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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315201

ABSTRACT

The mutations make uncertain to SARS-CoV-2 disease control and vaccine development. At population-level, single nucleotide polymorphism (SNPs) have displayed mutations for illustrating epidemiology, transmission, and pathogenesis of COVID-19. These mutations are to be expected by the analysis of intra-host level, which presented as intra-host variations (iSNVs). Here, we performed spatio-temporal analysis on iSNVs in 402 clinical samples from 170 patients, and observed an increase of genetic diversity along the day post symptom onset within individual patient and among subpopulations divided by gender, age, illness severity and viral shedding time, suggested a positive selection at intra-host level. The comparison of iSNVs and SNPs displayed that most of nonsynonymous mutations were not fixed suggested a purifying selection. This two-step fitness selection enforced iSNVs containing more nonsynonymous mutations, that highlight the potential characters of SARS-CoV-2 for viral infections and global transmissions.

2.
Cell Rep ; 38(2): 110205, 2022 01 11.
Article in English | MEDLINE | ID: covidwho-1588142

ABSTRACT

Spontaneous mutations introduce uncertainty into coronavirus disease 2019 (COVID-19) control procedures and vaccine development. Here, we perform a spatiotemporal analysis on intra-host single-nucleotide variants (iSNVs) in 402 clinical samples from 170 affected individuals, which reveals an increase in genetic diversity over time after symptom onset in individuals. Nonsynonymous mutations are overrepresented in the pool of iSNVs but underrepresented at the single-nucleotide polymorphism (SNP) level, suggesting a two-step fitness selection process: a large number of nonsynonymous substitutions are generated in the host (positive selection), and these substitutions tend to be unfixed as SNPs in the population (negative selection). Dynamic iSNV changes in subpopulations with different gender, age, illness severity, and viral shedding time displayed a varied fitness selection process among populations. Our study highlights that iSNVs provide a mutational pool shaping the rapid global evolution of the virus.


Subject(s)
COVID-19/virology , Host-Pathogen Interactions/genetics , SARS-CoV-2/genetics , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Genome, Viral/genetics , Humans , Infant , Infant, Newborn , Male , Middle Aged , Mutation/genetics , Phylogeny , Polymorphism, Single Nucleotide/genetics , Spike Glycoprotein, Coronavirus/genetics , Young Adult
4.
Open forum infectious diseases ; 8(Suppl 1):S361-S361, 2021.
Article in English | EuropePMC | ID: covidwho-1564485

ABSTRACT

Background BRII-196 and BRII-198 are human monoclonal antibodies (mAb) with an extended half-life targeting distinct epitopes of the spike protein on SARS-CoV-2. Mutations in these epitope regions are continuously emerging, potentially conferring resistance to COVID-19 therapeutics in development. Individual phase I studies showed that BRII-196 or BRII-198 alone were safe and well tolerated in healthy subjects. The BRII-196 and BRII-198 cocktail is currently under evaluation in Phase 2/3 studies for the treatment of COVID-19. Methods Preclinical study: BRII-196 and BRII-198 were evaluated in the microneutralization assay using pseudo-viruses encoding mutations identified in the spike protein of a panel of SARS-CoV-2 variants of concerns, including strains originating in UK, SA, BR, CA, and India. The fold-change in neutralization IC50 titers relative to wild-type virus was calculated. Phase 1 study: healthy adults received sequential IV BRII-196 and BRII-198 (n=9) or placebo (n=3);and were followed for 180 days. Two dose levels (750mg/750mg and 1500mg/1500mg) were evaluated for safety, pharmacokinetics and immunogenicity. Interim analysis results are presented. Results Preclinical: BRII-196 and BRII-198 exhibited neutralizing activity against pseudo-virus variants that contained spike mutations of a panel of variants including B.1.1.7 (UK), B.1.351(SA), P.1(BR), B.1.427/429 (CA), B.1.526 (NY), and B.1.617 (IN), comparable to that against wild-type virus. Phase I study: BRII-196 plus BRII-198 was well tolerated with no dose-limiting adverse events (AEs), deaths, serious adverse events, or infusion reactions. The majority of AEs were isolated asymptomatic grade 1-2 laboratory abnormalities. (Table 1). Each mAb displayed pharmacokinetic characteristics expected of extended half-life YTE-antibodies. Conclusion The BRII-196 and BRII-198 cocktail was well-tolerated, and maintains neutralization against currently reported circulating variants of concern. These preclinical and clinical results support further development of BRII-196 and BRII-198 as a therapeutic or prophylactic option for SARS-CoV-2. Disclosures David A. Margolis, MD MPH, Brii Biosciences (Employee) Yao Zhang, MD, Brii Biosciences (Employee) Yun Ji, PhD, Brii Biosciences (Employee, Shareholder)

