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2.
Preprint in English | EuropePMC | ID: ppcovidwho-293751

ABSTRACT

Background: Since December 2019, a novel coronavirus (2019-nCoV) associated pneumonia has emerged in Wuhan, China. The study aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia.<br><br>Methods: 99 cases admitted to Wuhan Jinyintan Hospital during January 1 to 20, 2020 and confirmed by real-time reverse-transcriptase polymerase-chain-reaction (RT-PCR) test were analyzed for epidemiological, demographic, clinical, radiological features, and laboratory data. <br><br>Findings: Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the South China Seafood Wholesale Market. The average age of the patients was 62.85 ± 11.99 years, including 67 males and 32 females. 2019-nCoV was detected in all patients by RT-PCR, and some of them also by serological testing, and metagenomics sequencing analysis. 50 cases (50.51%) had chronic basic diseases. Patients had clinical manifestations of fever (83%), cough (82%), shortness of breath (31%), muscle aches (11%), headache (8%), fuzzy confusion (7%), chest pain (2%), and diarrhea (2%). According to imaging examination, 74 patients showed bilateral pneumonia (74.75%), 25 patients showed multiple mottled and ground-glass opacity, and 1 patient had pneumothorax. Most patients received antiviral, antibiotics, supportive treatments, continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO), and had good prognosis. 17 patients developed acute Respiratory Distress Syndrome (ARDS) and among them, 2 patients worsened in a short period of time and died of multiple organ failure.<br><br>Interpretation: The infection of the 2019-nCoV can result in severe and even fatal respiratory disease like ARDS. It is very important to actively prevent complications and secondary infections, treat underlying diseases, and provide timely organ function support. Early diagnosis, early isolation, multiple treatment, and intervention of CRRT and ECMO when necessary can effectively reduce mortality caused by severe coronavirus pneumonia.<br><br>Funding: National Key R&D Program of China (No. 2017YFC1309700)<br><br>Declaration of Interest: The author reports no conflicts of interest in this work.<br><br>Ethical Approval: The study was approved by Jinyintan Hospital Ethics Committee and written informed consent was obtained from all patients involved before enrolment.

3.
Viruses ; 13(2)2021 01 21.
Article in English | MEDLINE | ID: covidwho-1456346

ABSTRACT

Rubella virus (RuV) is the infectious agent of a series of birth defect diseases termed congenital rubella syndrome, which is a major public health concern all around the world. RNA interference (RNAi) is a crucial antiviral defense mechanism in eukaryotes, and numerous viruses have been found to encode viral suppressors of RNAi (VSRs) to evade antiviral RNAi response. However, there is little knowledge about whether and how RuV antagonizes RNAi. In this study, we identified that the RuV capsid protein is a potent VSR that can efficiently suppress shRNA- and siRNA-induced RNAi in mammalian cells. Moreover, the VSR activity of the RuV capsid is dependent on its dimerization and double-stranded RNA (dsRNA)-binding activity. In addition, ectopic expression of the RuV capsid can effectively rescue the replication defect of a VSR-deficient virus or replicon, implying that the RuV capsid can act as a VSR in the context of viral infection. Together, our findings uncover that RuV encodes a VSR to evade antiviral RNAi response, which expands our understanding of RuV-host interaction and sheds light on the potential therapeutic target against RuV.


Subject(s)
Capsid Proteins/metabolism , Host-Pathogen Interactions , RNA Interference , Rubella virus/pathogenicity , Animals , Capsid , Capsid Proteins/genetics , Chlorocebus aethiops , HEK293 Cells , Humans , RNA, Double-Stranded , RNA, Small Interfering , Rubella virus/genetics , Vero Cells , Virion , Virus Replication
4.
J Clin Sleep Med ; 2021 Sep 21.
Article in English | MEDLINE | ID: covidwho-1431061

