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1.
Emerg Microbes Infect ; 11(1): 2466-2473, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2051170

ABSTRACT

In this study, we examined the clinical and electrophysiological outcomes of adolescents in Hong Kong who developed myocarditis or pericarditis following BNT162b2 vaccination for COVID-19, and followed-up for 60-180 days after their initial diagnosis. Clinical assessments included electrocardiogram (ECG) and echocardiogram at the initial admission and follow-up were compared. Treadmill testing was also performed in some cases. Between 14 June 2021 and 16 February 2022, 53 subjects were approached to participate in this follow-up study, of which 28 patients were followed up for >60 days with a median follow-up period of 100 days (range, 61-178 days) and were included in this study. On admission, 23 patients had ECG abnormalities but no high-grade atrioventricular block. Six patients had echocardiogram abnormalities, including reduced contractility, small rim pericardial effusions, and hyperechoic ventricular walls. All patients achieved complete recovery on follow-up. After discharge, 10 patients (35.7%) reported symptoms, including occasional chest pain, shortness of breath, reduced exercise tolerance, and recurrent vasovagal near-syncope. At follow-up, assessments, including ECGs, were almost all normal. Among the three patients with possible ECG abnormalities, all their echocardiograms or treadmill testings were normal. Sixteen patients (57.1%) underwent treadmill testing at a median of 117 days post-admission, which were also normal. However, at follow-up, there was a significant mean bodyweight increase of 1.81 kg (95%CI 0.47-3.1 kg, p = 0.01), possibly due to exercise restriction. In conclusion, most adolescents experiencing myocarditis and pericarditis following BNT162b2 vaccination achieved complete recovery. Some patients developed non-specific persistent symptoms, and bodyweight changes shall be monitored.


Subject(s)
BNT162 Vaccine , COVID-19 , Myocarditis , Pericarditis , Adolescent , Humans , BNT162 Vaccine/adverse effects , COVID-19/prevention & control , Follow-Up Studies , Hong Kong/epidemiology , Myocarditis/diagnosis , Myocarditis/etiology , Pericarditis/diagnosis , Pericarditis/etiology , Vaccination/adverse effects
2.
The Brazilian Journal of Infectious Diseases ; 26:102554, 2022.
Article in Portuguese | ScienceDirect | ID: covidwho-2007529

ABSTRACT

Introdução Com o surgimento da pandemia causada pelo SARS-CoV-2, tornou-se urgente entender a fisiopatologia e interação deste, com outros patógenos em diferentes situações clínicas, especialmente naquelas em que o paciente se encontra em maior risco e vulnerabilidade, como é o caso dos portadores de doença renal crônica submetidos ao transplante renal. Objetivo Verificar a soroprevalência de SARS-CoV-2 em crianças e adolescentes transplantados renais e um acompanhante (pai, mãe ou responsável). Método Trata-se de um estudo transversal desenvolvido no Ambulatório de Transplante Renal Pediátrico, do Hospital do Rim e Hipertensão (Fundação Oswaldo Ramos). Adotou-se como critérios de inclusão: idade ≤ a 18 anos, aceitar participar do estudo com assinatura do TALE/TCLE, realizar coleta de exames laboratoriais no laboratório do Hrim. Resultados Foram incluídos 18 crianças e adolescentes transplantados renais, com idade média 12,38 anos, mínima 4 e máxima 18 anos de idade. 11 (61,1%) participantes do sexo masculino. Em relação ao teste sorológico, 4 (22,2%) não haviam se vacinado contra COVID-19 no momento do teste. Destes, 2 (50%) apresentaram sorologia não reagente e 2 (50%) Reagente. Dentre os que receberam pelo menos 1 dose da vacina (14), 3 (21,4%) apresentaram resultado não reagente e 11 (78,6%) Reagente. Entre os 18 acompanhantes, a média de idade foi de 35 anos, 16 (88,88%) do sexo feminino. Para o teste sorológico, considerou-se 17 acompanhantes, visto que 1 não apresentou informações sobre a vacinação. 1 (5,88%) não recebeu vacina contra COVID-19 e apresentou teste sorológico Reagente. Dentre os 16 vacinados, todos estavam com sorologia Reagente para o SARS-CoV-2. Conclusão Os resultados demonstram a importância de conhecer o status sorológico de pacientes e acompanhantes, mesmo que vacinados, a fim de proporcionar maior segurança em saúde para todos os envolvidos no tratamento e acompanhamento ambulatorial do paciente transplantado. Além disso, estes achados poderão propor e mudar protocolos assistenciais, de prevenção e controle de infecção, estabelecer escore de risco, visto que se trata de uma população de maior risco e gravidade. Vale destacar o impacto social que medidas de prevenção e controle de infecção baratas, de fácil e imediata implantação no SUS, podem trazer à qualidade de vida, qualidade do cuidado, sobrevida do paciente e do enxerto, e para a segurança em saúde. Ag. Financiadora FAPESP;CAPES. Nr. Processo 2021/04492-1.

