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2.
Preprint Dans Anglais | bioRxiv | ID: ppbiorxiv-511571

Résumé

We seek to transform how new and emergent variants of pandemiccausing viruses, specifically SARS-CoV-2, are identified and classified. By adapting large language models (LLMs) for genomic data, we build genome-scale language models (GenSLMs) which can learn the evolutionary landscape of SARS-CoV-2 genomes. By pretraining on over 110 million prokaryotic gene sequences and finetuning a SARS-CoV-2-specific model on 1.5 million genomes, we show that GenSLMs can accurately and rapidly identify variants of concern. Thus, to our knowledge, GenSLMs represents one of the first whole genome scale foundation models which can generalize to other prediction tasks. We demonstrate scaling of GenSLMs on GPU-based supercomputers and AI-hardware accelerators utilizing 1.63 Zettaflops in training runs with a sustained performance of 121 PFLOPS in mixed precision and peak of 850 PFLOPS. We present initial scientific insights from examining GenSLMs in tracking evolutionary dynamics of SARS-CoV-2, paving the path to realizing this on large biological data.

3.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-22278025

Résumé

Identification of the plasma proteomic changes of Coronavirus disease 2019 (COVID-19) is essential to understanding the pathophysiology of the disease and developing predictive models and novel therapeutics. We performed plasma deep proteomic profiling from 332 COVID-19 patients and 150 controls and pursued replication in an independent cohort (297 cases and 76 controls) to find potential biomarkers and causal proteins for three COVID-19 outcomes (infection, ventilation, and death). We identified and replicated 1,449 proteins associated with any of the three outcomes (841 for infection, 833 for ventilation, and 253 for death) that can be query on a web portal (https://covid.proteomics.wustl.edu/). Using those proteins and machine learning approached we created and validated specific prediction models for ventilation (AUC>0.91), death (AUC>0.95) and either outcome (AUC>0.80). These proteins were also enriched in specific biological processes, including immune and cytokine signaling (FDR [≤] 3.72x10-14), Alzheimers disease (FDR [≤] 5.46x10-10) and coronary artery disease (FDR [≤] 4.64x10-2). Mendelian randomization using pQTL as instrumental variants nominated BCAT2 and GOLM1 as a causal proteins for COVID-19. Causal gene network analyses identified 141 highly connected key proteins, of which 35 have known drug targets with FDA-approved compounds. Our findings provide distinctive prognostic biomarkers for two severe COVID-19 outcomes (ventilation and death), reveal their relationship to Alzheimers disease and coronary artery disease, and identify potential therapeutic targets for COVID-19 outcomes.

4.
Chinese Journal of Integrated Traditional and Western Medicine ; 42(2):218-222, 2022.
Article Dans Chinois, Anglais | CAB Abstracts | ID: covidwho-1837498

Résumé

As evidence is rapidly accumulated and updated during the coronavirus disease 2019 (COVID-19) pandemic, rapid and living guidelines are needed to guide the clinical practice of Chinese medicine (CM), for which the WHO handbook of rapid guideline development should be referred to, and the characteristics of CM should be addressed. When constructing the body of evidence, we need to systematically search the studies related to COVID-19 (direct) and indirect diseases, and to collect the experience evidence from ancient documents and expert consensus, thereby maximumly presenting the advantages of CM. When the recommendations are developed, the co-existing direct and indirect evidence, as well as the co-existing research and experience evidence should be fully considered and synthesized by taking priority on whichever higher level evidence it is. The development of the rapid and living CM guidelines meets the ever-changing clinical needs during COVID-19 pandemic, and can provide CM evidence supports for decision making during public health emergencies.

5.
China CDC Weekly ; 4(6):1-3, 2021.
Article Dans Anglais | China CDC Weekly | ID: covidwho-1699561

Résumé

Vaccines are a crucial weapon in combating the global coronavirus disease 2019 (COVID-19) pandemic. At present, China is in a critical period of COVID-19 vaccination, and most of the approved vaccines are developed by inactivated vaccine technology, which contains the complete nucleic acid sequence of the virus (1-2). The inactivated COVID-19 vaccine may contaminate people and environments during the vaccination process, thus triggering a false alarm of the COVID-19 surveillance system. In this study, we selected some vaccination sites to assess the intensity and distribution of vaccine contamination.;;Before field study, we used Reverse Transcription-Polymerase Chain Reaction (RT-PCR) method with kits that produced by Da An Gene and ZJ Bio-Tech to estimate the signal strength of inactivated COVID-19 vaccine (SinovacBiotech). The average Cycle threshold (Ct) value of ORF1Ab /N gene of the vaccine solution was 15.30±0.77, while the Ct value of the kit’s positive control was 28.01±2.38.

