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1.
JMIR Med Inform ; 2021 Jan 12.
Article in English | MEDLINE | ID: covidwho-1030469

ABSTRACT

BACKGROUND: Chest examination by auscultation is essential in patients with coronavirus disease (COVID-19), especially those with poor respiratory conditions, such as severe pneumonia, respiratory dysfunction, and intensive cases who are intubated and assisted with ventilators. However, proper auscultation of such patients is difficult when medical workers wear personal protective equipment and when contact with patients is to be minimized. OBJECTIVE: The objective of our study was to design and develop a low-cost electronic stethoscope allowing ear-contactless auscultation, and digital storage for further analysis. The clinical feasibility of our device was assessed, in comparison to a standard electronic stethoscope. METHODS: We developed a prototype of the ear-contactless electronic stethoscope, called Auscul Pi, powered by Raspberry Pi and Python. Our device allows real-time capture of auscultation sounds with a micro-speaker instead of ear pieces, and it can store data files for later analysis. We assessed the feasibility of using this stethoscope by detecting abnormal heart and respiratory sounds from eight patients with heart failure or structural heart diseases and two healthy volunteers, and by comparing the results with those from a 3M Littmann electronic stethoscope. RESULTS: We were able to conveniently operate Auscul Pi and precisely record the patients' auscultation sounds. Auscul Pi showed real-time recording and playback performances as the 3M Littmann stethoscope. Phonocardiogram of data obtained with the two stethoscopes were consistent and could be aligned with cardiac cycle of electrocardiogram. Pearson's correlation analysis of amplitude data from the two types of phonocardiogram showed that the Auscul Pi was correlated with 3M Littmann with the coefficient of 0.3245-0.5570 for healthy subjects (P<.001) and 0.3449-0.5138 among four patients (P<.001). CONCLUSIONS: Auscul Pi can be used for auscultation in the clinical practice by applying real-time ear-contactless playback followed by quantitative analysis. Auscul Pi may allow accurate auscultation when medical workers are wearing protective suits and have difficulties in examining COVID-19. CLINICALTRIAL: This study was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=54971, ChiCTR2000033830).

2.
Shock ; 2021 Jan 13.
Article in English | MEDLINE | ID: covidwho-1029247

ABSTRACT

ABSTRACT: The ongoing coronavirus disease 2019 (COVID-19) pandemic has swept over the world and causes thousands of deaths. Although the clinical features of COVID-19 become much clearer than before, there are still further problems with the pathophysiological process and treatments of severe patients. One primary problem is with the paradoxical immune states in severe patients with COVID-19. Studies indicate that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can attack the immune system, manifested as a state of immunosuppression with a decrease in lymphocytes, whereas a state of hyperinflammation, presenting as elevated cytokine levels, is also detected in COVID-19. Therefore, discussing the specific status of immunity in COVID-19 will contribute to the understanding of its pathophysiology and the search for appropriate treatments. Here, we review all the available literature concerning the different immune states in COVID-19 and the underlying pathophysiological mechanisms. In addition, the association between immune states and the development and severity of disease as well as the impact on the selection of immunotherapy strategies are discussed in our review.

3.
Front Immunol ; 11: 602256, 2020.
Article in English | MEDLINE | ID: covidwho-1021889

ABSTRACT

Coronavirus Disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a newly emerged coronavirus, and has been pandemic since March 2020 and led to many fatalities. Vaccines represent the most efficient means to control and stop the pandemic of COVID-19. However, currently there is no effective COVID-19 vaccine approved to use worldwide except for two human adenovirus vector vaccines, three inactivated vaccines, and one peptide vaccine for early or limited use in China and Russia. Safe and effective vaccines against COVID-19 are in urgent need. Researchers around the world are developing 213 COVID-19 candidate vaccines, among which 44 are in human trials. In this review, we summarize and analyze vaccine progress against SARS-CoV, Middle-East respiratory syndrome Coronavirus (MERS-CoV), and SARS-CoV-2, including inactivated vaccines, live attenuated vaccines, subunit vaccines, virus like particles, nucleic acid vaccines, and viral vector vaccines. As SARS-CoV-2, SARS-CoV, and MERS-CoV share the common genus, Betacoronavirus, this review of the major research progress will provide a reference and new insights into the COVID-19 vaccine design and development.


