4.Discussion
Clinical treatment has found that platelet abnormal are prone to occur during the course of COVID-19 treatment. Continuous low platelets can be employed as an indicator of no improvement in disease and poor prognosis. We found that many COVID-19 patients were concurrent with PLT decrease when admitted to hospital. Zhong Nanshan also reported that 36.2% of COVID-19 patients had thrombocytopenia at admission(Huang et al.,2020). Early thrombocytopenia occurred in all types of COVID-19 patients, which were further confirmed in our study. However, the percentage of thrombocytopenia in our article is not as low as reported in this literature, except that our standard is lower (PLT <125×109/L, literature is <150×10 9/L)(Huang et al.,2020). we analyze that On the one hand, it may be related to the length of the isolation period, and antiviral treatment has been given before the nucleic acid test is positive; On the other hand, The case data of our study be later than the reported data in literature, and Whether or not the virulence of new crown pneumonia virus has abated? It needs for further study.
In this study, it was found that PLT abnormalities of COVID-19 patients at admission may be less correlated with PCT, IL-2, IL-10, IFN-γ, TNF-α, CD3, CD8, erythrocyte and hemoglobin. CD4/8, IL-6 and CRP were only difference compared with Group A and B,. IL-6 and CRP reflect the severity of inflammation and infection. The higher the value, the more severe the inflammation and the more sensitive the IL-6 response.
The literature confirms(Zhu,et al.,2014)that PLT is a repository of multiple inflammation and immunoregulatory factors, and act as ”capable coordinators” in inflammation and immune responses. However, it is still unclear about the cause of thrombocytopenia after viral infection. There may be two mechanisms used to explain(Yang,et al.,2004). First, virus infection damages hematopoietic stem cells and indirectly inhibit hematopoietic cells through immune mechanisms. Second, lung is one organ of megakaryocytes ( MKs ) maturing and PLT releasing(Lefrançais et al.2017). Due to extensive lung injury, megakaryocyte division is reduced, and inflammation lead to PLT aggregation and thrombosis, which increase PLT consumption and reduce production. However, early lung injury is not particularly serious, and platelets can return to normal levels as the lung inflammation or infection continues to worsen during treatment. In addition, some patients also platelet elevation. So the above mechanism obviously does not seem to fully explain the early thrombocytopenia in COVID-19 patients.
Robert A. Campbell found that(Campbell,et al.,2019)MKs have the ability to fight viruses through the IFITM3 factor. PLT IFITM3 factor isolated from patients infected with dengue fever (DENV) or influenza virus is significantly rising. Low expression of IFITM3 in PLT is associated with severity of disease and increased mortality. DENV-infected human MKs can selectively up-regulate type I interferons (IFNs) and IFITM3. Overexpression of IFITM3 in MKs can effectively prevent DENV infection. Whether PLT and MKs  can play the same role in COVID-19 patient has not been studied until now. So we think that if it can play the same role, It may be more reasonable to explain the early PLT reduction in COVID-19 patient than the above two possible mechanism. Because we found that most patients with early PLT reduction are ”transient”. We speculate that after the lung infection of the new coronavirus, a large number of early PLT and megakaryocytes were used to fight the virus instantly, resulting in a decrease of PLT, and the relatively slow response to inflammation, the platelet regulation mechanism gradually PLT returned to normal.
However. PLT was also found to be elevated in the early stage of COVID-19, which may be our first report. First of all. We consider whether there will be a difference in the virus incubation time between the PLT decreased and elevated group? . In this study, it was found that lymphocytes were less decreased in the PLT elevated group, and IL-4 was higher than that in the thrombocytopenia and PLT normal groups. In addition, the values of IL-6 and CRP in PLT elevated group, indicators of inflammation and infection, were also lower than those of the thrombocytopenia group, but were not different from those of the PLT normal group. Therefore, according to our analysis, it may be due to the different incubation time of the virus, the difference between drug control and individual patients, and the growth effect of PLT under relatively mild inflammation stimulation is stronger than the loss of PLT and megakarocyte against virus, but this growth advantage will be weakened with the aggravation of inflammation and infection. It has been confirmed in the literature that IL-6 has a similar role as thrombopenia in promoting the generation of PLT and regulating the proliferation and maturation of megakarocytic, but the specific mechanisms in vivo remain to be studied(Chen, et al 2017).
Clinical observation showed that thrombocytopenia may occur during the entire treatment process of COVID-19, and the early changes of PLT have not been directly correlated with the severity of this disease, and the treatment outcome of COVID-19 with early PLT elevate and decrease remains to be further studied. Therefore, early PLT changes cannot be used as an indicator of COVID-19 severity. However, there are also many COVID-19 patients with severe and rapid PLT decline, which is still difficult to explain, resulting in the risk of bleeding complications. At present, the effect of drug therapy for increasing PLT remains to be observed, and active treatment of the primary disease should be one of the best treatment methods. To explore changes and mechanism of PLT after COVID-19 may be helpful for us to have a more comprehensive understanding of the occurrence, development, treatment and outcome of COVID-19 disease.