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.