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1.
World J Crit Care Med ; 11(5): 311-316, 2022 Sep 09.
Article in English | MEDLINE | ID: covidwho-2044144

ABSTRACT

In this editorial, we comment on the current development and deployment of data science in intensive care units (ICUs). Data in ICUs can be classified into qualitative and quantitative data with different technologies needed to translate and interpret them. Data science, in the form of artificial intelligence (AI), should find the right interaction between physicians, data and algorithm. For individual patients and physicians, sepsis and mechanical ventilation have been two important aspects where AI has been extensively studied. However, major risks of bias, lack of generalizability and poor clinical values remain. AI deployment in the ICUs should be emphasized more to facilitate AI development. For ICU management, AI has a huge potential in transforming resource allocation. The coronavirus disease 2019 pandemic has given opportunities to establish such systems which should be investigated further. Ethical concerns must be addressed when designing such AI.

2.
International Journal of Contemporary Hospitality Management ; 2022.
Article in English | Web of Science | ID: covidwho-2032217

ABSTRACT

Purpose This study aims to understand Chinese consumers' perceived barriers to using peer-to-peer (P2P) accommodation before and after the outbreak of COVID-19 and the negotiation strategies they applied in overcoming the barriers and enabling consumption. Design/methodology/approach A qualitative research design with 28 semi-structured interviews was used. Data were analysed by content analysis. Findings Five psychological barriers and four functional barriers were found to inhibit consumers from using P2P accommodation both before and after the COVID-19 outbreak. In overcoming the perceived barriers, consumers applied both behavioural negotiation strategies, including seeking information, behavioural adaptation, selective choice and seeking social support, and cognitive negotiation strategies, including cognitive adaptation and trusting agents. COVID-19 was found to serve as both a barrier and a facilitator for using P2P accommodation. A barriers-negotiation framework was developed in the context. Research limitations/implications Theoretically, this study advances consumer resistance and perceived barriers literature by integrating negotiation and developing a barriers-negotiation framework of P2P accommodation usage. This study also offers insights for practitioners in the P2P accommodation industry. Originality/value This study showcases the role of negotiation in understanding barriers to using P2P accommodation, paving the way to extend relevant knowledge to advance consumer resistance research, which is an emerging topic in the broader management domain.

3.
CNS Neurosci Ther ; 28(4): 470-483, 2022 04.
Article in English | MEDLINE | ID: covidwho-1745958

ABSTRACT

Postoperative neurological disorders, including postoperative delirium (POD), postoperative cognitive dysfunction (POCD), postoperative covert ischemic stroke, and hemorrhagic stroke, are challenging clinical problems in the emerging aged surgical population. These disorders can deteriorate functional outcomes and long-term quality of life after surgery, resulting in a substantial social and financial burden to the family and society. Understanding predisposing and precipitating factors may promote individualized preventive treatment for each disorder, as several risk factors are modifiable. Besides prevention, timely identification and treatment of etiologies and symptoms can contribute to better recovery from postoperative neurological disorders and lower risk of long-term cognitive impairment, disability, and even death. Herein, we summarize the diagnosis, risk factors, prevention, and treatment of these postoperative complications, with emphasis on recent advances and perspectives.


Subject(s)
Cognitive Dysfunction , Delirium , Postoperative Cognitive Complications , Aged , Cognitive Dysfunction/etiology , Humans , Postoperative Complications , Quality of Life , Risk Factors
4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-312688

