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1.
Viruses ; 14(9)2022 09 13.
Article in English | MEDLINE | ID: covidwho-2033143

ABSTRACT

In late November 2021, the World Health Organization declared the SARS-CoV-2 lineage B.1.1.529 the fifth variant of concern, Omicron. This variant has acquired over 30 mutations in the spike protein (with 15 in the receptor-binding domain), raising concerns that Omicron could evade naturally acquired and vaccine-derived immunity. We utilized an authentic virus, multicycle neutralisation assay to demonstrate that sera collected one, three, and six months post-two doses of Pfizer-BioNTech BNT162b2 had a limited ability to neutralise SARS-CoV-2. However, four weeks after a third dose, neutralising antibody titres were boosted. Despite this increase, neutralising antibody titres were reduced fourfold for Omicron compared to lineage A.2.2 SARS-CoV-2.


Subject(s)
COVID-19 , Vaccines , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Humans , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins/genetics
2.
Front Microbiol ; 13: 824217, 2022.
Article in English | MEDLINE | ID: covidwho-1952411

ABSTRACT

Background: Low frequency intrahost single nucleotide variants (iSNVs) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have been increasingly recognised as predictive indicators of positive selection. Particularly as growing numbers of SARS-CoV-2 variants of interest (VOI) and concern (VOC) emerge. However, the dynamics of subgenomic RNA (sgRNA) expression and its impact on genomic diversity and infection outcome remain poorly understood. This study aims to investigate and quantify iSNVs and sgRNA expression in single and longitudinally sampled cohorts over the course of mild and severe SARS-CoV-2 infection, benchmarked against an in vitro infection model. Methods: Two clinical cohorts of SARS-CoV-2 positive cases in New South Wales, Australia collected between March 2020 and August 2021 were sequenced. Longitudinal samples from cases hospitalised due to SARS-CoV-2 infection (severe) (n = 16) were analysed and compared with cases that presented with SARS-CoV-2 symptoms but were not hospitalised (mild) (n = 23). SARS-CoV-2 genomic diversity profiles were also examined from daily sampling of culture experiments for three SARS-CoV-2 variants (Lineage A, B.1.351, and B.1.617.2) cultured in VeroE6 C1008 cells (n = 33). Results: Intrahost single nucleotide variants were detected in 83% (19/23) of the mild cohort cases and 100% (16/16) of the severe cohort cases. SNP profiles remained relatively fixed over time, with an average of 1.66 SNPs gained or lost, and an average of 4.2 and 5.9 low frequency variants per patient were detected in severe and mild infection, respectively. sgRNA was detected in 100% (25/25) of the mild genomes and 92% (24/26) of the severe genomes. Total sgRNA expressed across all genes in the mild cohort was significantly higher than that of the severe cohort. Significantly higher expression levels were detected in the spike and the nucleocapsid genes. There was significantly less sgRNA detected in the culture dilutions than the clinical cohorts. Discussion and Conclusion: The positions and frequencies of iSNVs in the severe and mild infection cohorts were dynamic overtime, highlighting the importance of continual monitoring, particularly during community outbreaks where multiple SARS-CoV-2 variants may co-circulate. sgRNA levels can vary across patients and the overall level of sgRNA reads compared to genomic RNA can be less than 1%. The relative contribution of sgRNA to the severity of illness warrants further investigation given the level of variation between genomes. Further monitoring of sgRNAs will improve the understanding of SARS-CoV-2 evolution and the effectiveness of therapeutic and public health containment measures during the pandemic.

4.
J Fungi (Basel) ; 8(1)2022 Jan 06.
Article in English | MEDLINE | ID: covidwho-1613854

ABSTRACT

Invasive fungal disease (IFD) associated with Coronavirus Disease 2019 (COVID-19) has focussed predominantly on invasive pulmonary aspergillosis. However, increasingly emergent are non-Aspergillus fungal infections including candidiasis, mucormycosis, pneumocystosis, cryptococcosis, and endemic mycoses. These infections are associated with poor outcomes, and their management is challenged by delayed diagnosis due to similarities of presentation to aspergillosis or to non-specific features in already critically ill patients. There has been a variability in the incidence of different IFDs often related to heterogeneity in patient populations, diagnostic protocols, and definitions used to classify IFD. Here, we summarise and address knowledge gaps related to the epidemiology, risks, diagnosis, and management of COVID-19-associated fungal infections other than aspergillosis.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296535

