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1.
Clin Rheumatol ; 2022 Mar 30.
Article in English | MEDLINE | ID: covidwho-1767510

ABSTRACT

OBJECTIVES: COVID-19 pandemic has already had a tremendous impact on the process of human society; the survival of mankind and the healthy living environment deterioration with the influence will last for many years. This meta-analysis aims to assess the risk of COVID-19 in patients with rheumatic diseases. METHODS: PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM) were systematically searched with no language restriction up to July 5, 2021. The pooled rates were synthesized by fixed effect model or random effect model depending on heterogeneity. RESULTS: A total of 83 articles were included in this meta-analysis. The incidence of COVID-19 in patient with rheumatic diseases was 0.0190 (95% CI: 0.0136-0.0252), and the hospitalization rate, intensive care unit admission rate, mechanical ventilation rate, and case fatality rate of patients with rheumatic diseases infected with COVID-19 were 0.4396 (95% CI: 0.3899-0.4898), 0.0635 (95% CI: 0.0453-0.0836), 0.0461 (95% CI: 0.0330-0.0609), and 0.0346 (95% CI: 0.0218-0.0493), respectively. CONCLUSIONS: Our research shows that patients with rheumatic diseases have great risk of COVID-19. Differences in COVID-19 incidence, hospitalization rates, and mortality rates in regions were statistically significant. We still need to pay attention to the risk of COVID-19 in patients with rheumatic diseases. KEY POINTS: • Although the risk of COVID-19 in patients with rheumatic diseases has been discussed in previous meta-analysis, their research directions were inconsistent, and few studies focus on prevalence or serious outcomes of COVID-19 in patient with rheumatic diseases, while the quality of these articles was variable. • The incidence of COVID-19 and serious clinical outcomes in patients with rheumatic diseases were still high along with differential risks in most regions. • The use of glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs did not affect the hospitalization rate and mortality in rheumatism patients with COVID-19.

2.
Sustainability ; 14(6):3598, 2022.
Article in English | ProQuest Central | ID: covidwho-1765905

ABSTRACT

The outbreak of COVID-19 forced billions of learners to stay at home in order to receive online education. The aim of the study is to construct an online sustainable educational model to facilitate this learning approach. This study included 53 peer-reviewed articles for the review study following the selection process of the Preferred Reporting Items for Systematic Review and Meta-analysis Protocol (PRISMA-P) and the clustering techniques of VOSviewer. It is concluded that the model consists of online educational platforms, online assessment systems, social media, and digital literacy. With these features, online education could be sustained. However, challenges should also be addressed to sustain online education during the pandemic. Designers, scientists, and teachers should make every effort to increase learning engagement, enhance learning supervision, formulate adequate emergency programs, minimize educational inequalities, solve technical issues, and formulate systematic learning management and organization. The sustainable online educational model may be updated and perfected by including more practical features in the future.

3.
Viruses ; 14(4):655, 2022.
Article in English | MDPI | ID: covidwho-1753696

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by infection of SARS-CoV-2 and its variants has posed serious threats to global public health, thus calling for the development of potent and broad-spectrum antivirals. We previously designed and developed a peptide-based pan-coronavirus (CoV) fusion inhibitor, EK1, which is effective against all human CoVs (HCoV) tested by targeting the HCoV S protein HR1 domain. However, its relatively short half-life may limit its clinical use. Therefore, we designed, constructed, and expressed a recombinant protein, FL-EK1, which consists of a modified fibronectin type III domain (FN3) with albumin-binding capacity, a flexible linker, and EK1. As with EK1, we found that FL-EK1 could also effectively inhibit infection of SARS-CoV-2 and its variants, as well as HCoV-OC43. Furthermore, it protected mice from infection by the SARS-CoV-2 Delta variant and HCoV-OC43. Importantly, the half-life of FL-EK1 (30 h) is about 15.7-fold longer than that of EK1 (1.8 h). These results suggest that FL-EK1 is a promising candidate for the development of a pan-CoV fusion inhibitor-based long-acting antiviral drug for preventing and treating infection by current and future SARS-CoV-2 variants, as well as other HCoVs.