3.
Nature ; 602(7898): 676-681, 2022 02.
Article in English | MEDLINE | ID: covidwho-1616993

ABSTRACT

The B.1.1.529/Omicron variant of SARS-CoV-2 was only recently detected in southern Africa, but its subsequent spread has been extensive, both regionally and globally1. It is expected to become dominant in the coming weeks2, probably due to enhanced transmissibility. A striking feature of this variant is the large number of spike mutations3 that pose a threat to the efficacy of current COVID-19 vaccines and antibody therapies4. This concern is amplified by the findings of our study. Here we found that B.1.1.529 is markedly resistant to neutralization by serum not only from patients who recovered from COVID-19, but also from individuals who were vaccinated with one of the four widely used COVID-19 vaccines. Even serum from individuals who were vaccinated and received a booster dose of mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies against all known epitope clusters on the spike protein, we noted that the activity of 17 out of the 19 antibodies tested were either abolished or impaired, including ones that are currently authorized or approved for use in patients. Moreover, we also identified four new spike mutations (S371L, N440K, G446S and Q493R) that confer greater antibody resistance on B.1.1.529. The Omicron variant presents a serious threat to many existing COVID-19 vaccines and therapies, compelling the development of new interventions that anticipate the evolutionary trajectory of SARS-CoV-2.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/virology , Immune Evasion/immunology , SARS-CoV-2/immunology , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/blood , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Cell Line , Convalescence , Evolution, Molecular , Humans , Immune Sera/immunology , Inhibitory Concentration 50 , Models, Molecular , Mutation , Neutralization Tests , SARS-CoV-2/chemistry , SARS-CoV-2/classification , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
4.
Front Immunol ; 12: 797919, 2021.
Article in English | MEDLINE | ID: covidwho-1608316

ABSTRACT

Persistence of protective immunity for SARS-CoV-2 is important against reinfection. Knowledge on SARS-CoV-2 immunity in pediatric patients is currently lacking. We opted to assess the SARS-CoV-2 adaptive immunity in recovered children and adolescents, addressing the pediatrics specific immunity towards COVID-19. Two independent assays were performed to investigate humoral and cellular immunological memory in pediatric convalescent COVID-19 patients. Specifically, RBD IgG, CD4+, and CD8+ T cell responses were identified and quantified in recovered children and adolescents. SARS-CoV-2-specific RBD IgG detected in recovered patients had a half-life of 121.6 days and estimated duration of 7.9 months compared with baseline levels in controls. The specific T cell response was shown to be independent of days after diagnosis. Both CD4+ and CD8+ T cells showed robust responses not only to spike (S) peptides (a main target of vaccine platforms) but were also similarly activated when stimulated by membrane (M) and nuclear (N) peptides. Importantly, we found the differences in the adaptive responses were correlated with the age of the recovered patients. The CD4+ T cell response to SARS-CoV-2 S peptide in children aged <12 years correlated with higher SARS-CoV-2 RBD IgG levels, suggesting the importance of a T cell-dependent humoral response in younger children under 12 years. Both cellular and humoral immunity against SARS-CoV-2 infections can be induced in pediatric patients. Our important findings provide fundamental knowledge on the immune memory responses to SARS-CoV-2 in recovered pediatric patients.