Subject(s)
/prevention & control , Vaccines , Animals , Antibody-Dependent Enhancement , Humans , /physiology
4.
Ann Intensive Care ; 11(1): 5, 2021 Jan 09.
Article in English | MEDLINE | ID: covidwho-1015901

ABSTRACT

BACKGROUND: Few specific medications have been proven effective for the treatment of patients with severe coronavirus disease 2019 (COVID-19). Here, we tested whether high-dose vitamin C infusion was effective for severe COVID-19. METHODS: This randomized, controlled, clinical trial was performed at 3 hospitals in Hubei, China. Patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the ICU were randomly assigned in as 1:1 ratio to either the high-dose intravenous vitamin C (HDIVC) or the placebo. HDIVC group received 12 g of vitamin C/50 ml every 12 h for 7 days at a rate of 12 ml/hour, and the placebo group received bacteriostatic water for injection in the same way within 48 h of arrival to ICU. The primary outcome was invasive mechanical ventilation-free days in 28 days (IMVFD28). Secondary outcomes were 28-day mortality, organ failure (Sequential Organ Failure Assessment (SOFA) score), and inflammation progression (interleukin-6). RESULTS: Only 56 critical COVID-19 patients were ultimately recruited due to the early control of the outbreak. There was no difference in IMVFD28 between two groups (26.0 [9.0-28.0] in HDIVC vs 22.0 [8.50-28.0] in control, p = 0.57). HDIVC failed to reduce 28-day mortality (P = 0.27). During the 7-day treatment period, patients in the HDIVC group had a steady rise in the PaO2/FiO2 (day 7: 229 vs. 151 mmHg, 95% CI 33 to 122, P = 0.01), which was not observed in the control group. IL-6 in the HDIVC group was lower than that in the control group (19.42 vs. 158.00; 95% CI -301.72 to -29.79; P = 0.04) on day 7. CONCLUSION: This pilot trial showed that HDIVC failed to improve IMVFD28, but might show a potential signal of benefit in oxygenation for critically ill patients with COVID-19 improving PaO2/FiO2 even though.

5.
PLoS Negl Trop Dis ; 15(1): e0009051, 2021 Jan 06.
Article in English | MEDLINE | ID: covidwho-1013204

ABSTRACT

BACKGROUND: Until now, no antiviral treatment has been proven to be effective for the coronavirus disease 2019 (COVID-19). The timing of oxygen therapy was considered to have a great influence on the symptomatic relief of hypoxemia and seeking medical intervention, especially in situations with insufficient medical resources, but the evidence on the timing of oxygen therapy is limited. METHODS AND FINDINGS: Medical charts review was carried out to collect the data of hospitalized patients with COVID-19 infection confirmed in Tongji hospital, Wuhan from 30th December 2019 to 8th March 2020. In this study, the appropriate timing of oxygen therapy and risk factors associated with severe and fatal illness were identified and the effectiveness of antivirus on disease progression was assessed. Among 1362 patients, the prevalence of hypoxia symptoms was significantly higher in those patients with severe and fatal illness than in those with less severe disease. The onset of hypoxia symptoms was most common in the second to third week after symptom onset, and patients with critical and fatal illness experienced these symptoms earlier than those with mild and severe illness. In multivariable analyses, the risk of death increased significantly when oxygen therapy was started more than 2 days after hypoxia symptoms onset among critical patients (OR, 1.92; 95%CI, 1.20 to 3.10). Compared to the critically ill patients without IFN-a, the patients who were treated with IFN-a had a lower mortality (OR, 0.60; 95%CI, 0.39 to 0.91). CONCLUSIONS: Early initiation of oxygen therapy was associated with lower mortality among critical patients. This study highlighted the importance of early oxygen therapy after the onset of hypoxia symptoms. Our results also lend support to potentially beneficial effects of IFNα on critical illness.

6.
Emerg Infect Dis ; 27(2)2021 Jan 04.
Article in English | MEDLINE | ID: covidwho-1006452

ABSTRACT

To assess transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a detention facility experiencing a coronavirus disease outbreak and evaluate testing strategies, we conducted a prospective cohort investigation in a facility in Louisiana, USA. We conducted SARS-CoV-2 testing for detained persons in 6 quarantined dormitories at various time points. Of 143 persons, 53 were positive at the initial test, and an additional 58 persons were positive at later time points (cumulative incidence 78%). In 1 dormitory, all 45 detained persons initially were negative; 18 days later, 40 (89%) were positive. Among persons who were SARS-CoV-2 positive, 47% (52/111) were asymptomatic at the time of specimen collection; 14 had replication-competent virus isolated. Serial SARS-CoV-2 testing might help interrupt transmission through medical isolation and quarantine. Testing in correctional and detention facilities will be most effective when initiated early in an outbreak, inclusive of all exposed persons, and paired with infection prevention and control.

