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1.
Virus evolution ; 2022.
Article in English | EuropePMC | ID: covidwho-1898319

ABSTRACT

Over the latest several decades, no emerging virus has had a profound impact on the world as the SARS-CoV-2 emerged at the end of 2019 has done. To know where SARS-CoV-2 is originated from and how it jumped into human population, we immediately started a surveillance investigation in wild mammals in and around Wuhan when we determined the agent. Herein, coronaviruses were screened in the lung, liver, intestinal tissue samples from 15 raccoon dogs, seven Siberian weasels, three hog badger and three Reeves’s muntjacs collected in Wuhan and 334 bats collected around Wuhan. Consequently, eight alphacoronaviruses were identified in raccoon dogs, while nine betacoronaviruses were found in bats. Notably, the newly-discovered alphacoronaviruses shared a high whole genome sequence similarity (97.9%) with the canine coronavirus strain 2020/7 sampled from domestic dog in the United Kingdom. Some of betacoronaviruses identified here were closely related to previously known bat SARS-CoV-related viruses sampled from Hubei province and its neighbors, while remaining betacoronaviruses exhibited a close evolutionary relationship to SARS-CoV-related bat viruses in the RdRp gene tree and clustered together with SARS-CoV-2-related bat coronaviruses in the M, N and S gene trees, but with relatively low similarity. Additionally, these newly-discovered betacoronaviruses seem unlikely to bind angiotensin-converting enzyme 2 (ACE2) because of the deletions in the two key regions of their receptor binding motifs. Finally, we did not find SARS-CoV-2 or its progenitor virus in these animal samples. Due to the high circulation of canine coronaviruses in raccoon dogs in Wuhan, more scientific efforts are warranted to better understand their diversity and evolution in China and the possibility of a potential human agent.

2.
Signal Transduct Target Ther ; 7(1): 91, 2022 03 18.
Article in English | MEDLINE | ID: covidwho-1751707

ABSTRACT

Currently, there is no effective drugs for treating clinically COVID-19 except dexamethasone. We previously revealed that human identical sequences of SARS-CoV-2 promote the COVID-19 progression by upregulating hyaluronic acid (HA). As the inhibitor of HA synthesis, hymecromone is an approved prescription drug used for treating biliary spasm. Here, we aimed to investigate the relation between HA and COVID-19, and evaluate the therapeutic effects of hymecromone on COVID-19. Firstly, HA was closely relevant to clinical parameters, including lymphocytes (n = 158; r = -0.50; P < 0.0001), C-reactive protein (n = 156; r = 0.55; P < 0.0001), D-dimer (n = 154; r = 0.38; P < 0.0001), and fibrinogen (n = 152; r = 0.37; P < 0.0001), as well as the mass (n = 78; r = 0.43; P < 0.0001) and volume (n = 78; r = 0.41; P = 0.0002) of ground-glass opacity, the mass (n = 78; r = 0.48; P < 0.0001) and volume (n = 78; r = 0.47; P < 0.0001) of consolidation in patient with low level of hyaluronan (HA < 48.43 ng/mL). Furthermore, hyaluronan could directly cause mouse pulmonary lesions. Besides, hymecromone remarkably reduced HA via downregulating HAS2/HAS3 expression. Moreover, 89% patients with hymecromone treatment had pulmonary lesion absorption while only 42% patients in control group had pulmonary lesion absorption (P < 0.0001). In addition, lymphocytes recovered more quickly in hymecromone-treated patients (n = 8) than control group (n = 5) (P < 0.05). These findings suggest that hymecromone is a promising drug for COVID-19 and deserves our further efforts to determine its effect in a larger cohort.