ABSTRACT

Objective: To determine key factors associated with sequela-free survival of patients with COVID-19.Design: Retrospective–prospective observational study.Setting: Leishenshan Hospital in Wuhan, China.Participants: Patients with COVID-19 admitted at Leishenshan Hospital in Wuhan, China between 15 February 2020 and 1 April 2020 and discharged.Main Outcomes: MeasuresSequela-free survival is defined as having none of the long-term sequelae measured with the Activity of Daily Living (ADL) Scale, Modified Medical Research Council (mMRC) Dyspnoea Scale, New York Heart Association (NYHA) classification, Self-rating Depression Scale (SDS), Carcinologic Handicap Index (CHI) and Modified Telephone Interview for Cognitive Status (TICS-M). Multivariable logistic regression was used to examine the key factors of sequela-free survival.ResultsThe follow-up period for the 464 patients was 10 August to 30 September 2020. Of these, 424 patients completed the assessment of all scales. 30.2% (128 of 424) were categorised as sequela-free at follow-up. The most common sequelae were psychosocial problems (254 [57.7%]), respiratory function abnormality (149 [32.6%]) and cardiac function abnormality (98 [21.5%]). Risk factors associated with COVID-19 sequelae were anaemia on admission, longer duration from the onset of symptoms to admission and advanced age, whereas anti-anaemia treatment was a protective factor against sequelae. A haemoglobin level of <113 g/l for female patients or <92 g/l for male patients at admission discriminated a higher risk of any COVID-19 sequelae.Conclusions: Only one third COVID-19 survivors were sequela-free. Anaemia on admission, longer duration from the onset of symptoms to admission and advanced age were the risk factors of any long-term sequela. Anti-anaemia treatment was associated with beneficial outcomes in COVID-19 survivors.Funding: This study was funded by grants to DSS from the National Natural Science Foundation of China (Nos.81771133, 81970995) (DSD grants), Shanghai Shenkang Hospital Development Center Founding (SHDC12017X11), Renji Hospital Clinical Innovation Foundation (PYMDT-007), Shanghai municipal Education Commission-Gaofeng Clinical Medicine Support (20191903), State Key Laboratory of Neuroscience(SKLN-201803), the National Natural Science Foundation of China (No.81701358) (DH grants), the Shanghai Municipal Commission of Health and Family Planning Funding (20184Y0205) (CYC grants) and Renji Hospital founding (RJZZ18-019) (LLH grants).Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Institutional Research Ethics Committee of Renji Hospital, School of Medicine, Shanghai Jiaotong University (ethics committee approval No. KY2020-34).

5.
Psychol Res Behav Manag ; 15: 193-212, 2022.
Article in English | MEDLINE | ID: covidwho-1666877

ABSTRACT

PURPOSE: Road safety research is important due to the large number of road traffic fatalities globally. This study investigated the influences of age, driving experience and other covariates on aggressive driving behavior. METHODS: A cross-sectional survey was conducted in Yixing City, Wuxi City, Jiangsu Province, China. Regression analysis was applied to explore the influences of age and driving experience and their interactions with other covariates on aggressive driving behavior. Two analyses methodologies were used to assess the simple effect of the interactions. Firstly, the Jamovi automatic analysis classification program was used to calculate the simple slope test. Second, the SPSS macro program was also used to calculate the simple slope test also. RESULTS: A total of 570 drivers (247 males, 282 females) participated in the survey. A negative correlation was found between age and aggressive driving behaviors, and a positive correlation was found between neuroticism and aggressive driving behaviors in the multiple regression analysis. Significant associations were also found between age, driving experience, and depression, as well as age, driving experience, and neuroticism. Simple slope tests showed that depressive symptoms could increase aggressive behaviors in the elderly and experienced drivers. When experiencing neuroticism, individuals with higher driving experience were more aggressive in driving than shorter experienced drivers. CONCLUSION: Age and neuroticism influenced aggressive driving behaviors. Veteran drivers could be aggressive drivers when experiencing depressive symptoms or neuroticism. Mobile intervention could be sent to the potentially risky drivers, which would be safe and broadly feasible to prevent aggressive driving behavior in the background of COVID-19.

6.
Tourism Management Perspectives ; 40(98), 2021.
Article in English | CAB Abstracts | ID: covidwho-1608713

ABSTRACT

Travel live streaming has become an important tool for tourism marketers to attract and engage potential travellers, especially after the outbreak of Covid-19. Drawing on the presence theory, this study empirically explored the factors influencing consumers' purchasing behaviour in live-streamed shopping for tourism products. Data were collected manually from live-streamed events and analysed using multiple linear regressions. The results show that the physical presence factor effectively alleviates unsalable situations (i.e., circumstances where the product is not sold), while social presence by itself is not an adequate stimulus to greatly improved sales outcomes. Some basic features of live-streamed shopping such as the professionalism level of the platforms and the live-streaming anchors also play a role. The novel feature of this study is the understanding of the relationships between presence and customers' actual purchasing behaviour in tourism live-streamed shopping (TLSS).

