ABSTRACT
There is limited data directly comparing the effectiveness of COVID-19 vaccines. We compared rates of SARS-CoV-2 Omicron BA.1/2 infection in Australian adults during March to May 2022 who had received one of four COVID-19 vaccines in the last 14-63 days as either a primary course or a booster dose. As a primary course, compared to recipients of BNT162b2 mRNA vaccine, adjusted hazard ratios for SARS-CoV-2 infection were 1.03 (95%CI 0.82-1.30), 1.19 (0.95-1.49), 1.70 (1.46-1.97) for respectively mRNA-1273, ChAdOx-1 nCov-19 and NVX-CoV2373. For booster dose, respective adjusted hazard ratios compared to BNT162b2 mRNA vaccine were 1.02 (95%CI 1.00-1.04), 1.20 (1.10-1.32), 1.39 (1.20-1.60). Our findings suggest relatively higher effectiveness of ancestral strain mRNA vaccines against SARS-CoV-2 Omicron infection than viral vector and protein subunit vaccines, but further studies are required due to small numbers of recipients of ChAdOx-1 nCov-19 and NVX-CoV2373.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Background: A key feature of the global public health response to contain and slow the spread of COVID-19 has been community-based quarantine and self-isolation. As part of The Optimise Study, this research sought to understand the factors that influence people’s ability to undertake home-based quarantine and isolation to contain the spread of COVID-19. Methods: Semi-structured qualitative phone interviews (n=25) were conducted by telephone with people who participated in community-based quarantine in Australia before 31 March 2020. The Capability Opportunity Motivation Behaviour model was used to conduct a thematic analysis. Results: Participants required clear, accessible and trusted information to guide them in home-based quarantine and isolation. A sense of social responsibility and belief in the efficacy of the restrictions to reduce viral transmission aided their motivation. Access to essential needs, supportive living environments, and emotional support were required to adhere to restrictions, but few were prepared. Conclusions: Findings demonstrate that in addition to having the capability and motivation to adhere to restrictions, it is vital that people are also encouraged to prepare for the challenge to ensure access to physical, social and emotional support. Findings also illustrate the importance of engaging communities in planning and preparedness for quarantine and self-isolation public health responses.
Subject(s)
COVID-19ABSTRACT
Although pregnancy poses a greater risk for severe COVID-19, the underlying immunological changes associated with SARS-CoV-2 infection during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in pregnant and non-pregnant women during acute and convalescent COVID-19 up to 258 days post symptom onset, quantifying 217 immunological parameters. Additionally, matched maternal and cord blood were collected from COVID-19 convalescent pregnancies. Although serological responses to SARS-CoV-2 were similar in pregnant and non-pregnant women, cellular immune analyses revealed marked differences in key NK cell and unconventional T cell responses during COVID-19 in pregnant women. While NK, γδ T cells and MAIT cells displayed pre-activated phenotypes in healthy pregnant women when compared to non-pregnant age-matched women, activation profiles of these pre-activated NK and unconventional T cells remained unchanged at acute and convalescent COVID-19 in pregnancy. Conversely, activation dynamics of NK and unconventional T cells were prototypical in non-pregnant women in COVID-19. In contrast, activation of αβ CD4 + and CD8 + T cells, T follicular helper cells and antibody-secreting cells was similar in pregnant and non-pregnant women with COVID-19. Elevated levels of IL-1β, IFN-γ, IL-8, IL-18 and IL-33 were also found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, our study provides the first comprehensive map of longitudinal immunological responses to SARS-CoV-2 infection in pregnant women, providing insights into patient management and education during COVID-19 pregnancy.