6.
EuropePMC; 2020.
Preprint Dans Anglais | EuropePMC | ID: ppcovidwho-315884

Résumé

Background: The Coronavirus Disease 2019 (COVID-19) epidemic has been largely controlled in China, to the point where case fatality rate (CFR) data can be comprehensively evaluated. Methods: Data on confirmed patients, with a final outcome reported as of 29 March 2020, were obtained from official websites and other internet sources. The hospitalized CFR (HCFR) was estimated, epidemiological features described, and risk factors for a fatal outcome identified. Findings: The overall CFR in China was estimated to be 4.6% (95% CI 4.5%-4.8%). It increased with age and was higher in males than females. The highest CFR observed was in male patients ≥70 years old. Although the outcome of infection is generally worse for males, this adverse effect from male sex decreased as people get old. Differential age/sex CFR patterns across geographical regions were found: the age effect on CFR was greater in other provinces outside Hubei than in Wuhan. An effect of longer interval from symptom onset to admission was only observed outside Hubei, not in Wuhan. By performing multivariate analysis and survival analysis, the higher CFR was associated with older age, and male sex. Only in regions outside Hubei, longer interval from symptom onset to admission, were associated with higher CFR. Interpretation: This up-to-date and comprehensive picture of COVID-19 CFR and its drivers will help healthcare givers target limited medical resources to patients with high risk of fatality.

7.
EuropePMC; 2021.
Preprint Dans Anglais | EuropePMC | ID: ppcovidwho-315588

Résumé

Medical imaging technologies, including computed tomography (CT) or chest X-Ray (CXR), are largely employed to facilitate the diagnosis of the COVID-19. Since manual report writing is usually too time-consuming, a more intelligent auxiliary medical system that could generate medical reports automatically and immediately is urgently needed. In this article, we propose to use the medical visual language BERT (Medical-VLBERT) model to identify the abnormality on the COVID-19 scans and generate the medical report automatically based on the detected lesion regions. To produce more accurate medical reports and minimize the visual-and-linguistic differences, this model adopts an alternate learning strategy with two procedures that are knowledge pretraining and transferring. To be more precise, the knowledge pretraining procedure is to memorize the knowledge from medical texts, while the transferring procedure is to utilize the acquired knowledge for professional medical sentences generations through observations of medical images. In practice, for automatic medical report generation on the COVID-19 cases, we constructed a dataset of 368 medical findings in Chinese and 1104 chest CT scans from The First Affiliated Hospital of Jinan University, Guangzhou, China, and The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China. Besides, to alleviate the insufficiency of the COVID-19 training samples, our model was first trained on the large-scale Chinese CX-CHR dataset and then transferred to the COVID-19 CT dataset for further fine-tuning. The experimental results showed that Medical-VLBERT achieved state-of-the-art performances on terminology prediction and report generation with the Chinese COVID-19 CT dataset and the CX-CHR dataset. The Chinese COVID-19 CT dataset is available at https://covid19ct.github.io/.

8.
EuropePMC; 2020.
Preprint Dans Anglais | EuropePMC | ID: ppcovidwho-308223

Résumé

Background: Novel coronavirus (COVID-19) is a new viral species that causes pneumonia. Currently, RT-PCR and IgM/IgG antibody assays have been recommended for the diagnosis of COVID-19 infection. However, the correlation between RT-PCR status and antibody (IgG, IgM) response remains unknown. Methods: : Consecutive COVID-19 patients admitted to our department between February 10, 2020 and March 10, 2020, were diagnosed by guidelines issued by the World Health Organization (WHO) and included in this study. RT-PCR and antibody (IgM/IgG) assays for COVID-19 infection were performed for all patients according to the manufactures’ protocols. Other data, such as demographic, clinical, laboratory, as well as treatment and outcome, were collected using data collection tables from electronic medical records. Results: : During the study period, a total of 103 patients were diagnosed as having a moderate type of COVID-19 at our department, including 55 males and 48 females, with an average age of 57.53 ± 1.65 years old (range 23 to 90 years old). The peak level of SARS-CoV-2 IgM antibody (243.10 ± 89.84 AU/ml) was reported 4 days after the negative RT-PCR (-) (all P < 0.05). Subsequently, the IgM decreased to 42.69 ± 22.39 AU/ml 21 days after RT-PCR (-). However, the IgG was maintained at a high level 4 days before RT-PCR (-) and later. The lymphocyte count was at the lowest level on day7 before the RT-PCR(-) result (P<0.05), and then elevated after RT-PCR conversion (viral clearance). Conclusions: : SARS-CoV-2 IgM/IgG levels did not correlate with RT-PCR status in our study sample. We found that SARS-CoV-2 IgM/IgG could be a potential biomarker to monitor clinical course, determine discharge, and assess recovery of those infected patients with the novel coronavirus. Trial registration: A prospective, open label, randomized, control trial for chloroquine or hydroxychloroquine in patients with mild and common novel coronavirus pulmonary (COVIP-19). ChiCTR2000030054. Registered 18 Feb,2020. http://www.chictr.org.cn/edit.aspx?pid=49869&htm=4

