Conclusion: A virtual discussion about the quantitative revolution’s legacy for past, present, and future

This chapter presents a virtual discussion about the quantitative revolution's legacy for past, present, and future by various authors. This virtual discussion was written during a time when actual in-person discussions were difficult due to COVID-19 and when the notion of an in-person meeting, such as the workshop, seemed impossible. Auantitative methods should be employed as much as possible so that the results can be measured and compared. Each day, conclusions based exclusively on field observations and analysis of examples become more contested due to the high degree of subjectivism and the impossibility of measuring the degree of generalization of the examples taken. A place-based narrative on the arrival of the quantitative revolution among Brazilian geographers reveals the crucial role of an international network of human and nonhuman actors responsible for disseminating new theories, methods, and techniques in geographical investigations. © 2022 selection and editorial matter, Ferenc Gyuris, Boris Michel and Katharina Paulus;individual chapters, the contributors.

COVID-19 Severity and Mortality after Vaccination against SARS-CoV-2 in Central Greece.

BACKGROUND: Vaccination against SARS-CoV-2 (COVID-19) has become crucial for limiting disease transmission and reducing its severity, hospitalizations and mortality; however, despite universal acceptance, vaccine hesitancy is still significant. In the present manuscript, we aim to assess COVID-19-attributed mortality after the prevalence of new variants of the virus (Delta and Omicron viral strains) and to evaluate the vaccination effect. METHODS: All patients that were hospitalized due to COVID-19 infection in the Respiratory Department of a tertiary referral center in central Greece between 1st of June 2021 and 1st of February 2022 were included in the present study. RESULTS: 760 consecutive patients were included in the study; 89 (11.7%) were diagnosed with severe COVID-19 and 220 (38.7%) patients were fully vaccinated. In logistic regression, increased age (aOR = 1.12, p < 0.001), male gender (aOR = 2.29, p = 0.013) and vaccination against SARS-CoV-2 virus (aOR = 0.2, p < 0.001) were associated with mortality attributed to COVID-19 with a statistically significant association. Moreover, increased age (aOR = 1.09, p < 0.001), male gender (aOR = 1.92, p = 0.025) and vaccination against SARS-CoV-2 virus (aOR = 0.25, p < 0.001) were statistically significantly associated with clinical severity of COVID-19 infection. However, when comparing the length of hospitalization between vaccinated and unvaccinated patients, the difference was not statistically significant between the two groups (p = 0.138). CONCLUSIONS: Vaccination against SARS-CoV-2 virus had a protective effect in terms of mortality and clinical severity of COVID-19 during the fourth wave of the pandemic in Central Greece. The national vaccination policy has to focus on vulnerable populations that are expected to benefit the most from the vaccine's protection.

For better or for worse: COVID-19 vaccination during or early after (immuno-) chemotherapy or hematopoietic progenitor cell transplantation

Background: Patients with hematologic conditions have a high mortality rate when infected with SARS-CoV-2 (Williamson, Nature 2020). Protection of this group from severe COVID-19 is therefore important. However, according to available vaccination guidelines, one should consider to postpone vaccination of patients on or early after chemotherapy, hematopoietic progenitor cell transplantation (HCT) or with graft versus host disease, because of anticipated poor efficacy. Based on previous (non-COVID-19) vaccination studies among hematology patients, we hypothesized that a significant group of patients may acquire sufficient protection following COVID-19 vaccination, despite disease and therapy related immunodeficiencies. Methods: We conducted a prospective cohort study with 17 cohorts of hematology patients of particular risk for severe COVID-19 who are considered to have no or limited benefit from vaccination. We evaluated humoral immune responses following 2 doses (28 days apart) of the mRNA-1273 vaccine (Moderna/Spikevax) in 722 patients, at baseline and 28 days after each vaccination as SARS-COV-2 S1- (spike)-specific serum IgG antibody concentrations by bead-based multiplex immune assay. The threshold for adequate antibody response is set at ≥300 binding antibody units (BAU)/ml according to the international WHO standard, and is associated with virus plaque reducing neutralization test titers of ≥40 PRNT 50. This study is registered as EudraCT 2021-001072-41, NL76768.029.21. Results: Patient cohorts and corresponding vaccine responses are depicted in Table 1. Vaccine efficacy, as measured by antibody concentration, 4 weeks after the 2nd mRNA-1273 vaccination was available for 691 out of 722 participants. The majority of patients (389/691;56%) obtained an S1 antibody titer that is considered adequate (≥300 BAU/ml). Twenty-nine percent of patients (198/691) did not seroconvert (S1 antibody titer <10 BAU/ml), while the remaining 15% (104/691) did seroconvert but not to sufficient levels (10-300 BAU/ml). Adequate responses were observed in the majority of patients with sickle cell disease using hydroxyurea, chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitor therapy, acute myeloid leukemia (AML) on or early after high dose chemotherapy, patients with myeloproliferative disorders on ruxolitinib, patients with multiple myeloma (MM), including those on daratumumab and those early after high-dose melphalan and autologous HCT, patients with untreated chronic lymphocytic leukemia (CLL), and patients with chronic GvHD. Insufficient or absent antibody responses were observed in the majority of AML patients receiving hypomethylating agents, CLL patients on ibrutinib, patients with B-cell non-Hodgkin's Lymphoma (NHL) during or shortly after rituximab-chemotherapy or following BEAM chemotherapy and autologous HCT, allogeneic HCT recipients <6 months after transplantation, and CAR-T cell therapy recipients. However, even in these low-responder groups considerable numbers of patients did mount sufficient antibody titers. In others, titers increased after each of both vaccinations, suggesting that booster vaccination may enhance antibody titers to sufficient levels (Figure 1). Conclusion: Vaccination with mRNA-1273 had significant efficacy in severely immunocompromised hematology patients. Adequate humoral immune responses after two dose vaccination were reached in the majority of patients receiving therapy for sickle cell disease, MPD, MM, CML and AML, in patients early after HCT and in patients with GvHD. We are currently evaluating clinical and immunologic parameters that correlate with sufficient antibody responses, pseudovirus neutralization and SARS-COV-2-specific B and T cell numbers, phenotype and function. Per study design, all participants with absent or insufficient antibody responses (<300 BAU/ml) will receive a booster vaccination 5 months after initial vaccination, and antibody responses to booster vaccinations will be presented as well. Unlike currently available guidelines, COVID-19 vaccination should not be postponed. Moreover, as antibody titers increased after each of both vaccinations, booster vaccination of patients with absent or insufficient antibody responses seems warranted. (Figure Presented) .