Subject(s)
COVID-19ABSTRACT
Although pregnancy poses a greater risk for severe COVID-19, the underlying immunological changes associated with SARS-CoV-2 infection during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in pregnant and non-pregnant women during acute and convalescent COVID-19 up to 258 days post symptom onset, quantifying 217 immunological parameters. Additionally, matched maternal and cord blood were collected from COVID-19 convalescent pregnancies. Although serological responses to SARS-CoV-2 were similar in pregnant and non-pregnant women, cellular immune analyses revealed marked differences in key NK cell and unconventional T cell responses during COVID-19 in pregnant women. While NK cells, {gamma}{delta} T cells and MAIT cells displayed pre-activated phenotypes in healthy pregnant women when compared to non-pregnant age-matched women, activation profiles of these pre-activated NK and unconventional T cells remained unchanged at acute and convalescent COVID-19 in pregnancy. Conversely, activation dynamics of NK and unconventional T cells were prototypical in non-pregnant women in COVID-19. In contrast, activation of {beta} CD4+ and CD8+ T cells, T follicular helper cells and antibody-secreting cells was similar in pregnant and non-pregnant women with COVID-19. Elevated levels of IL-1{beta}, IFN-{gamma}, IL-8, IL-18 and IL-33 were also found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, our study provides the first comprehensive map of longitudinal immunological responses to SARS-CoV-2 infection in pregnant women, providing insights into patient management and education during COVID-19 pregnancy.
Subject(s)
Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
As vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus; whether through infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure SARS-CoV-2 immunity, ideally with rapid turnaround and without the need for laboratory-based testing. Current rapid point-of-care (POC) tests measure antibodies (Ab) against the SARS-CoV-2 virus, however, these tests provide no information on whether the antibodies can neutralise virus infectivity and are potentially protective, especially against newly emerging variants of the virus. Neutralising Antibodies (NAb) are emerging as a strong correlate of protection, but most current NAb assays require many hours or days, samples of venous blood, and access to laboratory facilities, which is especially problematic in resource-limited settings. We have developed a lateral flow POC test that can measure levels of RBD-ACE2 neutralising antibodies from whole blood, with a result that can be determined by eye (semi-quantitative) or on a small instrument (quantitative), and results show high correlation with microneutralisation assays. This assay also provides a measure of total anti-RBD antibody, thereby providing evidence of exposure to SARS-CoV-2 or immunisation, regardless of whether NAb are present in the sample. By testing samples from immunised macaques, we demonstrate that this test is equally applicable for use with animal samples, and we show that this assay is readily adaptable to test for immunity to newly emerging SARS-CoV-2 variants. Lastly, using a cohort of vaccinated humans, we demonstrate that our whole-blood test correlates closely with microneutralisation assay data (R 2 =0.75, p<0.0001), and that fingerprick whole blood samples are sufficient for this test. Accordingly, the COVID-19 NAb-test™ device described here can provide a rapid readout of immunity to SARS-CoV-2 at the point of care.
Subject(s)
COVID-19ABSTRACT
The host response to SARS-CoV-2 infection provide insights into both viral pathogenesis and patient management. The host-encoded microRNA (miRNA) response to SARS-CoV-2 infection, however, remains poorly defined. Here we profiled circulating miRNAs from ten COVID-19 patients sampled longitudinally and ten age and gender matched healthy donors. We observed 55 miRNAs that were altered in COVID-19 patients during early-stage disease, with the inflammatory miR-31-5p the most strongly upregulated. Supervised machine learning analysis revealed that a three-miRNA signature (miR-423-5p, miR-23a-3p and miR-195-5p) independently classified COVID-19 cases with an accuracy of 99.9%. In a ferret COVID-19 model, the three-miRNA signature again detected SARS-CoV-2 infection with 99.7% accuracy, and distinguished SARS-CoV-2 infection from influenza A (H1N1) infection and healthy controls with 95% accuracy. Distinct miRNA profiles were also observed in COVID-19 patients requiring oxygenation. This study demonstrates that SARS-CoV-2 infection induces a robust host miRNA response that could improve COVID-19 detection and patient management
Subject(s)
COVID-19ABSTRACT
The Chinese government has established a photovoltaics poverty alleviation (PVPA) program to help reduce rural poverty and environmental inequality. However, there is a scarcity of detailed investigations into how social-psychological factors influence the rural poor's decision to adopt solar photovoltaics. The present study examines the local voices of low-income villagers in the Wuhan region towards the PVPA projects from a social-psychological perspective. While focusing on local villagers' opinions before the onset of the COVID-19 pandemic, our findings suggest that villagers' neighbors have the greatest influence on those who subequently adopt solar PV. Similarly, village agents play a crucial role in spreading information and creating a sense of trust, which is different than other countries' solar adoption. The common goals of improving the local community aesthetically, environmentally, and economically also increased villagers' adoption likelihood. These improvements boosted villagers' sense of pride, which, in a virtuous cycle, further encouraged participation in improving the community. Residents' fears were reduced through local social interactions which increased knowledge, such as village-wide technology demonstrations, conversations with local adopters, and town hall discussions with village leaders. However, --- the PVPA projects and skepticism about when or if they would receive promised government subsidies prevented many from adopting. These findings provide valuable implications for policymakers in China and other developing countries who wish to encourage renewable energy adoption after the pandemic.