4.
Psychol Trauma ; 2022 Mar 21.
Article in English | MEDLINE | ID: covidwho-1751692

ABSTRACT

OBJECTIVE: As an international public health emergency panic, Corona Virus Disease-19 (COVID-19) has caused substantial impacts on economic and daily life. The public were at high risk of mental health problems and posttraumatic stress symptoms (PTSS). This study aimed to evaluate the association between objective/subjective severity of COVID-19 pandemic and PTSS, and explore the moderating role of mindfulness. METHOD: Using longitudinal and 7-day ecological momentary assessment (EMA) designs, we gathered data from 109 college students who were home-quarantined to examined study hypotheses. In the EMA phase, participants completed questionnaires measuring subjective severity, mindfulness and PTSS three times per day. Objective severity was indicated using the daily new confirmed cases. Then participants completed a follow-up measure of PTSS 2 months later, when the epidemic initially became stable. RESULTS: The results of structural equation modeling showed that state mindfulness moderated the relationship between subjectivity severity of COVID-19 and PTSS. Specifically, the association between subjective severity of COVID-19 and PTSS was positive at the low level of state mindfulness, and negative at the high level of state mindfulness. Trait mindfulness did not moderate the relationship between objectivity severity of COVID-19 and PTSS. CONCLUSION: Mindfulness-based interventions can be used as preventive mental health education to the daily lives of the general public, and to deal with unpredictable crisis events. Implications of this study are drawn for theory, practice, and research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

5.
Viruses ; 14(3)2022 03 13.
Article in English | MEDLINE | ID: covidwho-1742726

ABSTRACT

The prolonged duration of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has resulted in the continuous emergence of variants of concern (VOC, e.g., Omicron) and variants of interest (VOI, e.g., Lambda). These variants have challenged the protective efficacy of current COVID-19 vaccines, thus calling for the development of novel therapeutics against SARS-CoV-2 and its VOCs. Here, we constructed a novel fusion inhibitor-based recombinant protein, denoted as 5-Helix, consisting of three heptad repeat 1 (HR1) and two heptad repeat 2 (HR2) fragments. The 5-Helix interacted with the HR2 domain of the viral S2 subunit, the most conserved region in spike (S) protein, to block homologous six-helix bundle (6-HB) formation between viral HR1 and HR2 domains and, hence, viral S-mediated cell-cell fusion. The 5-Helix potently inhibited infection by pseudotyped SARS-CoV-2 and its VOCs, including Delta and Omicron variants. The 5-Helix also inhibited infection by authentic SARS-CoV-2 wild-type (nCoV-SH01) strain and its Delta variant. Collectively, our findings suggest that 5-Helix can be further developed as either a therapeutic or prophylactic to treat and prevent infection by SARS-CoV-2 and its variants.


Subject(s)
COVID-19 , Viral Envelope Proteins , COVID-19 Vaccines , Humans , Membrane Glycoproteins/metabolism , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins/metabolism
6.
Viruses ; 14(3)2022 03 06.
Article in English | MEDLINE | ID: covidwho-1732247

ABSTRACT

Our previous studies have shown that cholesterol-conjugated, peptide-based pan-coronavirus (CoV) fusion inhibitors can potently inhibit human CoV infection. However, only palmitic acid (C16)-based lipopeptide drugs have been tested clinically, suggesting that the development of C16-based lipopeptide drugs is feasible. Here, we designed and synthesized a C16-modified pan-CoV fusion inhibitor, EK1-C16, and found that it potently inhibited infection by SARS-CoV-2 and its variants of concern (VOCs), including Omicron, and other human CoVs and bat SARS-related CoVs (SARSr-CoVs). These results suggest that EK1-C16 could be further developed for clinical use to prevent and treat infection by the currently circulating MERS-CoV, SARS-CoV-2 and its VOCs, as well as any future emerging or re-emerging coronaviruses.


