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3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325072

ABSTRACT

Background: COVID-19 is a new and highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is a paucity of data regarding long-term CT findings and pulmonary function in COVID-19 survivors. The aim of this study was to investigate the influence of COVID-19 pneumonia on pulmonary function and chest high-resolution computed tomography (CT) in convalescent patients. Methods: A retrospective study of COVID-19 pneumonia patients in the Beijing Youan Hospital, Capital Medical University, was conducted. Serial assessments, including pulmonary volumes (TLC), spirometry (VC, FVC, FEV1), pulmonary diffusing capacity for carbon monoxide (DLCO, DLCO/VA), and chest high-resolution CT were collected 3 months after discharge. Results: Forty-six patients completed the serial assessments. There were 38 non-severe and 8 severe cases. Abnormalities were detected in pulmonary function tests in 17 patients (37.8%). One (2.2%), 2 (4.3%), and 17 (37.8%) patients had FEV1/FVC ratio, TLC, and DLCO values less than 80% of predicted values, respectively. Twenty-eight patients (60.9%) had abnormal CT findings. Compared with patients with non-severe disease, those with severe disease had higher chest CT scores but a similar incidence of DLCO impairment. Similarly, patients who received glucocorticoids had higher chest CT scores but a similar incidence of DLCO impairment than those in the nonglucocorticoid group. Conclusions: Three months after discharge from the hospital, impaired diffusing capacity and CT abnormalities were detected in more than one third of COVID-19 patients. Compared with patients with non-severe disease, those with severe illness had a higher incidence of lung imaging abnormalities and similar lung function impairment.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324633

ABSTRACT

The receptor-binding domain (RBD) variants of SARS-CoV-2 could impair antibody-mediated neutralization of the virus by host immunity;thus, prospective surveillance for such antibody escape mutants is urgently needed. Here, we comprehensively profiled four antigenic sites of the RBD and mapped the binding hot spots for a panel of RBD-specific monoclonal antibodies isolated from COVID-19 convalescents, especially dominant VH3-53/3–66 antibodies, which are valuable indicators of antigenic changes in the RBD. We further demonstrated that several natural mutations, namely, K417N, F486L, N450K, L452R, E484K, F490S and R346S, significantly decreased the neutralizing activity of multiple human monoclonal antibodies and of human convalescent plasma obtained in the early stage of the COVID-19 pandemic. Of note, among the natural escape mutations, L452R enhanced ACE2 binding affinity, indicating that it potentially increased virulence. Overall, the in-depth maps may have far-reaching value for surveillance of SARS-CoV-2 immune escape variants and guidance of vaccine design.

5.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-296367

ABSTRACT

The high transmissibility acquisition of SARS-CoV-2 Variant of Concern (VOC) B.1.1.7 remains unclear and only mutations in coding regions have been examined. We analyzed 875,338 high-quality SARS-CoV-2 genomic sequences and the epidemiology metadata. The occurrence of a non-coding deletion (g.a28271-) in the B.1.1.7 background immediately causes the rapid spread of B.1.1.7. The number of B.1.1.7-like strains lacking the deletion is significantly less than that of B.1.1.7 strains ( n = 259 vs 92,688, P -value< 4.9 × 10 −324 ). The same highly significant statistics is observed in different countries, gender and age groups. However, the deletion alone does not cause such high viral transmissibility. The deletion and another mutation (g.gat28280cta) co-affect translational efficiency of the genes N and ORF9b by changing the core Kozak sites. The deletion interacts synergistically with S:p.P681H and S:p.T716I to increase viral transmissibility. Therefore, the Kozak-related non-coding deletion, also carried by the Delta VOC, is crucial for the high viral transmissibility of SARS-CoV-2.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296092

