Hematological Abnormalities in COVID-19: A Narrative Review.

COVID-19 is caused by SARS-CoV-2. Although pulmonary manifestations have been identified as the major symptoms, several hematological abnormalities have also been identified. This review summarizes the reported hematological abnormalities (changes in platelet, white blood cell, and hemoglobin, and coagulation/fibrinolytic alterations), explores their patho-mechanisms, and discusses its management. Common hematological abnormalities in COVID-19 are lymphopenia, thrombocytopenia, and elevated D-dimer levels. These alterations are significantly more common/prominent in patients with severe COVID-19 disease, and thus may serve as a possible biomarker for those needing hospitalization and intensive care unit care. Close attention needs to be paid to coagulation abnormalities, and steps should be taken to prevent these occurring or to mitigate their harmful effects. The effect of COVID-19 in patients with hematological abnormalities and recognized hematological drug toxicities of therapies for COVID-19 are also outlined.

Clinical characteristics and antibiotics treatment in suspected bacterial infection patients with COVID-19.

Coronavirus disease 2019 (COVID-19) pandemic has brought challenges to health and social care systems. However, the empirical use of antibiotics is still confusing. Presently, a total of 1123 patients with COVID-19 admitted to Renmin Hospital of Wuhan University was included in this retrospective cohort study. The clinical features, complications and outcomes were compared between the suspected bacterial infection and the no evidence of bacterial infection. The risk factors of mortality and the incidence of acute organ injury were analyzed. As a result, 473 patients were selected to suspected bacterial infection (SI) group based on higher white blood cell count and procalcitonin or bacterial pneumonia on chest radiography. 650 patients were selected to the no evidence of bacterial infection (NI) group. The SI group had more severely ill patients (70.2% vs. 39.8%), more death (20.5% vs. 2.2%), and more acute organ injury (40.2% vs. 11.2%). Antibiotics were found associated with improved mortality and an increased risk for acute organ injury in hospitalized patients with COVID-19. Intravenous moxifloxacin and meropenem increased the death rate in patients with suspected bacterial infection, while oral antibiotics reduced mortality in this group. Moreover, penicillin and meropenem treatments were associated with increased mortality of the patients with no evidence of bacterial infection. In conclusion, patients with suspected bacterial infection were more likely to have negative clinical outcomes than those without bacterial infection. Empirical use of antibiotics may not have the expected benefits.

Relationship between leukocyte, neutrophil, lymphocyte, platelet counts, and neutrophil to lymphocyte ratio and polymerase chain reaction positivity.

BACKGROUND: Exposure to viral or bacterial pathogens increases the number of neutrophils with a relative decrease in lymphocytes, leading to elevated neutrophil to lymphocyte ratio (NLR). This study aimed to investigate whether differences in NLR among real-time polymerase chain reaction (PCR)-positive and -negative patients presenting with a prediagnosis of COVID-19 pneumonia could be useful in the differential diagnosis. METHODS: The study included 174 patients admitted because of suspected COVID-19 infection between March and April 2020. Patients were divided into two groups: PCR-negative and PCR-positive. Hemogram, NLR, urea, creatinine, aspartate aminotransferase, alanine aminotransferase, bilirubin, ferritin, D-dimer, C-reactive protein, procalcitonin, troponin, and coagulation parameters were analyzed. RESULTS: On comparison of laboratory parameters between both groups at presentation, PCR-positive patients were significantly more likely to have leukopenia (p < 0.001), thrombocytopenia (p = 0.006), neutropenia (p < 0.001), lymphopenia (p = 0.001), and increased NLR (p = 0.003). Furthermore, PCR-positive patients showed significant elevations of ferritin (p = 0.012) and procalcitonin (p = 0.038) and significant lower potassium levels (p = 0.05). CONCLUSION: COVID-19 pneumonia has become a major global health problem. Early diagnosis and treatment of these patients are crucial, as COVID-19 pneumonia shows a rapid progression in most cases. Thus, leukopenia, thrombocytopenia, elevated NLR, and elevated ferritin may be useful as supplementary diagnostic tests in these patients, which may allow early initiation of treatment and may contribute to preventing progression in patients with abnormal results.

SARS-CoV-2 infection is associated with a pro-thrombotic platelet phenotype.

