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1.
Int J Infect Dis ; 118: 264-269, 2022 May.
Article in English | MEDLINE | ID: covidwho-1838867

ABSTRACT

OBJECTIVES: The study aimed to explore the efficacy and safety of linezolid-based chemotherapeutic regimens for patients with postoperative multidrug-resistant spinal tuberculosis. METHODS: The randomized controlled study included 50 Mycobacterium tuberculosis culture or pathological-confirmed multidrug resistant tuberculosis patients who received spinal surgery from January 2018 to February 2020. Twenty-five patients were assigned to the control group and the study group, respectively. Random number method was used for patient allocation and they were treated with levofloxacin, pyrazinamide, thioisonicotinamide enteric-coated tablet, amikacin sulfate injection, and sodium p-amino salicylate injection, accompanied by linezolid or not. RESULTS: The overall effective rate of the study group was higher than that of the control group (88.00% vs 64.00%, P<0.05). The severity of pain at 3 and 6 months postoperatively was lower in the study group than that in the control group (P<0.05). Postoperatively, the study group had higher bone graft fusion rate, shorter mean bone graft fusion time, and higher paraspinal cyst absorption rate than the control group (P<0.05). Postoperatively, the study group had lower levels of PCT, ESR, and CRP than the control group (P <0.05). All patients had normal hepatic and renal function, and no statistical difference of adverse effects between 2 groups were found. CONCLUSIONS: Linezolid-based chemotherapeutic regimens can effectively treat patients with postoperative multidrug-resistant spinal tuberculosis but have higher rates of adverse reactions.


Subject(s)
Linezolid , Tuberculosis, Multidrug-Resistant , Tuberculosis, Spinal , Humans , Linezolid/adverse effects , Mycobacterium tuberculosis/drug effects , Treatment Outcome , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/surgery , Tuberculosis, Spinal/drug therapy , Tuberculosis, Spinal/surgery
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311944

ABSTRACT

Background: The outbreak of the novel coronavirus in China (COVID-19) represents a significant and urgent threat to global health. We report here five cases of COVID-19 infection patients in our clinical practices who are medically stable and presumed to successfully “cleared” the virus after antiviral treatments. Case presentation: The clinical evaluation depends on the viral nucleic acid test in respiratory specimens by real-time PCR reverse transcription (RT-PCR) assays according to the authorized guidance. We found that the stool samples of these cured patients remain positive in RT-PCR assay while the virus is undetectable in respiratory specimens. RT-PCR molecular diagnostic assay was designed to specifically detect the presence of viral RNA. Thus, the positive result in the fecal specimens implies the existence of viable virions with the patients. Conclusions: : This highlights the importance to look closely at the assessment standard of medical treatment, as well as the need for reevaluation of the criteria for the initial screening, prevention, and care of patients with this emerging infection.

3.
Front Pediatr ; 9: 750012, 2021.
Article in English | MEDLINE | ID: covidwho-1566657

ABSTRACT

Background: There is little direct or indirect evidence of the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy on early childhood development. Methods: We conducted a prospective, observational cohort study in China from May 1 to October 31, 2020, that enrolled 135 mother-infant dyads: 57 dyads in the infection cohort and 78 in the non-infection cohort. Among all infants, 14.0% were preterm birth in the infection cohort and 6.4% in the non-infection cohort. Participants were followed by telephone interviews to collect demographic characteristics, medical records of coronavirus disease 2019, breastfeeding data, and early childhood development was assessed by the Age and Stage Questionnaire (ASQ-3) and Age and Stage Questionnaire Social-Emotional (ASQ:SE-2) Chinese versions at 3 months after childbirth. We used multivariable Poisson regression models to estimate the relative risk (RR) of SARS-CoV-2 infection. Multivariable linear regression models and a mediation model were used to test the direct and indirect associations between SARS-CoV-2 infection and the ASQ-3 score. This study was approved by the Peking University Third Hospital Medical Science Research Ethics Committee (No. IRB00006761-M2020127). Results: In the infection cohort, 13.6% of the children showed social-emotional developmental delay, and 13.5% showed overall developmental delay. The corresponding rates in the non-infection cohort were 23.4 and 8.1%. Compared with the non-infection cohort, SARS-CoV-2 infection during pregnancy did not increase the risk of social-emotional (RR = 0.87, 95% CI: 0.51-1.49) or overall (RR = 1.02, 95% CI: 0.60-1.73) developmental delay. The mediation model showed that SARS-CoV-2 infection indirectly affected the ASQ-3 score by increasing the length of mother-infant separation. Conclusions: SARS-CoV-2 during late pregnancy did not increase the risk of developmental delay of the offspring 3 months after delivery. However, SARS-CoV-2 may have indirect effects on early childhood development by increasing mother-infant separation.

