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1.
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

3.
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
4.
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
5.
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
6.
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.

7.
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.

8.
Engineering (Beijing) ; 2020 Mar 18.
Article in English | MEDLINE | ID: covidwho-9104

ABSTRACT

An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its caused coronavirus disease 2019 (COVID-19) has been reported in China since December 2019. More than 16% of patients developed acute respiratory distress syndrome, and the fatality ratio was about 1%-2%. No specific treatment has been reported. Herein, we examine the effects of Favipiravir (FPV) versus Lopinavir (LPV)/ritonavir (RTV) for the treatment of COVID-19. Patients with laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg twice daily; Days 2-14: 600 mg twice daily) plus interferon (IFN)-α by aerosol inhalation (5 million U twice daily) were included in the FPV arm of this study, whereas patients who were treated with LPV/RTV (Days 1-14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5 million U twice daily) were included in the control arm. Changes in chest computed tomography (CT), viral clearance, and drug safety were compared between the two groups. For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms. A shorter viral clearance time was found for the FPV arm versus the control arm (median (interquartile range, IQR), 4 (2.5-9) d versus 11 (8-13) d, P < 0.001). The FPV arm also showed significant improvement in chest imaging compared with the control arm, with an improvement rate of 91.43% versus 62.22% (P = 0.004). After adjustment for potential confounders, the FPV arm also showed a significantly higher improvement rate in chest imaging. Multivariable Cox regression showed that FPV was independently associated with faster viral clearance. In addition, fewer adverse reactions were found in the FPV arm than in the control arm. In this open-label nonrandomized control study, FPV showed significantly better treatment effects on COVID-19 in terms of disease progression and viral clearance; if causal, these results should be important information for establishing standard treatment guidelines to combat the SARS-CoV-2 infection.

9.
Emerg Infect Dis ; 26(6): 1320-1323, 2020 06.
Article in English | MEDLINE | ID: covidwho-3346

ABSTRACT

Since early January 2020, after the outbreak of coronavirus infection in Wuhan, China, ≈365 confirmed cases have been reported in Shenzhen, China. The mode of community and intrafamily transmission is threatening residents in Shenzhen. Strategies to strengthen prevention and interruption of these transmissions should be urgently addressed.


Subject(s)
Coronavirus Infections/transmission , Pneumonia, Viral/transmission , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus , Child , Child, Preschool , China/epidemiology , Female , Humans , Infant , Infectious Disease Incubation Period , Male , Middle Aged , Pandemics , Young Adult
10.
Sci China Life Sci ; 63(3): 364-374, 2020 03.
Article in English | MEDLINE | ID: covidwho-693

ABSTRACT

The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.


Subject(s)
Angiotensin II/blood , Betacoronavirus/pathogenicity , Biomarkers/blood , Coronavirus Infections/diagnosis , Lung Injury , Pneumonia, Viral/etiology , Respiratory Distress Syndrome, Adult/etiology , Viral Load , Adult , Aged , Blood Chemical Analysis , Child , Coronavirus Infections/complications , Coronavirus Infections/pathology , Humans , Male , Middle Aged , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/pathology , Severity of Illness Index
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