Novel coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state, characterized by abnormal coagulation parameters and by increased incidence of cardiovascular complications. With this study, we aimed to investigate the activation state and the expression of transmembrane proteins in platelets of hospitalized COVID-19 patients. We investigated transmembrane proteins expression with a customized mass cytometry panel of 21 antibodies. Platelets of 8 hospitalized COVID-19 patients not requiring intensive care support and without pre-existing conditions were compared to platelets of healthy controls (11 donors) with and without in vitro stimulation with thrombin receptor-activating peptide (TRAP). Mass cytometry of non-stimulated platelets detected an increased surface expression of activation markers P-Selectin (0.67 vs. 1.87 median signal intensity for controls vs. patients, p = 0.0015) and LAMP-3 (CD63, 0.37 vs. 0.81, p = 0.0004), the GPIIb/IIIa complex (4.58 vs. 5.03, p < 0.0001) and other adhesion molecules involved in platelet activation and platelet-leukocyte interactions. Upon TRAP stimulation, mass cytometry detected a higher expression of P-selectin in COVID-19 samples compared to controls (p < 0.0001). However, we observed a significantly reduced capacity of COVID-19 platelets to increase the expression of activation markers LAMP-3 and P-Selectin upon stimulation with TRAP. We detected a hyperactivated phenotype in platelets during SARS-CoV-2 infection, consisting of highly expressed platelet activation markers, which might contribute to the hypercoagulopathy observed in COVID-19. In addition, several transmembrane proteins were more highly expressed compared to healthy controls. These findings support research projects investigating antithrombotic and antiplatelet treatment regimes in COVID-19 patients, and provide new insights on the phenotypical platelet expression during SARS-CoV-2 infection.

Clinical Significance of CBC and WBC Morphology in the Diagnosis and Clinical Course of COVID-19 Infection.

OBJECTIVES: To investigate the clinical significance of numeric and morphologic peripheral blood (PB) changes in coronavirus disease 2019 (COVID-19)-positive patients in predicting the outcome, as well as to compare these changes between critically ill COVID-19-positive and COVID-19-negative patients. METHODS: The study included 90 COVID-19-positive (51 intensive care unit [ICU] and 39 non-ICU) patients and 30 COVID-19-negative ICU patients. We collected CBC parameters (both standard and research) and PB morphologic findings, which were independently scored by two hematopathologists. RESULTS: All patients with COVID-19 demonstrated striking numeric and morphologic WBC changes, which were different between mild and severe disease states. More severe disease was associated with significant neutrophilia and lymphopenia, which was intensified in critically ill patients. Abnormal WBC morphology, most pronounced in monocytes and lymphocytes, was associated with more mild disease; the changes were lost with disease progression. Between COVID-19-positive and COVID-19-negative ICU patients, significant differences in morphology-associated research parameters were indicative of changes due to the severe acute respiratory syndrome coronavirus 2 virus, including higher RNA content in monocytes, lower RNA content in lymphocytes, and smaller hypogranular neutrophils. CONCLUSIONS: Hospitalized patients with COVID-19 should undergo a comprehensive daily CBC with manual WBC differential to monitor for numerical and morphologic changes predictive of poor outcome and signs of disease progression.

COVID-19 and hematology findings based on the current evidences: A puzzle with many missing pieces.

In December 2019, a new type of coronavirus was detected for the first time in Wuhan, Hubei Province, China. According to the reported data, the emerging coronavirus has spread worldwide, infecting more than fifty-seven million individuals, leading to more than one million deaths. The current study aimed to review and discuss the hematological findings of COVID-19. Laboratory changes and hematologic abnormalities have been reported repeatedly in COVID-19 patients. WBC count and peripheral blood lymphocytes are normal or slightly reduced while these indicators may change with the progression of the disease. In addition, several studies demonstrated that decreased hemoglobin levels in COVID-19 patients were associated with the severity of the disease. Moreover, thrombocytopenia, which is reported in 5%-40% of patients, is known to be associated with poor prognosis of the disease. COVID-19 can present with various hematologic manifestations. In this regard, accurate evaluation of laboratory indicators at the beginning and during COVID-19 can help physicians to adjust appropriate treatment and provide special and prompt care for those in need.

Inflammasome formation in the lungs of patients with fatal COVID-19.