ABSTRACT

STUDY OBJECTIVES: The applicability of sleep-related scale in frontline medical staff of COVID-19 epidemic has not been fully proved, so the sleep survey results lack credibility and accuracy, which brings difficulties to the guidance and treatment of frontline medical staff with sleep disorders, and is not conducive to the prevention and control of COVID-19 epidemic. This study sought to analyze the reliability and validity of the Pittsburgh Sleep Quality Index (PSQI) among the frontline medical staff fighting against COVID-19 epidemic. METHODS: A network questionnaire survey was used to investigate PSQI among frontline medical staff who fought against COVID-19 in Wuhan from March 19 to April 15, 2020. Combined with classical test theory (CTT) and item response theory (IRT), the content validity, internal consistency, construct validity and others of PSQI were evaluated. RESULTS: According to CTT, content validity, criterion validity, and construct validity of PSQI was good. But the internal consistency was better after the deletion of "daytime dysfunction" subscale. As for IRT, difficulty, differential item function and wright map performed well. CONCLUSIONS: The original PSQI showed acceptable applicability in frontline anti-epidemic medical staff, and its characteristics moderately improved after "daytime dysfunction" subscale was removed.

5.
Front Cell Infect Microbiol ; 11: 706252, 2021.
Article in English | MEDLINE | ID: covidwho-1405403

ABSTRACT

The pandemic of COVID-19 by SARS-CoV-2 has become a global disaster. However, we still don't know how specific SARS-CoV-2-encoded proteins contribute to viral pathogenicity. We found that SARS-CoV-2-encoded membrane glycoprotein M could induce caspase-dependent apoptosis via interacting with PDK1 and inhibiting the activation of PDK1-PKB/Akt signaling. Our investigation further revealed that SARS-CoV-2-encoded nucleocapsid protein N could specifically enhance the M-induced apoptosis via interacting with both M and PDK1, therefore strengthening M-mediated attenuation of PDK1-PKB/Akt interaction. Furthermore, when the M-N interaction was disrupted via certain rationally designed peptides, the PDK1-PKB/Akt signaling was restored, and the boosting activity of N on the M-triggered apoptosis was abolished. Overall, our findings uncovered a novel mechanism by which SARS-CoV-2-encoded M triggers apoptosis with the assistance of N, which expands our understanding of the two key proteins of SARS-CoV-2 and sheds light on the pathogenicity of this life-threatening virus.


Subject(s)
COVID-19 , SARS-CoV-2 , Apoptosis , Humans , Membrane Glycoproteins , Nucleocapsid Proteins , Spike Glycoprotein, Coronavirus
7.
Theranostics ; 11(16): 8008-8026, 2021.
Article in English | MEDLINE | ID: covidwho-1337803

ABSTRACT

Rationale: Children usually develop less severe symptoms responding to Coronavirus Disease 2019 (COVID-19) than adults. However, little is known about the molecular alterations and pathogenesis of COVID-19 in children. Methods: We conducted plasma proteomic and metabolomic profilings of the blood samples of a cohort containing 18 COVID-19-children with mild symptoms and 12 healthy children, which were enrolled from hospital admissions and outpatients, respectively. Statistical analyses were performed to identify molecules specifically altered in COVID-19-children. We also developed a machine learning-based pipeline named inference of biomolecular combinations with minimal bias (iBM) to prioritize proteins and metabolites strongly altered in COVID-19-children, and experimentally validated the predictions. Results: By comparing to the multi-omic data in adults, we identified 44 proteins and 249 metabolites differentially altered in COVID-19-children against healthy children or COVID-19-adults. Further analyses demonstrated that both deteriorative immune response/inflammation processes and protective antioxidant or anti-inflammatory processes were markedly induced in COVID-19-children. Using iBM, we prioritized two combinations that contained 5 proteins and 5 metabolites, respectively, each exhibiting a total area under curve (AUC) value of 100% to accurately distinguish COVID-19-children from healthy children or COVID-19-adults. Further experiments validated that all the 5 proteins were up-regulated upon coronavirus infection. Interestingly, we found that the prioritized metabolites inhibited the expression of pro-inflammatory factors, and two of them, methylmalonic acid (MMA) and mannitol, also suppressed coronaviral replication, implying a protective role of these metabolites in COVID-19-children. Conclusion: The finding of a strong antagonism of deteriorative and protective effects provided new insights on the mechanism and pathogenesis of COVID-19 in children that mostly underwent mild symptoms. The identified metabolites strongly altered in COVID-19-children could serve as potential therapeutic agents of COVID-19.