4.
J Mol Cell Biol ; 13(10): 695-704, 2021 12 30.
Article in English | MEDLINE | ID: covidwho-1232219

ABSTRACT

The worldwide infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacts human health and life on multiple levels. People infected with SARS-CoV-2 suffer from physical disorders and psychological distress. At present, no direct evidence indicates that SARS-CoV-2 negatively influences human reproduction, and the possibility that gametes and embryos are affected requires further investigation. To evaluate the potential effects of SARS-CoV-2 infection on human reproduction and fetal health, this review summarizes the basic and clinical research of SARS-CoV-2 on reproduction up to date, hoping to offer guidance and advice to people at reproductive age and provide clues for the prevention and treatment of associated diseases.


Subject(s)
COVID-19/complications , Reproduction/immunology , SARS-CoV-2/immunology , COVID-19/epidemiology , COVID-19/immunology , COVID-19/virology , Humans
5.
Front Pharmacol ; 11: 585021, 2020.
Article in English | MEDLINE | ID: covidwho-1110321

ABSTRACT

In Feb 2020, we developed a physiologically-based pharmacokinetic (PBPK) model of hydroxychloroquine (HCQ) and integrated in vitro anti-viral effect to support dosing design of HCQ in the treatment of COVID-19 patients in China. This, along with emerging research and clinical findings, supported broader uptake of HCQ as a potential treatment for COVID-19 globally at the beginning of the pandemics. Therefore, many COVID-19 patients have been or will be exposed to HCQ, including specific populations with underlying intrinsic and/or extrinsic characteristics that may affect the disposition and drug actions of HCQ. It is critical to update our PBPK model of HCQ with adequate drug absorption and disposition mechanisms to support optimal dosing of HCQ in these specific populations. We conducted relevant in vitro and in vivo experiments to support HCQ PBPK model update. Different aspects of this model are validated using PK study from 11 published references. With parameterization informed by results from monkeys, a permeability-limited lung model is employed to describe HCQ distribution in the lung tissues. The updated model is applied to optimize HCQ dosing regimens for specific populations, including those taking concomitant medications. In order to meet predefined HCQ exposure target, HCQ dose may need to be reduced in young children, elderly subjects with organ impairment and/or coadministration with a strong CYP2C8/CYP2D6/CYP3A4 inhibitor, and be increased in pregnant women. The updated HCQ PBPK model informed by new metabolism and distribution data can be used to effectively support dosing recommendations for clinical trials in specific COVID-19 patients and treatment of patients with malaria or autoimmune diseases.

6.
Front Med ; 14(6): 752-759, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1064591

ABSTRACT

This study aimed to evaluate the efficacy of Chinese herbal medicine (CHM) in patients with severe/critical coronavirus disease 2019 (COVID-19). In this retrospective study, data were collected from 662 patients with severe/critical COVID-19 who were admitted to a designated hospital to treat patients with severe COVID-19 in Wuhan before March 20, 2020. All patients were divided into an exposed group (CHM users) and a control group (non-users). After propensity score matching in a 1:1 ratio, 156 CHM users were matched by propensity score to 156 non-users. No significant differences in seven baseline clinical variables were found between the two groups of patients. All-cause mortality was reported in 13 CHM users who died and 36 non-users who died. After multivariate adjustment, the mortality risk of CHM users was reduced by 82.2% (odds ratio 0.178, 95% CI 0.076-0.418; P < 0.001) compared with the non-users. Secondly, age (odds ratio 1.053, 95% CI 1.023-1.084; P < 0.001) and the proportion of severe/critical patients (odds ratio 0.063, 95% CI 0.028-0.143; P < 0.001) were the risk factors of mortality. These results show that the use of CHM may reduce the mortality of patients with severe/critical COVID-19.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , COVID-19/therapy , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Age Factors , Aged , China , Female , Humans , Male , Middle Aged , Odds Ratio , Propensity Score , Retrospective Studies , Survival Rate
10.
BMC Med ; 18(1): 347, 2020 11 04.
Article in English | MEDLINE | ID: covidwho-910201