Subject(s)
Adaptive Immunity/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Convalescence , SARS-CoV-2/immunology , Adolescent , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/virology , COVID-19/virology , Child , Child, Preschool , Female , Humans , Immunity, Humoral/immunology , Immunoglobulin G/immunology , Male , SARS-CoV-2/metabolism , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism
5.
EBioMedicine ; 68: 103405, 2021 06.
Article in English | MEDLINE | ID: covidwho-1242923
6.
Expert Rev Mol Diagn ; 21(7): 741-747, 2021 07.
Article in English | MEDLINE | ID: covidwho-1236167

ABSTRACT

OBJECTIVES: Sensitive molecular diagnostic assays are essential for COVID-19 diagnosis. We evaluated the Hecin Scientific SARS-CoV-2 nucleic acid test kit, a dual-target real-time RT-PCR assay targeting the SARS-CoV-2 N and ORF1ab genes. METHODS: The Hecin test kit's diagnostic performance in detecting SARS-CoV-2 RNA was compared to the LightMix Modular SARS and Wuhan CoV E-gene kit (TIB Molbiol) and an in-house single-tube nested real-time RT-PCR using 296 clinical specimens, 11 proficiency testing samples, and 30 low-positive deep throat saliva and nasopharyngeal swab (NPS) samples pooled into negative samples in ratios of 1:5, 1:10, and 1:30. RESULTS: The limit-of-detection of the Hecin test kit was around 500 dC/mL for the N and ORF1ab targets. Sensitivity and specificity of the Hecin test kit were 98.1% (95% CI: 93.4-99.8%) and 100% (98.1-100%), respectively, when measured against the reference method. The Hecin test kit showed fair sensitivity (80%) in low-positive NPS samples pooled in ratios of 1:5 and 1:10. Its performance in pooled samples could be dramatically improved by adjusting the assay Ct cutoff. CONCLUSION: The Hecin test kit enables sensitive and specific detection of SARS-CoV-2 in clinical samples and pooled samples.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19 , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , Specimen Handling , COVID-19/diagnosis , COVID-19/genetics , Humans , RNA, Viral/genetics
7.
Emerg Microbes Infect ; 10(1): 1016-1023, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1232169

ABSTRACT

Given the on-going SARS-CoV-2 pandemic, identification of immunogenic targets against the viral protein will provide crucial advances towards the development of sensitive diagnostic tools and vaccination strategies. Our previous study has found that ORF8 protein of SARS-CoV-2 is highly immunogenic and shows high sensitivity in identifying COVID-19 disease. In this study, by employing overlapping linear peptides, we characterized the IgG immunodominant regions on SARS-CoV-2 ORF8 protein that are seropositive in the sera from SARS-CoV-2-infected patients. The major immunogenic epitopes are localized at (1) N-termini alpha helix, (2) the resides spanning beta 2 and 3 sheets, and (3) the loop between beta 4 and 5 sheets. Additionally, hamster model infected by SARS-CoV-2 further validates the seropositivity of the linear epitopes in vivo, demonstrating a potential application of the linear peptide-based immunization strategy. Taken together, identification and validation of these B-cell linear epitopes will provide insights into the design of serological diagnostics and peptide-based vaccination approach against this pandemic virus of high priority.


