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1.
Asian J Psychiatr ; 54: 102269, 2020 Jun 30.
Article in English | MEDLINE | ID: covidwho-641323
2.
National Science Review ; 7(6):1003-1011, 2020.
Article | WHO COVID | ID: covidwho-635319

ABSTRACT

A recent outbreak of pneumonia in Wuhan, China was found to be caused by a 2019 novel coronavirus (2019-nCoV or SARS-CoV-2 or HCoV-19) We previously reported the clinical features of 12 patients with 2019-nCoV infections in Shenzhen, China To further understand the pathogenesis of COVID-19 and find better ways to monitor and treat the disease caused by 2019-nCoV, we measured the levels of 48 cytokines in the blood plasma of those 12 COVID-19 patients Thirty-eight out of the 48 measured cytokines in the plasma of 2019-nCoV-infected patients were significantly elevated compared to healthy individuals Seventeen cytokines were linked to 2019-nCoV loads Fifteen cytokines, namely M-CSF, IL-10, IFN-alpha 2, IL-17, IL-4, IP-10, IL-7, IL-1ra, G-CSF, IL-12, IFN-gamma, IL-1 alpha, IL-2, HGF and PDGF-BB, were strongly associated with the lung-injury Murray score and could be used to predict the disease severity of 2019-nCoV infections by calculating the area under the curve of the receiver-operating characteristics Our results suggest that 2019-nCoV infections trigger extensive changes in a wide array of cytokines, some of which could be potential biomarkers of disease severity of 2019-nCoV infections These findings will likely improve our understanding of the immunopathologic mechanisms of this emerging disease Our results also suggest that modulators of cytokine responses may play a therapeutic role in combating the disease once the functions of these elevated cytokines have been characterized

4.
Nature ; 2020 May 26.
Article in English | MEDLINE | ID: covidwho-381745

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a global health emergency that is in urgent need of intervention1-3. The entry of SARS-CoV-2 into its target cells depends on binding between the receptor-binding domain (RBD) of the viral spike protein and its cellular receptor, angiotensin-converting enzyme 2 (ACE2)2,4-6. Here we report the isolation and characterization of 206 RBD-specific monoclonal antibodies derived from single B cells from 8 individuals infected with SARS-CoV-2. We identified antibodies that potently neutralize SARS-CoV-2; this activity correlates with competition with ACE2 for binding to RBD. Unexpectedly, the anti-SARS-CoV-2 antibodies and the infected plasma did not cross-react with the RBDs of SARS-CoV or Middle East respiratory syndrome-related coronavirus (MERS-CoV), although there was substantial plasma cross-reactivity to their trimeric spike proteins. Analysis of the crystal structure of RBD-bound antibody revealed that steric hindrance inhibits viral engagement with ACE2, thereby blocking viral entry. These findings suggest that anti-RBD antibodies are largely viral-species-specific inhibitors. The antibodies identified here may be candidates for development of clinical interventions against SARS-CoV-2.

5.
Anal Chem ; 92(14): 9699-9705, 2020 07 21.
Article in English | MEDLINE | ID: covidwho-342681

ABSTRACT

A novel coronavirus (SARS-CoV-2) was recently identified in patients with acute respiratory disease and spread quickly worldwide. A specific and rapid diagnostic method is important for early identification. The reverse-transcription recombinase-aided amplification (RT-RAA) assay is a rapid detection method for several pathogens. Assays were performed within 5-15 min as a one-step single tube reaction at 39 °C. In this study, we established two RT-RAA assays for the S and orf1ab gene of SARS-CoV-2 using clinical specimens for validation. The analytical sensitivity of the RT-RAA assay was 10 copies for the S and one copy for the orf1ab gene per reaction. Cross-reactions were not observed with any of the other respiratory pathogens. A 100% agreement between the RT-RAA and real-time PCR assays was accomplished after testing 120 respiratory specimens. These results demonstrate that the proposed RT-RAA assay will be beneficial as it is a faster, more sensitive, and more specific tool for the detection of SARS-CoV-2.