Vulnerability of ß-Thalassemia Heterozygotes to COVID-19: Results from a Cohort Study.

Background: The assignment of mortality risk from SARS-CoV-2 virus (COVID-19) to vulnerable patient groups is an important step toward containment of the pandemic. Methods: A total of 760 patients with a positive molecular test for SARS-CoV-2 who were unvaccinated against COVID-19 were recruited between 1 January and 30 June 2021. Patients were grouped by age; sex; and common morbidities, such as atrial fibrillation, chronic respiratory disease, coronary disease, diabetes type II, neoplasia, hypertension and ß-Thalassemia heterozygosity. As a primary endpoint, we assessed mortality risk from COVID-19, and as secondary endpoints, we considered clinical severity and need for Intense Care Unit (ICU) admission. Results: In multivariate analysis, male sex (p < 0.001, OR = 2.59), increasing age (p < 0.001, OR = 1.049), ß-Thalassemia heterozygosity (p = 0.001, OR = 2.41) and chronic respiratory disease (p = 0.018, OR = 1.84) were identified as risk factors associated with mortality due to COVID-19. Moreover, male sex (p < 0.001, OR = 1.98), increasing age (p < 0.001, OR = 1.052) and ß-Thalassemia heterozygosity (p = 0.001, OR = 2.59) were associated with clinical severity in logistic regression. Regarding ICU admission, the risk factors were identified as male sex (p = 0.002, OR = 1.99), chronic respiratory disease (p = 0.007, OR = 2.06) and hypertension (p < 0.001, OR = 5.81). Conclusions: An increased mortality risk from COVID-19 was observed for older age, male sex, ß-Thalassemia heterozygosity and respiratory disease. Carriers of ß-Thalassemia were identified as more vulnerable for severe clinical symptomatology, but there was no increased possibility for ICU admission. Readjustment of these findings to consider impacts of variant strains prevailing during the latest viral outbreak among vulnerable patient groups may offer timely relief from the pandemic.

Susceptibility of ß-Thalassemia Heterozygotes to COVID-19.

BACKGROUND: ß-Thalassemia is the most prevalent single gene blood disorder, while the assessment of its susceptibility to coronavirus disease 2019 (COVID-19) warrants it a pressing biomedical priority. METHODS: We studied 255 positive COVID-19 participants unvaccinated against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), consecutively recruited during the last trimester of 2020. Patient characteristics including age, sex, current smoking status, atrial fibrillation, chronic respiratory disease, coronary disease, diabetes, neoplasia, hyperlipidemia, hypertension, and ß-thalassemia heterozygosity were assessed for COVID-19 severity, length of hospitalization, intensive care unit (ICU) admission and mortality from COVID-19. RESULTS: We assessed patient characteristics associated with clinical symptoms, ICU admission, and mortality from COVID-19. In multivariate analysis, severe-critical COVID-19 was strongly associated with male sex (p = 0.023), increased age (p < 0.001), and ß-thalassemia heterozygosity (p = 0.002, OR = 2.89). Regarding the requirement for ICU care, in multivariate analysis there was a statistically significant association with hypertension (p = 0.001, OR = 5.12), while ß-thalassemia heterozygosity had no effect (p = 0.508, OR = 1.33). Mortality was linked to male sex (p = 0.036, OR = 2.09), increased age (p < 0.001) and ß-thalassemia heterozygosity (p = 0.010, OR = 2.79) in multivariate analysis. It is worth noting that hyperlipidemia reduced mortality from COVID-19 (p = 0.008, OR = 0.38). No statistically significant association of current smoking status with patient characteristics studied was observed. CONCLUSIONS: Our pilot observations indicate enhanced mortality of ß-thalassemia heterozygotes from COVID-19.

