Secondary polycythemia in acutely ill COVID-19 patients is associated with higher mortality but not markedly higher thrombotic risk.

Secondary polycythemia is commonly observed among patients with chronic pulmonary diseases. However, its significance in the context of Coronavirus disease 2019 (COVID-19) is unknown. We retrospectively evaluated a total of 5872 hospitalized COVID-19 patients with mostly severe and critical symptoms, and without prior or subsequently diagnosed myeloproliferative neoplasm. Patients were stratified based on admission hemoglobin into four subgroups: anemia (hemoglobin <120 g/L for females and 130 g/L for males), normal hemoglobin, mild (hemoglobin 160-165 g/L for females and 165-185 g/L for males) and severe polycythemia (hemoglobin >165 g/L for females and >185 g/L for males). Among 5872 patients, a total of 158 (2.7%) had mild and 25 (0.4%) severe polycythemia. Polycythemia was significantly associated with higher respiratory and functional impairment, reduced plasma volume, higher serum osmolarity and comorbidity burden specific to the degree of polycythemia. Patients presenting with mild (odds ratio (OR) = 1.63, p = .003) and severe polycythemia (OR = 4.98, p < .001) had increased risk of death in comparison to patients with normal hemoglobin, whereas no significant associations with venous thromboembolism, arterial thrombosis nor major bleeding were observed. Anemia was associated with higher risk of death (OR = 1.42, p < .001), venous thromboembolism (OR = 1.34, p < .006) and major bleeding (OR = 2.27, p < .001) in comparison to normal hemoglobin. Associations of polycythemia and anemia with mortality diminished, and anemia with venous thromboembolism and major bleeding persisted, after multivariate adjustments for age, sex, comorbidities, COVID-19 severity and functional status. Secondary polycythemia in hospitalized COVID-19 patients without prior of subsequently diagnosed myeloproliferative neoplasm is rare and is associated with high mortality, increasing with degree of polycythemia, but not markedly higher thrombotic risk.

Hypoosmolar and hyperosmolar COVID-19 patients are predisposed to dismal clinical outcomes.

We aimed to investigate the associations of hypo- and hyperosmolarity at hospital admission with clinical characteristics and outcomes in 5645 consecutive hospitalized COVID-19 patients treated at a tertiary-level institution. Serum osmolarity was calculated as 2x Na (mmol/L) + urea (mmol/L) + glucose (mmol/L), with normal range from 275 to 295 mOsm/L. Median serum osmolarity was 292.9 mOsm/L with 51.8% normoosmolar, 5.3% hypoosmolar and 42.9% hyperosmolar patients present at the time of hospital admission. Hypoosmolarity was driven by hyponatremia, and was associated with the presence of chronic liver disease, liver cirrhosis, active malignancy and epilepsy. Hyperosmolarity was driven by an increase in urea and glucose and was associated with the presence of chronic metabolic and cardiovascular comorbidities. Both hypo- and hyperosmolar patients presented with more severe COVID-19 symptoms, higher inflammatory status, and experienced higher mortality in comparison to normoosmolar patients. In multivariate analysis, hypoosmolarity (adjusted odds ratio (aOR)=1.39, p = 0.024) and hyperosmolarity (aOR = 1.9, p < 0.001) remained significantly associated with higher mortality independently of older age, male sex, higher Charlson Comorbidity Index and more severe COVID-19. Disruptions in serum osmolarity are frequent in COVID-19 patients, may be easy to detect and target therapeutically, and thus potentially moderate associateds poor prognosis.

Hemochromatosis gene mutations may affect the survival of patients with myelodysplastic syndrome.

OBJECTIVES: The recent availability of potent oral iron chelators is renewing an interest in the assessment of the possible impact of HFE genetics in MDS. METHODS: Thirty six newly diagnosed patients with MDS were studied for parameters of iron metabolism in addition to C282Y and H63D mutations of the HFE gene. RESULTS: Mutations were present in 11 out of 36 patients (31%), which were not different from our general population and were equally distributed among MDS subtypes. Mutated patients had higher ferritin levels (P = 0.039) and lower TIBC (P = 0.018). Ferritin was found to be higher for the untransfused mutated patients (P = 0.017), but not for transfusion-dependent patients in whom ferritin levels correlated significantly with the number of blood units received (P = 0.04). There was no difference in the number of blood units received between the mutated and wild type patients. A new observation made was that the mutated patients had a lower overall survival in addition to a poorer leukemia free survival (LFS) (P = 0.004 and P = 0.003, respectively). DISCUSSION: The HFE gene mutations are not more frequent in MDS patients. Iron overload in mutated patients was higher but there was no correlation found using supportive therapy for anemia. The effect of mutations on survival could be mediated by changes in iron metabolism. CONCLUSION: The HFE genotype may predict MDS prognosis and there is a need for further studies. It remains a challenging question if HFE mutated MDS patients should be considered for potent iron chelation therapy.