key: cord-0781195-cnfijzie authors: Karimi Shahri, Mehdi; Niazkar, Hamid R.; Rad, Fariba title: COVID‐19 and hematology findings based on the current evidences: A puzzle with many missing pieces date: 2020-12-02 journal: Int J Lab Hematol DOI: 10.1111/ijlh.13412 sha: fb99d4dc6300d1e32df97e42b512f3fc5c7d86e3 doc_id: 781195 cord_uid: cnfijzie 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. In late 2019, a new coronavirus was isolated from pneumonia patients with unknown etiology for the first time in Wuhan, China. 1, 2 According to the latest reported data, the emerging coronavirus has crossed international borders, infecting more than thirty-seven million individuals, leading to more than million deaths. 3 The new coro- very similar to that of various viral infections. 6 In addition, studies have reported laboratory features of COVID-19 patients. 7 However, unfortunately, these studies are limited to one or few blood indicators. As the COVID-19 pandemic grows, it is crucial to raise the physicians' awareness about COVID-19 hematologic features. In this regard, the current study aimed to review and discuss the hematological findings of COVID-19 derived from automated hematology and clinical immunology/ flow cytometry. Zhao et al observed that SARS-CoV-2, similar to SARS-CoV, enters the host cells through angiotensin-converting enzyme 2 (ACE2) receptors. 8, 9 Studies showed that ACE2 is expressed in the alveolar epithelial cells type 2 and 1, myocytes, vascular endothelial cells, and some other cells, including hematopoietic stem cells and progenitors. 10 The bind of SARS-CoV-2 to ACE2 receptors increases the expression of this receptor, leading to further damage of alveolar cells, which may in turn cause a series of systemic reactions leading to death. After attaching to the ACE2 receptors, the spike proteins of SARS-CoV-2 are broken down through acid-dependent proteolysis by cathepsin, Transmembrane protease-serine 2 (TMPRSS2), or furin protease, and consequently, the SARS-CoV-2 merges with the cell membrane. Compared to the other coronavirus proteins, spike protein has the most variable sequence of amino acids among all coronavirus genes, which provides a strong option for coronavirus to adapt to its hosts. 11, 12 Recent studies suggested that SARS-CoV-2 may attack host cells via the CD147-spike protein (SP) pathway. In this regard, SP facilitates the virus invasion by connecting to CD147. The CD147, also known as BSG (Basigin) and extracellular matrix metalloproteinase inducer (EMMPRIN), is a plasma membrane protein from the immunoglobulin family, and it is encoded by the BSG gene in humans. 10, 13 This protein is expressed to a varying extent in the hematopoietic cells, mesenchymal stem cells, leukocytes, epithelial and endothelial cells, and has a wide range of physiological and pathological activities. Studies showed that CD147 expression on the red blood cells (as an adhesion molecule) plays a crucial role in the circulation of mature red blood cells from the spleen to the bloodstream. 13, 14 Figure 1 Possible invasion mechanism of SARS-CoV-2, CD147, and ACE2 acts as receptors of host cells for the invasion of SARS-CoV-2. Laboratory changes and hematologic abnormalities have been reported repeatedly in COVID-19 patients, which will be discussed in the following (Table 1) . Studies showed that in the early stages of COVID-19 disease when patients have no exclusive symptoms, White blood cells (WBC) count and peripheral blood lymphocytes are normal or slightly reduced while these indicators may change with the progression of the disease. 15 Zhang et al, 16 They observed that the absolute neutrophil count mostly increased in the first few days of hospitalization, while decreased slightly before or immediately after the treatment [42] Hematological findings and complications of COVID-19 Review Article They found that neutrophilic leukocytosis was associated with an increased risk of acute respiratory syndrome, risk of death, and elevated troponin level. [29] Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID- Baseline platelet levels and changes were associated with subsequent mortality. Monitoring platelets during hospitalization may be important in the prognosis of patients with coronavirus disease in 2019. [57] troponin levels and leukocyte counts, and patients with higher troponin had higher leukocyte counts, indicating a link between underlying disease and the leukocyte count in COVID-19 patients. 21 In a study by Mardani et al, 22 Therefore, another hypothesis that can be proposed is that the Monocytes trigger inflammation through the production of cy- They found that patients with COVID-19 have larger monocytes, along with the CD11b + , CD14 + , CD16 + , CD68 + , CD80 + , CD163 + , CD206 + , and the ability to secrete IL-6, IL-10, and TNF-α, which are compatible with an inflammatory phenotype. 27 Individuals with these kinds of monocytes required long-term hospitalization and ICU admission. Also, in a study by Zeng et al, 25 Terpos, it was found that neutrophilic leukocytosis was associated with an increased risk of acute respiratory syndrome, risk of death, and elevated troponin levels. 29 Another study indicated that the neutrophil-to-lymphocyte ratio (NLR ratio) was higher in severe COVID-19 patients. 44 NLR, which is easily calculated by dividing the absolute number of neutrophils by the absolute number of lymphocytes, is of great importance in expressing the general inflammatory condition of the patient. 45 The aforementioned study suggested that the calculation of NLR during and after hospitalization can be a pre- Platelets not only play a crucial role in homeostasis but also are responsible for inflammatory and defense mechanisms. Thrombocytopenia is one of the most common clinical manifestations of COVID-19, reported in 5%-40% of patients, and it is known to be associated with poor prognosis of the disease. 29, [55] [56] [57] In a meta-analysis by Lippi The study also found that platelet count and plateletcrit (PCT) are independent risk factors of mortality in COVID-19 patients. 57 In addition, a study by Chen et al observed a delayed antibody thrombocytopenia in COVID-19 patients. 60 Inflammatory cytokines can cause thrombocytopenia by destroying progenitors in the bone marrow and reducing platelet production. Finally, thrombocytopenia may be due to the presence of autoantibodies, and the destruction of platelets. Due to the relationship between platelet count and increased risk of COVID-19 mortality, the platelet count can be used as a prognostic marker during hospitalization. 26 COVID-19 can present with various hematologic manifestations. In this regard, accurate evaluation of laboratory indicators at the beginning and during the course of COVID-19 can help physicians to adjust appropriate treatment and provide special and prompt care for those in need. Authors declare that they have no conflict of interests. MK and FR designed the study and performed the research. HRN wrote the draft and MK and FR revised the draft. This article does not contain any studies with human participants or animals performed by any of the authors. No datasets were generated or analyzed during the current study. Mehdi Karimi Shahri https://orcid.org/0000-0003-4910-3134 Hamid R. 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