ABSTRACT

BACKGROUND: Evidence concerning the long-term impact of Covid-19 in pregnancy on mother's psychological disorder and infant's developmental delay is unknown. METHODS: This study is a longitudinal single-arm cohort study conducted in China between May 1 and July 31, 2020. Seventy-two pregnant patients with Covid-19 participated in follow-up surveys until 3 months after giving birth (57 cases) or having abortion (15 cases). We collected data from medical records regarding Covid-19, delivery or abortion, testing results of maternal and neonatal specimens, and questionnaires of quarantine, mother-baby separation, feeding, and measuring of mothers' mental disorders and infants' neurobehavioral disorders. RESULTS: All cases infected in the first trimester and 1/3 of cases infected in the second trimester had an abortion to terminate the pregnancy. 22.2% of pregnant patients were suffering from post-traumatic stress disorder or depression at 3 months after delivery or induced abortion. Among 57 live births, only one neonate was positive of nucleic acid testing for throat swab, but negative in repeated tests subsequently. The median duration of mother-baby separation was 35 days (interquartile range 16 to 52 days). After the termination of maternal quarantine, 49.1% of mothers chose to prolong the mother-baby separation (median 8 days; IQR 5 to 23 days). The breastfeeding rate was 8.8% at 1 week after birth, 19.3% at the age of 1 month, and 36.8% at the age of 3 months, respectively. The proportion of "monitoring" and "risk" in the social-emotional developmental domain at the age of 3 months was 22.7% and 63.6%, respectively. After the adjustment of preterm, neonatal sex, admitted to NICU, and the mother's Covid-19 condition, the negative associations were significantly identified (p < 0.05) between mother-baby separation days and three developmental domains: communication, gross motor, and personal-social. CONCLUSIONS: There is no definite evidence on vertical transmission of SARS-CoV-2. In addition to control infection risk, researchers and healthcare providers should pay more attention to maternal mental health and infant's feeding, closeness with parents, and early development.


Subject(s)
Betacoronavirus , Child Development , Coronavirus Infections/psychology , Infant Behavior/psychology , Infectious Disease Transmission, Vertical , Pneumonia, Viral/psychology , Pregnancy Complications, Infectious/psychology , Adult , COVID-19 , Child Development/physiology , China/epidemiology , Cohort Studies , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Female , Follow-Up Studies , Humans , Infant , Infant Behavior/physiology , Infant, Newborn , Longitudinal Studies , Male , Mothers/psychology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Pregnancy , Pregnancy Complications, Infectious/epidemiology , SARS-CoV-2 , Surveys and Questionnaires
11.
Engineering (Beijing) ; 6(10): 1162-1169, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-716696

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the world, leading to large-scale population infection. Angiotensin-converting enzyme 2 (ACE2) is the receptor of both severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. However, it is still controversial whether vertical transmission exists. In order to investigate the potential risk of SARS-CoV-2 vertical transmission, we explored ACE2 and TMPRSS2 (encoding transmembrane protease serine 2) expression patterns in peri-implantation embryos and the maternal-fetal interface using previously published single-cell transcriptome data. The results showed that day 6 (D6) trophectoderm (TE) cells in peri-implantation embryos, as well as syncytiotrophoblast (STB) at 8 weeks of gestation (STB_8W) and extravillous trophoblast (EVT) cells at 24 weeks of gestation (EVT_24W) in the maternal-fetal interface, strongly co-expressed ACE2 and TMPRSS2, indicating a SARS-CoV-2 infection susceptibility. The ACE2 positive-expressing cells in the three cell types mentioned above were found to share common characteristics, which were involved in autophagy and immune-related processes. ACE2 showed no gender bias in post-implantation embryos but showed a significant gender difference in D6_TE, D6 primitive endoderm (PE) cells, and ACE2 positive-expressing STBs. These findings suggest that there may be different SARS-CoV-2 infection susceptibilities of D6 embryos of different genders and during the gestation of different genders. Our results reveal potential SARS-CoV-2 infection risks during embryo transfer, peri-implantation embryo development, and gestation.