Subject(s)
Betacoronavirus/chemistry , Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Nucleic Acid Amplification Techniques/methods , Pneumonia, Viral/diagnosis , Polymerase Chain Reaction/methods , Bacteria/chemistry , Bacteria/genetics , Cross Reactions , DNA Probes , Genes, Viral , Humans , Pandemics , Plasmids , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , Sensitivity and Specificity , Viral Proteins/genetics , Viruses/chemistry , Viruses/genetics
7.
Nat Med ; 26(6): 842-844, 2020 06.
Article in English | MEDLINE | ID: covidwho-244490

ABSTRACT

Respiratory immune characteristics associated with Coronavirus Disease 2019 (COVID-19) severity are currently unclear. We characterized bronchoalveolar lavage fluid immune cells from patients with varying severity of COVID-19 and from healthy people by using single-cell RNA sequencing. Proinflammatory monocyte-derived macrophages were abundant in the bronchoalveolar lavage fluid from patients with severe COVID-9. Moderate cases were characterized by the presence of highly clonally expanded CD8+ T cells. This atlas of the bronchoalveolar immune microenvironment suggests potential mechanisms underlying pathogenesis and recovery in COVID-19.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Single-Cell Analysis , Bronchoalveolar Lavage Fluid/immunology , Bronchoalveolar Lavage Fluid/virology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/virology , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Humans , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology
8.
Histopathology ; 2020 May 06.
Article in English | MEDLINE | ID: covidwho-186376

ABSTRACT

AIMS: An ongoing outbreak of 2019 novel coronavirus (SARS-CoV-2) diseases (COVID-19) has been spreading in multiple countries. One of the reasons for the rapid spread is that the virus can be transmitted from infected individuals without symptoms. Revealing the pathological features of early phase COVID-19 pneumonia is important to the understanding of its pathogenesis. The aim of this study was to explore pulmonary pathology of early phase COVID-19 pneumonia in a patient with a benign lung lesion. METHODS AND RESULTS: We analyzed the pathological changes of lung tissue from a 55-year-old female patient with early phase SARS-CoV-2 infection. In this case, right lower lobectomy was performed for a benign pulmonary nodule. Detailed clinical, laboratory and radiological data were also described. This case was confirmed to have preoperative SARS-CoV-2 infection by real-time RT-PCR and RNA in situ hybridization on surgically removed lung tissues. Histologically, COVID-19 pneumonia was characterized by exudative inflammation. The closer to the visceral pleura, the more severe the exudation of monocytes and lymphocytes. Perivascular inflammatory infiltration, intraalveolar multinucleated giant cells, pneumocyte hyperplasia and intracytoplasmic viral-like inclusion bodies were seen. However, fibrinous exudate and hyaline membrane formation, which were typical pulmonary features of SARS pneumonia, were not evident in this case. Immunohistochemical staining results showed that an abnormal accumulation of CD4+ helper T lymphocytes and CD163+ M2 macrophages in the lung tissue. CONCLUSION: The results highlighted the pulmonary pathological changes of early phase SARS-CoV-2 infection and suggested a role of immune dysfunction in the pathogenesis of COVID-19 pneumonia.

9.
J Allergy Clin Immunol ; 146(1): 119-127.e4, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-170708

ABSTRACT

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan, December 2019, and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. OBJECTIVE: We sought to identify biomarkers for disease severity and progression of COVID-19. METHODS: Forty-eight cytokines in the plasma samples from 50 COVID-19 cases including 11 critically ill, 25 severe, and 14 moderate patients were measured and analyzed in combination with clinical data. RESULTS: Levels of 14 cytokines were found to be significantly elevated in COVID-19 cases and showed different expression profiles in patients with different disease severity. Moreover, expression levels of IFN-γ-induced protein 10, monocyte chemotactic protein-3, hepatocyte growth factor, monokine-induced gamma IFN, and macrophage inflammatory protein 1 alpha, which were shown to be highly associated with disease severity during disease progression, were remarkably higher in critically ill patients, followed by severe and then the moderate patients. Serial detection of the 5 cytokines in 16 cases showed that continuously high levels were associated with deteriorated progression of disease and fatal outcome. Furthermore, IFN-γ-induced protein 10 and monocyte chemotactic protein-3 were excellent predictors for the progression of COVID-19, and the combination of the 2 cytokines showed the biggest area under the curve of the receiver-operating characteristics calculations with a value of 0.99. CONCLUSIONS: In this study, we report biomarkers that are highly associated with disease severity and progression of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of severe acute respiratory syndrome coronavirus 2 infection, and provide potential therapeutic targets and strategies.