7.
Ann Transl Med ; 9(15): 1261, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1369970

ABSTRACT

OBJECTIVE: To discuss the pathogenesis of severe coronavirus disease 2019 (COVID-19) infection and the pharmacological effects of glucocorticoids (GCs) toward this infection. To review randomized controlled trials (RCTs) using GCs to treat patients with severe COVID-19, and investigate whether GC timing, dosage, or duration affect clinical outcomes. Finally. to discuss the use of biological markers, respiratory parameters, and radiological evidence to select patients for improved GC therapeutic precision. BACKGROUND: COVID-19 has become an unprecedented global challenge. As GCs have been used as key immunomodulators to treat inflammation-related diseases, they may play key roles in limiting disease progression by modulating immune responses, cytokine production, and endothelial function in patients with severe COVID-19, who often experience excessive cytokine production and endothelial and renin-angiotensin system (RAS) dysfunction. Current clinical trials have partially proven this efficacy, but GC timing, dosage, and duration vary greatly, with no unifying consensus, thereby creating confusion. METHODS: Publications through March 2021 were retrieved from the Web of Science and PubMed. Results from cited references in published articles were also included. CONCLUSIONS: GCs play key roles in treating severe COVID-19 infections. Pharmacologically, GCs could modulate immune cells, reduce cytokine and chemokine, and improve endothelial functions in patients with severe COVID-19. Benefits of GCs have been observed in multiple clinical trials, but the timing, dosage and duration vary across studies. Tapering as an option is not widely accepted. However, early initiation of treatment, a tailored dosage with appropriate tapering may be of particular importance, but evidence is inconclusive and more investigations are needed. Biological markers, respiratory parameters, and radiological evidence could also help select patients for specific tailored treatments.

8.
Genes (Basel) ; 12(7)2021 06 25.
Article in English | MEDLINE | ID: covidwho-1295802

ABSTRACT

Peripheral blood transcriptome is a highly promising area for biomarker development. However, transcript abundances (TA) in these cell mixture samples are confounded by proportions of the component leukocyte subpopulations. This poses a challenge to clinical applications, as the cell of origin of any change in TA is not known without prior cell separation procedure. We developed a framework to develop a cell-type informative TA biomarkers which enable determination of TA of a single cell-type (B lymphocytes) directly in cell mixture samples of peripheral blood (e.g., peripheral blood mononuclear cells, PBMC) without the need for subpopulation separation. It is applicable to a panel of genes called B cell informative genes. Then a ratio of two B cell informative genes (a target gene and a stably expressed reference gene) obtained in PBMC was used as a new biomarker to represent the target gene expression in purified B lymphocytes. This approach, which eliminates the tedious procedure of cell separation and directly determines TA of a leukocyte subpopulation in peripheral blood samples, is called the Direct LS-TA method. This method is applied to gene expression datasets collected in influenza vaccination trials as early predictive biomarkers of seroconversion. By using TNFRSF17 or TXNDC5 as the target genes and TNFRSF13C or FCRLA as the reference genes, the Direct LS-TA B cell biomarkers were determined directly in the PBMC transcriptome data and were highly correlated with TA of the corresponding target genes in purified B lymphocytes. Vaccination responders had almost a 2-fold higher Direct LS-TA biomarker level of TNFRSF17 (log 2 SMD = 0.84, 95% CI = 0.47-1.21) on day 7 after vaccination. The sensitivity of these Direct LS-TA biomarkers in the prediction of seroconversion was greater than 0.7 and area-under curves (AUC) were over 0.8 in many datasets. In this paper, we report a straightforward approach to directly estimate B lymphocyte gene expression in PBMC, which could be used in a routine clinical setting. Moreover, the method enables the practice of precision medicine in the prediction of vaccination response. More importantly, seroconversion could now be predicted as early as day 7. As the acquired immunology pathway is common to vaccination against influenza and COVID-19, these biomarkers could also be useful to predict seroconversion for the new COVID-19 vaccines.


