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1.
Biomed J ; 44(6 Suppl 1): S8-S14, 2021 12.
Article in English | MEDLINE | ID: covidwho-1930767

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) is highly contagious, with a potential to cause large nosocomial outbreaks in the hospital setting. We report the advance deployment of comprehensive, multi-level infection control measures in a 3,700-bed large hospital to prevent nosocomial outbreaks of COVID-19 during the pandemic. METHODS: We implemented a series of dynamic infection control policies during the pandemic. A confirmed COVID-19 case was defined by positive real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. All healthcare worker (HCW) having symptoms or close contact with the confirmed case received the RT-PCR test. RESULTS: A total of 5,722 patients were tested in our hospital from January to May 2020. Twenty-five patients were confirmed COVID-19, including two inpatients. A cluster of 4 HCWs with COVID-19 associated with the 2nd inpatient was identified in the early stage of epidemic. Our enhanced traffic control bundling, mask wearing, hand hygiene and environmental cleaning were reinforced after the outbreak. All other confirmed cases were identified at our outdoor quarantine station or epidemic clinic afterwards, and the results of testing for 146 symptomatic HCWs were all negative. CONCLUSIONS: Integrated teamwork, advance deployment of infection control measures and efficient diagnostic testing and response protected HCW and facilities from large SARS-CoV-2 outbreaks and preserved the capacity and function of the health care system during the pandemic.


Subject(s)
COVID-19 , Cross Infection , COVID-19/epidemiology , Cross Infection/prevention & control , Disease Outbreaks/prevention & control , Hospitals , Humans , Infection Control/methods , Pandemics/prevention & control , SARS-CoV-2 , Taiwan/epidemiology
2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315504

ABSTRACT

Background: A national outbreak of respiratory syncytial virus (RSV) has been observed in the community since August 2020 in Taiwan even under strict COVID-19 related public health measures.Methods: We reviewed a national laboratory-based surveillance network established by Taiwan Centers for Disease Control for respiratory viral pathogens between 2010 and 2020. A retrospective study of 257 children < 5 years old hospitalized with RSV infection at Chang Gung Memorial Hospital Lin Kou and Kaohsiung branches between 2018 and 2020 was conducted, and 193 samples positive for RSV-A were sequenced. Clinical data were obtained and stratified by genotype and year.Findings: National data from 2020 showed an enormous increase in RSV case numbers. The RSV positivity rate in 2020 had an approximately 4-fold surge compared to 2010 in Taiwan (OR 3.79;95% CI, 3.06–4.69;p < 0.001), surpassing previous years during which ON1 was prevalent. Phylogenetic analysis of G protein showed that novel ON1 variants in 2020 with 6 amino acid changes that emerged gradually in 2019 and a novel substitution, E257K were clustered separately from those of 2018 and 2019 seasons and ON1 reference strains. The F protein of the variant carried T12I and H514N substitutions, which weren’t at antigenic sites. Age (OR: 0.97;95% CI: 0.94–0.99;p =0.02) and 2020 ON1 variant (OR: 2.52;95% CI: 1.13–5.63;p = 0.025) were independently associated with oxygen saturation <94% during hospitalization.Interpretation: The unprecedented 2020 RSV epidemic caused by novel ON1 variants suggests that the mutations may confer a fitness advantage over other genotypes. Further studies on viral replication, antigenic changes, and virulence are required.Funding: This work was supported by the Chang Gung Memorial Hospital in Taiwan [Grant CMRPG3K1011 and CMRPG3K1141 ];Ministry of Science Technology in Taiwan [MOST 108-2314-B-182A-156-MY3];China Medical University, Taiwan [Grant CMU 108-S-23, CMU109-MF-111]Declaration of Interests: No potential conflict of interest was reported by the authors.Ethics Approval Statement: This study was approved by the Research and Ethics Committee of Chang Gung Memorial Hospital (IRB:202100450B0, 202100569A3).