Impact of the COVID-19 pandemic on clinical research in hospitals: observational study in the first epicenter of the epidemic during the general lockdown in France.

OBJECTIVE: The COVID-19 epidemic has had a strong impact on the entire healthcare sector in France with priority being given to research for new therapeutic options for COVID-19. Nevertheless, continuity of care for patients suffering from other diseases represents a crucial challenge, and clinical research is no exception in this respect. This study aims to assess the impact of the strict Covid-19 lockdown on non-Covid-19 clinical research in the French University Hospital of Strasbourg. MATERIALS AND METHODS: Clinical research activity (non-Covid-19) from the point of view of pharmacy department was estimated and compared to the pre-lockdown period. The impact of lockdown was assessed through five indicators: site initiation visits, the initiation of experimental therapies in non-Covid-19 patients, the delivery of non-Covid-19 investigational medical products, the number of drug shipments to patients' homes, and the number of monitoring or closure visits. RESULTS: During the study period, the number of site initiation visits decreased by 90%, total inclusions by 72%, and delivery of investigational medical products by 30%. During the lockdown period, 15 treatments were sent to patients' homes. Monitoring activity decreased by 98%. CONCLUSIONS: Although the COVID-19 outbreak has created an incredible momentum in the field of clinical research, research not focused on SaRS-CoV-2 has suffered greatly from this situation. The impact on patients is difficult to estimate but should be further investigated.

The importance of naturally attenuated SARS-CoV-2in the fight against COVID-19.

The current SARS-CoV-2 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID-19 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS-CoV-2 infections may, at least in part, be due also to differences between the viral subspecies with which individuals are infected. A more pertinent question is how we are to overcome the current pandemic. A vaccine against SARS-CoV-2 would offer significant relief, although vaccine developers have warned that design, testing and production of vaccines may take a year if not longer. Vaccines are based on a handful of different designs (i), but the earliest vaccines were based on the live, attenuated virus. As has been the case for other viruses during earlier pandemics, SARS-CoV-2 will mutate and may naturally attenuate over time (ii). What makes the current pandemic unique is that, thanks to state-of-the-art nucleic acid sequencing technologies, we can follow in detail how SARS-CoV-2 evolves while it spreads. We argue that knowledge of naturally emerging attenuated SARS-CoV-2 variants across the globe should be of key interest in our fight against the pandemic.

The influence of a statewide "Stay-at-Home" order on trauma volume and patterns at a level 1 trauma center in the united states.

The COVID pandemic of 2020 resulted in unprecedented restrictions of public life in most countries around the world, and many hospital systems experienced dramatic decreases in non-COVID related patient admissions. We aimed to compare trauma volumes, patient characteristics, and trauma mechanisms at a large, urban Level 1 trauma center in the United States during a state-wide "State of Emergency" and "stay-at-home" order to corresponding historic dates. All adult trauma activations from March 1 through April 30, 2020 and a historic control from March 1 through April 30, 2018 and 2019 were reviewed in the institution's trauma registry. Trauma volumes, patient characteristics, and trauma mechanisms were compared over time as increasingly stricter COVID-related restrictions were enacted in the Commonwealth of Virginia. After declaration of a state-wide "Public Health Emergency" on March 17, 2020, the daily number of trauma activations significantly declined to a mean of 4.7 (standard deviation, SD = 2.6), a decrease by 43% from a mean of 8.2 (SD = 0.3) for the same dates in 2018 and 2019. Trauma activations during COVID restrictions vs. historic control were characterized by significantly higher prevalence of chronic alcohol use (15.5% vs. 6.8%, p < 0.01), higher median (25th - 75th percentile) Injury Severity Score of 9 (5 - 16) vs. 6 (4 - 14), p = 0.01, and shorter median (25th - 75th percentile) length of hospital stay of 2 (1 - 6) days vs. 3 (1 - 7) days, p = 0.03. The COVID-related Public Health Emergency and "stay-at-home" order in the Commonwealth of Virginia dramatically reduced overall trauma volumes with minor but interesting changes in trauma patterns.

Controversies in Tracheostomy for Patients With COVID-19: The When, Where, and How.

COVID-19 has impacted how we deliver care to patients, and much remains unknown regarding optimal management of respiratory failure in this patient population. There are significant controversies regarding tracheostomy in patients with COVID-19 related to timing, location of procedure, and technique. In this narrative review, we explore the recent literature, publicly available guidelines, protocols from different institutions, and clinical reports to provide critical insights on how to deliver the most benefit to our patients while safeguarding the health care force. Consensus can be reached that patients with COVID-19 should be managed in a negative-pressure environment with proper personal protective equipment, and that performing tracheostomy is a complex decision that should be made through multidisciplinary discussions considering patient prognosis, institutional resources, staff experience, and risks to essential health care workers. A broad range of practices exist because there is no conclusive guidance regarding the optimal timing or technique for tracheostomy.