9.
EuropePMC; 2020.
Preprint Dans Anglais | EuropePMC | ID: ppcovidwho-313430

Résumé

Background: With the outbreak of unknown pneumonia in Wuhan, China in December 2019, a new coronavirus (SARS-CoV-2) attracted worldwide attention. Although coronaviruses typically infect the upper or lower respiratory tract, discovery of the virus in plasma is common. Therefore, the risk of transmitting coronavirus through transfusion of blood products remains. As more asymptomatic infections are found in COVID-19 cases, blood safety is shown to be particularly important, especially in endemic areas. Study Design and Methods BX-1, an ‘AIDS treatment instrument’ based on methylene blue (MB) photochemical technology, developed by Boxin (Beijing) Biotechnology Development LTD, has proven that inactivation of lipid-enveloped viruses such as HIV-1 in plasma has high efficiency, without damage to other components in the plasma, and proved safe and reliable in clinical trials of HIV treatment. In order to confirm the inactivation effect of BX-1 in SARS-CoV-2, we used the SARS-CoV-2 virus strain isolated from Zhejiang University for plasma virus inactivation studies. Results: and Conclusion BX-1 can effectively eliminate SARS-CoV-2 within 2 mins, and the virus titer decline can reach 4.5 log10 TCID50/mL. Faced with the expanding epidemic, BX-1 is safe for blood transfusion and plasma transfusion therapy in recovery patients, and the inactivated vaccine preparation has great potential for treatment in the current outbreak.

10.
EuropePMC; 2020.
Preprint Dans Anglais | EuropePMC | ID: ppcovidwho-313360

Résumé

The resurgence of coronavirus disease 2019 (COVID-19) has been seen in many counties where outbreaks appear to be leveling off. While China experienced a dramatic decline of COVID-19 at the outset of 2020, regional outbreaks continuously emerged in recent months. In Guangzhou, a small outbreak emerged in March and April involving less than 100 residents, and a comprehensive and near-real-time genomic surveillance of SARS-CoV-2 was conducted. When confirmed cases among overseas travelers increased, public health authorities enhanced measures as shifting self-quarantine to central quarantine and SARS-CoV-2 testing for all overseas travelers. From 109 imported cases we found diverse viral variants distributing in the global viral phylogeny, which were usually shared within households but not among passengers on the same flight. Nonetheless, local transmission was predominately attributed to two specific variants imported from Africa, including the local cases who reported no direct/indirect contact with imported cases. The introducing events of the virus were identified or deduced before enhanced measures were taken. These results show that the interventions are effective in containing the spread of SARS-CoV-2, and also rule out the possibility of cryptic transmission of viral variants from the first wave in January and February. Moreover, we found that intra-host viral diversity was usually different between close contacts, implying a transmission bottleneck of SARS-CoV-2. Our study provides evidence and emphasizes the importance of controls for oversea travelers in the context of the pandemic, and exemplifies how viral genomic data facilitates COVID-19 surveillance and prevention.Funding: This study was supported by National Natural Science Foundation of China (31870079, 91953122, 31871326), National Science and Technology Major Project of the Ministry of Science and Technology of China (2017ZX10103011, 2018ZX10305410, 2018ZX10201001), Guangdong Provincial Novel Coronavirus Scientific and Technological Project (2020111107001), Guangdong Basic and Applied Basic Research Foundation (2020A1515010776 and 2020B1515020057) and the Beijing Nova Program (Z181100006218114 and Z181100006218110) to M.N. and P.L..Conflict of Interest: The authors declare no competing interests.Ethical Approval: This study was approved by the ethics committee of the Center for Disease Control and Prevention (CDC) of Guangzhou (GZCDC-ECHR-2020P0002). Written informed consent was obtained from patients about the surveillance and data related to disease control and further analysis. All information regarding individual persons has been anonymized in this study.