3.
J Microbiol Immunol Infect ; 55(3): 436-444, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1336662

ABSTRACT

BACKGROUND/PURPOSE: Superspreading events (SSEs) are pivotal in the spread of SARS-CoV-2. This study aimed to investigate an SSE of COVID-19 in a hospital and explore the transmission dynamics and heterogeneity of SSE. METHODS: We performed contact tracing for all close contacts in a cluster. We did nasopharyngeal or throat swabbing for SARS-CoV-2 by real-time RT-PCR. Environmental survey was performed. The epidemiological and clinical characteristics of the SSE were studied. RESULTS: Patient 1 with congestive heart failure and cellulitis, who had onset of COVID-19 two weeks after hospitalization, was the index case. Patient 1 led to 8 confirmed cases, including four health care workers (HCW). Persons tested positive for SARS-CoV-2 were HCW (n = 4), patient 1's family (n = 2), an accompanying person of an un-infected in-patient (n = 1), and an in-patient admitted before the SSE (n = 1). The attack rate among the HCW was 3.2 % (4/127). Environmental survey confirmed contamination at the bed rails, mattresses, and sink in the room patient 1 stayed, suggesting fomite transmission. The index case's sputum remained positive on illness day 35. Except one asymptomatic patient, at least three patients acquired the infection from the index case at the pre-symptomatic period. The effective reproduction number (Rt) was 0.9 (8/9). CONCLUSION: The host factor (heart failure, longer viral shedding), transmissibility of SARS-CoV-2 (Rt, pre-symptomatic transmission), and possible multiple modes of transmission altogether contributed to the SSE. Rapid response and advance deployment of multi-level protection in hospitals could mitigate COVID-19 transmission to one generation, thereby reducing its impact on the healthcare system.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Contact Tracing , Hospitals , Humans , Virus Shedding
4.
Pathogens ; 10(6)2021 Jun 13.
Article in English | MEDLINE | ID: covidwho-1270098

ABSTRACT

A total of 15 RT-PCR confirmed COVID-19 patients were admitted to our hospital during the in-itial outbreak in Taiwan. The average time of virus clearance was delayed in seven patients, 24.14 ± 4.33 days compared to 10.25 ± 0.56 days post-symptom onset (PSO) in the other eight pa-tients. There was strong antibody response in patients with viral persistence at the pharynx, with peak values of serum antibody 677.2 ± 217.8 vs. 76.70 ± 32.11 in patients with delayed versus rapid virus clearance. The patients with delayed viral clearance had excessive antibodies of compromised quality in an early stage with the delay in peak virus neutralization efficacy, 34.14 ± 7.15 versus 12.50 ± 2.35 days PSO in patients with rapid virus clearance. Weak antibody re-sponse of patients with rapid viral clearance was also effective, with substantial and comparable neutralization efficacy, 35.70 ± 8.78 versus 41.37 ± 11.49 of patients with delayed virus clearance. Human Cytokine 48-Plex Screening of the serial sera samples revealed elevated concentrations of proinflammatory cytokines and chemokines in a deceased patient with delayed virus clear-ance and severe disease. The levels were comparatively less in the other two patients who suf-fered from severe disease but eventually survived.

5.
J Clin Microbiol ; 58(8)2020 07 23.
Article in English | MEDLINE | ID: covidwho-999208

ABSTRACT

Real-time reverse transcription-PCR (RT-PCR) is currently the most sensitive method to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). However, the correlation between detectable viral RNA and culturable virus in clinical specimens remains unclear. Here, we performed virus culture for 60 specimens that were confirmed to be positive for SARS-CoV-2 RNA by real-time RT-PCR. The virus could be successfully isolated from 12 throat and nine nasopharyngeal swabs and two sputum specimens. The lowest copy number required for virus isolation was determined to be 5.4, 6.0, and 5.7 log10 genome copies/ml sample for detecting the nsp12, E, and N genes, respectively. We further examined the correlation of genome copy number and virus isolation in different regions of the viral genome, demonstrating that culturable specimens are characterized by high copy numbers with a linear correlation observed between copy numbers of amplicons targeting structural and nonstructural regions. Overall, these results indicate that in addition to the copy number, the integrity of the viral genome should be considered when evaluating the infectivity of clinical SARS-CoV-2 specimens.