Subject(s)
COVID-19 , Hyaluronic Acid , Animals , COVID-19/drug therapy , Humans , Hymecromone/metabolism , Hymecromone/pharmacology , Mice , Prescriptions , SARS-CoV-2
3.
Chin Med J (Engl) ; 133(9): 1039-1043, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-1722619

ABSTRACT

BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). CONCLUSIONS: In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/genetics , Pneumonia, Viral/genetics , RNA, Viral/genetics , Adult , Aged , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/rehabilitation , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/rehabilitation , Real-Time Polymerase Chain Reaction , Retrospective Studies , SARS-CoV-2
4.
PLoS Pathog ; 18(2): e1010259, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1690683

ABSTRACT

At the end of 2019 Wuhan witnessed an outbreak of "atypical pneumonia" that later developed into a global pandemic. Metagenomic sequencing rapidly revealed the causative agent of this outbreak to be a novel coronavirus denoted SARS-CoV-2. To provide a snapshot of the pathogens in pneumonia-associated respiratory samples from Wuhan prior to the emergence of SARS-CoV-2, we collected bronchoalveolar lavage fluid samples from 408 patients presenting with pneumonia and acute respiratory infections at the Central Hospital of Wuhan between 2016 and 2017. Unbiased total RNA sequencing was performed to reveal their "total infectome", including viruses, bacteria and fungi. We identified 35 pathogen species, comprising 13 RNA viruses, 3 DNA viruses, 16 bacteria and 3 fungi, often at high abundance and including multiple co-infections (13.5%). SARS-CoV-2 was not present. These data depict a stable core infectome comprising common respiratory pathogens such as rhinoviruses and influenza viruses, an atypical respiratory virus (EV-D68), and a single case of a sporadic zoonotic pathogen-Chlamydia psittaci. Samples from patients experiencing respiratory disease on average had higher pathogen abundance than healthy controls. Phylogenetic analyses of individual pathogens revealed multiple origins and global transmission histories, highlighting the connectedness of the Wuhan population. This study provides a comprehensive overview of the pathogens associated with acute respiratory infections and pneumonia, which were more diverse and complex than obtained using targeted PCR or qPCR approaches. These data also suggest that SARS-CoV-2 or closely related viruses were absent from Wuhan in 2016-2017.


Subject(s)
COVID-19/epidemiology , Disease Outbreaks , Pneumonia/epidemiology , Respiratory Tract Infections/epidemiology , SARS-CoV-2/isolation & purification , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Bronchoalveolar Lavage Fluid/microbiology , COVID-19/virology , China/epidemiology , Cohort Studies , Female , Gene Expression Profiling , Humans , Male , Metagenomics , Middle Aged , Phylogeny , Pneumonia/microbiology , Respiratory Tract Infections/microbiology , Young Adult
5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324115

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic, and little is known regarding the gut microbiota dynamics of the disease that often features a drastic and swift progression. Here we employed analyses of 16S rRNA gene sequencing and metatranscriptome to investigate the gut microbiome characteristics of a group of COVID-19 patients over the course of a probiotics-assisted therapy. Results: The COVID-19 patients exhibited apparent microbiota alterations characterized by prominent compositional and functional shifts, which included taxonomic changes (e.g., increased relative abundance of Enterococcus and Rhodococcus , and decreased relative abundance of Faecalibacterium and Clostridium XlVa) and transcriptional changes (e.g., increased transcriptional activities of Escherichia coli and Klebsiella pneumoniae , virulence factors, and antibiotic resistance genes, and decreased activities of Faecalibacterium prausnitzii ). Importantly, there were great interpersonal heterogeneity and intertimepoint fluctuations, as the most abundant or transcriptionally active taxa often greatly differed among individual patients and timepoints. Coincided with the resolution of respiratory symptoms, after the therapy some patients showed signs of recovery in the gut microbiome abnormalities. Associations were identified between gut and airway taxa and serum factors. Conclusion: Our findings suggested that there is a lack of gut microbiota stability in COVID-19 patients and that measures are needed to ameliorate the gut microbiome perturbations in the patients to improve the prognosis. In addition, inclusion of probiotics is safe for treating COVID-19 patients and may improve their prognosis. Trial registration ISRCTN, ChiCTR2000029999. Registered 19 February 2020, http://www.chictr.org.cn/showprojen.aspx?proj=49717