Subject(s)
COVID-19/blood , COVID-19/virology , Adult , COVID-19/epidemiology , COVID-19/immunology , Child , Child, Preschool , China/epidemiology , Female , Hospitalization , Humans , Male , Metabolomics/methods , Middle Aged , Proteomics/methods , SARS-CoV-2/isolation & purification
8.
Semin Dial ; 2021 Jun 16.
Article in English | MEDLINE | ID: covidwho-1276770

ABSTRACT

INTRODUCTION: Maintenance hemodialysis (MHD) patients are highly threatened in the novel coronavirus disease 2019 (COVID-19) pandemic, but evidence of risk factors for mortality in this population is still lacking. METHODS: We followed outcomes of the overall MHD population of Wuhan, including 7154 MHD patients from 65 hemodialysis centers, from January 1 to May 4, 2020. Among them, 130 were diagnosed with COVID-19. The demographic and clinical data of them were collected and compared between survivors and nonsurvivors. RESULTS: Compared to the corresponding period of last year, the all-cause mortality rate of the Wuhan MHD population significantly rose in February, and dropped down in March 2020. Of the 130 COVID-19 cases, 51 (39.2%) were deceased. Advanced age, decreased oxygen saturation, low diastolic blood pressure (DBP) on admission, and complications including acute cardiac injury (HR 5.03 [95% CI 2.21-11.14], p < 0.001), cerebrovascular event (HR 2.80 [95% CI 1.14-6.86], p = 0.025) and acute respiratory distress syndrome (HR 3.50 [95% CI 1.63-7.51], p = 0.001) were identified as independent risk factors for the death of COVID-19. The median virus shedding period of survivors was 25 days, longer than the general population. CONCLUSIONS: Maintenance hemodialysis patients are a highly vulnerable population at increased risk of mortality and prolonged virus shedding period in the ongoing COVID-19 pandemic. Advanced age, decreased oxygen saturation, low DBP on admission, and complications like acute cardiac injury are parameters independently associated with poor prognosis.

9.
Environ Res ; 197: 111085, 2021 06.
Article in English | MEDLINE | ID: covidwho-1163737

ABSTRACT

BACKGROUND: To evaluate the impact of air pollution exposure on semen quality parameters during COVID-19 outbreak in China, and to identify potential windows of susceptibility for semen quality. METHODS: A retrospective observational study was carried out on 1991 semen samples collected between November 23, 2019 and July 23, 2020 (a period covering COVID-19 lock-down in China) from 781 sperm donor candidates at University-affiliated Sichuan Provincial Human Sperm Bank. Multivariate mixed-effects regression models were constructed to investigate the relationship between pollution exposure, windows of susceptibility, and semen quality, while controlling for biographic and meteorologic confounders. RESULT(S): The results indicated multiple windows of susceptibility for semen quality, especially sperm motility, due to ambient pollution exposure. Exposure to particulate matters (PM2.5 and PM10), O3 and NO2 during late stages of spermatogenesis appeared to have weak but positive association with semen quality. Exposure to CO late in sperm development appeared to have inverse relationship with sperm movement parameters. Exposure to SO2 appeared to influence semen quality throughout spermatogenesis. CONCLUSION(S): Potential windows of susceptibility for semen quality varied depending on air pollutants. Sperm motility was sensitive to pollution exposure. Findings from current study further elucidate the importance of sensitive periods during spermatogenesis and provide new evidence for the determinants of male fertility.


Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Air Pollutants/analysis , Air Pollutants/toxicity , Air Pollution/adverse effects , Air Pollution/analysis , China/epidemiology , Communicable Disease Control , Disease Outbreaks , Humans , Male , Particulate Matter/analysis , SARS-CoV-2 , Semen Analysis , Sperm Motility
10.
Natl Sci Rev ; 7(7): 1157-1168, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-1114858

ABSTRACT

The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. The symptoms of COVID-19 range from mild to severe, but the physiological changes associated with COVID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of patients with COVID-19 who had experienced different symptoms. We found that metabolite and lipid alterations exhibit apparent correlation with the course of disease in these patients, indicating that the development of COVID-19 affected their whole-body metabolism. In particular, malic acid of the TCA cycle and carbamoyl phosphate of the urea cycle result in altered energy metabolism and hepatic dysfunction, respectively. It should be noted that carbamoyl phosphate is profoundly down-regulated in patients who died compared with patients with mild symptoms. And, more importantly, guanosine monophosphate (GMP), which is mediated not only by GMP synthase but also by CD39 and CD73, is significantly changed between healthy subjects and patients with COVID-19, as well as between the mild and fatal cases. In addition, dyslipidemia was observed in patients with COVID-19. Overall, the disturbed metabolic patterns have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about plasma biomarkers associated with COVID-19 and potential therapeutic targets, as well as an important resource for further studies of the pathogenesis of COVID-19.

11.
Cell Rep ; 34(7): 108761, 2021 02 16.
Article in English | MEDLINE | ID: covidwho-1062276

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a current global health threat caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging evidence indicates that SARS-CoV-2 elicits a dysregulated immune response and a delayed interferon (IFN) expression in patients, which contribute largely to the viral pathogenesis and development of COVID-19. However, underlying mechanisms remain to be elucidated. Here, we report the activation and repression of the innate immune response by SARS-CoV-2. We show that SARS-CoV-2 RNA activates the RIG-I-MAVS-dependent IFN signaling pathway. We further uncover that ORF9b immediately accumulates and antagonizes the antiviral type I IFN response during SARS-CoV-2 infection on primary human pulmonary alveolar epithelial cells. ORF9b targets the nuclear factor κB (NF-κB) essential modulator NEMO and interrupts its K63-linked polyubiquitination upon viral stimulation, thereby inhibiting the canonical IκB kinase alpha (IKKα)/ß/γ-NF-κB signaling and subsequent IFN production. Our findings thus unveil the innate immunosuppression by ORF9b and provide insights into the host-virus interplay during the early stage of SARS-CoV-2 infection.


Subject(s)
Coronavirus Nucleocapsid Proteins/genetics , I-kappa B Kinase/metabolism , SARS-CoV-2/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/virology , COVID-19/immunology , COVID-19/metabolism , Coronavirus Nucleocapsid Proteins/metabolism , HEK293 Cells , Humans , Immunity, Innate/immunology , Interferon Type I/metabolism , Interferons/metabolism , NF-kappa B/metabolism , Phosphoproteins/genetics , Phosphoproteins/metabolism , Primary Cell Culture , Receptors, Retinoic Acid/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Signal Transduction , Ubiquitination
12.
JCI Insight ; 6(4)2021 02 22.
Article in English | MEDLINE | ID: covidwho-1039950

ABSTRACT

The coronavirus disease 19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the worst public health crisis in a century. However, knowledge about the dynamics of antibody responses in patients with COVID-19 is still poorly understood. In this study, we performed a serological study with serum specimens collected at the acute and the convalescent phases from 104 patients with severe COVID-19 who were part of the first wave of COVID-19 cases in Wuhan, China. Our findings revealed that neutralizing antibodies to SARS-CoV-2 are persistent for at least 6 months in patients with severe COVID-19, despite that IgG levels against the receptor binding domain (RBD) and nucleocapsid protein (N) IgG declined from the acute to the convalescent phase. Moreover, we demonstrate that the level of RBD-IgG is capable of correlating with SARS-CoV-2-neutralizing activities in COVID-19 serum. In summary, our findings identify the magnitude, functionality, and longevity of antibody responses in patients with COVID-19, which sheds light on the humoral immune response to COVID-19 and would be beneficial for developing vaccines.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/isolation & purification , Antibodies, Viral/blood , Antibodies, Viral/isolation & purification , COVID-19/blood , COVID-19/diagnosis , COVID-19/virology , China , Cohort Studies , Female , Humans , Immune Sera , Immunity, Humoral , Immunoglobulin G/blood , Immunoglobulin G/isolation & purification , Male , Middle Aged , Survivors , Time Factors
13.
Front Neurosci ; 14: 631025, 2020.
Article in English | MEDLINE | ID: covidwho-1040119