5.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-296307

ABSTRACT

In the search for treatment schemes of COVID-19, we start by examining the general weakness of coronaviruses and then identify approved drugs attacking that weakness. The approach, if successful, should identify drugs with a specific mechanism that is at least as effective as the best drugs proposed and are ready for clinical trials. All coronaviruses translate their non-structural proteins (∼16) in concatenation, resulting in a very large super-protein. Homo-harringtonine (HHT), which has been approved for the treatment of leukemia, blocks protein elongation very effectively. Hence, HHT can repress the replication of many coronaviruses at the nano-molar concentration. In two mouse models, HHT clears SARS-CoV-2 in 3 days, especially by nasal dripping of 40 ug per day. We also use dogs to confirm the safety of HHT delivered by nebulization. The nebulization scheme could be ready for large-scale applications at the onset of the next epidemics. For the current COVID-19, a clinical trial has been approved by the Ditan hospital of Beijing but could not be implemented for want of patients. The protocol is available to qualified medical facilities.

6.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-296272

ABSTRACT

New SARS-CoV-2 variants continue to emerge from the current global pandemic, some of which can replicate faster and with greater transmissibility and pathogenicity. In particular, UK501Y.V1 identified in UK, SA501Y.V2 in South Africa, and BR501Y.V3 in Brazil are raising serious concerns as they spread quickly and contain spike protein mutations that may facilitate escape from current antibody therapies and vaccine protection. Here, we constructed a panel of 28 SARS-CoV-2 pseudoviruses bearing single or combined mutations found in the spike protein of these three variants, as well as additional nine mutations that within or close by the major antigenic sites in the spike protein identified in the GISAID database. These pseudoviruses were tested against a panel of monoclonal antibodies (mAbs), including some approved for emergency use to treat SARS-CoV-2 infection, and convalescent patient plasma collected early in the pandemic. SA501Y.V2 pseudovirus was the most resistant, in magnitude and breadth, against mAbs and convalescent plasma, followed by BR501Y.V3, and then UK501Y.V1. This resistance hierarchy corresponds with Y144del and 242-244del mutations in the N-terminal domain as well as K417N/T, E484K and N501Y mutations in the receptor binding domain (RBD). Crystal structural analysis of RBD carrying triple K417N-E484K-N501Y mutations found in SA501Y.V2 bound with mAb P2C-1F11 revealed a molecular basis for antibody neutralization and escape. SA501Y.V2 and BR501Y.V3 also acquired substantial ability to use mouse and mink ACE2 for entry. Taken together, our results clearly demonstrate major antigenic shifts and potentially broadening the host range of SA501Y.V2 and BR501Y.V3, which pose serious challenges to our current antibody therapies and vaccine protection.

7.
Clin Infect Dis ; 73(9): e2814-e2817, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1501023

ABSTRACT

Intrahost analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences identified 2 viral haplotypes comprised of 3 genetically linked mutations from the respiratory and intestinal tracts of a patient with coronavirus disease 2019. Spatiotemporal data suggest that this patient initially had dual infection of 2 SARS-CoV-2 variants, which subsequently redistributed into the 2 systems.