6.
BMC Med ; 20(1): 24, 2022 01 20.
Article in English | MEDLINE | ID: covidwho-1638127

ABSTRACT

BACKGROUND: COVID-19 is an infectious disease characterized by multiple respiratory and extrapulmonary manifestations, including gastrointestinal symptoms. Although recent studies have linked gut microbiota to infectious diseases such as influenza, little is known about the role of the gut microbiota in COVID-19 pathophysiology. METHODS: To better understand the host-gut microbiota interactions in COVID-19, we characterized the gut microbial community and gut barrier function using metagenomic and metaproteomic approaches in 63 COVID-19 patients and 8 non-infected controls. Both immunohematological parameters and transcriptional profiles were measured to reflect the immune response in COVID-19 patients. RESULTS: Altered gut microbial composition was observed in COVID-19 patients, which was characterized by decreased commensal species and increased opportunistic pathogenic species. Severe illness was associated with higher abundance of four microbial species (i.e., Burkholderia contaminans, Bacteroides nordii, Bifidobacterium longum, and Blautia sp. CAG 257), six microbial pathways (e.g., glycolysis and fermentation), and 10 virulence genes. These severity-related microbial features were further associated with host immune response. For example, the abundance of Bu. contaminans was associated with higher levels of inflammation biomarkers and lower levels of immune cells. Furthermore, human-origin proteins identified from both blood and fecal samples suggested gut barrier dysfunction in COVID-19 patients. The circulating levels of lipopolysaccharide-binding protein increased in patients with severe illness and were associated with circulating inflammation biomarkers and immune cells. Besides, proteins of disease-related bacteria (e.g., B. longum) were detectable in blood samples from patients. CONCLUSIONS: Our results suggest that the dysbiosis of the gut microbiome and the dysfunction of the gut barrier might play a role in the pathophysiology of COVID-19 by affecting host immune homeostasis.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Dysbiosis , Homeostasis , Humans , SARS-CoV-2
8.
Emerg Microbes Infect ; 10(1): 2090-2097, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1479918

ABSTRACT

Since December 2019, coronavirus disease 2019 (COVID-19) caused by SARS coronavirus 2 (SARS-CoV-2) has spread and threatens public health worldwide. The recurrence of SARS-CoV-2 RNA detection in patients after discharge from hospital signals a risk of transmission from such patients to the community and challenges the current discharge criteria of COVID-19 patients. A wide range of clinical specimens has been used to detect SARS-CoV-2. However, to date, a consensus has not been reached regarding the most appropriate specimens to use for viral RNA detection in assessing COVID-19 patients for discharge. An anal swab sample was proposed as the standard because of prolonged viral detection. In this retrospective longitudinal study of viral RNA detection in 60 confirmed COVID-19 patients, we used saliva, oropharyngeal/nasopharyngeal swab (O/N swab) and anal swab procedures from admission to discharge. The conversion times of saliva and anal swab were longer than that of O/N swab. The conversion time of hyper sensitive-CRP was the shortest and correlated with that of CT scanning and viral detection. Some patients were found to be RNA-positive in saliva while RNA-negative in anal swab while the reverse was true in some other patients, which indicated that false negatives were inevitable if only the anal swab is used for evaluating suitability for discharge. These results indicated that double-checking for viral RNA using multiple and diverse specimens was essential, and saliva could be a candidate to supplement anal swabs to reduce false-negative results and facilitate pandemic control.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Saliva/virology , Adult , Anal Canal/virology , False Negative Reactions , Female , Humans , Male , Middle Aged , Nasopharynx/virology , Oropharynx/virology , Patient Discharge , RNA, Viral/analysis , Retrospective Studies , Young Adult
9.
Front Cell Infect Microbiol ; 11: 653794, 2021.
Article in English | MEDLINE | ID: covidwho-1325515

