtain the COVID-19 vaccine themselves, and the possibility of their children developing adverse effects. Our findings also showed that parents are highly interested in having their children vaccinated. Nonetheless, parents expressed high levels of concern involving their children in developing adverse effects from the vaccine. In addition, obtaining influenza immunization prompted interest in obtaining the COVID-19 vaccine, and younger-aged parents are much more concerned with having their children vaccinated. Therefore, in order to ensure successful vaccination programs, policymakers and health authorities should design strategies to gain confidence and provide security amongst the population, including giving continuous information about the benefits of vaccination and presenting the frequency of side effects to bring parents on board with vaccinating their children.

Systematic Genomic and Clinical Analysis of Severe Acute Respiratory Syndrome Coronavirus 2 Reinfections and Recurrences Involving the Same Strain.

Estimates of the burden of severe acute respiratory syndrome coronavirus 2 reinfections are limited by the scarcity of population-level studies incorporating genomic support. We conducted a systematic study of reinfections in Madrid, Spain, supported by genomic viral analysis and host genetic analysis, to cleanse laboratory errors and to discriminate between reinfections and recurrences involving the same strain. Among the 41,195 cases diagnosed (March 2020-March 2021), 93 (0.23%) had 2 positive reverse transcription PCR tests (55-346 days apart). After eliminating cases with specimens not stored, of suboptimal sequence quality, or belonging to different persons, we obtained valid data from 22 cases. Of those, 4 (0.01%) cases were recurrences involving the same strain; case-patients were 39-93 years of age, and 3 were immunosuppressed. Eighteen (0.04%) cases were reinfections; patients were 19-84 years of age, and most had no relevant clinical history. The second episode was more severe in 8 cases.

Different dynamics of mean SARS-CoV-2 RT-PCR Ct values between the first and second COVID-19 waves in the Madrid population.

SARS-CoV-2 RT-PCR cycle threshold values from 18,803 cases (2 March-4 October) in Madrid define three stages: (i) initial ten weeks with sustained reduction in viral load (Ct: 23.4-32.3), (ii) stability with low viral loads (Ct: 31.9-35.5) in the next nine weeks and (iii) sudden increase with progressive higher viral loads until reaching stability at high levels in the next twelve weeks, coinciding with an increased percentage of positive cases and reduced median age. These data indicate differential virological/epidemiological patterns between the first and second COVID-19 waves in Madrid.

SARS-CoV-2 B.1.1.7 Decline Is Not Driven by the Introduction of a More Successful Variant.

The SARS-CoV-2 variant of concern (VOC) Delta (B.617.2 lineage) displaced the predominant VOC Alpha (B.1.1.7 lineage) in the United Kingdom. In Madrid, recent start of the decline of predominant VOC Alpha suggested an equivalent phenomenon. However, 11 different variants, none overrepresented in frequency, occupied progressively over a period of 7 weeks the niche previously dominated by VOC Alpha. Only after these 7 weeks, VOC Delta started to emerge. Viral competition due to the entry of VOC Delta is not the major force driving the start of VOC Alpha decline in Madrid. IMPORTANCE Our data indicate that the dynamics of SARS-CoV-2 VOCs turnover in our setting differ from those proposed for other countries. A systematic genomic analysis, updated on a weekly basis, of representative randomly selected samples of SARS-CoV-2 circulating variants allowed us to define a lapse of 7 weeks between the start of VOC Alpha decline and the final emergence of VOC Delta. During this period, VOC Alpha showed a sustained decline, while 11 VOCs, variants of interest (VOIs), and other identified variants, none overrepresented, occupied the niche left by VOC Alpha. Only after these 7 weeks, emergence of VOC Delta occurred, indicating that viral competition involving VOC Delta was not the exclusive direct driving force behind the starting of VOC Alpha decline.

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.