Subject(s)
COVID-19 , SARS-CoV-2 , Genomics , Humans , Respiratory System
8.
Nat Metab ; 3(7): 909-922, 2021 07.
Article in English | MEDLINE | ID: covidwho-1279905

ABSTRACT

Exosomes represent a subtype of extracellular vesicle that is released through retrograde transport and fusion of multivesicular bodies with the plasma membrane1. Although no perfect methodologies currently exist for the high-throughput, unbiased isolation of pure plasma exosomes2,3, investigation of exosome-enriched plasma fractions of extracellular vesicles can confer a glimpse into the endocytic pathway on a systems level. Here we conduct high-coverage lipidomics with an emphasis on sterols and oxysterols, and proteomic analyses of exosome-enriched extracellular vesicles (EVs hereafter) from patients at different temporal stages of COVID-19, including the presymptomatic, hyperinflammatory, resolution and convalescent phases. Our study highlights dysregulated raft lipid metabolism that underlies changes in EV lipid membrane anisotropy that alter the exosomal localization of presenilin-1 (PS-1) in the hyperinflammatory phase. We also show in vitro that EVs from different temporal phases trigger distinct metabolic and transcriptional responses in recipient cells, including in alveolar epithelial cells, which denote the primary site of infection, and liver hepatocytes, which represent a distal secondary site. In comparison to the hyperinflammatory phase, EVs from the resolution phase induce opposing effects on eukaryotic translation and Notch signalling. Our results provide insights into cellular lipid metabolism and inter-tissue crosstalk at different stages of COVID-19 and are a resource to increase our understanding of metabolic dysregulation in COVID-19.


Subject(s)
COVID-19/metabolism , COVID-19/virology , Extracellular Vesicles/metabolism , Lipidomics , Metabolomics , SARS-CoV-2 , Biological Transport , COVID-19/epidemiology , Cell Fractionation , Cell Membrane/metabolism , Chemical Fractionation , Cluster Analysis , Computational Biology/methods , Exosomes/metabolism , Host-Pathogen Interactions , Humans , Lipidomics/methods , Metabolome , Metabolomics/methods , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/immunology
9.
Immunity ; 54(7): 1611-1621.e5, 2021 07 13.
Article in English | MEDLINE | ID: covidwho-1260761

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge during the global pandemic and may facilitate escape from current antibody therapies and vaccine protection. Here we showed that the South African variant B.1.351 was the most resistant to current monoclonal antibodies and convalescent plasma from coronavirus disease 2019 (COVID-19)-infected individuals, followed by the Brazilian variant P.1 and the United Kingdom variant B.1.1.7. This resistance hierarchy corresponded with Y144del and 242-244del mutations in the N-terminal domain and K417N/T, E484K, and N501Y mutations in the receptor-binding domain (RBD) of SARS-CoV-2. Crystal structure analysis of the B.1.351 triple mutant (417N-484K-501Y) RBD complexed with the monoclonal antibody P2C-1F11 revealed the molecular basis for antibody neutralization and escape. B.1.351 and P.1 also acquired the ability to use mouse and mink ACE2 receptors for entry. Our results demonstrate major antigenic shifts and potential broadening of the host range for B.1.351 and P.1 variants, which poses serious challenges to current antibody therapies and vaccine protection.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Neutralizing/immunology , Immune Evasion , SARS-CoV-2/immunology , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/chemistry , Antigenic Variation/genetics , COVID-19/immunology , COVID-19/virology , Host Specificity , Humans , Immune Evasion/genetics , Mice , Mink , Mutation , Protein Binding , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization
11.
Natl Sci Rev ; 8(4): nwab006, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1254806

ABSTRACT

After a short recovery period, COVID-19 reinfections could occur in convalescent patients, even those with measurable levels of neutralizing antibodies. Effective vaccinations and protective public health measures are recommended for the convalescent COVID-19 patients.