ABSTRACT

Purpose: To investigate the sensitivity of SARS-CoV-2 testing in specimens collected from the anterior nasal vestibules of COVID-19 patients. Methods: A cross-sectional analysis was performed on 30 patients with a confirmed diagnosis of COVID-19 at the Shanghai Public Health Clinical Center from March 14, 2020 to March 21, 2020. Paired specimens were collected from both the anterior nasal vestibule and the oropharynx from all patients. All specimens were tested for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) assays. Results: Of the 30 patients with confirmed COVID-19, 17 patients (56.7%) tested positive for SARS-CoV-2 when oropharyngeal specimens were used, while 20 patients (66.7%) tested positive when nasal swab specimens were used. There was no statistically significant difference in sensitivity between the two methods. Conclusions: Respiratory swabs collected from the nasal vestibule offer a less invasive alternative to oropharyngeal swabs for specimen collection in the detection of SARS-CoV-2 infection, and have adequate sensitivity.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Testing , China/epidemiology , Cross-Sectional Studies , Humans , Nasopharynx , Specimen Handling
10.
Virol Sin ; 35(6): 785-792, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1217481

ABSTRACT

Healthcare workers (HCWs) are at high risk of occupational exposure to the new pandemic human coronavirus, SARS-CoV-2, and are a source of nosocomial transmission in airborne infectious isolation rooms (AIIRs). Here, we performed comprehensive environmental contamination surveillance to evaluate the risk of viral transmission in AIIRs with 115 rooms in three buildings at the Shanghai Public Health Clinical Center, Shanghai, during the treatment of 334 patients infected with SARS-CoV-2. The results showed that the risk of airborne transmission of SARS-CoV-2 in AIIRs was low (1.62%, 25/1544) due to the directional airflow and strong environmental hygiene procedures. However, we detected viral RNA on the surface of foot-operated openers and bathroom sinks in AIIRs (viral load: 55.00-3154.50 copies/mL). This might be a source of contamination to connecting corridors and object surfaces through the footwear and gloves used by HCWs. The risk of infection was eliminated by the use of disposable footwear covers and the application of more effective environmental and personal hygiene measures. With the help of effective infection control procedures, none of 290 HCWs was infected when working in the AIIRs at this hospital. This study has provided information pertinent for infection control in AIIRs during the treatment of COVID-19 patients.


Subject(s)
COVID-19/transmission , Environmental Monitoring/methods , Hospitals, Isolation , SARS-CoV-2/isolation & purification , Air Microbiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , China/epidemiology , Cross Infection/transmission , Environmental Microbiology , Health Personnel , Humans , Infection Control/instrumentation , Infection Control/methods , Pandemics/prevention & control , RNA, Viral/isolation & purification , Risk Factors , Viral Load
11.
Emerg Microbes Infect ; 10(1): 612-618, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1127286

ABSTRACT

Phage therapy is recognized as a promising alternative to antibiotics in treating pulmonary bacterial infections, however, its use has not been reported for treating secondary bacterial infections during virus pandemics such as coronavirus disease 2019 (COVID-19). We enrolled 4 patients hospitalized with critical COVID-19 and pulmonary carbapenem-resistant Acinetobacter baumannii (CRAB) infections to compassionate phage therapy (at 2 successive doses of 109 plaque-forming unit phages). All patients in our COVID-19-specific intensive care unit (ICU) with CRAB positive in bronchoalveolar lavage fluid or sputum samples were eligible for study inclusion if antibiotic treatment failed to eradicate their CRAB infections. While phage susceptibility testing revealed an identical profile of CRAB strains from these patients, treatment with a pre-optimized 2-phage cocktail was associated with reduced CRAB burdens. Our results suggest the potential of phages on rapid responses to secondary CRAB outbreak in COVID-19 patients.