Subject(s)
COVID-19 , Middle East Respiratory Syndrome Coronavirus , COVID-19/drug therapy , Humans , Lipopeptides/pharmacology , Palmitic Acid/pharmacology , SARS-CoV-2
8.
Viruses ; 14(3)2022 02 27.
Article in English | MEDLINE | ID: covidwho-1715777

ABSTRACT

In recent years, infectious diseases caused by viral infections have seriously endangered human health, especially COVID-19, caused by SARS-CoV-2, which continues to spread worldwide. The development of broad-spectrum antiviral inhibitors is urgently needed. Here, we report a series of small-molecule compounds that proved effective against human coronaviruses (HCoV), such as SARS-CoV-2 and its variants of concern (VOCs), including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529), SARS-CoV, MERS-CoV, HCoV-OC43, and other viruses with class I viral fusion proteins, such as influenza virus, Ebola virus (EBOV), Nipah virus (NiV), and Lassa fever virus (LASV). They are also effective against class II enveloped viruses represented by ZIKV and class III enveloped viruses represented by vesicular stomatitis virus (VSV). Further studies have shown that these compounds may exert antiviral effects through a variety of mechanisms, including inhibiting the formation of the six-helix bundle, which is a typical feature of enveloped virus fusion with cell membranes, and/or targeting viral membrane to inactivate cell-free virions. These compounds are expected to become drug candidates against SARS-CoV-2 and other enveloped viruses.


Subject(s)
COVID-19 , Rhodanine , Zika Virus Infection , Zika Virus , COVID-19/drug therapy , Humans , SARS-CoV-2
10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325502

ABSTRACT

We present a corpus of 7,500 tweets annotated with COVID-19 events, including positive test results, denied access to testing, and more. We show that our corpus enables automatic identification of COVID-19 events mentioned in Twitter with text spans that fill a set of pre-defined slots for each event. We also present analyses on the self-reporting cases and user's demographic information. We will make our annotated corpus and extraction tools available for the research community to use upon publication at https://github.com/viczong/extract_COVID19_events_from_Twitter

11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324321

ABSTRACT

SARS-CoV-2 can remain viable on the protective face masks surface for several days. Mask touching, reuse and disposal occurs frequently, leading to increased risk of cross-contamination, infection and further transmission. Cuprous-oxide has potent virucidal properties. We determined the capacity of surgical face masks (type IIR) made with nonwoven fabric impregnated with cuprous-oxide microparticles (Test Fabric), to inactivate SARS-CoV-2 when in direct contact with the virus. The Test Fabric reduced the infectious titers of SARS-CoV-2 by 0.73, 3.02 and 4.19 log10 within 5, 30 and 60 minutes, respectively. In contrast, the infectious titers of the virus were reduced by Control Fabric by 0.24, 0.67 and 0.97 within 5, 30 and 60 minutes, respectively. The reductions were significantly higher in the Test Fabric than in the Control Fabric (0.49, 2.35 and 3.22 log difference, accordingly), reaching a statistically significant difference after 5 minutes (p < 0.01). The mask filtration properties were not affected by the presence of the cuprous oxide microparticles. We conclude that the use of cuprous-oxide containing face masks in the external layers of respiratory face masks may significantly reduce the risk of SARS-CoV-2 cross-contamination, transmission and infection, due to masks handling and disposal, especially when used by the general population.