Subject(s)
B-Lymphocytes/physiology , Gene Expression , Influenza Vaccines/immunology , Seroconversion/genetics , B-Cell Activation Factor Receptor/genetics , Biomarkers/analysis , COVID-19 Vaccines/immunology , Computational Biology/methods , Databases, Genetic , Humans , Leukocytes, Mononuclear/physiology , Models, Theoretical , Network Meta-Analysis , Protein Disulfide-Isomerases/genetics , ROC Curve , Receptors, Fc/genetics , Seroconversion/physiology
9.
International Journal of Hospitality Management ; 97:103009, 2021.
Article in English | ScienceDirect | ID: covidwho-1272469

ABSTRACT

Micro-entrepreneurs (hosts) of peer-to-peer (P2P) accommodation are receiving an increasing amount of research attention;meanwhile little is known about their health and well-being. To maintain their well-being, this study aims to explore their stress and coping strategies after the outbreak of COVID-19. A qualitative approach was undertaken, and data were collected using semi-structured interviews with 21 hosts. Qualitative content analysis was applied to analyse the data. The findings revealed four stressors that caused the hosts’ stress: economic stressors, uncertainty, operation-related stressors and social stressors. They used 12 different strategies to cope with their stress, which were further grouped into problem-focused coping and emotion-focused coping strategies. This study suggests that micro-entrepreneurs of P2P accommodation use multiple coping strategies to deal with a stressful situation in naturalistic settings. Coping strategies were discussed regarding their helpfulness for hosts to maintain wellbeing by comparing the findings with psychology literature.

10.
Int J Med Sci ; 18(5): 1207-1215, 2021.
Article in English | MEDLINE | ID: covidwho-1055257

ABSTRACT

Objective: This study aimed to identify the predictive value of simple markers in routine blood and coagulation tests for the severity of coronavirus disease 2019 (COVID-19). Methods: A total of 311 consecutive COVID-19 patients, including 281 patients with mild/moderate COVID-19 and 30 patients with severe/life-threatening COVID-19, were retrospectively enrolled. Logistic modeling and ROC curve analyses were used to assess the indexes for identifying disease severity. Results: Lymphocyte and eosinophil counts of COVID-19 patients in the severe/life-threatening group were significantly lower than those of patients in the mild/moderate group (P < 0.001). Coagulation parameters, high-sensitivity C-reactive protein (hsCRP) levels and procalcitonin levels were higher in the severe/life-threatening group compared with the mild/moderate group (all P < 0.05). Univariate and multivariate logistic models revealed that hsCRP and fibrinogen degradation products (FDPs) were predictors of severe COVID-19 (OR = 1.072, P = 0.036; and OR = 1.831, P = 0.036, respectively). The AUROCs of hsCRP and FDP for predicting severe/life-threatening COVID-19 were 0.850 and 0.766, respectively. The optimal cutoffs of hsCRP and FDP for the severe/life-threatening type of COVID-19 were 22.41 mg/L and 0.95 µg/ml, respectively. Conclusion: Serum CRP and FDP levels are positively related to the severity of COVID-19. This finding indicates that CRP and FDP levels may potentially be used as early predictors for severe illness and help physicians triage numerous patients in a short time.


Subject(s)
Biomarkers/blood , Blood Coagulation , COVID-19/blood , Adult , Female , Humans , Male , Middle Aged , Retrospective Studies , Severity of Illness Index
11.
Int Urol Nephrol ; 53(4): 797-802, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1002141