ABSTRACT

The recurrent outbreak of coronaviruses and variants underscores the need for broadly reactive antivirals and vaccines. Here, a novel broad-spectrum human antibody named 76E1 was isolated from a COVID-19 convalescent patient and showed broad neutralization activity against multiple α- and β-coronaviruses, including the SARS-CoV-2 variants and also exhibited the binding breath to peptides containing the epitope from γ- and δ- coronaviruses. 76E1 cross-protects mice from SARS-CoV-2 and HCoV-OC43 infection in both prophylactic and treatment models. The epitope including the fusion peptide and S2’ cleavage site recognized by 76E1 was significantly conserved among α-, β-, γ- and δ- coronaviruses. We uncovered a novel mechanism of antibody neutralization that the epitope of 76E1 was proportionally less exposed in the prefusion trimeric structure of spike protein but could be unmasked by binding to the receptor ACE2. Once the epitope exposed, 76E1 inhibited S2’ cleavage, thus blocked the membrane fusion process. Our data demonstrate a key epitope targeted by broadly-neutralizing antibodies and will guide next-generation epitope-based pan-coronavirus vaccine design.

7.
Genome Med ; 13(1): 164, 2021 10 14.
Article in English | MEDLINE | ID: covidwho-1542128

ABSTRACT

BACKGROUND: The receptor-binding domain (RBD) variants of SARS-CoV-2 could impair antibody-mediated neutralization of the virus by host immunity; thus, prospective surveillance of antibody escape mutants and understanding the evolution of RBD are urgently needed. METHODS: Using the single B cell cloning technology, we isolated and characterized 93 RBD-specific antibodies from the memory B cells of four COVID-19 convalescent individuals in the early stage of the pandemic. Then, global RBD alanine scanning with a panel of 19 selected neutralizing antibodies (NAbs), including several broadly reactive NAbs, was performed. Furthermore, we assessed the impact of single natural mutation or co-mutations of concern at key positions of RBD on the neutralization escape and ACE2 binding function by recombinant proteins and pseudoviruses. RESULTS: Thirty-three amino acid positions within four independent antigenic sites (1 to 4) of RBD were identified as valuable indicators of antigenic changes in the RBD. The comprehensive escape mutation map not only confirms the widely circulating strains carrying important immune escape RBD mutations such as K417N, E484K, and L452R, but also facilitates the discovery of new immune escape-enabling mutations such as F486L, N450K, F490S, and R346S. Of note, these escape mutations could not affect the ACE2 binding affinity of RBD, among which L452R even enhanced binding. Furthermore, we showed that RBD co-mutations K417N, E484K, and N501Y present in B.1.351 appear more resistant to NAbs and human convalescent plasma from the early stage of the pandemic, possibly due to an additive effect. Conversely, double mutations E484Q and L452R present in B.1.617.1 variant show partial antibody evasion with no evidence for an additive effect. CONCLUSIONS: Our study provides a global view of the determinants for neutralizing antibody recognition, antigenic conservation, and RBD conformation. The in-depth escape maps may have value for prospective surveillance of SARS-CoV-2 immune escape variants. Special attention should be paid to the accumulation of co-mutations at distinct major antigenic sites. Finally, the new broadly reactive NAbs described here represent new potential opportunities for the prevention and treatment of COVID-19.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 , Immune Evasion , Mutation , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Adult , Aged , B-Lymphocytes/immunology , COVID-19/genetics , COVID-19/immunology , Female , Humans , Immunologic Memory , Male , Middle Aged , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
8.
Sci Adv ; 7(38): eabb5933, 2021 Sep 17.
Article in English | MEDLINE | ID: covidwho-1440796

ABSTRACT

Growing evidence indicates the vital role of lipid metabolites in innate immunity. The lipid lysophosphatidic acid (LPA) concentrations are enhanced in patients upon HCV or SARS-CoV-2 infection, but the function of LPA and its receptors in innate immunity is largely unknown. Here, we found that viral infection promoted the G protein­coupled receptor LPA1 expression, and LPA restrained type I/III interferon production through LPA1. Mechanistically, LPA1 signaling activated ROCK1/2, which phosphorylated IRF3 Ser97 to suppress IRF3 activation. Targeting LPA1 or ROCK in macrophages, fibroblasts, epithelial cells, and LPA1 conditional KO mice promoted interferon-induced clearance of multiple viruses. LPA1 was colocalized with the receptor ACE2 in lung and intestine. Together with previous findings that LPA1 and ROCK1/2 promoted vascular leaking or lung fibrosis, we propose that the current available preclinical drugs targeting the LPA1-ROCK module might protect from SARS-CoV-2 or various virus infections in the intestine or lung.

