Prognostic factors associated with COVID-19 related severity in sickle cell disease.

BACKGROUND: Equipoise exists regarding sickle cell disease (SCD) as a risk factor for COVID-19 disease severity and variables that increase risk of COVID-19 severity in SCD. Given our health system's large SCD patient catchment, we analyzed our own experience in this regard. STUDY METHODS: Retrospective analysis of the clinical course and factors associated with need for hospitalization and ICU admission of SCD patients diagnosed with COVID-19 through the Northwell Health system from March 1 to Dec 31, 2020. RESULTS: Of 1098 patients with SCD, 3.3% were diagnosed with COVID-19. Overall rates of hospitalization, ICU admission, cohort mortality, and in-hospital mortality were 80%, 19%, 2.5%,and 3.1%, respectively. By multivariable analysis, hospitalization risk was decreased by 60% for every 1 g/dL increase in admission Hb. ICU admission risk was increased by 84% as a health care worker; increased by 45% for every 1000/uL increase in admission immature granulocyte count; and decreased by 17% with hydroxyurea use. DISCUSSION: High hospitalization rates are compatible with worsened severity upon COVID-19 infection in SCD compared to the general population. Patients should be placed on hydroxyurea to increase their Hb and perhaps lower their neutrophil counts. Health care workers with SCD may warrant special safety precautions.

COVID-19 Infection in Sickle Cell Patients in a Developing Country: A Case Series.

Sickle cell disease is characterized by vaso-occlusive phenomena and haemolytic anaemia. There is a significant concern that the overlap of COVID-19 lung disease with acute chest syndrome that occurs in sickle cell patients may result in serious complications. Case reports of sickle cell patients with COVID-19 have been published. Here, we present a case series of COVID-19 infection in sickle cell patients in a developing country (Brazil). Only 10 patients tested positive so far for SARS-CoV-2 of 600 patients followed at our institution, of which 8 needed hospitalization (one in the intensive care unit), with no deaths. Even in a middle-income country, COVID-19 was reported to be relatively mild in sickle cell patients. In relation to risk factors, blood type O seems to confer some protection against developing severe COVID-19, a finding that could guide clinicians to adopt more clinical surveillance for patients with non-O blood type in sickle cell patients.

Impact of COVID-19 on vasooclusive crisis in patients with sickle cell anaemia.

OBJECTIVES: The study aimed to assess COVID-19 impact on the morbidity and mortality of vasooclusive crisis (VOC) in sickle cell anaemia (SCA) patients. METHODS: A prospective cohort study of 100 SCA patients; 50 with COVID-19 (COVID group) and 50 without (non-COVID group). All patients signed written informed consent. RESULTS: The COVID group had a significantly higher VOC episode median per year; 3 (IQR,1-6) vs 2 (IQR,2-12) (P < 0.05). The need for hospitalisation was similar in both groups. The non-COVID group had more history of culture-proven infection (P = 0.05). The COVID-group had more osteonecrosis (P < 0.05), splenic sequestration, splenomegaly and hepatic crisis (P = 0.05, 0.006, 0.02; respectively) and significantly higher (P < 0.05) symptoms of fever, cough, fatigue, abdominal pain and anosmia. Mean haemoglobin, lymphocyte subset, platelets, and reticulocytes were reduced in both groups, while lactate dehydrogenase and ferritin levels were significantly elevated. In the COVID group, the rise in white blood cell count, reticulocyte percentage, platelets and ferritin was subdued (P < 0.05). Two patients in the COVID group and 3 in the non-COVID group died; there was no statistically significant difference in mortality. CONCLUSIONS: Although COVID-19 may have triggered the onset of VOC, it did not significantly influence VOC-related morbidity or mortality in this SCA cohort.

Blood flow, capillary transit times, and tissue oxygenation: the centennial of capillary recruitment.