Subject(s)
Acinetobacter Infections/etiology , Acinetobacter Infections/therapy , Acinetobacter baumannii/virology , Bacteriophages/physiology , COVID-19/complications , Coinfection/therapy , Phage Therapy , Podoviridae/physiology , Acinetobacter Infections/microbiology , Acinetobacter baumannii/physiology , Aged , Aged, 80 and over , COVID-19/virology , Coinfection/microbiology , Female , Humans , Male , SARS-CoV-2/physiology
12.
J Infect Dis ; 223(4): 568-580, 2021 02 24.
Article in English | MEDLINE | ID: covidwho-1101847

ABSTRACT

BACKGROUND: The immune protective mechanisms during severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection remain to be deciphered for the development of an effective intervention approach. METHODS: We examined early responses of interleukin 37 (IL-37), a powerful anti-inflammatory cytokine, in 254 SARS-CoV-2-infected patients before any clinical intervention and determined its correlation with clinical prognosis. RESULTS: Our results demonstrated that SARS-CoV-2 infection causes elevation of plasma IL-37. Higher early IL-37 responses were correlated with earlier viral RNA negative conversion, chest computed tomographic improvement, and cough relief, consequently resulted in earlier hospital discharge. Further assays showed that higher IL-37 was associated with lower interleukin 6 and interleukin 8 (IL-8) and higher interferon α responses and facilitated biochemical homeostasis. Low IL-37 responses predicted severe clinical prognosis in combination with IL-8 and C-reactive protein. In addition, we observed that IL-37 administration was able to attenuate lung inflammation and alleviate respiratory tissue damage in human angiotensin-converting enzyme 2-transgenic mice infected with SARS-CoV-2. CONCLUSIONS: Overall, we found that IL-37 plays a protective role by antagonizing inflammatory responses while retaining type I interferon, thereby maintaining the functionalities of vital organs. IL-37, IL-8, and C-reactive protein might be formulated as a precise prediction model for screening severe clinical cases and have good value in clinical practice.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/virology , Interleukin-1/blood , Adult , Animals , C-Reactive Protein/metabolism , COVID-19/blood , Female , Humans , Inflammation/immunology , Inflammation/virology , Interleukin-8/blood , Male , Mice , Mice, Transgenic , Middle Aged
13.
Ann Transl Med ; 9(2): 100, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1079877

ABSTRACT

BACKGROUND: To investigate the temporal pattern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presence on ocular surfaces using conjunctival swabs in coronavirus disease 2019 (COVID-19) patients. METHODS: This study included 59 patients (32 newly admitted and 27 hospitalized for ≥2 weeks) with a COVID-19-confirmed diagnosis at the Shanghai Public Health Clinical Center from March 3, 2020, to March 21, 2020. Conjunctival swab samples were collected from both eyes of all the 59 patients and were tested by reverse transcription polymerase chain reaction (RT-PCR) assay. The range of sampling time lies widely between 1 and 50 days since symptom onset. RESULTS: Among the 32 newly admitted patients, positive RT-PCR results for SARS-CoV-2 in conjunctival swab samples were reported in 2 patients (one eye for each) without ocular discomfort, but 1 positive case had conjunctival congestion. The positive results were detected on Day 5 for 1 patient and Day 7 for the other, but repeated tests after 1 week were negative for both patients. All 27 patients who had been hospitalized for ≥2 weeks had negative test results. The mean time from symptom onset to sampling of 2 positive cases was significantly less than that of 57 negative cases (P<0.001). CONCLUSIONS: SARS-CoV-2 on the ocular surface can be detected in the early phase of COVID-19. The risk of ocular transmission remains and might be higher in the early phase.