9.
ACS Nano ; 15(9): 14915-14927, 2021 09 28.
Article in English | MEDLINE | ID: covidwho-1368905

ABSTRACT

The rise in coronavirus variants has resulted in surges of the disease across the globe. The mutations in the spike protein on the surface of the virion membrane not only allow for greater transmission but also raise concerns about vaccine effectiveness. Preventing the spread of SARS-CoV-2, its variants, and other viruses from person to person via airborne or surface transmission requires effective inactivation of the virus. Here, we report a water-borne spray-on coating for the complete inactivation of viral particles and degradation of their RNA. Our nanoworms efficiently bind and, through subsequent large nanoscale conformational changes, rupture the viral membrane and subsequently bind and degrade its RNA. Our coating completely inactivated SARS-CoV-2 (VIC01) and an evolved SARS-CoV-2 variant of concern (B.1.1.7 (alpha)), influenza A, and a surrogate capsid pseudovirus expressing the influenza A virus attachment glycoprotein, hemagglutinin. The polygalactose functionality on the nanoworms targets the conserved S2 subunit on the SARS-CoV-2 virion surface spike glycoprotein for stronger binding, and the additional attachment of guanidine groups catalyze the degradation of its RNA genome. Coating surgical masks with our nanoworms resulted in complete inactivation of VIC01 and B.1.1.7, providing a powerful control measure for SARS-CoV-2 and its variants. Inactivation was further observed for the influenza A and an AAV-HA capsid pseudovirus, providing broad viral inactivation when using the nanoworm system. The technology described here represents an environmentally friendly coating with a proposed nanomechanical mechanism for inactivation of both enveloped and capsid viruses. The functional nanoworms can be easily modified to target viruses in future pandemics, and is compatible with large scale manufacturing processes.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Pandemics , Water
10.
J Cancer ; 12(12): 3558-3565, 2021.
Article in English | MEDLINE | ID: covidwho-1355160

ABSTRACT

Purpose: Data are extremely limited with regards to the impact of COVID-19 on cancer patients. Our study explored the distinct clinical features of COVID-19 patients with cancer. Experimental Design: 189 COVID-19 patients, including 16 cancer patients and 173 patients without cancer, were recruited. Propensity score 1:4 matching (PSM) was performed between cancer patients and patients without cancer based on age, gender and comorbidities. Survival was calculated by the Kaplan-Meier method and the difference was compared by the log-rank test. Results: PSM analysis yielded 16 cancer patients and 64 propensity score-matched patients without cancer. Compared to patients without cancer, cancer patients tended to have leukopenia and elevated high-sensitivity C-reactive protein (hs-CRP) and procalcitonin. For those with critical COVID-19, cancer patients had an inferior survival than those without cancer. Also, cancer patients with severe/critical COVID-19 tended to be male and present with low SPO2 and albumin, and high hs-CRP, lactate dehydrogenase and blood urea nitrogen on admission compared to those with mild COVID-19. In terms of risk factors, recent cancer diagnosis (within 1 year of onset of COVID-19) and anti-tumor treatment within 3 months of COVID-19 diagnosis were associated with inferior survival. Conclusions: We found COVID-19 patients with cancer have distinct clinical features as compared to patients without cancer. Importantly, cancer patients with critical COVID-19 were found to have poorer outcomes compared to those without cancer. In the cancer cohort, patients with severe/critical COVID-19 presented with a distinct clinical profile from those with mild COVID-19; short cancer history and recent anti-cancer treatment were associated with inferior survival.