12.
Int J Infect Dis ; 107: 242-246, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1208961

ABSTRACT

OBJECTIVE: The real-time polymerase chain reaction (RT-PCR) test is recommended for the diagnosis of COVID-19 and provides a powerful tool to identify new infections and facilitate contact tracing. In fact, as the prevalence of COVID-19 decreases, this RT-PCR testing remains as the main preventive measure to avoid rebound. However, inconsistent results can lead to misdiagnoses in the clinic. These inconsistencies are due to the variability in (1) the collection times of biological samples post infection, and (2) sampling procedures. METHODS: We applied the Kaplan-Meier method and multivariate logistic regression on RT-PCR results from 258 confirmed patients with COVID-19 to evaluate the factors associated with negative conversion. We also estimated the proportion (%) of negative conversion among patients who had tested twice or more, and compared the proportions arising from oropharyngeal swabs, sputum, and combined double testing, respectively. MAIN RESULTS: The proportion of negative conversion was 6.7% on day 4, 16.4% on day 7, 41.0% at 2 weeks, and 61.0% at 3 weeks post-admission. We also found that 34.1% and 60.3% of subjects had at least one negative RT-PCR result on days 7 and 14 after the onset of symptoms, respectively. The proportion of negative conversions following sputum testing was higher than that from oropharyngeal swabs in the early stages but this declined after the onset of symptoms. CONCLUSION: In the absence of effective treatments or vaccines, efficient testing strategies are critical if we are to control the COVID-19 epidemic. According to this study, early, consecutive and combined double testing, will be the key to identify infected patients, particularly for asymptomatic and mild symptomatic cases. These strategies will minimize misdiagnosis and the ineffective isolation of infected patients.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , Oropharynx/virology , SARS-CoV-2/isolation & purification , Sputum/virology , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Young Adult
13.
Clin Infect Dis ; 72(8): 1490-1491, 2021 04 26.
Article in English | MEDLINE | ID: covidwho-1207259
15.
J Acquir Immune Defic Syndr ; 85(2): 239-243, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-1165586

ABSTRACT

BACKGROUND: The effectiveness of lopinavir/ritonavir (LPV/r) and chloroquine treatment for COVID-19 has not been verified. METHODS: We conducted a retrospective study to summarize the clinical practices of nonsevere patients with COVID-19 receiving the standard care, LPV/r or chloroquine in Beijing Ditan Hospital from January 20 to March 26, 2020. The main outcome measurements include the changes of cycle threshold values of open reading frame 1 ab (ORF1ab) and nucleocapsid (N) genes by reverse transcriptase-polymerase chain reaction assay from day 1 to 7 after admission for patients receiving standard care or after treatment being initiated for patients receiving either LPV/r or chloroquine. The proportion of developing severe illness, fever duration and the time from symptom onset to chest computer tomography improvement, and negative conversion of nucleic acid were compared. RESULTS: Of the 129 patients included in the study, 59 received the standard care, 51 received LPV/r, and 19 received chloroquine. The demographics and baseline characteristics were comparable among the 3 groups. The median duration of fever, median time from symptom onset to chest computer tomography improvement, and negative conversion of the nucleic acid were similar among the 3 groups. The median increase in cycle threshold values of N and ORF1ab gene for patients receiving LPV/r or chloroquine or the standard care during the treatment course was 7.0 and 8.5, 8.0, and 7.6, 5.0, and 4.0, respectively. These figures were not found significantly different among the 3 groups. CONCLUSIONS: Antiviral therapy using LPV/r or chloroquine seemed not to improve the prognosis or shorten the clinical course of COVID-19.


Subject(s)
Chloroquine/therapeutic use , Coronavirus Infections/drug therapy , Lopinavir/therapeutic use , Pneumonia, Viral/drug therapy , Ritonavir/therapeutic use , Adult , Antimalarials/therapeutic use , COVID-19 , Chronic Disease , Coronavirus Infections/complications , Drug Combinations , Female , Fever , HIV Protease Inhibitors/therapeutic use , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Retrospective Studies , Treatment Outcome , Young Adult
16.
Innovation (N Y) ; 2(2): 100099, 2021 May 28.
Article in English | MEDLINE | ID: covidwho-1142304

ABSTRACT

SARS-CoV-2 has caused over 100 million deaths and continues to spread rapidly around the world. Asymptomatic transmission of SARS-CoV-2 is the Achilles' heel of COVID-19 public health control measures. Phylogenomic data on SARS-CoV-2 could provide more direct information about asymptomatic transmission. In this study, using a novel MINERVA sequencing technology, we traced asymptomatic transmission of COVID-19 patients in Beijing, China. One hundred and seventy-eight close contacts were quarantined, and 14 COVID-19 patients were laboratory confirmed by RT-PCR. We provide direct phylogenomic evidence of asymptomatic transmission by constructing the median joining network in the cluster. These data could help us to determine whether the current symptom-based screening should cover asymptomatic persons.