12.
Sci China Life Sci ; 63(7): 1006-1015, 2020 07.
Article in English | MEDLINE | ID: covidwho-177413

ABSTRACT

Being infected by SARS-CoV-2 may cause damage to multiple organs in patients, such as the lung, liver and heart. Angiotensin-converting enzyme 2 (ACE2), reported as a SARS-CoV-2 receptor, is also expressed in human male testes. This suggests a potential risk in human male reproductive system. However, the characteristics of ACE2-positive cells and the expression of other SARS-CoV-2 process-related genes are still worthy of further investigation. Here, we performed singlecell RNA seq (scRNA-seq) analysis on 853 male embryo primordial germ cells (PGCs) and 2,854 normal testis cells to assess the effects of the SARS-CoV-2 virus on the male reproductive system from embryonic stage to adulthood. We also collected and constructed the scRNA-seq library on 228 Sertoli cells from three non-obstructive azoospermia (NOA) patients to assess the effects at disease state. We found that ACE2 expressing cells existed in almost all testis cell types and Sertoli cells had highest expression level and positive cells ratio. Moreover, ACE2 was also expressed in human male PGCs. In adulthood, the level of ACE2 expression decreased with the increase of age. We also found that ACE2 positive cells had high expressions of stress response and immune activation-related genes. Interestingly, some potential SARS-CoV-2 process-related genes such as TMPRSS2, BSG, CTSL and CTSB had different expression patterns in the same cell type. Furthermore, ACE2 expression level in NOA donors' Sertoli cells was significantly decreased. Our work would help to assess the risk of SARS-CoV-2 infection in the male reproductive system.


Subject(s)
Azoospermia/genetics , Betacoronavirus/pathogenicity , Coronavirus Infections , Pandemics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral , Testis/metabolism , Testis/virology , Adult , Angiotensin-Converting Enzyme 2 , Azoospermia/complications , Azoospermia/metabolism , Betacoronavirus/metabolism , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Embryonic Germ Cells/metabolism , Embryonic Germ Cells/virology , Gene Expression , Gene Expression Profiling , Gene Regulatory Networks , Humans , Male , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/complications , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , Receptors, Virus/genetics , Receptors, Virus/metabolism , SARS-CoV-2 , Sertoli Cells/metabolism , Sertoli Cells/virology , Single-Cell Analysis , Spermatogenesis/genetics , Spermatogenesis/physiology , Testis/cytology
13.
Reprod Biomed Online ; 41(1): 89-95, 2020 07.
Article in English | MEDLINE | ID: covidwho-154707

ABSTRACT

The outbreak of 2019 novel coronavirus disease (COVID-19) has become a major pandemic threat worldwide. Such a public health emergency can greatly impact various aspects of people's health and lives. This paper focuses on its potential risks for reproductive health, including the reproductive system and its functioning, as well as gamete and embryo development, which could be affected by the virus itself, drug treatments, chemical disinfectants and psychological effects related to panic during the COVID-19 outbreak.


Subject(s)
Coronavirus Infections/psychology , Pneumonia, Viral/psychology , Antiviral Agents/adverse effects , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Female , Humans , Infertility/virology , Male , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/therapy , Reproductive Health , Stress, Psychological
14.
Acta Pharm Sin B ; 10(7): 1216-1227, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-88718

ABSTRACT

Chloroquine (CQ) phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019 (COVID-19). To develop a physiologically-based pharmacokinetic (PBPK) model for predicting tissue distribution of CQ and apply it to optimize dosage regimens, a PBPK model, with parameterization of drug distribution extrapolated from animal data, was developed to predict human tissue distribution of CQ. The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism. Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships. The model was also validated by clinical data from Chinese patients with COVID-19. The novel PBPK model allows in-depth description of the pharmacokinetics of CQ in several key organs (lung, heart, liver, and kidney), and was applied to design dosing strategies in patients with acute COVID-19 (Day 1: 750 mg BID, Days 2-5: 500 mg BID, CQ phosphate), patients with moderate COVID-19 (Day 1: 750 mg and 500 mg, Days 2-3: 500 mg BID, Days 4-5: 250 mg BID, CQ phosphate), and other vulnerable populations (e.g., renal and hepatic impairment and elderly patients, Days 1-5: 250 mg BID, CQ phosphate). A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.

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