12.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324181

ABSTRACT

Background: Recently, more patients recovered from the novel coronavirus disease 2019 (COVID-19) may later test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) again using reverse transcription polymerase chain reaction (RT-PCR) testing. Even though it is still controversial about the possible explanation of “re-positive” patients, it remains unclear whether the persistent viral shedding means re-infection or recurrence.Methods: Specimens were collected from three COVID-19- confirmed patients, and whole genome sequencing was performed on these clinical specimens during their first hospital admission. Laboratory tests were examined and analyzed throughout the whole course of the disease. Phylogenetic analysis was carried out for SARS-CoV-2 haplotypes.Findings: We found haplotypes of SARS-CoV-2 co-infection in two COVID-19 patients (YW01 and YW03) with a long period of hospitalization. However, only one haplotype was observed in the other patient with chronic lymphocytic leukemia (YW02), who was verified to have one kind of viral haplotype. Patient YW01 and YW02 belonged to the same family cluster infection case, but they had different haplotype characteristics in the early stage of infection;YW01 and YW03 were from different infection sources;however, similar haplotypes were found together.Interpretation: These findings showed that haplotype diversity of SARS-CoV-2 may result in viral adaptation for persistent shedding in multiple recurrences of COVID-19 patients, who met the discharge requirement, but there was no absolute correlation between haplotype diversity of SARS-CoV-2 virus and immune status. It showed important implications for the clinical management strategies for COVID-19 patients with long-term hospitalization or cases of recurrence.Funding Statement: This work was supported by grants from Zhejiang Province Public Welfare Technology Application Research Project (No. LBY21H190001 to YP Wu), Guangdong Key Project in “Development of new tools for diagnosis and treatment of Autism” (No. 2018B030335001 to K Xing), Jinhua Science and Technology Bureau (No. 2020XG- 28 to XP Xia and No. 2018-4-141 to YP Wu), and Department of the Education of Zhejiang Province (No. Y201839729 and Y202045827 to YP Wu).Declaration of Interests: All authors declare no conflict of interest.Ethics Approval Statement: This study was approved by the Ethics Committee of the Fourth Affiliated Hospital, College of Medicine, Zhejiang University (Approval No.K20200026).

13.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-321336

ABSTRACT

Background: The 2019 coronavirus disease (COVID-19) epidemic poses a challenge to individuals' mental health. Increased stress, negative affect (NA), and posttraumatic stress symptoms (PTSS) that are being experienced globally may lead to eating problems. The purpose of this study was to explore the impacts of the perceived severity of COVID-19 on eating problems as well as the mediating effects of stress/NA/PTSS both at the within-person level and between-person level. MethodsDuring the COVID-19 outbreak, a total of 108 college students were recruited to report their perceived severity of COVID-19, stress, NA, PTSS, and eating problems 3 times a day for 7 consecutive days using Ecological Momentary Assessment (EMA). Results: State perceived severity of COVID-19 predicted fewer subsequent eating problems in daily life at the within-person level. Both state NA and PTSS were positively associated with eating problems in daily life. At the between-person level, trait-like perceived severity of COVID-19, stress, NA, and PTSS were positively associated with overall eating problems. There were no mediating effects of stress/ NA /PTSS on the relations between perceived severity of COVID-19 and eating problems at the within-person/between-person level. ConclusionsThe perceived severity of COVID-19, stress, NA, and PTSS might increase the risk of eating problems.

14.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-313429

ABSTRACT

Accumulating mutations on SARS-CoV-2 Spike (S) protein may increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, in a panel of receptor binding domain (S-RBD) specific monoclonal antibodies (mAbs) with high neutralizing potency against authentic SARS-CoV-2, at least 6 of them were found to efficiently block the pseudovirus of 501Y.V2, a highly transmissible SARS-CoV-2 variant with escape mutations. The top 3 neutralizing Abs (13G9, 58G6 and 510A5) exhibited comparative ultrapotency as those being actively pursued for clinical development. Interestingly, the antigenic sites for the majority of our neutralizing Abs overlapped with a single epitope (13G9e) on S-RBD. Further, the 3-dimensional structures of 2 ultrapotent neutralizing Abs 13G9 or 58G6 in complex with SARS-CoV-2 S trimer demonstrated that both Abs bound to a steric region within S 472–490 . Moreover, a specific linear region (S 450–457 ) was identified as an additional target for 58G6. Importantly, our cryo-electron microscopy (cryo-EM) analysis revealed a unique phenomenon that the S-RBDs interacting with the fragments of antigen binding (Fabs) of 13G9 or 58G6 encoded by the IGHV1-58 and the IGKV3-20 gene segments were universally in the ‘up’ conformation in all observed particles. The potent neutralizing Abs presented in the current study may be promising candidates to fulfill the urgent needs for the current pandemic of SARS-CoV-2, and may of fundamental value for the next-generation vaccine development.