ABSTRACT

In late November 2021, the World Health Organization declared the SARS-CoV-2 lineage B.1.1.529 the fifth variant of concern, Omicron. This variant has acquired 15 mutations in the receptor binding domain of the spike protein, raising concerns that Omicron could evade naturally acquired and vaccine-derived immunity. We utilized an authentic virus, multicycle neutralisation assay to demonstrate that sera collected 1, 3, and 6 months post-two doses of Pfizer-BioNTech BNT162b2 has a limited ability to neutralise SARS-CoV-2. However, four weeks after a third dose, neutralizing antibody titres are boosted. Despite this increase, neutralising antibody titres are reduced 4-fold for Omicron compared to lineage A.2.2 SARS-CoV-2.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292984

ABSTRACT

Background: Low frequency intrahost single nucleotide variants (iSNVs) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have been increasingly recognised as predictive indicators of positive selection. Particularly as growing numbers of SARS-CoV-2 variants of interest (VOI) and concern (VOC) emerge. However, the dynamics of subgenomic RNA (sgRNA) expression and its impact on genomic diversity and infection outcome remain poorly understood. This study aims to investigate and quantify iSNVs and sgRNA expression in single and longitudinally sampled cohorts over the course of mild and severe SARS-CoV-2 infection benchmarked against an in-vitro infection model. Methods: Two clinical cohorts of SARS-CoV-2 positive cases in New South Wales, Australia collected between March 2020 and August 2021 were sequenced. Longitudinal samples from cases hospitalised due to SARS-CoV-2 infection (severe) were analysed and compared with cases that presented with SARS-CoV-2 symptoms but were not hospitalised (mild). SARS-CoV-2 genomic diversity profiles were also examined from daily sampling of culture experiments for three SARS-CoV-2 variants (Lineage A, B.1.351, and B.1.617.2) cultured in VeroE6 C1008 cells (n = 33). Results: ISNVs were detected in 83% (19/23) of the mild cohort cases and 100% (16/16) of the severe cohort cases. SNP profiles remained relatively fixed over time, with an average of 1.66 SNPs gained or lost and an average of 4.2 and 5.9 low frequency variants per patient were detected in severe and mild infection, respectively. SgRNA was detected in 100% (25/25) of the mild genomes and 92% (24/26) of the severe genomes. Total sgRNA expressed across all genes in the mild cohort was significantly higher than that of the severe cohort. Significantly higher expression levels were detected in the spike and the nucleocapsid genes. There was significantly less sgRNA detected in the culture cohort than the clinical. Discussion and Conclusions: The positions and frequencies of iSNVs in the severe and mild infection cohorts were dynamic overtime, highlighting the importance of continual monitoring, particularly during community outbreaks where multiple SARS-Cov-2 variants may co-circulate. SgRNA levels can vary across patients and the overall level of sgRNA reads compared to genomic RNA can be less than 1%. The relative contribution of sgRNA to the severity of illness warrants further investigation given the level of variation between genomes. Further monitoring of sgRNAs will improve the understanding of SARS-CoV-2 evolution and the effectiveness of therapeutic and public health containment measures during the pandemic.

7.
Clin Infect Dis ; 73(9): e2952-e2959, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1501018

ABSTRACT

BACKGROUND: The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by reverse-transcription polymerase chain reaction (PCR) does not necessarily indicate shedding of infective virions. There are limited data on the correlation between the isolation of SARS-CoV-2, which likely indicates infectivity, and PCR. METHODS: A total of 195 patients with Coronavirus disease 2019 were tested (outpatients, n = 178; inpatients, n = 12; and critically unwell patients admitted to the intensive care unit [ICU] patients, n = 5). SARS-CoV-2 PCR-positive samples were cultured in Vero C1008 cells and inspected daily for cytopathic effect (CPE). SARS-CoV-2-induced CPE was confirmed by PCR of culture supernatant. Where no CPE was observed, PCR was performed on day 4 to confirm absence of virus replication. The cycle thresholds (Cts) of the day 4 PCR (Ctculture) and the PCR of the original clinical sample (Ctsample) were compared, and positive cultures were defined where Ctsample - Ctculture was ≥3. RESULTS: Of 234 samples collected, 228 (97%) were from the upper respiratory tract. SARS-CoV-2 was isolated from 56 (24%), including in 28 of 181 (15%), 19 of 42 (45%), and 9 of 11 samples (82%) collected from outpatients, inpatients, and ICU patients, respectively. All 56 samples had Ctsample ≤32; CPE was observed in 46 (20%). The mean duration from symptom onset to culture positivity was 4.5 days (range, 0-18). SARS-CoV-2 was significantly more likely to be isolated from samples collected from inpatients (P < .001) and ICU patients (P < .0001) compared with outpatients, and in samples with lower Ctsample. CONCLUSIONS: SARS-CoV-2 culture may be used as a surrogate marker for infectivity and inform de-isolation protocols.