17.
BMC Infect Dis ; 20(1): 910, 2020 Dec 01.
Article in English | MEDLINE | ID: covidwho-953531

ABSTRACT

BACKGROUND: Both COVID-19 and influenza A contribute to increased mortality among the elderly and those with existing comorbidities. Changes in the underlying immune mechanisms determine patient prognosis. This study aimed to analyze the role of lymphocyte subsets in the immunopathogenesisof COVID-19 and severe influenza A, and examined the clinical significance of their alterations in the prognosis and recovery duration. METHODS: By retrospectively reviewing of patients in four groups (healthy controls, severe influenza A, non-severe COVID-19 and severe COVID-19) who were admitted to Ditan hospital between 2018 to 2020, we performed flow cytometric analysis and compared the absolute counts of leukocytes, lymphocytes, and lymphocyte subsets of the patients at different time points (weeks 1-4). RESULTS: We reviewed the patients' data of 94 healthy blood donors, 80 Non-severe-COVID-19, 19 Severe-COVID-19 and 37 severe influenza A. We found total lymphocytes (0.81 × 109/L vs 1.74 × 109/L, P = 0.001; 0.87 × 109/L vs 1.74 × 109/L, P < 0.0001, respectively) and lymphocyte subsets (T cells, CD4+ and CD8+ T cell subsets) of severe COVID-19 and severe influenza A patients to be significantly lower than those of healthy donors at early infection stages. Further, significant dynamic variations were observed at different time points (weeks 1-4). CONCLUSIONS: Our study suggests the plausible role of lymphocyte subsets in disease progression, which in turn affects prognosis and recovery duration in patients with severe COVID-19 and influenza A.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Influenza A virus/genetics , Influenza, Human/immunology , SARS-CoV-2/genetics , Severity of Illness Index , Adult , Aged , Beijing/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Comorbidity , Cross-Sectional Studies , Disease Progression , Female , Flow Cytometry , Humans , Influenza, Human/epidemiology , Influenza, Human/virology , Lymphocyte Count , Male , Middle Aged , Prognosis , Retrospective Studies
18.
Open Forum Infect Dis ; 7(10): ofaa379, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-952938

ABSTRACT

BACKGROUND: Few studies have compared the yield of reverse transcription polymerase chain reaction (RT-PCR) assays in nasopharyngeal swabs, oropharyngeal swabs, and sputum for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection. METHODS: We conducted an observational study in Beijing Ditan Hospital, China. Specimens including nasopharyngeal swabs, oropharyngeal swabs, and sputum from confirmed coronavirus 2019 patients were collected for RT-PCR testing. Disease duration was calculated from the date of symptom onset to the date of specimen collection and divided into 3 groups: ≤14 days, 14-21 days, and >21 days. We compared positive rates across the 3 specimens collected. The kappa coefficient was used to evaluate the consistency of RT-PCR results between different specimens. RESULTS: A total of 291 specimens were collected and tested from 43 confirmed patients. Among specimens collected with a disease duration of ≤14 days, the positive rate was highest in sputum (79.2%); this rate was significantly higher than that in nasopharyngeal swabs (37.5%; P = .003) and oropharyngeal swabs (20.8%; P < .001). Similar findings were observed with the disease durations of 14-21 days and >21 days. The consistency of testing results between nasopharyngeal swabs and oropharyngeal swabs was low with the disease durations of ≤14 days and >21 days. The consistency between the sputum and oropharyngeal swabs and between the sputum and nasopharyngeal swabs was very low across all 3 disease durations, with statistical significance. CONCLUSIONS: Compared with nasopharyngeal swabs and oropharyngeal swabs, sputum had the highest yield of SARS-CoV-2 detection. Nasopharyngeal swabs and oropharyngeal swabs had a similar yield. If sputum is not feasible, a nasopharyngeal swab can be recommended for the detection of SARS-CoV-2, and early testing is needed.