OBJECTIVE: The orf8b protein of the coronavirus SARS-CoV, analogous to SARS-CoV-2, triggers the NLRP3 inflammasome in macrophages in vitro. Deregulated inflammasome-mediated release of interleukin-1 family cytokines is important in hyper-inflammatory syndromes, like happens in SARS-CoV-2-mediated cytokine release syndrome. We propose that an intense inflammasome formation characterizes the lungs of patients with fatal COVID-19 disease due to pneumonia and acute respiratory distress syndrome (ARDS). METHODS: Samples from four patients with confirmed COVID-19 pneumonia who had been hospitalized at the Hospital of the University of Trieste (Italy) and died of ARDS and four lung samples from a historical repository from subjects who had died of cardiopulmonary arrest and had not been placed on mechanical ventilation and without evidence of pulmonary infection at postmortem examination were collected. Pathology samples had been fixed in formalin 10% at time of collection and subsequently embedded in paraffin. We conducted staining for ASC (Apoptosis-associated Speck-like protein containing a Caspase recruitment domain), NLRP3 (NACHT, LRR, and PYD domains-containing protein 3), and cleaved caspase-1. RESULTS: Intense expression of the inflammasome was detected, mainly in leukocytes, within the lungs of all patients with fatal COVID-19 in the areas of lung injury. The number of ASC inflammasome specks per high power fields was significantly higher in the lungs of patients with fatal COVID-19 as compared with the lungs of control subjects (52 ± 22 vs 6 ± 3, P = 0.0064). CONCLUSIONS: These findings identify the presence of NLRP3 inflammasome aggregates in the lungs of fatal COVID-19 pneumonia thus providing the potential molecular link between viral infection and cytokine release syndrome.

Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection.

Recent reports highlight a new clinical syndrome in children related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1-multisystem inflammatory syndrome in children (MIS-C)-which comprises multiorgan dysfunction and systemic inflammation2-13. We performed peripheral leukocyte phenotyping in 25 children with MIS-C, in the acute (n = 23; worst illness within 72 h of admission), resolution (n = 14; clinical improvement) and convalescent (n = 10; first outpatient visit) phases of the illness and used samples from seven age-matched healthy controls for comparisons. Among the MIS-C cohort, 17 (68%) children were SARS-CoV-2 seropositive, suggesting previous SARS-CoV-2 infections14,15, and these children had more severe disease. In the acute phase of MIS-C, we observed high levels of interleukin-1ß (IL-1ß), IL-6, IL-8, IL-10, IL-17, interferon-γ and differential T and B cell subset lymphopenia. High CD64 expression on neutrophils and monocytes, and high HLA-DR expression on γδ and CD4+CCR7+ T cells in the acute phase, suggested that these immune cell populations were activated. Antigen-presenting cells had low HLA-DR and CD86 expression, potentially indicative of impaired antigen presentation. These features normalized over the resolution and convalescence phases. Overall, MIS-C presents as an immunopathogenic illness1 and appears distinct from Kawasaki disease.

Clinical features in 52 patients with COVID-19 who have increased leukocyte count: a retrospective analysis.

Recent reports have showed that a proportion of patients with Coronavirus Disease 2019 (COVID-19) presented elevated leukocyte count. Clinical data about these patients is scarce. We aimed to evaluate the clinical findings of patients with COVID-19 who have increased leukocyte at admission. We retrospectively collected the clinical data on the 52 patients who have increased leukocyte count at admission from the 619 patients with confirmed COVID-19 who had pneumonia with abnormal features on chest CT scan in Renmin Hospital of Wuhan University in Wuhan, China, from February 3 to March 3, 2020. The mean age of the 52 patients with increased leukocyte count was 64.7 (SD 11.4) years, 32 (61.5%) were men and 47 (90.4%) had fever. Compared with the patients with non-increased leukocyte count, the patients with increased leukocyte count were significantly older (P < 0.01), were more likely to have underlying chronic diseases (P < 0.01), more likely to develop critically illness (P < 0.01), more likely to admit to an ICU (P < 0.01), more likely to receive mechanical ventilation (P < 0.01), had higher rate of death (P < 0.01) and the blood levels of neutrophil count and the serum concentrations of CRP and IL-6 were significantly increased, (P < 0.01). The older patients with COVID-19 who had underlying chronic disorders are more likely to develop leukocytosis. These patients are more likely to develop critical illness, with a high admission to an ICU and a high mortality rate.