ABSTRACT

BACKGROUND: The recent outbreak of Coronavirus Disease 2019 (COVID-19) is a public health emergency of international concern. In China, Wuhan, Hubei Province was the epicenter. The disease is more severe in patients with high comorbidities and dialysis patients fall into this category. METHODS: In this report, we reviewed the whole course of the epidemic emerged in the HD center of Wuhan NO.1 Hospital by 28 February 2020. We compared the differences on the epidemiological characteristics and clinical features between patients surviving from COVID-19 and patients who died. RESULT: In this hospital, at time of the present report, 627 patients were on chronic hemodialysis and the prevalence of affected cases was 11.8% (74/627).The median age of the COVID-19-positive patients was 63 years (range 31-88), with an almost even gender distribution (females accounted for 54.4%).The most frequent presenting symptom was cough (41.9%), followed by fatigue (24.2%), fever (17.2%) and dyspnea (14.8%); 22.4% of the cases were and asymptomatic. Fourteen of the 74 patients died (19%), as for presenting symptoms, cough was more frequent in patients who died (P < 0.05). Surviving patients had higher levels of phosphate and albumin, and lower levels of C-reactive protein (CRP). Chest CT scan was positive in all cases, including in asymptomatic ones, and revealed in about three fourths of the cases bilateral (76.2%) lesions; in each lung lesions were multiple in about half of the cases of the cases (52.3%). After diagnosis, median time to death was 7 days in the 14 patients who died, with a range between 4 and 18 days. CONCLUSION: This preliminary, single Center study identifies hemodialysis patients as a population at high risk of severe, and deadly COVID-19 infection. While classic baseline clinical conditions, including age, kidney disease and gender, are not significantly associated with survival in COVID-19 infected hemodialysis, our study also suggests a significant association between risk of and death, poor nutritional status and less than optimal metabolic balance.


Subject(s)
COVID-19/mortality , Kidney Failure, Chronic/mortality , Renal Dialysis , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/diagnosis , China , Female , Hospitalization , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Middle Aged , Retrospective Studies , Survival Rate
12.
Front Psychiatry ; 11: 602315, 2020.
Article in English | MEDLINE | ID: covidwho-1000155

ABSTRACT

Background: The outbreak of novel coronavirus disease (COVID-19) has brought serious psychological pressure to people, especially medical health staff. At present, there are few studies on insomnia and related factors of medical health staff in the middle and late stage of the epidemic of COVID-19. Therefore, the purpose of this study was to investigate the prevalence of insomnia and its related risk factors among medical workers in China in the middle and later stage of COVID-19 epidemic, as well as the relationship between insomnia and psychological resilience. Methods: From February 14 to March 29, 2020, a cross-sectional survey was conducted among 606 medical staff in China through Ranxing Technology's "SurveyStar" network platform. All subjects were assessed with the Insomnia Severity Index (ISI) and simplified Chinese version of Connor-Davidson Resilience scale (CD-RISC-10). Results: In the middle and later stages of the COVID-19 outbreak, the incidence of insomnia among medical staff was 32.0%. Compared with non-insomnia group, the insomnia group had younger age, lower education level, longer daily working hours and less psychological resilience. In addition, the prevalence of insomnia was higher in medical staff with a history of somatic diseases. The severity of insomnia of Chinese medical staff was associated with age, education level, daily working hours, psychological resilience and somatic diseases. Conclusions: Our study shows that nearly 1/3 of Chinese medical workers suffer from insomnia nearly a month after the COVID-19 outbreak. Compared with the general population, medical staff who are working with COVID are more prone to insomnia. Risk factors for insomnia include younger age, lower education level, longer working hours per day, and physical illness. The tenacious dimension of psychological resilience is a protective factor for insomnia.

14.
Brain Behav ; 10(11): e01818, 2020 11.
Article in English | MEDLINE | ID: covidwho-739165

ABSTRACT

OBJECTIVE: As a result of the pandemic of COVID-19, the public have been experiencing psychological distress. However, the prevalence of psychological distress during the COVID-19 pandemic remains unknown. Our objective was to evaluate the prevalence of psychological distress during COVID-19 outbreak and their risk factors, especially their internal paths and causality. METHODS: A nationwide cross-sectional survey of the prevalence of mental disorders was conducted. We used Hospital Anxiety and Depression Scale (HADS) to estimate the prevalence of anxiety and depression. The internal paths and the causality of the psychological health were analyzed using a structural equation modeling (SEM) approach. RESULTS: A total of 24,789 respondents completed the survey. We found that the overall prevalence of anxiety, depression, combination of anxiety, and depression were 51.6% (95% CI: 51.0-52.2), 47.5% (95% CI: 46.9-48.1), and 24.5% (95% CI: 24.0-25.0), respectively. The risk of psychological disorders in men was higher than that in women. The status of psychological health was different across different age groups, education levels, occupations, and income levels. The SEM analysis revealed that inadequate material supplies, low income, low education, lack of knowledge or confidence of the epidemic, and lack of exercise are major risk factors for psychological distress. CONCLUSIONS: The evidence from this survey poses serious challenges related to the high prevalence of psychological distress, but also offers strategies to deal with the mental health problems caused by the COVID-19 pandemic.