11.
Cells ; 10(2)2021 02 13.
Article in English | MEDLINE | ID: covidwho-1085116

ABSTRACT

As the SARS-CoV-2 pandemic continues, reports have demonstrated neurologic sequelae following COVID-19 recovery. Mechanisms to explain long-term neurological sequelae are unknown and need to be identified. Plasma from 24 individuals recovering from COVID-19 at 1 to 3 months after initial infection were collected for cytokine and antibody levels and neuronal-enriched extracellular vesicle (nEV) protein cargo analyses. Plasma cytokine IL-4 was increased in all COVID-19 participants. Volunteers with self-reported neurological problems (nCoV, n = 8) had a positive correlation of IL6 with age or severity of the sequalae, at least one co-morbidity and increased SARS-CoV-2 antibody compared to those COVID-19 individuals without neurological issues (CoV, n = 16). Protein markers of neuronal dysfunction including amyloid beta, neurofilament light, neurogranin, total tau, and p-T181-tau were all significantly increased in the nEVs of all participants recovering from COVID-19 compared to historic controls. This study suggests ongoing peripheral and neuroinflammation after COVID-19 infection that may influence neurological sequelae by altering nEV proteins. Individuals recovering from COVID-19 may have occult neural damage while those with demonstrative neurological symptoms additionally had more severe infection. Longitudinal studies to monitor plasma biomarkers and nEV cargo are warranted to assess persistent neurodegeneration and systemic effects.


Subject(s)
COVID-19/complications , Extracellular Vesicles/pathology , Nervous System Diseases/etiology , Adult , Aged , Amyloid beta-Peptides/analysis , Biomarkers/analysis , Biomarkers/blood , COVID-19/blood , COVID-19/pathology , Female , Humans , Immunoglobulin G/blood , Interleukin-4/blood , Interleukin-6/blood , Male , Middle Aged , Nervous System Diseases/blood , Nervous System Diseases/pathology , Neurofilament Proteins/analysis , Neurogranin/analysis , Neurons/pathology , tau Proteins/analysis
12.
Respiration ; 100(2): 116-126, 2021.
Article in English | MEDLINE | ID: covidwho-1044350

ABSTRACT

BACKGROUND: There is still no clinical evidence available to support or to oppose corticosteroid treatment for coronavirus disease 2019 (COVID-19) pneumonia. OBJECTIVE: To investigate the efficacy and safety of corticosteroid given to the hospitalized patients with COVID-19 pneumonia. METHODS: This was a prospective, multicenter, single-blind, randomized control trial. Adult patients with COVID-19 pneumonia who were admitted to the general ward were randomly assigned to either receive methylprednisolone or not for 7 days. The primary end point was the incidence of clinical deterioration 14 days after randomization. RESULTS: We terminated this trial early because the number of patients with COVID-19 pneumonia in all the centers decreased in late March. Finally, a total of 86 COVID-19 patients underwent randomization. There was no difference of the incidence of clinical deterioration between the methylprednisolone group and control group (4.8 vs. 4.8%, p = 1.000). The duration of throat viral RNA detectability in the methylprednisolone group was 11 days (interquartile range, 6-16 days), which was significantly longer than that in the control group (8 days [2-12 days], p = 0.030). There were no significant differences between the 2 groups in other secondary outcomes. Mass cytometry discovered CD3+ T cells, CD8+ T cells, and NK cells in the methylprednisolone group which were significantly lower than those in the control group after randomization (p < 0.05). CONCLUSIONS: From this prematurely closed trial, we found that the short-term early use of corticosteroid could suppress the immune cells, which may prolong severe acute respiratory syndrome coronavirus 2 shedding in patients with COVID-19 pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04273321.