7.
MMWR Morb Mortal Wkly Rep ; 69(5152): 1642-1647, 2021 Jan 01.
Article in English | MEDLINE | ID: covidwho-1005171

ABSTRACT

Antigen-based tests for SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), are inexpensive and can return results within 15 minutes (1). Antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in asymptomatic and symptomatic persons within the first 5-12 days after symptom onset (2). These tests have been used at U.S. colleges and universities and other congregate settings (e.g., nursing homes and correctional and detention facilities), where serial testing of asymptomatic persons might facilitate early case identification (3-5). However, test performance data from symptomatic and asymptomatic persons are limited. This investigation evaluated performance of the Sofia SARS Antigen Fluorescent Immunoassay (FIA) (Quidel Corporation) compared with real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 detection among asymptomatic and symptomatic persons at two universities in Wisconsin. During September 28-October 9, a total of 1,098 paired nasal swabs were tested using the Sofia SARS Antigen FIA and real-time RT-PCR. Virus culture was attempted on all antigen-positive or real-time RT-PCR-positive specimens. Among 871 (79%) paired swabs from asymptomatic participants, the antigen test sensitivity was 41.2%, specificity was 98.4%, and in this population the estimated positive predictive value (PPV) was 33.3%, and negative predictive value (NPV) was 98.8%. Antigen test performance was improved among 227 (21%) paired swabs from participants who reported one or more symptoms at specimen collection (sensitivity = 80.0%; specificity = 98.9%; PPV = 94.1%; NPV = 95.9%). Virus was isolated from 34 (46.6%) of 73 antigen-positive or real-time RT-PCR-positive nasal swab specimens, including two of 18 that were antigen-negative and real-time RT-PCR-positive (false-negatives). The advantages of antigen tests such as low cost and rapid turnaround might allow for rapid identification of infectious persons. However, these advantages need to be balanced against lower sensitivity and lower PPV, especially among asymptomatic persons. Confirmatory testing with an FDA-authorized nucleic acid amplification test (NAAT), such as RT-PCR, should be considered after negative antigen test results in symptomatic persons, and after positive antigen test results in asymptomatic persons (1).


Subject(s)
Antigens, Viral/analysis , /diagnosis , Student Health Services , Adolescent , Adult , Asymptomatic Diseases , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , Universities , Wisconsin/epidemiology , Young Adult
8.
Signal Transduct Target Ther ; 5(1): 299, 2020 12 28.
Article in English | MEDLINE | ID: covidwho-997814

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly spread worldwide and has affected more than 10 million individuals. A typical feature of COVID-19 is the suppression of type I and III interferon (IFN)-mediated antiviral immunity. However, the molecular mechanism by which SARS-CoV-2 evades antiviral immunity remains elusive. Here, we reported that the SARS-CoV-2 membrane (M) protein inhibits the production of type I and III IFNs induced by the cytosolic dsRNA-sensing pathway mediated by RIG-I/MDA-5-MAVS signaling. In addition, the SARS-CoV-2 M protein suppresses type I and III IFN induction stimulated by SeV infection or poly (I:C) transfection. Mechanistically, the SARS-CoV-2 M protein interacts with RIG-I, MAVS, and TBK1, thus preventing the formation of the multiprotein complex containing RIG-I, MAVS, TRAF3, and TBK1 and subsequently impeding the phosphorylation, nuclear translocation, and activation of IRF3. Consequently, ectopic expression of the SARS-CoV-2 M protein facilitates the replication of vesicular stomatitis virus. Taken together, these results indicate that the SARS-CoV-2 M protein antagonizes type I and III IFN production by targeting RIG-I/MDA-5 signaling, which subsequently attenuates antiviral immunity and enhances viral replication. This study provides insight into the interpretation of SARS-CoV-2-induced antiviral immune suppression and illuminates the pathogenic mechanism of COVID-19.