15.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312631

ABSTRACT

Background: Severe coronavirus disease 2019 (COVID-19) is associated with high mortality, whereas mild cases generally have a good prognosis. Therefore, the rapid assessment and timely classification of patients with COVID-19-related pneumonia are very important. However, no scoring system has been designated for the rapid assessment and prognosis of patients with COVID-19. Such a system is urgently needed. Objective: To explore the factors affecting mortality in patients with COVID-19 and to verify if the predictive value of the three rapid scoring scales [the Modified Early Warning Score (MEWS), Rapid Acute Physiology Score (RAPS) and Rapid Emergency Medicine Score (REMS)] that are commonly used in emergency departments can also be used for the prognostication of COVID-19 patients. Methods: : The study included adult patients diagnosed with COVID-19 in Wuhan, China from February 7 to March 7, 2020. Kaplan–Meier and Cox survival analyses were performed to identify the risk factors associated with COVID-19-related death. C-index analysis was used to evaluate the abilities of the three scoring scales and their combined score to predict the prognosis of COVID-19 patients. Results: : Older age, decreased lymphocyte count, increased respiration frequency, and low blood oxygen saturation level were identified as independent risk factors for mortality among patients with COVID-19. The Cox regression analysis demonstrated that MEWS, RAPS, and REMS had a statistically significant ability to predict mortality in COVID-19 patients (P < 0.05). Stats the C-index of MEWS, RAPS, REMS, and the combined score resulted 0.7,0.66, 0.82, and 0.83 respectively. Conclusion: Patients with an old age, increased respiration frequency, low blood oxygen saturation level, and decreased lymphocyte count are at a high risk of COVID-19-related mortality. Moreover, our analysis revealed that the REMS had a better prognostic ability than the MEWS and RAPS when applied to COVID-19 patients. Our findings suggest that the REMS can be used as a rapid scoring tool for the early assessment of COVID-19 severity.

16.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311951

ABSTRACT

After the epidemic of COVID-19, neutralizing antibodies (NAbs) against SARS-CoV-2 has been developed for the preventative and therapeutic purposes. However, few methodologies are reported in detail on how to rapidly and efficiently generate NAbs of interest. Here, we present a strategically optimized screening method for NAbs, which has enabled us to obtain SARS-CoV-2 receptor-binding domain (RBD) specific monoclonal Abs within 4 days, followed by additional 2 days to evaluate their neutralizing activities. Using this method, we obtained 198 specific Abs against SARS-CoV-2 RBD from the blood samples of COVID-19 convalescent patients, and 96 of them showed neutralizing activity. At least 20% of these NAbs exhibited high neutralizing potency. The top 2 NAbs showed the half-maximal inhibitory concentration (IC50) to block authentic SARS-CoV-2 at 9.88 and 11.13 ng/ml, respectively. Altogether, our study provides a fundamental methodology for discovering NAbs with potential preventative and therapeutic value for emerging infectious diseases.

17.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311938

ABSTRACT

Background: This study aimed to investigate the relationship between echocardiography results and lung ultrasound score (LUS) in coronavirus diseases 2019 (COVID-19) pneumonia patients and to evaluate the impact of their combined application in the diagnosis and treatment of COVID-19 pneumonia. Methods: : Hospitalized COVID-19 pneumonia patients who underwent lung ultrasound and echocardiography daily were included in this study. Patients with tricuspid regurgitation within 3 days of admission were enrolled, and the correlation and differences between their pulmonary artery pressure (PAP) and LUS on days 3, 8, and 13 were compared. The inner diameter of the pulmonary artery root and the size of the atria and ventricles were also observed. Results: : Pulmonary artery pressure within 3 days (on day 3, 8 and 13) of admission was positively correlated with LUS ( r = 0.448, p = 0.003;r = 0.738, p = 0.000;r = 0.325, p = 0.036). On day 8 the values of both PAP and LUS were higher than their corresponding values on days 3 and 13 ( p < 0.01). On day 8 the positive rate for increased PAP and LUS was 92.9% (39/42) and 90.5% (38/42), respectively, and the combined positive rate for these two was 97.6% (41/42). On day 8 the inner diameters of the right atrium, right ventricle, and pulmonary artery differed significantly from their corresponding values on days 3 and 13 ( p < 0.05). Conclusions: : PAP is positively correlated with LUS. The two should be combined for a more informative assessment of the status of recovery from COVID-19 pneumonia.