11.
IEEE Intelligent Transportation Systems Magazine ; 14(1):4-5, 2022.
Article Dans Anglais | ProQuest Central | ID: covidwho-1621797

Résumé

By the time this issue of IEEE Intelligent Transportation Systems Magazine is published, I will have completed my term as president of the IEEE Intelligent Transportation Systems (ITS) Society. My two-year service coincided with an unprecedented time—the COVID-19 crisis. During the past two years, the pandemic has dramatically changed the lives of everyone on Earth and, most certainly, greatly impacted how the ITS Society operates. Fortunately, our colleagues have made substantial efforts to adapt to the new reality of the pandemic and created opportunities and environments for the Society to innovate and grow.

12.
Journal of Hydrology ; 603:N.PAG-N.PAG, 2021.
Article Dans Anglais | Academic Search Complete | ID: covidwho-1568844

Résumé

• Hybrid ELM models (PSO-ELM, GA-ELM and ABC-ELM) were proposed for estimating ET 0 in different climate zones of China. • PSO-ELM model had the highest accuracy, followed by GA-ELM and ABC-ELM. • Hybrid ELM models outperformed standalone ELM and empirical models in different climate zones. • PSO-ELM model with T max , T min and RH obtained accurate ET 0 estimates in TCZ, SMZ and TMZ. • PSO-ELM model with only T max and T min was better performance on ET 0 estimates in MPZ. Accurate prediction of reference crop evapotranspiration (ET 0) is important for regional water resources management and optimal design of agricultural irrigation system. In this study, three hybrid models (PSO-ELM, GA-ELM and ABC-ELM) integrating the extreme learning machine model (ELM) with three biological heuristic algorithms, i.e., PSO, GA and ABC, were proposed for predicting daily ET 0 based on daily meteorological data from 2000 to 2019 at twelve representative stations in different climatic zones of China. The performances of the three hybrid ELM models were further compared with the standalone ELM model and three empirical models (Hargreaves, Priestley-Talor and Makkink models). The results showed that the hybrid ELM models (R 2 = 0.973–0.999) all performed better than the standalone ELM model (R 2 = 0.955–0.989) in four climatic regions in China. The estimation accuracy of the empirical models was relatively lower, with R2 of 0.822–0.887 and RMSE of 0.381–1.951 mm/d. The R 2 values of PSO-ELM, GA-ELM and ABC-ELM models were 0.993, 0.986 and 0.981 and the RMSE values were 0.266 mm/d, 0.306 mm/d and 0.404 mm/d, respectively, indicating that the PSO-ELM model had the best performance. When setting T max , T min and RH as the model inputs, the PSO-ELM model presented better performance in the temperate continental zone (TCZ), subtropical monsoon region (SMZ) and temperate monsoon zone (TMZ) climate zones, with R 2 of 0.892, 0866 and 0.870 and RMSE of 0.773 mm/d, 0.597 mm/d and 0.832 mm/d, respectively. The PSO-ELM model also performed in the mountain plateau region (MPZ) when only T max and T min data were available, with R2 of 0.808 and RMSE of 0.651 mm/d. All the three biological heuristic algorithms effectively improved the performance of the ELM model. Particularly, the PSO-ELM was recommended as a promising model realizing the high-precision estimation of daily ET 0 with fewer meteorological parameters in different climatic zones of China. [ FROM AUTHOR] Copyright of Journal of Hydrology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

13.
IEEE Intelligent Transportation Systems Magazine ; 13(4):5, 2021.
Article Dans Anglais | ProQuest Central | ID: covidwho-1494329

Résumé

The IEEE Intelligent Transportation Systems (ITS) Society’s flagship conferences take place in summer and fall each year. In July, the 32nd IEEE Intelligent Vehicle Symposium (IV) was successfully organized in Nagoya, Japan, through virtual means with great support from Nagoya University and a number of Japanese partners and organizations. The conference committee, led by Kazuya Takeda, Nagoya University, planned a large-scale demonstration of connected and automated vehicle technologies. Many of us were excited for the opportunity to experience cutting-edge intelligent vehicle technologies showcased at the Tokyo Olympics. Unfortunately, with the COVID-19 pandemic persisting, the demonstration could not happen. The Organizing Committee worked hard to transition the conference into a virtual event that offered engaging interactive experiences. IV’21 received 446 papers;220 papers plus additional invited talks were given. The presentations are available on YouTube for easy access.