Subject(s)
COVID-19/immunology , Epitopes, B-Lymphocyte , SARS-CoV-2/immunology , Viral Proteins/chemistry , Animals , Antibodies, Viral , Cricetinae , Humans , Immunodominant Epitopes , Mesocricetus , Models, Molecular , Protein Conformation , Viral Proteins/immunology
8.
Journal of the Endocrine Society ; 5(Supplement_1):A840-A841, 2021.
Article in English | PMC | ID: covidwho-1221837

ABSTRACT

Objective: Occurrence of Graves’ disease and Hashimoto’s thyroiditis after coronavirus disease 2019 (COVID-19) raised the concern about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggering thyroid autoimmunity. Uncertainties remain regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. We carried out a prospective study to characterize the evolution of thyroid function and autoimmunity among COVID-19 survivors. Method: Consecutive adult patients, without known thyroid disorders, admitted to Queen Mary Hospital for confirmed COVID-19 from 21 July to 21 September 2020 were included. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and anti-thyroid antibodies were measured on admission and at 3 months. Positive anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) was defined by &gt;100 units. Results: Among 200 COVID-19 survivors, 122 had reassessment thyroid function tests (TFTs) (median age: 57.5 years;49.2% men). Baseline characteristics of patients who did and did not have reassessment were comparable. Among the 20 patients with baseline abnormal TFTs on admission, mostly low fT3, 15 recovered. Of the 102 patients with normal TFTs on admission, two (2.0%) had new onset abnormal TFTs, which may represent TFTs in different phases of thyroiditis (one had mildly elevated TSH 5.8 mIU/L, with normal fT4 [16 pmol/L] and fT3 [4.3 pmol/L], the other had mildly raised fT4 25 pmol/L with normal TSH [1.1 mIU/L] and fT3 [4.7 pmol/L]). Among 104 patients with anti-thyroid antibody titers reassessed, we observed increases in anti-TPO (baseline: 28.3 units [IQR 14.0-67.4] vs reassessment: 35.0 units [IQR: 18.8-99.0];p&lt;0.001) and anti-Tg titers (baseline: 6.6 units [IQR 4.9-15.6] vs reassessment: 8.7 units [IQR: 6.6-15.4];p&lt;0.001), but no change in anti-TSHR titer (baseline: 1.0 IU/L [IQR: 0.8-1.2] vs reassessment: 1.0 IU/L [IQR: 0.8-1.3];p=0.486). Of the 82 patients with negative anti-TPO at baseline, 16 had significant interval increase in anti-TPO titer by &gt;12 units (2×6 [precision of the anti-TPO assay in normal range being 6 units per SD]), of these, four became anti-TPO positive. Factors associated a significant increase in anti-TPO titer included worse baseline clinical severity (p=0.018), elevated C-reactive protein during hospitalization (p=0.033), and higher baseline anti-TPO titer (p=0.005). Conclusion: Majority of thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis could occur during convalescence, though uncommon. Importantly, we provided the novel observation of an increase in anti-thyroid antibody titers post-COVID-19, suggesting the potential of SARS-CoV-2 in triggering thyroid autoimmunity, which warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.