Subject(s)
Biomarkers/blood , Chemokine CCL7/blood , Chemokine CXCL10/blood , Coronavirus Infections/blood , Pneumonia, Viral/blood , Adult , Aged , Betacoronavirus , Critical Illness , Cytokines/blood , Disease Progression , Female , Humans , Male , Middle Aged , Pandemics , Young Adult
10.
BMC Infect Dis ; 20(1): 317, 2020 Apr 30.
Article in English | MEDLINE | ID: covidwho-144086

ABSTRACT

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) outbreak started in Wuhan, Hubei, China since Dec 2019 and cases of infection have been continuously reported in various countries. It is now clear that the SARS-COV-2 coronavirus is transmissible from human to human. Nucleic acid detection is considered as the gold standard for the diagnosis of COVID-19. In this case report, we describe our experience in detection of SARS-COV-2 from a confirmed patient using nucleic acid test of bronchoalveolar-lavage fluid (BALF) samples but not nasopharyngeal swabs. CASE PRESENTATION: We present a case of severely ill SARS-COV-2 infected 46-year-old man with fever, coughing and chest tightness. We performed viral detection using his BALF samples and imaging method (CT) for confirmation. The patient received combination of interferonalfa-1b and ribavirin, lopinavir and ritonavir for antiviral treatment at different stages. Other medication was also given to him in combination for anti-inflammation, intestinal microbial regulation, phlegm elimination, liver protection and pulmonary fibrosis prevention purposes. We provided oxygen supply to him using BIPAP ventilator and high-flow humidification oxygen therapy instrument to facilitate respiration. The patient was cured and discharged. CONCLUSION: This case report described an effective supportive medication scheme to treat SARS-COV-2 infected patient and emphasized the necessity of detection of the viral genome using BALF samples and its significance in the diagnosis and prognosis of the disease.


Subject(s)
Bronchoalveolar Lavage Fluid/virology , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , RNA, Viral/isolation & purification , Antiviral Agents/therapeutic use , Betacoronavirus , China , Coronavirus Infections/drug therapy , Cough/etiology , Fever/etiology , Humans , Lung/diagnostic imaging , Male , Middle Aged , Nasopharynx/virology , Pandemics , Pneumonia, Viral/drug therapy
14.
Clin Infect Dis ; 71(15): 799-806, 2020 07 28.
Article in English | MEDLINE | ID: covidwho-45908

ABSTRACT

BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding. METHODS: In this retrospective study, risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from 2 hospitals outside Wuhan. RESULTS: The median (interquartile range) duration of SARS-CoV-2 RNA detection was 17 (13-22) days as measured from illness onset. When comparing patients with early (<15 days) and late (≥15 days after illness onset) viral RNA clearance, prolonged SARS-CoV-2 RNA shedding was associated with male sex (P = .009), old age (P = .033), concomitant hypertension (P = .009), delayed admission to hospital after illness onset (P = .001), severe illness at admission (P = .049), invasive mechanical ventilation (P = .006), and corticosteroid treatment (P = .025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (P < .001) and focal absorption on radiograph images (P < .001) than patients with early SARS-CoV-2 RNA clearance. Male sex (OR, 3.24; 95% CI, 1.31-8.02), delayed hospital admission (OR, 1.30; 95% CI, 1.10-1.54), and invasive mechanical ventilation (OR, 9.88; 95% CI, 1.11-88.02) were independent risk factors for prolonged SARS-CoV-2 RNA shedding. CONCLUSIONS: Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients.