Subject(s)
/metabolism , DEAD Box Protein 58/metabolism , Interferon Type I/biosynthesis , Interferon-Induced Helicase, IFIH1/metabolism , Interferons/biosynthesis , Signal Transduction , Viral Matrix Proteins/metabolism , Animals , Chlorocebus aethiops , DEAD Box Protein 58/genetics , HEK293 Cells , HeLa Cells , Humans , Interferon Type I/genetics , Interferon-Induced Helicase, IFIH1/genetics , Interferons/genetics , Vero Cells , Viral Matrix Proteins/genetics
10.
Journal of Chinese Economic and Business Studies ; : 1-9, 2020.
Article | WHO COVID | ID: covidwho-977338
11.
Int J Environ Res Public Health ; 17(22)2020 11 23.
Article in English | MEDLINE | ID: covidwho-945814

ABSTRACT

During the COVID-19 pandemic, when individuals were confronted with social distancing, social media served as a significant platform for expressing feelings and seeking emotional support. However, a group of automated actors known as social bots have been found to coexist with human users in discussions regarding the coronavirus crisis, which may pose threats to public health. To figure out how these actors distorted public opinion and sentiment expressions in the outbreak, this study selected three critical timepoints in the development of the pandemic and conducted a topic-based sentiment analysis for bot-generated and human-generated tweets. The findings show that suspected social bots contributed to as much as 9.27% of COVID-19 discussions on Twitter. Social bots and humans shared a similar trend on sentiment polarity-positive or negative-for almost all topics. For the most negative topics, social bots were even more negative than humans. Their sentiment expressions were weaker than those of humans for most topics, except for COVID-19 in the US and the healthcare system. In most cases, social bots were more likely to actively amplify humans' emotions, rather than to trigger humans' amplification. In discussions of COVID-19 in the US, social bots managed to trigger bot-to-human anger transmission. Although these automated accounts expressed more sadness towards health risks, they failed to pass sadness to humans.


Subject(s)
Artificial Intelligence , Pandemics , Social Media , Emergencies , Humans
13.
Journal of Medical Virology ; 92(11):2693-2701, 2020.
Article | WHO COVID | ID: covidwho-942394

ABSTRACT

The ongoing outbreak of a new coronavirus (2019-nCoV, or severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) has caused an epidemic of the acute respiratory syndrome known as coronavirus disease (COVID-19) in humans SARS-CoV-2 rapidly spread to multiple regions of China and multiple other countries, posing a serious threat to public health The spike (S) proteins of SARS-CoV-1 and SARS-CoV-2 may use the same host cellular receptor, angiotensin-converting enzyme 2 (ACE2), for entering host cells The affinity between ACE2 and the SARS-CoV-2 S protein is much higher than that of ACE2 binding to the SARS-CoV S protein, explaining why SARS-CoV-2 seems to be more readily transmitted from human to human Here, we report that ACE2 can be significantly upregulated after infection of various viruses, including SARS-CoV-1 and SARS-CoV-2, or by the stimulation with inflammatory cytokines such as interferons We propose that SARS-CoV-2 may positively induce its cellular entry receptor, ACE2, to accelerate its replication and spread;high inflammatory cytokine levels increase ACE2 expression and act as high-risk factors for developing COVID-19, and the infection of other viruses may increase the risk of SARS-CoV-2 infection Therefore, drugs targeting ACE2 may be developed for the future emerging infectious diseases caused by this cluster of coronaviruses

14.
J Adv Nurs ; 2020 Nov 22.
Article in English | MEDLINE | ID: covidwho-938330

ABSTRACT

AIMS: To determine psychological symptoms of patients with mild symptoms of coronavirus disease 2019 in China and to explore the influencing factors. DESIGN: A cross-sectional study. METHODS: A convenience sample of 296 mild coronavirus disease 2019 patients were recruited from a Fangcang hospital in Wuhan, Hubei Province, from 3rd March to 5th March, 2020. Participants were assessed using a sociodemographic and clinical characteristics questionnaire, and Symptom Check List 90. The binary logistic regression was utilized to explore the influencing factors of psychological symptoms of patients with mild symptoms of coronavirus disease 2019. RESULTS: In total, 296 of 299 patients with mild symptoms of coronavirus disease 2019 participated in the study (response rate: 99.0%). The findings revealed that 12.8% patients with mild symptoms have mental-health problems; the most common psychological symptoms are phobic anxiety (58.4%), paranoid ideation (50.7%), and psychoticism (40.2%). Female patients [OR=3.587, 95%CI (1.694-7.598)] and those having physical symptoms currently [OR =2.813, 95%CI (1.210-6.539)] are at higher risk, while those in the middle duration of hospitalization [OR =0.278, 95% CI (0.121-0.639)] protect against mental-health problems. CONCLUSIONS: The minority of patients with mild symptoms of coronavirus disease 2019 were still suffering from psychological symptoms. Health-care providers are recommended to pay particular attention to screening these high-risk groups (females, those in the initial stages of hospitalization and those with physical symptoms currently) and implement targeted psychological care as required. IMPACT: This study found that most patients of Coronavirus Disease 2019 in Fangcang hospital exhibited normal mental-health at par with the general Chinese norm and the minority of them were suffering from psychological symptoms. The findings can provide a reference for health-care providers to screen high-risk psychological symptoms groups and implement targeted psychological intervention for patients with Coronavirus Disease 2019.