9.
JAMA Netw Open ; 4(5): e218824, 2021 05 03.
Article in English | MEDLINE | ID: covidwho-1210567

ABSTRACT

Importance: Schools were closed intermittently across Hong Kong to control the COVID-19 outbreak, which led to significant physical and psychosocial problems among children and youths. Objective: To compare the clinical characteristics and sources of infection among children and youths with COVID-19 during the 3 waves of outbreaks in Hong Kong in 2020. Design, Setting, and Participants: This cross-sectional study involved children and youths aged 18 years or younger with COVID-19 in the 3 waves of outbreaks from January 23 through December 2, 2020. Data were analyzed from December 2020 through January 2021. Main Outcomes and Measures: Demographic characteristics, travel and contact histories, lengths of hospital stay, and symptoms were captured through the central electronic database. Individuals who were infected without recent international travel were defined as having domestic infections. Results: Among 397 children and youths confirmed with COVID-19 infections, the mean (SD) age was 9.95 (5.34) years, 220 individuals (55.4%) were male, and 154 individuals (38.8%) were asymptomatic. There were significantly more individuals who were infected without symptoms in the second wave (59 of 118 individuals [50.0%]) and third wave (94 of 265 individuals [35.5%]) than in the first wave (1 of 14 individuals [7.1%]) (P = .001). Significantly fewer individuals who were infected in the second and third waves, compared with the first wave, had fever (first wave: 10 individuals [71.4%]; second wave: 22 individuals [18.5%]; third wave: 98 individuals [37.0%]; P < .001) or cough (first wave: 6 individuals [42.9%]; second wave: 15 individuals [12.7%]; third wave: 52 individuals [19.6%]; P = .02). Among all individuals, 394 individuals (99.2%) had mild illness. One patient developed chilblains (ie, COVID toes), 1 patient developed multisystem inflammatory syndrome in children, and 1 patient developed post-COVID-19 autoimmune hemolytic anemia. In all 3 waves, 204 patients with COVID-19 (51.4%) had domestic infections. Among these individuals, 186 (91.2%) reported having a contact history with another individual with COVID-19, of which most (183 individuals [90.0%]) were family members. In the third wave, 18 individuals with domestic infections had unknown contact histories. Three schoolmates were confirmed with COVID-19 on the same day and were reported to be close contacts. Conclusions and Relevance: This cross-sectional study found that nearly all children and youths with COVID-19 in Hong Kong had mild illness. These findings suggest that household transmission was the main source of infection for children and youths with domestic infections and that the risk of being infected at school was small.


Subject(s)
Asymptomatic Infections/epidemiology , COVID-19 , Contact Tracing , SARS-CoV-2/isolation & purification , Symptom Assessment , Adolescent , COVID-19/epidemiology , COVID-19/therapy , COVID-19/transmission , Child , Contact Tracing/methods , Contact Tracing/statistics & numerical data , Cross-Sectional Studies , Disease Transmission, Infectious/prevention & control , Disease Transmission, Infectious/statistics & numerical data , Family Characteristics , Female , Hong Kong/epidemiology , Hospitalization/statistics & numerical data , Humans , Male , Severity of Illness Index , Symptom Assessment/methods , Symptom Assessment/statistics & numerical data , Travel-Related Illness
10.
Nat Commun ; 12(1): 1517, 2021 03 09.
Article in English | MEDLINE | ID: covidwho-1125914

ABSTRACT

Up to date, effective antivirals have not been widely available for treating COVID-19. In this study, we identify a dual-functional cross-linking peptide 8P9R which can inhibit the two entry pathways (endocytic pathway and TMPRSS2-mediated surface pathway) of SARS-CoV-2 in cells. The endosomal acidification inhibitors (8P9R and chloroquine) can synergistically enhance the activity of arbidol, a spike-ACE2 fusion inhibitor, against SARS-CoV-2 and SARS-CoV in cells. In vivo studies indicate that 8P9R or the combination of repurposed drugs (umifenovir also known as arbidol, chloroquine and camostat which is a TMPRSS2 inhibitor), simultaneously interfering with the two entry pathways of coronaviruses, can significantly suppress SARS-CoV-2 replication in hamsters and SARS-CoV in mice. Here, we use drug combination (arbidol, chloroquine, and camostat) and a dual-functional 8P9R to demonstrate that blocking the two entry pathways of coronavirus can be a promising and achievable approach for inhibiting SARS-CoV-2 replication in vivo. Cocktail therapy of these drug combinations should be considered in treatment trials for COVID-19.


Subject(s)
Antiviral Agents/pharmacology , COVID-19 Drug Treatment , Drug Repositioning , Peptides/pharmacology , SARS-CoV-2/drug effects , Virus Internalization/drug effects , Animals , COVID-19/virology , Chlorocebus aethiops , Chloroquine/pharmacology , Drug Discovery , Female , HEK293 Cells , Humans , Indoles/pharmacology , Mice , Mice, Inbred BALB C , Serine Endopeptidases/metabolism , Vero Cells
11.
Emerg Microbes Infect ; 10(1): 235-241, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1038269