19.
Nat Commun ; 11(1): 5503, 2020 10 30.
Article in English | MEDLINE | ID: covidwho-894393

ABSTRACT

The spread of SARS-CoV-2 in Beijing before May, 2020 resulted from transmission following both domestic and global importation of cases. Here we present genomic surveillance data on 102 imported cases, which account for 17.2% of the total cases in Beijing. Our data suggest that all of the cases in Beijing can be broadly classified into one of three groups: Wuhan exposure, local transmission and overseas imports. We classify all sequenced genomes into seven clusters based on representative high-frequency single nucleotide polymorphisms (SNPs). Genomic comparisons reveal higher genomic diversity in the imported group compared to both the Wuhan exposure and local transmission groups, indicating continuous genomic evolution during global transmission. The imported group show region-specific SNPs, while the intra-host single nucleotide variations present as random features, and show no significant differences among groups. Epidemiological data suggest that detection of cases at immigration with mandatory quarantine may be an effective way to prevent recurring outbreaks triggered by imported cases. Notably, we also identify a set of novel indels. Our data imply that SARS-CoV-2 genomes may have high mutational tolerance.


Subject(s)
Betacoronavirus/growth & development , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Beijing/epidemiology , COVID-19 , Coronavirus Infections/epidemiology , Female , Genome, Viral , Genomics , Genotype , Humans , Male , Middle Aged , Mutation , Pandemics , Phylogeny , Pneumonia, Viral/epidemiology , Polymorphism, Single Nucleotide , SARS-CoV-2 , Travel , Young Adult
20.
Med Sci Monit ; 26: e925974, 2020 Sep 25.
Article in English | MEDLINE | ID: covidwho-796268

ABSTRACT

BACKGROUND Coronavirus disease 2019 (COVID-19) is a new infectious disease, and acute respiratory syndrome (ARDS) plays an important role in the process of disease aggravation. The detailed clinical course and risk factors of ARDS have not been well described. MATERIAL AND METHODS We retrospectively investigated the demographic, clinical, and laboratory data of adult confirmed cases of COVID-19 in Beijing Ditan Hospital from Jan 20 to Feb 29, 2020 and compared the differences between ARDS cases and non-ARDS cases. Univariate and multivariate logistic regression methods were employed to explore the risk factors associated with ARDS. RESULTS Of the 130 adult patients enrolled in this study, the median age was 46.5 (34-62) years and 76 (58.5%) were male. ARDS developed in 26 (20.0%) and 1 (0.8%) death occurred. Fever occurred in 114 patients, with a median highest temperature of 38.5 (38-39)°C and median fever duration of 8 (3-11) days. The median time from illness onset to ARDS was 10 (6-13) days, the median time to chest CT improvement was 17 (14-21) days, and median time to negative nucleic acid test result was 27 (17-33) days. Multivariate regression analysis showed increasing odds of ARDS associated with age older than 65 years (OR=4.75, 95% CL1.26-17.89, P=0.021), lymphocyte counts [0.5-1×109/L (OR=8.80, 95% CL 2.22-34.99, P=0.002); <0.5×109/L(OR=36.23, 95% CL 4.63-2083.48, P=0.001)], and temperature peak ≥39.1°C (OR=5.35, 95% CL 1.38-20.76, P=0.015). CONCLUSIONS ARDS tended to occur in the second week of the disease course. Potential risk factors for ARDS were older age (>65 years), lymphopenia (≤1.0×109/L), and temperature peak (≥39.1°C). These findings could help clinicians to predict which patients will have a poor prognosis at an early stage.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Pandemics , Pneumonia, Viral/complications , Respiratory Distress Syndrome/etiology , Adult , Aged , Aged, 80 and over , Bacterial Infections/etiology , COVID-19 , China , Cities/epidemiology , Comorbidity , Coronavirus Infections/epidemiology , Female , Fever/etiology , Humans , Logistic Models , Lymphopenia/etiology , Male , Middle Aged , Pneumonia, Viral/epidemiology , Retrospective Studies , Risk Factors , SARS-CoV-2
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