In a Plenary Paper, Mittelman and colleagues assess the relative clinical efficacy of mRNA vaccination on COVID-19 disease incidence and outcomes in patients with hematologic malignancies compared with healthy matched controls. This population-based study from Israel links prior observations of poor serologic responses to vaccination to higher risk for breakthrough infection, hospitalization, and death in patients with blood cancer, especially those on active antineoplastic therapy. In an accompanying Letter to Blood, Pagano et al provide supportive data using a multination survey approach to capture outcomes for COVID-19 in vaccinated patients with hematologic neoplasms. They also emphasize the higher risk among patients with lymphoid malignancies. Together, these findings argue for both continued deployment of booster programs and ongoing public health guidance for this vulnerable group.

(1) Background: Different clinical presentations in COVID-19 are described to date, from mild to severe cases. This study aims to identify different clinical phenotypes in COVID-19 pneumonia using cluster analysis and to assess the prognostic impact among identified clusters in such patients. (2) Methods: Cluster analysis including 11 phenotypic variables was performed in a large cohort of 12,066 COVID-19 patients, collected and followed-up from 1 March to 31 July 2020, from the nationwide Spanish Society of Internal Medicine (SEMI)-COVID-19 Registry. (3) Results: Of the total of 12,066 patients included in the study, most were males (7052, 58.5%) and Caucasian (10,635, 89.5%), with a mean age at diagnosis of 67 years (standard deviation (SD) 16). The main pre-admission comorbidities were arterial hypertension (6030, 50%), hyperlipidemia (4741, 39.4%) and diabetes mellitus (2309, 19.2%). The average number of days from COVID-19 symptom onset to hospital admission was 6.7 (SD 7). The triad of fever, cough, and dyspnea was present almost uniformly in all 4 clinical phenotypes identified by clustering. Cluster C1 (8737 patients, 72.4%) was the largest, and comprised patients with the triad alone. Cluster C2 (1196 patients, 9.9%) also presented with ageusia and anosmia; cluster C3 (880 patients, 7.3%) also had arthromyalgia, headache, and sore throat; and cluster C4 (1253 patients, 10.4%) also manifested with diarrhea, vomiting, and abdominal pain. Compared to each other, cluster C1 presented the highest in-hospital mortality (24.1% vs. 4.3% vs. 14.7% vs. 18.6%; p < 0.001). The multivariate study identified age, gender (male), body mass index (BMI), arterial hypertension, chronic obstructive pulmonary disease (COPD), ischemic cardiopathy, chronic heart failure, chronic hepatopathy, Charlson’s index, heart rate and respiratory rate upon admission >20 bpm, lower PaO2/FiO2 at admission, higher levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH), and the phenotypic cluster as independent factors for in-hospital death. (4) Conclusions: The present study identified 4 phenotypic clusters in patients with COVID-19 pneumonia, which predicted the in-hospital prognosis of clinical outcomes.

Objectives: A decrease in blood cell counts, especially lymphocytes and eosinophils, has been described in patients with serious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), but there is no knowledge of their potential role of the recovery in these patients’ prognosis. This article aims to analyse the effect of blood cell depletion and blood cell recovery on mortality due to COVID-19. Design: This work was a retrospective, multicentre cohort study of 9644 hospitalised patients with confirmed COVID-19 from the Spanish Society of Internal Medicine’s SEMI-COVID-19 Registry. Setting: This study examined patients hospitalised in 147 hospitals throughout Spain. Participants: This work analysed 9644 patients (57.12% male) out of a cohort of 12,826 patients ≥18 years of age hospitalised with COVID-19 in Spain included in the SEMI-COVID-19 Registry as of 29 May 2020. Main outcome measures: The main outcome measure of this work is the effect of blood cell depletion and blood cell recovery on mortality due to COVID-19. Univariate analysis was performed to determine possible predictors of death, and then multivariate analysis was carried out to control for potential confounders. Results: An increase in the eosinophil count on the seventh day of hospitalisation was associated with a better prognosis, including lower mortality rates (5.2% vs. 22.6% in non-recoverers, OR 0.234; 95% CI, 0.154 to 0.354) and lower complication rates, especially regarding the development of acute respiratory distress syndrome (8% vs. 20.1%, p = 0.000) and ICU admission (5.4% vs. 10.8%, p = 0.000). Lymphocyte recovery was found to have no effect on prognosis. Treatment with inhaled or systemic glucocorticoids was not found to be a confounding factor. Conclusion: Eosinophil recovery in patients with COVID-19 who required hospitalisation had an independent prognostic value for all-cause mortality and a milder course.

(1) Background: The inflammation or cytokine storm that accompanies COVID-19 marks the prognosis. This study aimed to identify three risk categories based on inflammatory parameters on admission. (2) Methods: Retrospective cohort study of patients diagnosed with COVID-19, collected and followed-up from 1 March to 31 July 2020, from the nationwide Spanish SEMI-COVID-19 Registry. The three categories of low, intermediate, and high risk were determined by taking into consideration the terciles of the total lymphocyte count and the values of C-reactive protein, lactate dehydrogenase, ferritin, and D-dimer taken at the time of admission. (3) Results: A total of 17,122 patients were included in the study. The high-risk group was older (57.9 vs. 64.2 vs. 70.4 years; p < 0.001) and predominantly male (37.5% vs. 46.9% vs. 60.1%; p < 0.001). They had a higher degree of dependence in daily tasks prior to admission (moderate-severe dependency in 10.8% vs. 14.1% vs. 17%; p < 0.001), arterial hypertension (36.9% vs. 45.2% vs. 52.8%; p < 0.001), dyslipidemia (28.4% vs. 37% vs. 40.6%; p < 0.001), diabetes mellitus (11.9% vs. 17.1% vs. 20.5%; p < 0.001), ischemic heart disease (3.7% vs. 6.5% vs. 8.4%; p < 0.001), heart failure (3.4% vs. 5.2% vs. 7.6%; p < 0.001), liver disease (1.1% vs. 3% vs. 3.9%; p = 0.002), chronic renal failure (2.3% vs. 3.6% vs. 6.7%; p < 0.001), cancer (6.5% vs. 7.2% vs. 11.1%; p < 0.001), and chronic obstructive pulmonary disease (5.7% vs. 5.4% vs. 7.1%; p < 0.001). They presented more frequently with fever, dyspnea, and vomiting. These patients more frequently required high flow nasal cannula (3.1% vs. 4.4% vs. 9.7%; p < 0.001), non-invasive mechanical ventilation (0.9% vs. 3% vs. 6.3%; p < 0.001), invasive mechanical ventilation (0.6% vs. 2.7% vs. 8.7%; p < 0.001), and ICU admission (0.9% vs. 3.6% vs. 10.6%; p < 0.001), and had a higher percentage of in-hospital mortality (2.3% vs. 6.2% vs. 23.9%; p < 0.001). The three risk categories proved to be an independent risk factor in multivariate analyses. (4) Conclusion: The present study identifies three risk categories for the requirement of high flow nasal cannula, mechanical ventilation, ICU admission, and in-hospital mortality based on lymphopenia and inflammatory parameters.