Subject(s)
COVID-19 , Animals , Chlorocebus aethiops , Critical Care , Humans , Immunologic Tests , SARS-CoV-2 , Vero Cells
9.
Virus Evol ; 6(1): veaa027, 2020 Jan.
Article in English | MEDLINE | ID: covidwho-1388022

ABSTRACT

The SARS-CoV-2 epidemic has rapidly spread outside China with major outbreaks occurring in Italy, South Korea, and Iran. Phylogenetic analyses of whole-genome sequencing data identified a distinct SARS-CoV-2 clade linked to travellers returning from Iran to Australia and New Zealand. This study highlights potential viral diversity driving the epidemic in Iran, and underscores the power of rapid genome sequencing and public data sharing to improve the detection and management of emerging infectious diseases.

10.
Open Forum Infect Dis ; 7(9): ofaa387, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1205747

ABSTRACT

BACKGROUND: Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies has become an important tool, complementing nucleic acid tests (NATs) for diagnosis and for determining the prevalence of coronavirus disease 2019 (COVID-19) in population serosurveys. The magnitude and persistence of antibody responses are critical for assessing the duration of immunity. METHODS: A SARS-CoV-2-specific immunofluorescent antibody (IFA) assay for immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) was developed and prospectively evaluated by comparison to the reference standard of NAT on respiratory tract samples from individuals with suspected COVID-19. Neutralizing antibody responses were measured in a subset of samples using a standard microneutralization assay. RESULTS: A total of 2753 individuals were eligible for the study (126 NAT-positive; prevalence, 4.6%). The median "window period" from illness onset to appearance of antibodies (range) was 10.2 (5.8-14.4) days. The sensitivity and specificity of either SARS-CoV-2 IgG, IgA, or IgM when collected ≥14 days after symptom onset were 91.3% (95% CI, 84.9%-95.6%) and 98.9% (95% CI, 98.4%-99.3%), respectively. The negative predictive value was 99.6% (95% CI, 99.3%-99.8%). The positive predictive value of detecting any antibody class was 79.9% (95% CI, 73.3%-85.1%); this increased to 96.8% (95% CI, 90.7%-99.0%) for the combination of IgG and IgA. CONCLUSIONS: Measurement of SARS-CoV-2-specific antibody by IFA is an accurate method to diagnose COVID-19. Serological testing should be incorporated into diagnostic algorithms for SARS-CoV-2 infection to identify additional cases where NAT was not performed and resolve cases where false-negative and false-positive NATs are suspected. The majority of individuals develop robust antibody responses following infection, but the duration of these responses and implications for immunity remain to be established.

11.
BMJ Case Rep ; 14(1)2021 Jan 18.
Article in English | MEDLINE | ID: covidwho-1066836

ABSTRACT

This case represents a rare fulminant course of fried-rice associated food poisoning in an immunocompetent person due to pre-formed exotoxin produced by Bacillus cereus, with severe manifestations of sepsis, including multi-organ (hepatic, renal, cardiac, respiratory and neurological) failure, shock, metabolic acidosis, rhabdomyolysis and coagulopathy. Despite maximal supportive measures (continuous renal replacement therapy, plasmapheresis, N-acetylcysteine infusion and blood products, and broad-spectrum antimicrobials) and input from a multidisciplinary team (consisting of infectious diseases, intensive care, gastroenterology, surgery, toxicology, immunology and haematology), mortality resulted. This case is the first to use whole genome sequencing techniques to confirm the toxigenic potential of B. cereus It has important implications for food preparation and storage, particularly given its occurrence in home isolation during the COVID-19 pandemic.


Subject(s)
Bacillus cereus/genetics , Exotoxins/genetics , Foodborne Diseases/diagnosis , Acetylcysteine/therapeutic use , Acidosis/physiopathology , Acidosis/therapy , Adult , Anti-Arrhythmia Agents/therapeutic use , Anti-Bacterial Agents/therapeutic use , Arrhythmias, Cardiac/physiopathology , Arrhythmias, Cardiac/therapy , Bacillus cereus/isolation & purification , Blood Coagulation Disorders/physiopathology , Blood Coagulation Disorders/therapy , Blood Transfusion , Brain Diseases , Continuous Renal Replacement Therapy , Fatal Outcome , Female , Foodborne Diseases/microbiology , Foodborne Diseases/physiopathology , Foodborne Diseases/therapy , Free Radical Scavengers/therapeutic use , Humans , Immunocompetence , Liver Failure/physiopathology , Liver Failure/therapy , Multiple Organ Failure/physiopathology , Multiple Organ Failure/therapy , Plasmapheresis , Renal Insufficiency/physiopathology , Renal Insufficiency/therapy , Rhabdomyolysis/physiopathology , Rhabdomyolysis/therapy , Sepsis/physiopathology , Sepsis/therapy , Shock/physiopathology , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Whole Genome Sequencing
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