15.
Clin Infect Dis ; 2020 Apr 08.
Article in English | MEDLINE | ID: covidwho-45838

ABSTRACT

We report the observation that 14.5% of COVID-19 patients had positive RT-PCR testing again after discharge. We describe correlations between laboratory parameters and treatment duration (r= -0.637; p=0.002) and time to virus recrudescence (r= 0.52; p=0.008) respectively, suggesting the need for additional measures to confirm illness resolution in COVID-19 patients.

16.
Infection ; 2020 Apr 10.
Article in English | MEDLINE | ID: covidwho-45828

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis. CASE PRESENTATION: A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission. He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of interleukin-6 was 272.40 pg/ml. Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia. Laboratory test results for viruses that cause myocarditis were all negative. The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/mL. Moreover, the LVEF of the patient gradually recovered to 68%. The patient died of aggravation of secondary infection on the 33rd day of hospitalization. CONCLUSION: COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure. This is the first report of COVID-19 complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.

17.
Clin Infect Dis ; 2020 Mar 28.
Article in English | MEDLINE | ID: covidwho-17886

ABSTRACT

BACKGROUND: The novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patient remains largely unknown, and the clinical values of antibody testing have not been fully demonstrated. METHODS: A total of 173 patients with SARS-CoV-2 infection were enrolled. Their serial plasma samples (n=535) collected during the hospitalization were tested for total antibodies (Ab), IgM and IgG against SARS-CoV-2. The dynamics of antibodies with the disease progress was analyzed. RESULTS: Among 173 patients, the seroconversion rate for Ab, IgM and IgG was 93.1%, 82.7% and 64.7%, respectively. The reason for the negative antibody findings in 12 patients might due to the lack of blood samples at the later stage of illness. The median seroconversion time for Ab, IgM and then IgG were day-11, day-12 and day-14, separately. The presence of antibodies was <40% among patients within 1-week since onset, and rapidly increased to 100.0% (Ab), 94.3% (IgM) and 79.8% (IgG) since day-15 after onset. In contrast, RNA detectability decreased from 66.7% (58/87) in samples collected before day-7 to 45.5% (25/55) during day 15-39. Combining RNA and antibody detections significantly improved the sensitivity of pathogenic diagnosis for COVID-19 (p<0.001), even in early phase of 1-week since onset (p=0.007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (p=0.006). CONCLUSIONS: The antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.

18.
Inflamm Res ; 69(6): 599-606, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-17695

ABSTRACT

OBJECTIVE: This study aims to evaluate the correlation between viral clearance and blood biochemical index of 94 discharged patients with COVID-19 infection in Shenzhen Third People's Hospital, enrolled from Jan 5 to Feb 13, 2020. METHODS: The clinical and laboratory findings were extracted from the electronic medical records of the patients. The data were analysed and reviewed by a trained team of physicians. Information on clinical signs and symptoms, medical treatment, virus clearance, and laboratory parameters including interleukin 6 (IL-6) and C-reactive protein were collected. RESULTS: COVID-19 mRNA clearance ratio was identified significantly correlated with the decline of serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Furthermore, COVID-19 mRNA clearance time was positively correlated with the length of hospital stay in patients treated with either IFN-α + lopinavir/ritonavir or IFN-α + lopinavir/ritonavir + ribavirin. CONCLUSIONS: Therapeutic regimens of IFN-α + lopinavir/ritonavir and IFN-α + lopinavir/ritonavir + ribavirin might be beneficial for treatment of COVID-19. Serum LDH or CK decline may predict a favorable response to treatment of COVID-19 infection.


Subject(s)
Coronavirus Infections/blood , Coronavirus Infections/virology , Pneumonia, Viral/blood , Pneumonia, Viral/virology , Adolescent , Adult , Aged , Child , Child, Preschool , China , Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Creatine Kinase/blood , Drug Combinations , Humans , Interferon-alpha/therapeutic use , L-Lactate Dehydrogenase/blood , Lopinavir/therapeutic use , Middle Aged , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/physiopathology , Polymerase Chain Reaction , RNA, Viral/analysis , Retrospective Studies , Ritonavir/therapeutic use , Young Adult
19.
Int J Infect Dis ; 95: 311-315, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-17667

