Background
At present, novel coronavirus disease 2019 (COVID-19) has become a serious global public health problem. The current meta-analysis aimed to find risk factors for the COVID-19-related ...death, helping to enhance the efficacy and reduce the mortality of COVID-19.
Methods
We searched PubMed, Embase, medRxiv, and Cochrane Library for articles published between January 1, 2020, and April 13, 2020. We statistically analyzed the risk factors of the COVID-19 deceased with meta-analysis.
Results
A total of 2401 patients in 15 articles were included in this study. Meta-analysis showed that 66.6% of COVID-19 deceased were male, with a median age of 69.9 years. Common symptoms of deceased included fever (70.6–100%), dyspnea (38.89–85.7%), cough (22.4–78%), and fatigue (22–61.9%). The incidence of hypertension, chronic cardiovascular disease, diabetes, and chronic cerebrovascular disease among the COVID-19 deceased were 38.56% (95% confidence interval (CI) 25.84 ~ 52.12%), 17.54% (95% CI 13.38 ~ 21.69%), 22.2% (95% CI 19.30 ~ 25.10%), and 15.58% (95% CI 10.05 ~ 21.12%), respectively. Compared with the surviving COVID-19 patients, the deceased had lower platelet levels (mean difference (MD) = − 39.35, 95% CI − 55.78 ~ − 22.93) and higher C-reactive protein (CRP) (MD = 80.85, 95% CI 62.53 ~ 99.18) and lactate dehydrogenase (LDH) (MD = 246.65, 95% CI 157.43 ~ 335.88) at admission. The most common complications of the deceased were acute respiratory distress syndrome (ARDS) (OR = 100.36, 95% CI 64.44 ~ 156.32) and shock (OR = 96.60, 95% CI 23.80 ~ 392.14).
Conclusion
Most of the COVID-19 deceased were elderly males. Fever, dyspnea, dry cough, fatigue, hypertension, chronic cardiovascular and cerebrovascular disease, diabetes, and laboratory examinations showed low levels of platelet content, increased CRP and LDH were associated with the risk of dying. ARDS and shock were risk factors for death in COVID-19 patients.
Background
Traditional drug susceptibility testing cannot be performed in clinical laboratories due to the slow-growing characteristics of
Mycoplasma genitalium
when cultured
in vitro
. Sanger ...sequencing is the standard method for detecting drug resistance-associated mutations. It has been used in some laboratories to guide the choice of macrolide antibiotics for
Mycoplasma genitalium
infected patients. Furthermore, resistance to fluoroquinolone has become another emerging clinical challenge.
Objective
Sequencing analysis can detect unknown mutations, but it is time-consuming, requires professional analytical skills and the appropriate testing equipment. The main objective of this study was to establish a nested real-time PCR method for the simultaneous detection of
23S rRNA
and
parC
genotypes in relation to the macrolide and fluoroquinolone resistance.
Results
105 MG-positive samples and 27 samples containing other pathogens were used for validation. The limit of the nested real-time PCR detection was 500 copies/reaction and there was no cross-reaction with
Ureaplasma urealyticum
,
Mycoplasma hominis
,
Chlamydia trachomatis
,
Neisseria gonorrhoeae
,
Human papillomavirus
,
Herpes simplex virus
,
Candida albicans
and
Ureaplasma parvum
, but the
23S rRNA
assay cross-reacted with
Mycoplasma pneumoniae
. Compared with sequencing results, the sensitivity of
23S rRNA
was 100% (95% CI; 93.3 -100), the specificity was 94.3% (95% CI; 79.4 - 99.0), the overall consistency was 98% (95% CI; 92.5 - 99.7) and
kappa
value was 0.96 (
P
< 0.001); the sensitivity of
parC
was 100% (95% CI; 93.4 - 100), the specificity was 89.7% (95% CI; 71.5 - 97.3) and the overall consistency was 96.9% (95% CI; 90.7 - 99.2) with a
kappa
value of 0.92 (
P
< 0.001).
Conclusions
The results of this sensitive and rapid alternative for identifying resistant genotypes of
Mycoplasma genitalium
are intuitive and easy to interpret, especially for mixed MG populations. Although the relevant
23S rRNA
primers need further adjustment, this reliable method would provide an effective diagnostic tool for the selection of antibiotics in clinical practice.