ABSTRACT

Objectives: Nightmares were related to emotion and behavioral problems and also emerged as one of the core features of post-traumatic stress disorder (PTSD). Our study aimed to investigate the associations of frequent nightmares with sleep duration and sleep efficiency among frontline medical workers in Wuhan during the coronavirus disease 2019 (COVID-19) outbreak. Methods: A total of 528 health-care workers from the province of Fujian providing medical aid in Wuhan completed the online questionnaires. There were 114 doctors and 414 nurses. The age, sex, marital status, and work situation were recorded. A battery of scales including the Pittsburgh Sleep Quality Index (PSQI) and the 12-item General Health Questionnaire (GHQ-12) were used to evaluate subjects' sleep and general mental health. Frequent nightmares were defined as the response of at least once a week in the item of "nightmare" of PSQI. Results: Frequent nightmares were found in 27.3% of subjects. The frequent nightmare group had a higher score of PSQI-sleep duration and PSQI-habitual sleep efficiency (frequent nightmares vs. non-frequent nightmares: PSQI-sleep duration, 1.08 ± 0.97 vs. 0.74 ± 0.85, P < 0.001; PSQI-habitual sleep efficiency, 1.08 ± 1.10 vs. 0.62 ± 0.88, P < 0.001). Reduced sleep duration and reduced sleep efficiency were independently associated with frequent nightmares after adjustment for age, sex, poor mental health, and regular sleeping medication use (reduced sleep duration: OR = 1.96, 95% CI = 1.07-3.58, P = 0.029; reduced sleep efficiency: OR = 2.17, 95% CI = 1.09-4.32, P = 0.027). Subjects with both reduced sleep duration and sleep efficiency were also associated with frequent nightmares (OR = 2.70, 95% CI = 1.57-4.65, P < 0.001). Conclusion: The present study found that sleep duration and sleep efficiency were both independently associated with frequent nightmares among frontline medical workers in Wuhan during the COVID-19 pandemic. We should pay attention to nightmares and even the ensuing PTSD symptoms among subjects with reduced sleep duration or sleep efficiency facing potential traumatic exposure.

14.
Front Microbiol ; 11: 600989, 2020.
Article in English | MEDLINE | ID: covidwho-1021898

ABSTRACT

SARS-coronavirus-2-induced immune dysregulation and inflammatory responses are involved in the pathogenesis of coronavirus disease-2019 (COVID-19). However, very little is known about immune cell and cytokine alterations in specific organs of COVID-19 patients. Here, we evaluated immune cells and cytokines in postmortem tissues, i.e., lungs, intestine, liver, kidneys, and spleen of three patients with COVID-19. Imaging mass cytometry revealed monocyte, macrophage, and dendritic cell (DC) infiltration in the lung, intestine, kidney, and liver tissues. Moreover, in patients with COVID-19, natural killer T cells infiltrated the liver, lungs, and intestine, whereas B cells infiltrated the kidneys, lungs, and intestine. CD11b+ macrophages and CD11c+ DCs also infiltrated the lungs and intestine, a phenomenon that was accompanied by overproduction of the immunosuppressive cytokine interleukin (IL)-10. However, CD11b+ macrophages and CD11c+ DCs in the lungs or intestine of COVID-19 patients did not express human leukocyte antigen DR isotype. In contrast, tumor necrosis factor (TNF)-α expression was higher in the lungs, intestine, liver, and kidneys, but not in the spleen, of all COVID-19 patients (compared to levels in controls). Collectively, these findings suggested that IL-10 and TNF-α as immunosuppressive and pro-inflammatory agents, respectively,-might be prognostic and could serve as therapeutic targets for COVID-19.

