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.

Comparing COVID-19 in the antipodes: Insights from pandemic containment strategies on both sides of the Pacific.

That the COVID-19 pandemic is unprecedented in terms of its scale, spread and shocks can be evinced by the myriad of ever-changing responses cities all around the world have rolled out throughout the different waves of outbreaks. Although the threat is similar across the world, it took some time before its reach became global and the waves of outbreak are experienced by cities at different times. While this staggered spread imply that some cities might manage the virus better as they learn from the experiences of cities which had been amongst the earliest to face the virus, the reality is more complicated. In the early stages of the pandemic, the global consensus on the best way to contain the virus swiftly converged in the interlinked strategies of restricting the movement of people and minimizing their social contact. However, the effectiveness of these strategies differ greatly between cities. To that end, this study focuses on COVID-19 responses in two regions (Latin America and Southeast Asia) and examines the evolution of the first wave of COVID-19 outbreaks during 2020 in Singapore, Jakarta (Indonesia), Bogotá (Colombia) and Santiago (Chile). The study is based on a comparative approach and uses a variety of data sources, namely morphology, density, housing concentration, mobility, and governance in the four analyzed cities. The goal is to shed light on the response of city governments in these two different regions in terms of mobility restrictions in order to reduce the cases of new infections. The results show the relevance of urban policies and their territorial approaches, particularly in terms of mobility and public transport networks in the four cities.

Cerebral Hemodynamic Reserve Abnormalities Detected Via Transcranial Doppler Ultrasound in Recovered COVID-19 Patients.

INTRODUCTION: SARS-CoV-2 infection can produce endothelial injury and microvascular damage, one cause of the multiorgan failure associated with COVID-19. Cerebrovascular endothelial damage increases the risk of stroke in COVID-19 patients, which makes prompt diagnosis important. Endothelial dysfunction can be evaluated by using transcranial Doppler ultrasound to study cerebral hemodynamic reserve, but there are few of these studies in patients with COVID-19, and the technique is not included in COVID-19 action and follow-up guidelines nationally or internationally. OBJECTIVE: Estimate baseline cerebral hemodynamic patterns, cerebral hemodynamic reserve, and breath-holding index in recovered COVID-19 patients. METHOD: We conducted an exploratory study in 51 people; 27 men and 24 women 20-78 years of age, divided into two groups. One group comprised 25 recovered COVID-19 patients, following clinical and epidemiological discharge, who suffered differing degrees of disease severity, and who had no neurological symptoms or disease at the time they were incorporated into the study. The second group comprised 26 people who had not been diagnosed with COVID-19 and who tested negative by RT-PCR at the time of study enrollment. Recovered patients were further divided into two groups: those who had been asymptomatic or had mild disease, and those who had severe or critical disease. We performed transcranial Doppler ultrasounds to obtain baseline and post-apnea tests of cerebral hemodynamic patterns to evaluate cerebral hemodynamic reserve and breath-holding indices. We characterized the recovered patient group and the control group through simple descriptive statistics (means and standard deviations). RESULTS: There were no measurable differences in baseline cerebral hemodynamics between the groups. However, cerebral hemodynamic reserve and breath-holding index were lower in those who had COVID-19 than among control participants (19.9% vs. 36.8% and 0.7 vs. 1.2 respectively). These variables were similar for patients who had asymptomatic or mild disease (19.9% vs.19.8%) and for those who had severe or critical disease (0.7 vs. 0.7). CONCLUSIONS: Patients recovered from SARS-CoV-2 infection showed decreased cerebral hemodynamic reserve and breath-holding index regardless of the disease's clinical severity or presence of neurological symptoms. These abnormalities may be associated with endothelial damage caused by COVID-19. It would be useful to include transcranial Doppler ultrasound in evaluation and follow-up protocols for patients with COVID-19.

Nimotuzumab for COVID-19: case series.