14.
Preprint Dans Anglais | bioRxiv | ID: ppbiorxiv-452256

Résumé

The coronavirus disease 2019 (COVID-19) pandemic has affected tens of millions of individuals and caused hundreds of thousands of deaths worldwide. Due to its rapid surge, there is a shortage of information on viral behavior and host response after SARS-CoV-2 infection. Here we present a comprehensive, multiscale network analysis of the transcriptional response to the virus. We particularly focus on key-regulators, cell-receptors, and host-processes that are hijacked by the virus for its advantage. ACE2-controlled processes involve a key-regulator CD300e (a TYROBP receptor) and the activation of IL-2 pro-inflammatory cytokine signaling. We further investigate the age-dependency of such receptors and identify the adipose and the brain as potentially contributing tissues for the diseases severity in old patients. In contrast, several other tissues in the young population are more susceptible to SARS-CoV-2 infection. In summary, this present study provides novel insights into the gene regulatory organization during the SARS-CoV-2 infection and the tissue-specific age dependence of the cell receptors involved in COVID-19.

15.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21252221

Résumé

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal (Mycoplasma salivarium), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.

16.
Fundamental Research ; 2021.
Article Dans Anglais | ScienceDirect | ID: covidwho-1051638

Résumé

The present study aimed to establish a prognostic nomogram to stratify high-risk patients with Coronavirus Disease 2019 (COVID-19) who progressed from the nonsevere condition on admission to severe during hospitalization. This multicenter retrospective study included patients with nonsevere COVID-19 on admission from Jan 10, 2020 to Feb 7, 2020. In the training cohort, independent risk factors associated with disease progression were identified by univariate and multivariate analyses. The prognostic nomogram was established and then validated externally using C-index. The study included 351 patients (293 and 58 in the training and validation cohorts, respectively), with 27 (9.2%) and 5 (8.6%) patients progressed, respectively. In the training cohort, older age (OR 1.036, 95% CI 1.000-1.073), more lobes involved on chest CT (OR 1.841, 95% CI 1.117-3.035), comorbidity present (OR 2.478, 95% CI 1.020-6.018), and lower lymphocyte count (OR 0.081, 95% CI 0.019-0.349) were identified as independent risk factors. The prognostic nomogram was established in the training cohort with satisfied external prognostic performance (C-index 0.906, 95% CI 0.806-1.000). In conclusion, older age, comorbidity present, more lobes involved on chest CT, and lower lymphocyte count are independent risk factors associated with disease progression during hospitalization for patients with nonsevere COVID-19.

17.
Preprint Dans Anglais | bioRxiv | ID: ppbiorxiv-376277

Résumé

Studies on human monocytes historically focused on characterization of bulk responses, whereas functional heterogeneity is largely unknown. Here, we identified an inducible population of CD127-expressing human monocytes under inflammatory conditions and named the subset M127. M127 is nearly absent in healthy individuals yet abundantly present in patients with infectious and inflammatory conditions such as COVID-19 and rheumatoid arthritis. Multiple genomic and functional approaches revealed unique gene signatures of M127 and unified anti-inflammatory properties imposed by the CD127-STAT5 axis. M127 expansion correlated with mild COVID-19 disease outcomes. Thereby, we phenotypically and molecularly characterized a human monocyte subset marked by CD127 that retained anti-inflammatory properties within the pro-inflammatory environments, uncovering remarkable functional diversity among monocytes and signifying M127 as a potential therapeutic target for human inflammatory disorders.