16.
Biosaf Health ; 2020 Nov 19.
Article in English | MEDLINE | ID: covidwho-932794

ABSTRACT

Coronavirus disease (COVID-19) pandemic has spread in 220 countries/regions to wreak havoc to human beings around the world. At present, the second wave of COVID-19 has begun in many European countries. The complete control of COVID-19 is very urgent. Although China quickly brought the virus under control, there have been eight sporadic outbreaks in China since then. Both in Xinfadi of Beijing and Dalian outbreak of COVID-19, environmental swab samples related to imported cold chain food were tested nucleic acid positive for SARS-CoV-2. In this outbreak in Qingdao, we directly isolated SARS-CoV-2 from the cod outer package's surface swab samples. This is the first time worldwide, SARS-CoV-2 were isolated from the imported frozen cod outer package's surface, which showed that imported frozen food industry could import SARS-CoV-2 virus.

17.
Pediatr Pulmonol ; 55(12): 3602-3609, 2020 12.
Article in English | MEDLINE | ID: covidwho-915178

ABSTRACT

OBJECTIVE: To identify the risk factors for redetectable positivity (RP), and to provide a basis for prevention and control of coronavirus disease-2019 (COVID-19) in children. METHODS: A retrospective study was performed on all pediatric patients diagnosed with COVID-19. RP was defined as the positive result of real-time reverse transcriptase polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after symptom resolution and discharge. Children were defined as being less than 18 years old. RESULTS: Fourteen out of 38 (36.8%) pediatric patients exhibited RP. Compared with the non-RP group (n = 24), the RP group (n = 14) had more family cluster infections, relatively higher white blood cell (WBC) count and longer plasma prothrombin time (PT), while age and gender were insignificant. T lymphocyte subclassification was observed at five-time points: the first test after admission, 2 weeks, and 1, 2, and 3 months after discharge. The RP group had a higher percentage and count of CD8+ T lymphocytes and lower CD4+/CD8+ ratio at 2 weeks, while a lower percentage and count of CD4+ T lymphocytes and lower CD4+/CD8+ ratio at 2 months. The positive rate of nasopharyngeal swabs by RT-PCR was higher during the onset, while that of anal swabs was higher during the recovery of COVID-19. CONCLUSIONS: Family cluster infection, higher WBC count, and longer PT are the early risk factors for RP in recovered COVID-19 children. The dynamic changes in number and ratio of CD4+ and CD8+ T lymphocytes may be involved in prolonged SARS-CoV-2 clearance. Nasopharyngeal swabs sampling during the onset and anal swabs sampling during the recovery may improve the positivity rate of RT-PCR.


Subject(s)
Anal Canal/virology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Coronavirus Infections/diagnosis , Nasopharynx/virology , Pneumonia, Viral/diagnosis , Betacoronavirus , CD4 Lymphocyte Count , CD4-CD8 Ratio , Child , Child, Preschool , Clinical Laboratory Techniques , Coronavirus , Coronavirus Infections/blood , Coronavirus Infections/immunology , Coronavirus Infections/transmission , Female , Hospitalization , Humans , Length of Stay , Leukocyte Count , Male , Pandemics , Patient Discharge , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , Pneumonia, Viral/transmission , Prothrombin Time , Real-Time Polymerase Chain Reaction , Recurrence , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Risk Factors , Virus Shedding
18.
Am J Chin Med ; 48(7): 1523-1538, 2020.
Article in English | MEDLINE | ID: covidwho-910318