Subject(s)
Betacoronavirus/growth & development , Betacoronavirus/isolation & purification , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Virus Cultivation/methods , Betacoronavirus/genetics , COVID-19 , COVID-19 Testing , COVID-19 Vaccines , Correlation of Data , Humans , Nasopharynx/virology , Pandemics , Pharynx/virology , Real-Time Polymerase Chain Reaction/methods , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2
6.
Sci Rep ; 10(1): 20085, 2020 11 18.
Article in English | MEDLINE | ID: covidwho-933722

ABSTRACT

The COVID-19 pandemic is a worldwide health emergency which calls for an unprecedented race for vaccines and treatment. In developing a COVID-19 vaccine, we applied technology previously used for MERS-CoV to produce a prefusion-stabilized SARS-CoV-2 spike protein, S-2P. To enhance immunogenicity and mitigate the potential vaccine-induced immunopathology, CpG 1018, a Th1-biasing synthetic toll-like receptor 9 (TLR9) agonist was selected as an adjuvant candidate. S-2P in combination with CpG 1018 and aluminum hydroxide (alum) was found to be the most potent immunogen and induced high titer of neutralizing antibodies in sera of immunized mice against pseudotyped lentivirus reporter or live wild-type SARS-CoV-2. In addition, the antibodies elicited were able to cross-neutralize pseudovirus containing the spike protein of the D614G variant, indicating the potential for broad spectrum protection. A marked Th1 dominant response was noted from cytokines secreted by splenocytes of mice immunized with CpG 1018 and alum. No vaccine-related serious adverse effects were found in the dose-ranging study in rats administered single- or two-dose regimens of S-2P combined with CpG 1018 alone or CpG 1018 with alum. These data support continued development of CHO-derived S-2P formulated with CpG 1018 and alum as a candidate vaccine to prevent COVID-19 disease.


Subject(s)
COVID-19 Vaccines/immunology , Immunogenicity, Vaccine , Spike Glycoprotein, Coronavirus/immunology , Adjuvants, Immunologic/therapeutic use , Aluminum Hydroxide/therapeutic use , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , CHO Cells , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/therapeutic use , Cricetinae , Cricetulus , Cytokines/blood , Cytokines/metabolism , Female , HEK293 Cells , Humans , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Oligodeoxyribonucleotides/therapeutic use , Rats , Rats, Sprague-Dawley , Spleen/immunology , Th1 Cells/immunology
7.
Emerg Microbes Infect ; 9(1): 1457-1466, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-599993

ABSTRACT

Taiwan experienced two waves of imported infections with Coronavirus Disease 2019 (COVID-19). This study aimed at investigating the genomic variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Taiwan and compared their evolutionary trajectories with the global strains. We performed culture and full-genome sequencing of SARS-CoV-2 strains followed by phylogenetic analysis. A 382-nucleotides deletion in open reading frame 8 (ORF8) was found in a Taiwanese strain isolated from a patient on February 4, 2020 who had a travel history to Wuhan. Patients in the first wave also included several sporadic, local transmission cases. Genomes of 5 strains sequenced from clustered infections were classified into a new clade with ORF1ab-V378I mutation, in addition to 3 dominant clades ORF8-L84S, ORF3a-G251V and S-D614G. This highlighted clade also included some strains isolated from patients who had a travel history to Turkey and Iran. The second wave mostly resulted from patients who had a travel history to Europe and Americas. All Taiwanese viruses were classified into various clades. Genomic surveillance of SARS-CoV-2 in Taiwan revealed a new ORF8-deletion mutant and a virus clade that may be associated with infections in the Middle East, which contributed to a better understanding of the global SARS-CoV-2 transmission dynamics.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/virology , Genome, Viral , Pneumonia, Viral/virology , Animals , Betacoronavirus/classification , Betacoronavirus/isolation & purification , COVID-19 , Cell Line , Chlorocebus aethiops , Haemophilus parainfluenzae/isolation & purification , Humans , Middle East , Open Reading Frames , Pandemics , Phylogeny , RNA, Viral , SARS-CoV-2 , Sequence Deletion , Taiwan , Travel , Vero Cells , Virus Cultivation , Whole Genome Sequencing
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