Background: In COVID-19, EGFR production is upregulated in the alveolar epithelial cells. EGFR overexpression further activates STAT-3 and increases lung pathology. The EGFR pathway is also one of the major nodes in pulmonary fibrosis. Methods: Nimotuzumab, a humanized anti-EGFR antibody, was used to treat three patients with severe or moderate COVID-19. The antibody was administered in combination with other drugs included in the national COVID-19 protocol. Results: Nimotuzumab was well tolerated. IL-6 decreased from the first antibody infusion. Clinical symptoms significantly improved after nimotuzumab administration, and the CT scans at discharge showed major resolution of the lung lesions and no signs of fibrosis. Conclusion: Safe anti-EGFR antibodies like nimotuzumab may modulate COVID-19-associated hyperinflammation and prevent fibrosis. Clinical Trial Registration: RPCEC00000369 (RPCEC rpcec.sld.cu).

Lay abstract Background: In COVID-19, the protein EGFR is overactive in the infected lung cells. Methods: Nimotuzumab, an anti-EGFR antibody, was used to treat three patients with severe or moderate COVID-19. The antibody was administered in combination with other drugs included in the national COVID-19 protocol. Results: Nimotuzumab was safe. The most important inflammatory markers decreased from the first administration. The patients' clinical symptoms and imaging results improved significantly. Conclusion: Anti-EGFR antibodies like nimotuzumab may contribute to the recovery of COVID-19 patients without long-term consequences.

Impact of hematologic malignancy and type of cancer therapy on COVID-19 severity and mortality: lessons from a large population-based registry study.

BACKGROUND: Patients with cancer have been shown to have a higher risk of clinical severity and mortality compared to non-cancer patients with COVID-19. Patients with hematologic malignancies typically are known to have higher levels of immunosuppression and may develop more severe respiratory viral infections than patients with solid tumors. Data on COVID-19 in patients with hematologic malignancies are limited. Here we characterize disease severity and mortality and evaluate potential prognostic factors for mortality. METHODS: In this population-based registry study, we collected de-identified data on clinical characteristics, treatment and outcomes in adult patients with hematologic malignancies and confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection within the Madrid region of Spain. Our case series included all patients admitted to 22 regional health service hospitals and 5 private healthcare centers between February 28 and May 25, 2020. The primary study outcome was all-cause mortality. We assessed the association between mortality and potential prognostic factors using Cox regression analyses adjusted for age, sex, comorbidities, hematologic malignancy and recent active cancer therapy. RESULTS: Of 833 patients reported, 697 were included in the analyses. Median age was 72 years (IQR 60-79), 413 (60%) patients were male and 479 (69%) and 218 (31%) had lymphoid and myeloid malignancies, respectively. Clinical severity of COVID-19 was severe/critical in 429 (62%) patients. At data cutoff, 230 (33%) patients had died. Age ≥ 60 years (hazard ratios 3.17-10.1 vs < 50 years), > 2 comorbidities (1.41 vs ≤ 2), acute myeloid leukemia (2.22 vs non-Hodgkin lymphoma) and active antineoplastic treatment with monoclonal antibodies (2·02) were associated with increased mortality; conventional chemotherapy showed borderline significance (1.50 vs no active therapy). Conversely, Ph-negative myeloproliferative neoplasms (0.33) and active treatment with hypomethylating agents (0.47) were associated with lower mortality. Overall, 574 (82%) patients received antiviral therapy. Mortality with severe/critical COVID-19 was higher with no therapy vs any antiviral combination therapy (2.20). CONCLUSIONS: In this series of patients with hematologic malignancies and COVID-19, mortality was associated with higher age, more comorbidities, type of hematological malignancy and type of antineoplastic therapy. Further studies and long-term follow-up are required to validate these criteria for risk stratification.

Jakarta: A city of cities.

Jakarta, Indonesia's primate city and the world's second largest urban agglomeration, is undergoing a deep transformation. A fresh city profile of Jakarta is long overdue, given that there have been major events and developments since the turn of the millennium (the Asian Financial crisis and decentralisation in Indonesia, among the most important), as well as the fact that the city is a living entity with its own processes to be examined. The inhabitants of the city have also taken centre stage now in these urban processes, including the recent pandemic COVID-19 response. Our paper profiles Jakarta heuristically in two cuts: presenting the city from conventional and academic perspectives of megacities like it, which includes contending with its negative perceptions, and more originally, observing the city from below by paying attention to the viewpoints of citizens and practitioners of the city. In doing so, we draw from history, geography, anthropology, sociology and political science as well as from our experience as researchers who are based in the region and have witnessed the transformation of this megacity from within, with the idea that the portrayal of the city is a project permanently under construction.