18.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20144873

Résumé

In China, the patients with previously negative RT-PCR results again test positive during the post-discharge isolation period. We aimed to determine the clinical characteristics of these "recurrent-positive" patients. We retrospectively reviewed the data of 15 recurrent-positive patients and 107 control patients with non-recurrent, moderate COVID-19 treated in Wuhan, China. Clinical data and laboratory results were comparatively analyzed. We found that recurrent-positive patients had moderate disease. The rate of recurrent-positive disease in our hospital was 1.87%. Recurrent-positive patients were significantly younger (43(35-54) years) than control patients (60(43-69) years) (P=0.011). The early LOS (length of stay in hospital before recurrence) was significantly longer in recurrent-positive patients (36(34-45) days) than in control patients (15(7-30) days) (P =0.001). The time required for the first conversion of RT-PCR results from positive to negative was significantly longer in recurrent-positive patients (14(10-17) days) than in control patients (6(3-9) days) (P =0.011). Serum COVID-19 antibody levels were significantly lower in recurrent-positive patients than in control patients (IgM: 13.69 {+/-} 4.38 vs. 68.10 {+/-} 20.85 AU/mL, P = 0.015; IgG: 78.53 {+/-} 9.30 vs. 147.85 {+/-} 13.33 AU/mL, P < 0.0001). Recurrent-positive patients were younger than control patients. The early LOS (length of stay in hospital before recurrence) was significantly longer in recurrent-positive group than that in control group. COVID-19 IgM/IgG antibody levels were significantly lower in recurrent-positive group than those in control group, which might explain why the virus RNA RT-PCR was positive after the initial "clinical cure"(with three times of virus RNA RT-PCR negative). The virus might not be fully eliminated because of the lower IgG level and their later replicating might result in recurrent-positive virus RNA RT-PCR.

19.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20136093

Résumé

The outbreak of novel coronavirus disease 2019 (COVID-19) has become a pandemic. Drug repurposing may represent a rapid way to fill the urgent need for effective treatment. We evaluated the clinical utility of chloroquine and hydroxychloroquine in treating COVID-19. Forty-eight patients with moderate COVID-19 were randomized to oral treatment with chloroquine (1000 mg QD on Day 1, then 500 mg QD for 9 days; n=18), hydroxychloroquine (200 mg BID for 10 days; n=18), or control treatment (n=12). Adverse events were mild, except for one case of Grade 2 ALT elevation. Adverse events were more commonly observed in the chloroquine group (44.44%) and the hydroxychloroquine group (50.00%) than in the control group (16.67%). The chloroquine group achieved shorter time to clinical recovery (TTCR) than the control group (P=0.019). There was a trend toward reduced TTCR in the hydroxychloroquine group (P=0.049). The time to reach viral RNA negativity was significantly faster in the chloroquine group and the hydroxychloroquine group than in the control group (P=0.006 and P=0.010, respectively). The median numbers of days to reach RNA negativity in the chloroquine, hydroxychloroquine, and control groups was 2.5 (IQR: 2.0-3.8) days, 2.0 (IQR: 2.0-3.5) days, and 7.0 (IQR: 3.0-10.0) days, respectively. The chloroquine and hydroxychloroquine groups also showed trends toward improvement in the duration of hospitalization and findings on lung computerized tomography (CT). This study provides evidence that (hydroxy)chloroquine may be used effectively in treating moderate COVID-19 and supports larger trials.

20.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20056010

Résumé

BackgroundAs of April 2, 2020, the global reported number of COVID-19 cases has crossed over 1 million with more than 55,000 deaths. The household transmissibility of SARS-CoV-2, the causative pathogen, remains elusive. MethodsBased on a comprehensive contact-tracing dataset from Guangzhou, we estimated both the population-level effective reproductive number and individual-level secondary attack rate (SAR) in the household setting. We assessed age effects on transmissibility and the infectivity of COVID-19 cases during their incubation period. ResultsA total of 195 unrelated clusters with 212 primary cases, 137 nonprimary (secondary or tertiary) cases and 1938 uninfected close contacts were traced. We estimated the household SAR to be 13.8% (95% CI: 11.1-17.0%) if household contacts are defined as all close relatives and 19.3% (95% CI: 15.5-23.9%) if household contacts only include those at the same residential address as the cases, assuming a mean incubation period of 4 days and a maximum infectious period of 13 days. The odds of infection among children (<20 years old) was only 0.26 (95% CI: 0.13-0.54) times of that among the elderly ([≥]60 years old). There was no gender difference in the risk of infection. COVID-19 cases were at least as infectious during their incubation period as during their illness. On average, a COVID-19 case infected 0.48 (95% CI: 0.39-0.58) close contacts. Had isolation not been implemented, this number increases to 0.62 (95% CI: 0.51-0.75). The effective reproductive number in Guangzhou dropped from above 1 to below 0.5 in about 1 week. ConclusionSARS-CoV-2 is more transmissible in households than SARS-CoV and MERS-CoV, and the elderly [≥]60 years old are the most vulnerable to household transmission. Case finding and isolation alone may be inadequate to contain the pandemic and need to be used in conjunction with heightened restriction of human movement as implemented in Guangzhou.

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