14.
EClinicalMedicine ; 25: 100478, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1047557

ABSTRACT

BACKGROUND: The outbreak of a new coronavirus (SARS-CoV-2) poses a great challenge to global public health. New and effective intervention strategies are urgently needed to combat the disease. METHODS: We conducted an open-label, non-randomized, clinical trial involving moderate COVID-19 patients according to study protocol. Patients were assigned in a 1:2 ratio to receive either aerosol inhalation treatment with IFN-κ and TFF2, every 48 h for three consecutive dosages, in addition to standard treatment (experimental group), or standard treatment alone (control group). The end point was the time to discharge from the hospital. This study is registered with chictr.org.cn, ChiCTR2000030262. FINDINGS: A total of thirty-three eligible COVID-19 patients were enrolled from February 1, 2020 to April 6, 2020, eleven were assigned to the IFN-κ plus TFF2 group, and twenty-two to the control group. Safety and efficacy were evaluated for both groups. No treatment-associated severe adverse effects (SAE) were observed in the group treated with aerosol inhalation of IFN-κ plus TFF2, and no significant differences in the safety evaluations were observed between experimental and control groups. CT imaging was performed in all patients with the median improvement time of 5.0 days (IQR 3.0-9.0) in the experimental group versus 8.5 days (IQR 3.0-17.0) in the control group (p<0.05). In addition, the experimental group had a significant shorten median time in cough relief (4.5 days [IQR 2.0-7.0]) than the control group did (10.0 days [IQR 6.0-21.0])(p<0.005), in viral RNA reversion of 6.0 days (IQR 2.0-13.0) in the experimental group vs 9.5 days (IQR 3.0-23.0) in the control group (p < 0.05), and in the median hospitalization stays of 12.0 days (IQR 7.0-20.0) in the experimental group vs 15.0 days (IQR 10.0-25.0) in the control group (p<0.001), respectively. INTERPRETATION: Aerosol inhalation of IFN-κ plus TFF2 is a safe treatment and is likely to significantly facilitate clinical improvement, including cough relief, CT imaging improvement, and viral RNA reversion, thereby achieves an early release from hospitalization. These data support to explore a scale-up trial with IFN-κ plus TFF2. FUNDING: National Major Project for Control and Prevention of Infectious Disease in China, Shanghai Science and Technology Commission, Shanghai Municipal Health Commission.

15.
EMBO J ; 39(24): e105896, 2020 12 15.
Article in English | MEDLINE | ID: covidwho-903069

ABSTRACT

COVID-19 is characterized by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID-19 pathophysiology, we combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID-19-infected patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites, and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN-I signaling, and a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID-19-infected patients experiencing milder disease symptoms showed robust T-cell responses. Finally, we identified genes, proteins, and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19.


Subject(s)
COVID-19/blood , COVID-19/pathology , Biomarkers/blood , COVID-19/immunology , COVID-19/virology , Female , Genomics/methods , Humans , Lipoproteins/metabolism , Male , Metabolomics/methods , SARS-CoV-2/physiology , Severity of Illness Index , Viral Load
16.
EClinicalMedicine ; 27: 100547, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-898762