Subject(s)
COVID-19/drug therapy , Glucocorticoids/therapeutic use , Hospitalization , Methylprednisolone/therapeutic use , Pharynx/chemistry , RNA, Viral/isolation & purification , Virus Shedding , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , CD3 Complex , CD8-Positive T-Lymphocytes , COVID-19/blood , COVID-19/therapy , COVID-19/transmission , COVID-19 Nucleic Acid Testing , Disease Progression , Early Medical Intervention , Extracorporeal Membrane Oxygenation , Female , Humans , Killer Cells, Natural , Lymphocyte Count , Male , Middle Aged , Oxygen Inhalation Therapy , Patients' Rooms , Pharynx/virology , Proportional Hazards Models , Respiration, Artificial , SARS-CoV-2 , Single-Blind Method , T-Lymphocyte Subsets , T-Lymphocytes , Time Factors , Treatment Outcome
14.
Cell Mol Immunol ; 17(6): 621-630, 2020 06.
Article in English | MEDLINE | ID: covidwho-262594

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by the novel human coronavirus SARS-CoV-2, is currently a major threat to public health worldwide. The viral spike protein binds the host receptor angiotensin-converting enzyme 2 (ACE2) via the receptor-binding domain (RBD), and thus is believed to be a major target to block viral entry. Both SARS-CoV-2 and SARS-CoV share this mechanism. Here we functionally analyzed the key amino acid residues located within receptor binding motif of RBD that may interact with human ACE2 and available neutralizing antibodies. The in vivo experiments showed that immunization with either the SARS-CoV RBD or SARS-CoV-2 RBD was able to induce strong clade-specific neutralizing antibodies in mice; however, the cross-neutralizing activity was much weaker, indicating that there are distinct antigenic features in the RBDs of the two viruses. This finding was confirmed with the available neutralizing monoclonal antibodies against SARS-CoV or SARS-CoV-2. It is worth noting that a newly developed SARS-CoV-2 human antibody, HA001, was able to neutralize SARS-CoV-2, but failed to recognize SARS-CoV. Moreover, the potential epitope residues of HA001 were identified as A475 and F486 in the SARS-CoV-2 RBD, representing new binding sites for neutralizing antibodies. Overall, our study has revealed the presence of different key epitopes between SARS-CoV and SARS-CoV-2, which indicates the necessity to develop new prophylactic vaccine and antibody drugs for specific control of the COVID-19 pandemic although the available agents obtained from the SARS-CoV study are unneglectable.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/immunology , Peptidyl-Dipeptidase A/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Amino Acid Motifs , Angiotensin-Converting Enzyme 2 , Animals , Antibodies, Monoclonal/immunology , Antibodies, Viral/metabolism , Betacoronavirus/metabolism , Betacoronavirus/physiology , Binding Sites , Cross Reactions , Epitopes , HEK293 Cells , Humans , Male , Mice , Mice, Inbred C57BL , Protein Interaction Domains and Motifs/immunology , Receptors, Coronavirus , Receptors, Virus/metabolism , SARS Virus/immunology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Virus Internalization
16.
Chest ; 158(1): 195-205, 2020 07.
Article in English | MEDLINE | ID: covidwho-100891