18.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316015

ABSTRACT

Objectives: The novel coronavirus pneumonia (COVID-19),spread rapidly world wide, was first reported in December 2019. Meanwhile, there are still a large number of patients who need to undergo various surgical treatments. However, the consensus on whether patients with COVID-19 receive emergency or elective surgery will influence their perioperative mortality and complications still cannot be reached. Therefore, we used meta-analysis to explore the impact of patients with COVID-19 perioperative mortality and complications, aiming to provide evidence for clinical decision-making.Methods: We searched PubMed, Embase, Web of Science, Wan Fang database, date from December 2019 to July 2020 for collecting clinical trail on the impact of patients with COVID-19 perioperative mortality and complications. According to the Cochrane system evaluation method, the data is meta-analyzed with RevMan5.3 software.Results: Eight studies involving 2037 patients, 261 (12.81%) patients with COVID-19 and 1776(87.19%) without COVID-19, were included. The results of meta-analysis showed: the COVID-19 group vs Non-COVID-19 group , perioperative mortality and postoperative pneumonia syndrome increased in COVID-19 group(OR:3.84,95%CI:2.10-7.02,I2 =46%, P <0.0001), (OR: 33.42,95%CI:15.49-72.07,I 2 =0%, P <0.00001), The number of postoperative fever were significantly higher in COVID-19 , There were no significant difference in postoperative complications and ICU admission between the two groups.Conclusions: In our study, The risk of perioperative death and postoperative pulmonary is significantly increased in patients with COVID-19. These data suggested that consideration should be taken for postponing non-critical procedures and promoting nonoperative treatment to delay or avoid the need for surgery during the pandemic of COVID-19.Funding Statement: Natural Science Foundation of China, Grant number: 31760327/ 81760191Declaration of Interests: The authors declare no competing interests.

19.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315723

ABSTRACT

The pandemic of COVID-19 caused by SARS-CoV-2 has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to ACE2 receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.

20.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315281

ABSTRACT

Objective: Recently, the CALL score based on comorbidity, age, lymphocyte and lactate dehydrogenase was reported to predict COVID-19 progression in two studies, which had relatively small samples (208 and 210 patients) and come to the opposite conclusion. We aimed to optimize and validate the CALL score in a large sample cohort. Methods: In this retrospective study, 651 patients with COVID-19 were divided into stable group (n=633) and progressive group (n=18) based on whether they progressed to severe cases. D-Dimer, CD4+ T cell count, and CRP was separately added to the CALL score to form the CALL-DD score, CALL-CD4 score, and CALL-CRP score, respectively. Results: For predicting COVID-19 progression, the CALL-DD score yielded a significantly higher AUROC compared with CALL-CD4, CALL-CRP, and CALL score (0.90, 0.84, 0.83, and 0.81, respectively). Using a cutoff of 7 points, the sensitivity and negative predictive value (NPV) of the CALL-DD score was 94% and 99%, respectively. Using a cutoff of 11 points, the specificity and NPV was 91% and 99%, respectively. Conclusion: Adding D-Dimer might further improve the performance of CALL score for the prediction of COVID-19 progression. The CALL-DD score had worth of applying in regulating the large flow of patients with COVID-19 between primary health care and tertiary centers.Funding Statement: This study was supported by grant NO.17411969700 from Shanghai Association for Science and Technology and grant NO.19YF1441200 from Shanghai Sailing Plan Program.Declaration of Interests: None.Ethics Approval Statement: The verbal informed consents were obtained from all participants. The ethics committee of Shanghai Public Health Clinical Center approved this study (JY-2020-S097-02). This study was performed in accordance with the declaration of Helsinki.

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