ABSTRACT

This study aimed to investigate the efficacy of Traditional Chinese Medicine (TCM) decoction with different intervention timepoints in the treatment of coronavirus disease 2019 (COVID-19) patients. We retrospectively collected the medical records and evaluated the outcomes of COVID-19 patients that received TCM decoction treatment at different timepoints. A total of 234 COVID-19 patients were included in this study. Patients who received TCM decoction therapy within 3 days or 7 days after admission could achieve shorter hospitalization days and disease periods compared to those who received TCM decoction [Formula: see text] 7 days after admission (all [Formula: see text]). Patients who received TCM decoction therapy within 3 days had significantly fewer days to negative SARS-CoV-2 from nasopharyngeal/oral swab and days to negative SARS-CoV-2 from urine/stool/blood samples compared to those received TCM decoction [Formula: see text] days after admission (all [Formula: see text]). Patients who received TCM decoction therapy on the 3rd to 7th day after admission had a faster achievement of negative SARS-CoV-2 from urine/stool/blood samples compared to those who received TCM decoction [Formula: see text] days after admission ([Formula: see text]). Logistic models revealed that more days from TCM decoction to admission [Formula: see text] days might be a risk factor for long hospitalization days, disease period, and slower negative-conversion of SARS-CoV-2 (all [Formula: see text]). Conclusively, our results suggest that TCM decoction therapy should be considered at the early stage of COVID-19 patients.


Subject(s)
/drug therapy , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional/methods , /drug effects , Adult , Aged , /virology , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Pandemics/prevention & control , Retrospective Studies , Treatment Outcome
19.
Antiviral Res ; 182: 104868, 2020 10.
Article in English | MEDLINE | ID: covidwho-909531

ABSTRACT

COVID-19, which is caused by the emerging human coronavirus SARS-CoV-2, has become a global pandemic that poses a serious threat to human health. To date, no vaccines or specific antiviral drugs have been approved for the treatment of this disease in clinic. Herein, therapeutic antibodies for SARS-CoV-2 were obtained from hyperimmune equine plasma. First, a recombinant SARS-CoV-2 spike protein receptor-binding domain (RBD) was obtained in gram-level quantities through high-cell density fermentation of Chinese hamster ovary cells. Then, the binding of the RBD to the SARS-CoV-2 receptor, human angiotensin-converting enzyme 2, was verified by several biochemical methods. The efficacy of the RBD in triggering antibody response in vivo was subsequently tested in both mice and equines, and the results showed that the RBD triggered high-titer neutralizing antibody production in vivo. Immunoglobulin F(ab')2 fragments were prepared from equine antisera via removal of the Fc region from the immunoglobulins. Finally, a neutralization test with live virus demonstrated that RBD-specific F(ab')2 inhibited SARS-CoV-2 with an EC50 of 0.07 µg/ml and an EC80 of 0.18 µg/ml, showing a potent inhibitory effect on SARS-CoV-2. These results highlight RBD-specific equine immunoglobulin F(ab')2 fragment as a candidate for the treatment of SARS-CoV-2.


Subject(s)
Antibodies, Neutralizing/immunology , Betacoronavirus/immunology , Coronavirus Infections/therapy , Coronavirus Infections/virology , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , Receptors, Immunologic/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Viral/immunology , Chlorocebus aethiops , Female , HeLa Cells , Humans , Mice, Inbred BALB C , Neutralization Tests , Pandemics , Protein Binding , Vero Cells
20.
Vet Microbiol ; 252: 108918, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-909094

ABSTRACT

Porcine haemagglutinating encephalomyelitis virus (PHEV) is a member of coronavirus that causes acute infectious disease and high mortality in piglets. The transcription factor IRF3 is a central regulator of type I interferon (IFN) innate immune signalling. Here, we report that PHEV infection of RAW264.7 cells results in strong suppression of IFN-ß production in the early stage. A comparative analysis of the upstream effector of IFN-ß transcription demonstrated that deactivation of IRF3, but not p65 or ATF-2 proteins, is uniquely attributed to failure of early IFN-ß induction. Moreover, the RIG-I/MDA5/MAVS/TBK1-dependent protective response that regulates the IRF3 pathway is not disrupted by PHEV and works well underlying the deactivated IRF3-mediated IFN-ß inhibition. After challenge with poly(I:C), a synthetic analogue of dsRNA used to stimulate IFN-ß secretion in the TLR-controlled pathway, we show that PHEV and poly(I:C) regulate IFN-ß-induction via two different pathways. Collectively, our findings reveal that deactivation of IRF3 is a specific mechanism that contributes to termination of type I IFN signalling during early infection with PHEV independent of the conserved RIG-I/MAVS/MDA5/TBK1-mediated innate immune response.


Subject(s)
Betacoronavirus 1/immunology , Coronavirus Infections/veterinary , Interferon Regulatory Factor-3/genetics , Interferon-beta/immunology , Animals , Betacoronavirus 1/genetics , Coronavirus Infections/immunology , Coronavirus Infections/virology , Immunity, Innate , Interferon Regulatory Factor-3/immunology , Mice , Poly I-C/pharmacology , RAW 264.7 Cells , Signal Transduction/immunology
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