15.
Preprint | SciFinder | ID: ppcovidwho-4751

ABSTRACT

A review. The on-going pneumonia epidemic (COVID-19) caused by the novel human coronavirus (2019-nCov) has brought back the importance of understanding aerosol and its effect on public health. With the aim to provide educational information for the general public, the current article reviews both the existing knowledge on aerosols and the growing literature on COVID-19 for the following purposes: (1) to summarize the pertinent characteristics of aerosols, (2) to articulate the role aerosol plays in virus transmission, and (3) to propose relevant measures for protection and prevention.

16.
Virol Sin ; 35(3): 321-329, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-959357

ABSTRACT

The ongoing outbreak of Coronavirus Disease 2019 (COVID-19) has become a global public health emergency. SARS-coronavirus-2 (SARS-CoV-2), the causative pathogen of COVID-19, is a positive-sense single-stranded RNA virus belonging to the family Coronaviridae. For RNA viruses, virus-encoded RNA helicases have long been recognized to play pivotal roles during viral life cycles by facilitating the correct folding and replication of viral RNAs. Here, our studies show that SARS-CoV-2-encoded nonstructural protein 13 (nsp13) possesses the nucleoside triphosphate hydrolase (NTPase) and RNA helicase activities that can hydrolyze all types of NTPs and unwind RNA helices dependently of the presence of NTP, and further characterize the biochemical characteristics of these two enzymatic activities associated with SARS-CoV-2 nsp13. Moreover, we found that some bismuth salts could effectively inhibit both the NTPase and RNA helicase activities of SARS-CoV-2 nsp13 in a dose-dependent manner. Thus, our findings demonstrate the NTPase and helicase activities of SARS-CoV-2 nsp13, which may play an important role in SARS-CoV-2 replication and serve as a target for antivirals.


Subject(s)
Betacoronavirus/metabolism , Bismuth/pharmacology , Methyltransferases/metabolism , Nucleoside-Triphosphatase/drug effects , RNA Helicases/drug effects , Salts/pharmacology , Viral Nonstructural Proteins/metabolism , Adenosine Triphosphatases/drug effects , Adenosine Triphosphatases/metabolism , Betacoronavirus/enzymology , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/virology , Humans , Methyltransferases/genetics , Nucleoside-Triphosphatase/genetics , Nucleoside-Triphosphatase/metabolism , Pandemics , Pneumonia, Viral/virology , RNA Helicases/genetics , RNA Helicases/metabolism , Recombinant Proteins , SARS-CoV-2 , Severe Acute Respiratory Syndrome , Viral Nonstructural Proteins/genetics , Virus Replication
18.
Immunity ; 53(5): 1108-1122.e5, 2020 11 17.
Article in English | MEDLINE | ID: covidwho-880509

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic is a global public health crisis. However, little is known about the pathogenesis and biomarkers of COVID-19. Here, we profiled host responses to COVID-19 by performing plasma proteomics of a cohort of COVID-19 patients, including non-survivors and survivors recovered from mild or severe symptoms, and uncovered numerous COVID-19-associated alterations of plasma proteins. We developed a machine-learning-based pipeline to identify 11 proteins as biomarkers and a set of biomarker combinations, which were validated by an independent cohort and accurately distinguished and predicted COVID-19 outcomes. Some of the biomarkers were further validated by enzyme-linked immunosorbent assay (ELISA) using a larger cohort. These markedly altered proteins, including the biomarkers, mediate pathophysiological pathways, such as immune or inflammatory responses, platelet degranulation and coagulation, and metabolism, that likely contribute to the pathogenesis. Our findings provide valuable knowledge about COVID-19 biomarkers and shed light on the pathogenesis and potential therapeutic targets of COVID-19.


Subject(s)
Coronavirus Infections/blood , Coronavirus Infections/pathology , Plasma/metabolism , Pneumonia, Viral/blood , Pneumonia, Viral/pathology , Adult , Aged , Aged, 80 and over , Betacoronavirus , Biomarkers/blood , Blood Proteins/metabolism , COVID-19 , Coronavirus Infections/classification , Coronavirus Infections/metabolism , Female , Humans , Machine Learning , Male , Middle Aged , Pandemics/classification , Pneumonia, Viral/classification , Pneumonia, Viral/metabolism , Proteomics , Reproducibility of Results , SARS-CoV-2
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