CD103 is an important marker of tissue-resident memory T cells (TRM) which play important roles in fighting against infection. However, the immunological characteristics of CD103
+
T cells are not ...thoroughly elucidated in the liver of mouse infected with Plasmodium. Six- to eight-week-old C57BL/6 mice were infected with
Plasmodium yoelii nigeriensis
NSM. Mice were sacrificed on 12–16 days after infection and the livers were picked out. Sections of the livers were stained, and serum aspartate aminotransferase (AST) and alanine transaminase (ALT) levels were measured. Moreover, lymphocytes in the liver were isolated, and the expression of CD103 was determined by using qPCR. The percentage of CD103 on different immune cell populations was dynamically observed by using flow cytometry (FCM). In addition, the phenotype and cytokine production characteristics of CD103
+
CD8
+
Tc cell were analyzed by using flow cytometry, respectively. Erythrocyte stage plasmodium infection could result in severe hepatic damage, a widespread inflammatory response and the decrease of CD103 expression on hepatic immune cells. Only CD8
+
Tc and γδT cells expressed higher levels of CD103 in the uninfected state.CD103 expression in CD8
+
Tc cells significantly decreased after infection. Compared to that of CD103
−
CD8
+
Tc cells, CD103
+
CD8
+
Tc cells from the infected mice expressed lower level of CD69, higher level of CD62L, and secreted more IL-4, IL-10, IL-17, and secreted less IFN-γ. CD103
+
CD8
+
Tc cells might mediate the hepatic immune response by secreting IL-4, IL-10, and IL-17 except IFN-γ in the mice infected with the erythrocytic phase plasmodium, which could be involved in the pathogenesis of severe liver damage resulted from the erythrocytic phase plasmodium
yoelii nigeriensis
NSM infection.
The morbidity and mortality of malaria are still high. Programmed cell death-1(PD-1) is an important co-inhibitory factor and CD8 T cells with PD-1 were reported to be exhausted cells. It remains ...unknown what the role of CD4 T cells expressing PD-1 is and what the upstream regulating molecules of PD-1 in CD4 T cells are. The C57BL/6 mice were injected with
Plasmodium yoelii
(
P. yoelii
) in this study. Expressions of PD-1, activation markers, and cytokines were tested. The differentially expressed genes between PD-1
+/-
CD4 T cells were detected by microarray sequencing. Western blot, chromatin immunoprecipitation (ChIP), siRNA, hypoxia inducible factor-1α (HIF-1α) inducer and inhibitor were used to explore PD-1’s upstream molecules, respectively. The proportions of PD-1
+
CD4 T cells increased post
P. yoelii
infection. PD-1
+
CD4 T cells expressed more activated surface markers and could produce more cytokines. Nuclear factor of activated T cells 1 (NFATc1) was found to be a key transcription factor to induce PD-1 expression after infection. Both the inducer and the inhibitor of HIF-1α could change the expressions of NFATc1 and PD-1
in vivo
and
in vitro
, respectively. Taken together,
P. yoelii
infection induced NFATc1 expression by HIF-1α. The highly expressed NFATc1 entered the nucleus and initiated PD-1 expression. PD-1
+
CD4 T cells appeared to be more activated and could secrete more cytokines to regulate the host’s immune responses against malaria.
The pandemic of corona virus disease 2019 (COVID-19) caused by SARS-CoV-2 is ravaging the world. Diagnosis and isolation of persons who are infected with SARS-CoV-2 is very important medical ...emergency to contain the epidemic of COVID-19. To date, the diagnosis of COVID-19 is mainly depending on positive quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) results for SARS-CoV-2. In the present study, we reported that two cases with uncommon symptoms from a family cluster were ultimately diagnosed as COVID-19 after more than twice of collecting samples and qRT-PCR tests were done. It is easily to miss diagnosis of COVID-19 especially for patients with uncommon symptoms. More attention should be paid to observe the clinical characteristics of it and invent more accurate and convenient methods to detect SARS-CoV-2 as soon as possible.
Few studies were conducted to assess safety and efficacy of continuous antiviral therapy administrated from preconception. In the present study, 136 eligible women with chronic HBV infection were ...recruited, and assigned to active chronic hepatitis B (CHB) (Group A, B or C) or chronic HBV carrier (Group D). Antiviral therapy was administrated in preconception (Group A), in early (Group B) or late pregnancy (Group C and Group D). Immunoprophylaxis was administrated to all infants. Mothers' HBV status and ALT were assessed at delivery and 7 months postpartum. Offspring's HBV status was examined at 7 months old. Group A women showed low HBV DNA level and normal ALT throughout pregnancy. All women at delivery had an HBV DNA level of less than 10
IU/ml, but the proportion of patients with lower HBV DNA level in Group A was higher than any of other three groups (P < 0.05). No differences in obstetrical complications were found among the four groups. None of infants who completed follow-up showed positive HBsAg at age of 7 months. Congenital malformation and infant growth indicators were similar among study cohorts. Continuous antiviral therapy from preconception to entire pregnancy is effective and safe for active CHB mothers and their infants.