ABSTRACT

OBJECTIVES: As a global pandemic is inevitable, real-time monitoring of transmission is vital for containing the spread of COVID-19. The main objective of this study was to report the real-time effective reproduction numbers (R(t)) and case fatality rates (CFR) in Europe. METHODS: Data for this study were obtained mainly from the World Health Organization website, up to March 9, 2020. R(t) were estimated by exponential growth rate (EG) and time-dependent (TD) methods. 'R0' package in R was employed to estimate R(t) by fitting the existing epidemic curve. Both the naïve CFR (nCFR) and adjusted CFR (aCFR) were estimated. RESULTS: With the EG method, R(t) was 3.27 (95% confidence interval (CI) 3.17-3.38) for Italy, 6.32 (95% CI 5.72-6.99) for France, 6.07 (95% CI 5.51-6.69) for Germany, and 5.08 (95% CI 4.51-5.74) for Spain. With the TD method, the R value for March 9 was 3.10 (95% CI 2.21-4.11) for Italy, 6.56 (95% CI 2.04-12.26) for France, 4.43 (95% CI 1.83-7.92) for Germany, and 3.95 (95% CI 0-10.19) for Spain. CONCLUSIONS: This study provides important findings on the early outbreak of COVID-19 in Europe. Due to the recent rapid increase in new cases of COVID-19, real-time monitoring of the transmissibility and mortality in Spain and France is a priority.


Subject(s)
Betacoronavirus , Coronavirus Infections/transmission , Pneumonia, Viral/transmission , Basic Reproduction Number , Coronavirus Infections/mortality , Disease Outbreaks , France/epidemiology , Germany/epidemiology , Humans , Italy/epidemiology , Pandemics , Pneumonia, Viral/mortality , Spain/epidemiology
20.
JAMA ; 2020 Mar 27.
Article in English | MEDLINE | ID: covidwho-17630

ABSTRACT

Importance: Coronavirus disease 2019 (COVID-19) is a pandemic with no specific therapeutic agents and substantial mortality. It is critical to find new treatments. Objective: To determine whether convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design, Setting, and Participants: Case series of 5 critically ill patients with laboratory-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment; Pao2/Fio2 <300; and mechanical ventilation. All 5 were treated with convalescent plasma transfusion. The study was conducted at the infectious disease department, Shenzhen Third People's Hospital in Shenzhen, China, from January 20, 2020, to March 25, 2020; final date of follow-up was March 25, 2020. Clinical outcomes were compared before and after convalescent plasma transfusion. Exposures: Patients received transfusion with convalescent plasma with a SARS-CoV-2-specific antibody (IgG) binding titer greater than 1:1000 (end point dilution titer, by enzyme-linked immunosorbent assay [ELISA]) and a neutralization titer greater than 40 (end point dilution titer) that had been obtained from 5 patients who recovered from COVID-19. Convalescent plasma was administered between 10 and 22 days after admission. Main Outcomes and Measures: Changes of body temperature, Sequential Organ Failure Assessment (SOFA) score (range 0-24, with higher scores indicating more severe illness), Pao2/Fio2, viral load, serum antibody titer, routine blood biochemical index, ARDS, and ventilatory and extracorporeal membrane oxygenation (ECMO) supports before and after convalescent plasma transfusion. Results: All 5 patients (age range, 36-65 years; 2 women) were receiving mechanical ventilation at the time of treatment and all had received antiviral agents and methylprednisolone. Following plasma transfusion, body temperature normalized within 3 days in 4 of 5 patients, the SOFA score decreased, and Pao2/Fio2 increased within 12 days (range, 172-276 before and 284-366 after). Viral loads also decreased and became negative within 12 days after the transfusion, and SARS-CoV-2-specific ELISA and neutralizing antibody titers increased following the transfusion (range, 40-60 before and 80-320 on day 7). ARDS resolved in 4 patients at 12 days after transfusion, and 3 patients were weaned from mechanical ventilation within 2 weeks of treatment. Of the 5 patients, 3 have been discharged from the hospital (length of stay: 53, 51, and 55 days), and 2 are in stable condition at 37 days after transfusion. Conclusions and Relevance: In this preliminary uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.

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