ABSTRACT

BACKGROUND: Pediatric COVID-19 studies exploring the relationships between NPS and saliva viral loads, clinical and immunological profiles are lacking. METHODS: Demographics, immunological profiles, nasopharyngeal swab (NPS), and saliva samples collected on admission, and hospital length of stay (LOS) were assessed in children below 18 years with COVID-19. FINDINGS: 91 patients were included between March and August 20 20. NPS and saliva viral loads were correlated (r = 0.315, p = 0.01). Symptomatic patients had significantly higher NPS and saliva viral loads than asymptomatic patients. Serial NPS and saliva viral load measurements showed that the log10 NPS (r = -0.532, p < 0.001) and saliva (r = -0.417, p < 0.001) viral loads for all patients were inversely correlated with the days from symptom onset with statistical significance. Patients with cough, sputum, and headache had significantly higher saliva, but not NPS, viral loads. Higher saliva, but not NPS, viral loads were associated with total lymphopenia, CD3 and CD4 lymphopenia (all p < 0.05), and were inversely correlated with total lymphocyte (r = -0.43), CD3 (r = -0.55), CD4 (r = -0.60), CD8 (r = -0.41), B (r = -0.482), and NK (r = -0.416) lymphocyte counts (all p < 0.05). INTERPRETATION: Saliva viral loads on admission in children correlated better with clinical and immunological profiles than NPS.


Subject(s)
COVID-19/virology , SARS-CoV-2/physiology , Saliva/virology , Viral Load , Adolescent , COVID-19/blood , COVID-19/diagnosis , COVID-19/immunology , Child , Child, Preschool , Female , Humans , Lymphocyte Count , Male , Nasopharynx/virology , SARS-CoV-2/genetics
12.
mBio ; 11(5)2020 10 20.
Article in English | MEDLINE | ID: covidwho-883315

ABSTRACT

An accurate diagnostic test for early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the key weapon to control the coronavirus disease 2019 (COVID-19) pandemic. We previously reported that the SARS-CoV-2 genome contains a unique orf8 accessory gene absent from other human-pathogenic coronaviruses. Here, we characterized the SARS-CoV-2 orf8 as a novel immunogenic secreted protein and utilized it for the accurate diagnosis of COVID-19. Extracellular orf8 protein was detected in cell culture supernatant and in sera of COVID-19 patients. In addition, orf8 was found highly immunogenic in COVID-19 patients, who showed early seropositivity for anti-orf8 IgM, IgG, and IgA. We hypothesize that orf8 secretion during SARS-CoV-2 infection facilitates early mounting of B cell response. The serological test detecting anti-orf8 IgG antibody can be used for the early and accurate diagnosis of COVID-19.IMPORTANCE Current commercially available serological tests for COVID-19 patients are detecting antibodies against SARS-CoV-2 nucleoprotein and spike glycoprotein. The antinucleoprotein and antispike antibodies can be accurately detected in patients during the mid or late stage of infection, and therefore, these assays have not been widely used for early diagnosis of COVID-19. In this study, we characterized the secretory property of a SARS-CoV-2 orf8 protein and proposed that orf8 secretion during infection facilitates early mounting of the B cell response. We demonstrated the presence of anti-orf8 antibodies in both symptomatic and asymptomatic patients during the early stage of infection, while the anti-N antibody is not detected. Our serological test detecting anti-orf8 antibodies may facilitate the development of early and accurate diagnosis for COVID-19.


Subject(s)
Antigens, Viral/immunology , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Viral Proteins/immunology , Antibodies, Viral/blood , Antigens, Viral/blood , Antigens, Viral/metabolism , COVID-19 , Cell Line , Coronavirus Infections/blood , Early Diagnosis , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin G/blood , Pandemics , Pneumonia, Viral/blood , SARS-CoV-2 , Viral Proteins/blood , Viral Proteins/metabolism
13.
Nat Commun ; 11(1): 4252, 2020 08 25.
Article in English | MEDLINE | ID: covidwho-741685