Splenomegaly is a prominent clinical manifestation of malaria and the causes remain incompletely clear. Anemia is induced in malaria and extramedullary splenic erythropoiesis is compensation for the ...loss of erythrocytes. However, the regulation of extramedullary splenic erythropoiesis in malaria is unknown. An inflammatory response could facilitate extramedullary splenic erythropoiesis in the settings of infection and inflammation. Here, when mice were infected with rodent parasites,
NSM, TLR7 expression in splenocytes was increased. To explore the roles of TLR7 in splenic erythropoiesis, we infected wild-type and
C57BL/6 mice with
NSM and found that the development of splenic erythroid progenitor cells was impeded in
mice. Contrarily, the treatment of the TLR7 agonist, R848, promoted extramedullary splenic erythropoiesis in wild-type infected mice, which highlights the implication of TLR7 on splenic erythropoiesis. Then, we found that TLR7 promoted the production of IFN-γ that could enhance phagocytosis of infected erythrocytes by RAW264.7. After phagocytosis of infected erythrocytes, the iron metabolism of RAW264.7 was upregulated, evidenced by higher iron content and expression of
and
. Additionally, the neutralization of IFN-γ impeded the extramedullary splenic erythropoiesis modestly and reduced the iron accumulation in the spleen of infected mice. In conclusion, TLR7 promoted extramedullary splenic erythropoiesis in
NSM-infected mice. TLR7 enhanced the production of IFN-γ, and IFN-γ promoted phagocytosis of infected erythrocytes and the iron metabolism of macrophages
, which may be related to the regulation of extramedullary splenic erythropoiesis by TLR7.
Th cells (helper T cells) have multiple functions in
(
) infection. Inducible co-stimulator (ICOS) is induced and expressed in activated T lymphocytes, which enhances the development of B cells and ...antibody production through the ICOS/ICOSL pathway. It remains unclear about the role and possible regulating mechanism of ICOS
Th cells in the spleen of
-infected C57BL/6 mice.
C57BL/6 mice were infected with cercariae of
through the abdomen. The expression of ICOS, activation markers, and the cytokine production on CD4
ICOS
Th cells were detected by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR). Moreover, the differentially expressed gene data of ICOS
and ICOS
Th cells from the spleen of infected mice were obtained by mRNA sequencing. Besides, Western blot and chromatin immunoprecipitation (ChIP) were used to explore the role of Ikzf2 on ICOS expression.
After
infection, the expression of ICOS molecules gradually increased in splenic lymphocytes, especially in Th cells (
< 0.01). Compared with ICOS
Th cells, more ICOS
Th cells expressed CD69, CD25, CXCR5, and CD40L (
< 0.05), while less of them expressed CD62L (
< 0.05). Also, ICOS
Th cells expressed more cytokines, such as IFN-γ, IL-4, IL-10, IL-2, and IL-21 (
< 0.05). RNA sequencing results showed that many transcription factors were increased significantly in ICOS
Th cells, especially Ikzf2 (
< 0.05). And then, the expression of Ikzf2 was verified to be significantly increased and mainly located in the nuclear of ICOS
Th cells. Finally, ChIP experiments and dual-luciferase reporter assay confirmed that Ikzf2 could directly bind to the ICOS promoter in Th cells.
In this study, ICOS
Th cells were found to play an important role in
infection to induce immune response in the spleen of C57BL/6 mice. Additionally, Ikzf2 was found to be one important transcription factor that could regulate the expression of ICOS in the spleen of
-infected C57BL/6 mice.
Previous work conducted by our group has shown that the accumulation of hepatic natural killer (NK) cells and the up-regulation of natural cytotoxicity receptors (NKP30 and NKP46) on NK cells from ...patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) were correlated with disease progression in HBV-ACLF. The natural cytotoxicity receptors expressed on NK cells are believed to be probable candidates involved in the NK cell-mediated hepatocyte damage in HBV-ACLF. However, the underlying mechanisms remain to be elucidated. In the present study, we aimed to discover the role of NKP30-B7-H6 interaction in NK cells-mediated hepatocyte damage in HBV-ACLF.
Hepatic expressions of B7-H6 and interleukin-32 (IL-32) were examined by immunochemistry staining in samples from patients with HBV-ACLF or mild chronic hepatitis B (CHB). The cytotoxicity of NK-92 cell against target cells (Huh-7 and LO2) was evaluated by CCK8 assay. Expression of IL-32 in liver NK cell, T cells and NK-92 cell line was detected by the flow cytometric analysis. The effect of IL-32 on the apoptosis of Huh7 cells was evaluated using Annexin V/PI staining analysis.
An enhancement of hepatic B7-H6 and IL-32 expression was associated with the severity of liver injury in HBV-ACLF. And there was a positive association between hepatic B7-H6 and IL-32 expression. Expressions of IL-32 in liver NK cells and T cells were increased in HBV-ACLF patients. In vitro NK-92 cells are highly capable of killing the high B7-H6 expressing Huh7 cells and B7-H6-tansfected hepatocyte line LO2 cells dependent on NKP30 and B7-H6 interaction. Furthermore, NK-92 cells exhibited elevated IL-32 expression when stimulated with anti-NKP30 antibodies or when co-cultured with Huh7 cells. IL-32 can induce the apoptosis of Huh7 cells in a dose-dependent manner.
Our results suggest that NKP30-B7-H6 interaction can aggravate hepatocyte damage, probably through up-regulation of IL-32 expression in HBV-ACLF.
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