ABSTRACT

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19) in China in December 2019, considerable attention has been focused on its elucidation. However, it is also important for clinicians and epidemiologists to differentiate COVID-19 from other respiratory infectious diseases such as influenza viruses. RESEARCH QUESTION: The aim of this study was to explore the different clinical presentations between COVID-19 and influenza A (H1N1) pneumonia in patients with ARDS. STUDY DESIGN AND METHODS: This analysis was a retrospective case-control study. Two independent cohorts of patients with ARDS infected with either COVID-19 (n = 73) or H1N1 (n = 75) were compared. Their clinical manifestations, imaging characteristics, treatments, and prognosis were analyzed and compared. RESULTS: The median age of patients with COVID-19 was higher than that of patients with H1N1, and there was a higher proportion of male subjects among the H1N1 cohort (P < .05). Patients with COVID-19 exhibited higher proportions of nonproductive coughs, fatigue, and GI symptoms than those of patients with H1N1 (P < .05). Patients with H1N1 had higher Sequential Organ Failure Assessment (SOFA) scores than patients with COVID-19 (P < .05). The Pao2/Fio2 of 198.5 mm Hg in the COVID-19 cohort was significantly higher than the Pao2/Fio2 of 107.0 mm Hg in the H1N1 cohort (P < .001). Ground-glass opacities was more common in patients with COVID-19 than in patients with H1N1 (P < .001). There was a greater variety of antiviral therapies administered to COVID-19 patients than to H1N1 patients. The in-hospital mortality of patients with COVID-19 was 28.8%, whereas that of patients with H1N1 was 34.7% (P = .483). SOFA score-adjusted mortality of H1N1 patients was significantly higher than that of COVID-19 patients, with a rate ratio of 2.009 (95% CI, 1.563-2.583; P < .001). INTERPRETATION: There were many differences in clinical presentations between patients with ARDS infected with either COVID-19 or H1N1. Compared with H1N1 patients, patients with COVID-19-induced ARDS had lower severity of illness scores at presentation and lower SOFA score-adjusted mortality.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections , Hospital Mortality , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human , Pandemics , Pneumonia, Viral , Symptom Assessment , Age Factors , Antiviral Agents/therapeutic use , COVID-19 , Case-Control Studies , China/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Diagnosis, Differential , Female , Humans , Influenza, Human/diagnosis , Influenza, Human/mortality , Influenza, Human/physiopathology , Male , Middle Aged , Organ Dysfunction Scores , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Prognosis , SARS-CoV-2 , Severity of Illness Index , Sex Factors , Symptom Assessment/methods , Symptom Assessment/statistics & numerical data
17.
Ann Am Thorac Soc ; 17(7): 839-846, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-38758

ABSTRACT

Rationale: The current outbreak of coronavirus disease (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, spreads across national and international borders. The overall death rate of COVID-19 pneumonia in the Chinese population was 4%.Objectives: To describe the process of hospitalization and critical care of patients who died of COVID-19 pneumonia.Methods: This was a multicenter observational study of 109 decedents with COVID-19 pneumonia from three hospitals in Wuhan. Demographic, clinical, laboratory, and treatment data were collected and analyzed, and the final date of follow-up was February 24, 2020.Results: The mean age of 109 decedents with COVID-19 pneumonia was 70.7 years, 35 patients (32.1%) were female, and 85 patients (78.0%) suffered from one or more underlying comorbidities. Multiple organ failure, especially respiratory failure and heart failure, appeared in all patients even at the early stage of disease. Overall, the mean time from onset of symptoms to death was 22.3 days. All 109 hospitalized patients needed admission to an intensive care unit (ICU); however, because of limited availability, only 51 (46.8%) could be admitted. The period from hospitalization to death in the ICU group and non-ICU group was 15.9 days (standard deviation = 8.8 d) and 12.5 days (8.6 d, P = 0.044), respectively.Conclusions: Mortality due to COVID-19 pneumonia was concentrated in patients above the age of 65 years, especially those with major comorbidities. Patients who were admitted to the ICU lived longer than those who were not. Our findings should aid in the recognition and clinical management of such infections, especially with regard to ICU resource allocation.


Subject(s)
Betacoronavirus , Coronavirus Infections , Critical Care/methods , Multiple Organ Failure , Pandemics , Pneumonia, Viral , Respiratory Insufficiency , Aged , Betacoronavirus/isolation & purification , Betacoronavirus/pathogenicity , COVID-19 , China/epidemiology , Comorbidity , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Female , Hospitalization/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Male , Mortality , Multiple Organ Failure/diagnosis , Multiple Organ Failure/etiology , Outcome and Process Assessment, Health Care , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/etiology , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Prognosis , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Risk Assessment , Risk Factors , SARS-CoV-2
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