ABSTRACT

The 2019 novel respiratory virus (SARS-CoV-2) causes COVID-19 with rapid global socioeconomic disruptions and disease burden to healthcare. The COVID-19 and previous emerging virus outbreaks highlight the urgent need for broad-spectrum antivirals. Here, we show that a defensin-like peptide P9R exhibited potent antiviral activity against pH-dependent viruses that require endosomal acidification for virus infection, including the enveloped pandemic A(H1N1)pdm09 virus, avian influenza A(H7N9) virus, coronaviruses (SARS-CoV-2, MERS-CoV and SARS-CoV), and the non-enveloped rhinovirus. P9R can significantly protect mice from lethal challenge by A(H1N1)pdm09 virus and shows low possibility to cause drug-resistant virus. Mechanistic studies indicate that the antiviral activity of P9R depends on the direct binding to viruses and the inhibition of virus-host endosomal acidification, which provides a proof of concept that virus-binding alkaline peptides can broadly inhibit pH-dependent viruses. These results suggest that the dual-functional virus- and host-targeting P9R can be a promising candidate for combating pH-dependent respiratory viruses.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus/drug effects , Influenza A virus/drug effects , Peptides/pharmacology , Amino Acid Sequence , Animals , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Antiviral Agents/therapeutic use , Cell Line , Endosomes/chemistry , Endosomes/drug effects , Female , Humans , Hydrogen-Ion Concentration , Influenza A virus/metabolism , Mice , Mice, Inbred BALB C , Orthomyxoviridae Infections/drug therapy , Orthomyxoviridae Infections/metabolism , Peptides/chemistry , Peptides/metabolism , Peptides/therapeutic use , Protein Binding , Protein Conformation , Rhinovirus/drug effects , Rhinovirus/metabolism , Viral Load/drug effects , Virus Replication/drug effects
14.
J Clin Pathol ; 2020 Aug 07.
Article in English | MEDLINE | ID: covidwho-706992

ABSTRACT

The COVID-19 (caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) epidemic started in Wuhan (Hubei Province, China) in mid-December 2019 and quickly spread across the world as a pandemic. As a key to tracing the disease and to implement strategies aimed at breaking the chain of disease transmission, extensive testing for SARS-CoV-2 was suggested. Although nasopharyngeal/oropharyngeal swabs are the most commonly used biological samples for SARS-CoV-2 diagnosis, they have a number of limitations related to sample collection and healthcare personnel safety. In this context, saliva is emerging as a promising alternative to nasopharyngeal/oropharyngeal swabs for COVID-19 diagnosis and monitoring. Saliva collection, being a non-invasive approach with possibility for self-collection, circumvents to a great extent the limitations associated with the use of nasopharyngeal/oropharyngeal swabs. In addition, various salivary biomarkers including the salivary metabolomics offer a high promise to be useful for better understanding of COVID-19 and possibly in the identification of patients with various degrees of severity, including asymptomatic carriers. This review summarises the clinical and scientific basis for the potential use of saliva for COVID-19 diagnosis and disease monitoring. Additionally, we discuss saliva-based biomarkers and their potential clinical and research applications related to COVID-19.