Subject(s)
Anxiety Disorders/epidemiology , COVID-19/psychology , Depressive Disorder/epidemiology , Psychological Distress , Adult , Anxiety Disorders/psychology , China/epidemiology , Cross-Sectional Studies , Depressive Disorder/psychology , Female , Health Surveys/statistics & numerical data , Humans , Male , Middle Aged , Pandemics , Prevalence , Risk Factors , SARS-CoV-2 , Young Adult
15.
Open Forum Infect Dis ; 7(7): ofaa241, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-608812

ABSTRACT

BACKGROUND: We aimed to evaluate the antiviral activity and safety of darunavir/cobicistat (DRV/c) in treating COVID-19 patients. METHODS: In this single-center, randomized, and open-label trial, mild patients with polymerase chain reaction (PCR)-confirmed COVID-19 were enrolled in Shanghai, China. Participants were randomized to receive DRV/c for 5 days on the top of interferon alpha 2b inhaling or interferon alpha 2b inhaling alone. The primary end point was the virological clearance rate of oropharyngeal swabs at day 7 after randomization in the intention-to-treat population (clinicaltrials.gov: NCT04252274). RESULTS: From January 30, 2020, to February 6, 2020, a total of 30 patients were enrolled, of whom 18 (60%) were male, aged 47.2 ±â€…2.8 years; 63.3% (19/30) of the participants had fever, and 46.7% (14/30) had cough at enrollment. The participants were randomized (range) at 4 (2-5) days after onset of symptoms. The proportion of negative PCR results at day 7 was 46.7% (7/15) and 60.0% (9/15) in the DRV/c and control groups (P = .72), respectively. The viral clearance rate at day 3 was 20% (3/15) in both study groups, while the number increased to 26.7% (4/15) in the DRV/c group and remained 20% (3/15) in the control group at day 5. Fourteen days after randomization, 1 participant in the DRV/c group progressed to critical illness and discontinued DRV/c, while all the patients in the control group were stable (P = 1.0). The frequencies of adverse events in the 2 groups were comparable. CONCLUSIONS: Five days of DRV/c did not increase the proportion of negative conversion vs standard of care alone, although it was well tolerated.

16.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 2020.
Article | WHO COVID | ID: covidwho-242643

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of hydroxychloroquine (HCQ) in the treatment of patients with moderate coronavirus disease 2019 (COVID-19). METHODS: We prospectively enrolled 30 treatment-naive patients with confirmed COVID-19 after informed consent at Shanghai Public Health Clinical Center. The patients were randomized 11 to HCQ group and the control group. Patients in HCQ group were given HCQ 400 mg per day for 5 days plus conventional treatments, while those in the control group were given conventional treatment only. The primary endpoint was negative conversion rate of SARS-CoV-2 nucleic acid in respiratory pharyngeal swab on days 7 after randomization. This study has been approved by the Ethics Committee of Shanghai Public Health Clinical Center and registered online (NCT04261517). RESULTS: One patient in HCQ group developed to severe during the treatment. On day 7, nucleic acid of throat swabs was negative in 13 (86.7%) cases in the HCQ group and 14 (93.3%) cases in the control group (P>0.05). The median duration from hospitalization to virus nucleic acid negative conservation was 4 (1,9) days in HCQ group, which is comparable to that in the control group [2 (1,4) days, Z=1.27, P>0.05]. The median time for body temperature normalization in HCQ group was 1 (0,2) day after hospitalization, which was also comparable to that in the control group [1 (0,3) day]. Radiological progression was shown on CT images in 5 cases (33.3%) of the HCQ group and 7 cases (46.7%) of the control group, and all patients showed improvement in follow-up examinations. Four cases (26.7%) of the HCQ group and 3 cases (20%) of the control group had transient diarrhea and abnormal liver function (P>0.05). CONCLUSIONS: The prognosis of COVID-19 moderate patients is good. Larger sample size study are needed to investigate the effects of HCQ in the treatment of COVID-19. Subsequent research should determine better endpoint and fully consider the feasibility of experiments such as sample size.

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