ABSTRACT

BACKGROUND: Epidemic outbreaks caused by SARS-CoV-2 are worsening around the world, and there are no target drugs to treat COVID-19. IFN-κ inhibits the replication of SARS-CoV-2; and TFF2 is a small secreted polypeptide that promotes the repair of mucosal injury and reduces the inflammatory responses. We used the synergistic effect of both proteins to treat COVID-19. METHODS: We conducted an open-label, randomized, clinical trial involving patients with moderate COVID-19. Patients were assigned in a 1:1 ratio to receive either aerosol inhalation treatment with IFN-κ and TFF2 every 24 h for six consecutive dosages in addition to standard care (experimental group) or standard care alone (control group). The primary endpoint was the time until a viral RNA negative conversion for SARS-CoV-2 in all clinical samples. The secondary clinical endpoint was the time of CT imaging improvement. Data analysis was performed per protocol. This study was registered with chictr.org.cn, ChiCTR2000030262. FINDINGS: Between March 23 and May 23 of 2020, 86 COVID-19 patients with symptoms of moderate illness were recruited, and 6 patients were excluded due to not matching the inclusion criteria (patients with pneumonia through chest radiography). Among the remaining 80 patients, 40 patients were assigned to experimental group, and the others were assigned to control group to only receive standard care. Efficacy and safety were evaluated for both groups. The time of viral RNA negative conversion in experimental group (Mean, 3·80 days, 95% CI 2·07-5·53), was significantly shorter than that in control group (7·40 days, 95% CI 4·57 to 10·23) (p = 0.031), and difference between means was 3·60 days. The percentage of patients in experimental group with reversion to negative viral RNA was significantly increased compared with control group on all sampling days (every day during the 12-day observation period) (p = 0·037). For the secondary endpoint, the experimental group had a significantly shorter time until improvement was seen by CT (Mean 6·21 days, N = 38/40, 95% CI 5·11-7·31) than that in control group (8·76 days, N = 34/40, 95% CI 7·57-9·96) (p = 0.002), and difference between means was 2·55 days. No discomfort or complications during aerosol inhalation were reported to the nurses by any experimental patients. INTERPRETATION: In conclusion, we found that aerosol inhalation of IFN-κ plus TFF2 in combination with standard care is safe and superior to standard care alone in shortening the time up to viral RNA negative conversion in all clinical samples. In addition, the patients in experimental group had a significantly shortened CT imaging improvement time than those in control group. This study suggested that this combination treatment is able to facilitate clinical improvement (negative for virus, improvement by CT, reduced hospitalization stay) and thereby result in an early release from the hospital. These data support the need for exploration with a large-scale trial of IFN-κ plus TFF2 to treat COVID-19. FUNDING: Funding was provided by the National Natural Science Foundation of China, National Major Project for Control and Prevention of Infectious Disease in China, Shanghai Science and Technology Commission, Shanghai Municipal Health Commission.

17.
Open Forum Infect Dis ; 7(9): ofaa286, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-665998

ABSTRACT

BACKGROUND: The course of disease in mild and moderate COVID-19 has many implications for mobile patients, such as the risk of spread of the infection, precautions taken, and investigations targeted at preventing transmission. METHODS: Three hundred thirty-one adults were hospitalized from January 21 to February 22, 2020, and classified as severe (10%) or critical (4.8%) cases; 1.5% died. Two hundred eighty-two (85.2%) mild or moderate cases were admitted to regular wards. Epidemiological, demographic, clinical, chest computed tomography (CT) scan, laboratory, treatment, and outcome data from patient records were analyzed retrospectively. RESULTS: Patients were symptomatic for 9.82±5.75 (1-37) days. Pulmonary involvement was demonstrated on a chest CT scan in 97.9% of cases. It took 16.81±8.54 (3-49) days from the appearance of the first symptom until 274 patients tested virus-negative in naso- and oropharyngeal (NP) swabs, blood, urine, and stool, and 234 (83%) patients were asymptomatic for 9.09±7.82 (1-44) days. Subsequently, 131 patients were discharged. One hundred sixty-nine remained in the hospital; these patients tested virus-free and were clinically asymptomatic because of widespread persisting or increasing pulmonary infiltrates. Hospitalization took 16.24±7.57 (2-47) days; the time interval from the first symptom to discharge was 21.37±7.85 (3-52) days. CONCLUSIONS: With an asymptomatic phase, disease courses are unexpectedly long until the stage of virus negativity. NP swabs are not reliable in the later stages of COVID-19. Pneumonia outlasts virus-positive tests if sputum is not acquired. Imminent pulmonary fibrosis in high-risk groups demands follow-up examinations. Investigation of promising antiviral agents should heed the specific needs of mild and moderate COVID-19 patients.