15.
Am J Infect Control ; 48(8): 890-896, 2020 08.
Article in English | MEDLINE | ID: covidwho-629078

ABSTRACT

BACKGROUND: To describe the infection control strategy to achieve zero nosocomial transmission of symptomatic coronavirus disease (COVID-19) due to SARS-CoV-2 during the prepandemic phase (the first 72 days after announcement of pneumonia cases in Wuhan) in Hong Kong. METHODS: Administrative support with the aim of zero nosocomial transmission by reducing elective clinical services, decanting wards, mobilizing isolation facilities, providing adequate personal protective equipment, coordinating laboratory network for rapid molecular diagnosis under 4-tier active surveillance for hospitalized patients and outpatients, and organizing staff forum and training was implemented under the framework of preparedness plan in Hospital Authority. The trend of SARS-CoV-2 in the first 72 days was compared with that of SARS-CoV 2003. RESULTS: Up to day 72 of the epidemic, 130 (0.40%) of 32,443 patients being screened confirmed to have SARS-CoV-2 by reverse transcription polymerase chain reaction. Compared with SARS outbreak in 2003, the SARS-CoV-2 case load constituted 8.9% (130 SARS-CoV-2/1458 SARS-CoV) of SARS-CoV infected cases at day 72 of the outbreak. The incidences of nosocomial acquisition of SARS-CoV per 1,000 SARS-patient-day and per 100 SARS-patient-admission were 7.9 and 16.9, respectively, which were significantly higher than the corresponding incidences of SARS-CoV-2 (zero infection, P <.001). CONCLUSIONS: Administrative support to infection control could minimize the risk of nosocomial transmission of SARS-CoV-2.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Cross Infection/epidemiology , Cross Infection/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/transmission , Cross Infection/transmission , Disease Outbreaks/prevention & control , Female , Hong Kong/epidemiology , Humans , Infection Control/methods , Male , Middle Aged , Pneumonia, Viral/transmission , SARS-CoV-2 , Young Adult
16.
Gastroenterology ; 159(1): 81-95, 2020 07.
Article in English | MEDLINE | ID: covidwho-40729

ABSTRACT

BACKGROUND & AIMS: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which has been characterized by fever, respiratory, and gastrointestinal symptoms as well as shedding of virus RNA into feces. We performed a systematic review and meta-analysis of published gastrointestinal symptoms and detection of virus in stool and also summarized data from a cohort of patients with COVID-19 in Hong Kong. METHODS: We collected data from the cohort of patients with COVID-19 in Hong Kong (N = 59; diagnosis from February 2 through February 29, 2020),and searched PubMed, Embase, Cochrane, and 3 Chinese databases through March 11, 2020, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We analyzed pooled data on the prevalence of overall and individual gastrointestinal symptoms (loss of appetite, nausea, vomiting, diarrhea, and abdominal pain or discomfort) using a random effects model. RESULTS: Among the 59 patients with COVID-19 in Hong Kong, 15 patients (25.4%) had gastrointestinal symptoms, and 9 patients (15.3%) had stool that tested positive for virus RNA. Stool viral RNA was detected in 38.5% and 8.7% among those with and without diarrhea, respectively (P = .02). The median fecal viral load was 5.1 log10 copies per milliliter in patients with diarrhea vs 3.9 log10 copies per milliliter in patients without diarrhea (P = .06). In a meta-analysis of 60 studies comprising 4243 patients, the pooled prevalence of all gastrointestinal symptoms was 17.6% (95% confidence interval [CI], 12.3-24.5); 11.8% of patients with nonsevere COVID-19 had gastrointestinal symptoms (95% CI, 4.1-29.1), and 17.1% of patients with severe COVID-19 had gastrointestinal symptoms (95% CI, 6.9-36.7). In the meta-analysis, the pooled prevalence of stool samples that were positive for virus RNA was 48.1% (95% CI, 38.3-57.9); of these samples, 70.3% of those collected after loss of virus from respiratory specimens tested positive for the virus (95% CI, 49.6-85.1). CONCLUSIONS: In an analysis of data from the Hong Kong cohort of patients with COVID-19 and a meta-analysis of findings from publications, we found that 17.6% of patients with COVID-19 had gastrointestinal symptoms. Virus RNA was detected in stool samples from 48.1% patients, even in stool collected after respiratory samples had negative test results. Health care workers should therefore exercise caution in collecting fecal samples or performing endoscopic procedures in patients with COVID-19, even during patient recovery.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/prevention & control , Diarrhea/virology , Feces/virology , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Load , Betacoronavirus/genetics , Betacoronavirus/pathogenicity , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Diarrhea/diagnosis , Diarrhea/epidemiology , Endoscopy, Gastrointestinal/standards , Gastrointestinal Tract/diagnostic imaging , Gastrointestinal Tract/virology , Hong Kong/epidemiology , Humans , Infection Control/standards , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Prevalence , RNA, Viral/isolation & purification , SARS-CoV-2
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