The transport of oxygen between blood and tissue is limited by blood's capillary transit time, understood as the time available for diffusion exchange before blood returns to the heart. If all capillaries contribute equally to tissue oxygenation at all times, this physical limitation would render vasodilation and increased blood flow insufficient means to meet increased metabolic demands in the heart, muscle, and other organs. In 1920, Danish physiologist August Krogh was awarded the Nobel Prize in Physiology or Medicine for his mathematical and quantitative, experimental demonstration of a solution to this conceptual problem: capillary recruitment, the active opening of previously closed capillaries to meet metabolic demands. Today, capillary recruitment is still mentioned in textbooks. When we suspect symptoms might represent hypoxia of a vascular origin, however, we search for relevant, flow-limiting conditions in our patients and rarely ascribe hypoxia or hypoxemia to short capillary transit times. This review describes how natural changes in capillary transit-time heterogeneity (CTH) and capillary hematocrit (HCT) across open capillaries during blood flow increases can account for a match of oxygen availability to metabolic demands in normal tissue. CTH and HCT depend on a number of factors: on blood properties, including plasma viscosity, the number, size, and deformability of blood cells, and blood cell interactions with capillary endothelium; on anatomical factors including glycocalyx, endothelial cells, basement membrane, and pericytes that affect the capillary diameter; and on any external compression. The review describes how risk factor- and disease-related changes in CTH and HCT interfere with flow-metabolism coupling and tissue oxygenation and discusses whether such capillary dysfunction contributes to vascular disease pathology.

Clinical predictors of poor outcomes in patients with sickle cell disease and COVID-19 infection.

We aimed to identify predictors of outcomes and survival in patients living in 4 major metropolitan areas who had sickle cell disease (SCD) and COVID-19 to inform best approaches to prevention and care. Data were collected at baseline and during the clinical course in SCD patients diagnosed with COVID-19 in four COVID-19 epicenters. Patients were followed up posthospital discharge for up to 3 months. Of sixty-six SCD patients with COVID-19, fifty patients (75%) required hospitalization, and seven died (10.6%). Patients with preexisting kidney disease (chronic kidney disease) were more likely to be hospitalized. The most common presenting symptom was vaso-occlusive pain. Acute chest syndrome occurred in 30 (60%) of the 50 hospitalized patients and in all who died. Older age and histories of pulmonary hypertension, congestive heart failure, chronic kidney disease, and stroke were more prevalent in patients who died, as were higher creatinine, lactate dehydrogenase, and D-dimer levels. Anticoagulation use while inpatient was twice less common in patients who died. All deaths occurred in individuals not taking hydroxyurea or any other SCD-modifying therapy. Patients with SCD and COVID-19 exhibited a broad range of disease severity. We cannot definitively state that the overall mortality is higher in patients with SCD, although our case fatality rate was ∼10% compared with ∼3% in the general population, despite a median age of 34 years. Individuals with SCD aged >50 years, with preexisting cardiopulmonary, renal disease, and/or stroke not receiving hydroxyurea, who present with high serum creatinine, lactate dehydrogenase, and D-dimer levels, are at higher risk of death, irrespective of genotype or sex.

Coagulation Status and Venous Thromboembolism Risk in African Americans: A Potential Risk Factor in COVID-19.

Severe acute respiratory syndrome coronavirus 2 infection (COVID-19) is known to induce severe inflammation and activation of the coagulation system, resulting in a prothrombotic state. Although inflammatory conditions and organ-specific diseases have been shown to be strong determinants of morbidity and mortality in patients with COVID-19, it is unclear whether preexisting differences in coagulation impact the severity of COVID-19. African Americans have higher rates of COVID-19 infection and disease-related morbidity and mortality. Moreover, African Americans are known to be at a higher risk for thrombotic events due to both biological and socioeconomic factors. In this review, we explore whether differences in baseline coagulation status and medical management of coagulation play an important role in COVID-19 disease severity and contribute to racial disparity trends within COVID-19.