18.
Emerg Microbes Infect ; 9(1): 1537-1545, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-611841

ABSTRACT

Background: Novel coronavirus pneumonia (COVID-19) is prevalent around the world. We aimed to describe epidemiological features and clinical course in Shanghai. Methods: We retrospectively analysed 325 cases admitted at Shanghai Public Health Clinical Center, between January 20 and February 29, 2020. Results: 47.4% (154/325) had visited Wuhan within 2 weeks of illness onset. 57.2% occurred in 67 clusters; 40% were situated within 53 family clusters. 83.7% developed fever during the disease course. Median times from onset to first medical care, hospitalization and negative detection of nucleic acid by nasopharyngeal swab were 1, 4 and 8 days. Patients with mild disease using glucocorticoid tended to have longer viral shedding in blood and feces. At admission, 69.8% presented with lymphopenia and 38.8% had elevated D-dimers. Pneumonia was identified in 97.5% (314/322) of cases by chest CT scan. Severe-critical patients were 8% with a median time from onset to critical disease of 10.5 days. Half required oxygen therapy and 7.1% high-flow nasal oxygen. The case fatality rate was 0.92% with median time from onset to death of 16 days. Conclusion: COVID-19 cases in Shanghai were imported. Rapid identification, and effective control measures helped to contain the outbreak and prevent community transmission.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19 , China/epidemiology , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Female , Follow-Up Studies , Health Status Indicators , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Retrospective Studies , Time Factors , Treatment Outcome , Virus Shedding , Young Adult
19.
Nature ; 580(7803): E7, 2020 04.
Article in English | MEDLINE | ID: covidwho-73543

ABSTRACT

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

20.
J Infect ; 80(5): e1-e6, 2020 05.
Article in English | MEDLINE | ID: covidwho-7451

ABSTRACT

BACKGROUND: Studies on the 2019 novel coronavirus disease (COVID-19) have generally been limited to the description of the epidemiology and initial clinical characteristics. We investigated the temporal progression in patients with COVID-19. METHODS: In this retrospective, single-center study, we included confirmed cases of COVID-19 from Jan 20 to Feb 6, 2020 in Shanghai. Final date of follow-up was February 25, 2020. RESULTS: Of the 249 patients enrolled, the median age was 51 years old, and 126 (50.6%) were male. The duration from onset of symptoms to hospitalization was 4(2-7) days in symptomatic patients. Fever was occurred in 235(94.3%) patients. A total of 215 (86.3%) patients had been discharged after 16(12-20) days hospitalization. The estimated median duration of fever in all the patients with fever was 10 days (95 confidential intervals [CIs]: 8-11 days) after onset of symptoms. Patients who were transferred to intensive care units (ICU) had significantly longer duration of fever as compared to those not in ICU (31 days v.s. 9 days after onset of symptoms, respectively, P <0.0001). Radiological aggravation of initial image was observed in 163 (65.7%) patients on day 7 after onset of symptoms. 154(94.5%) of these patients showed radiological improvement on day 14. The median duration to negative reverse-transcriptase PCR tests of upper respiratory tract samples was 11 days (95 CIs: 10-12 days). Viral clearance was more likely to be delayed in patients in ICU than those not in ICU (P <0.0001). In multivariate logistical analysis, age (Odds ratio [OR] = 1.06) and CD4 T cell count (OR = 0.55 per 100 cells/ul increase) were independently associated with ICU admission. CONCLUSIONS: The majority of COVID-19 cases are mild. The clinical progression pattern suggests that early control of viral replication and application of host-directed therapy in later stage is essential to improve the prognosis of CVOID-19.


Subject(s)
Coronavirus Infections/pathology , Disease Progression , Pneumonia, Viral/pathology , Adult , Betacoronavirus , COVID-19 , China , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Female , Fever/etiology , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Prognosis , Retrospective Studies , SARS-CoV-2 , Time Factors , Tomography, X-Ray Computed
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