ABSTRACT
Disrupted antiviral immune responses are associated with severe COVID-19, the disease caused by SAR-CoV-2. Here, we show that the 73-amino-acid protein encoded by ORF9c of the viral genome contains a putative transmembrane domain, interacts with membrane proteins in multiple cellular compartments, and impairs antiviral processes in a lung epithelial cell line. Proteomic, interactome, and transcriptomic analyses, combined with bioinformatic analysis, revealed that expression of only this highly unstable small viral protein impaired interferon signaling, antigen presentation, and complement signaling, while inducing IL-6 signaling. Furthermore, we showed that interfering with ORF9c degradation by either proteasome inhibition or inhibition of the ATPase VCP blunted the effects of ORF9c. Our study indicated that ORF9c enables immune evasion and coordinates cellular changes essential for the SARS-CoV-2 life cycle. One-sentence summarySARS-CoV-2 ORF9c is the first human coronavirus protein localized to membrane, suppressing antiviral response, resembling full viral infection.
Subject(s)
COVID-19ABSTRACT
There is an urgent need to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) that leads to COVID-19 and respiratory failure. Our study is to discover differentially expressed genes (DEGs) and biological signaling pathways by using a bioinformatics approach to elucidate their potential pathogenesis. The gene expression profiles of the GSE150819 datasets were originally produced using an Illumina NextSeq 500 (Homo sapiens). KEGG (Kyoto Encyclopedia of Genes and Genomes) and GO (Gene Ontology) were utilized to identify functional categories and significant pathways. KEGG and GO results suggested that the Cytokine-cytokine receptor interaction, P53 signaling pathway, and Apoptosis are the main signaling pathways in SARS-CoV-2 infected human bronchial organoids (hBOs). Furthermore, NFKBIA, C3, and CCL20 may be key genes in SARS-CoV-2 infected hBOs. Therefore, our study provides further insights into the therapy of COVID-19.
Subject(s)
Coronavirus Infections , Severe Acute Respiratory Syndrome , COVID-19 , Respiratory InsufficiencyABSTRACT
An improved understanding of human T-cell-mediated immunity in COVID-19 is important if we are to optimize therapeutic and vaccine strategies. Experience with influenza shows that infection primes CD8+ T-cell memory to shared peptides presented by common HLA types like HLA-A2. Following re-infection, cross-reactive CD8+ T-cells enhance recovery and diminish clinical severity. Stimulating peripheral blood mononuclear cells from COVID-19 convalescent patients with overlapping peptides from SARS-CoV-2 Spike, Nucleocapsid and Membrane proteins led to the clonal expansion of SARS-CoV-2-specific CD8+ and CD4+ T-cells in vitro, with CD4+ sets being typically robust. For CD8+ T-cells taken directly ex vivo, we identified two HLA-A*02:01-restricted SARS-CoV-2 epitopes, A2/S269-277 and A2/Orf1ab3183-3191. Using peptide-HLA tetramer enrichment, direct ex vivo assessment of the A2/S269+CD8+ and A2/Orf1ab3183+CD8+ populations indicated that the more prominent A2/S269+CD8+ set was detected at comparable frequency ([~]1.3x10-5) in acute and convalescent HLA-A*02:01+ patients. But, while the numbers were higher than those found in uninfected HLA-A*02:01+ donors ([~]2.5x10-6), they were low when compared with frequencies for influenza-specific (A2/M158) and EBV-specific (A2/BMLF1280) ([~]1.38x10-4) populations. Phenotypic analysis ex vivo of A2/S269+CD8+ T-cells from COVID-19 convalescents showed that A2/S269+CD8+ T-cells were predominantly negative for the CD38, HLA-DR, PD-1 and CD71 activation markers, although the majority of total CD8+ T-cells were granzyme and/or perforin-positive. Furthermore, the bias towards naive, stem cell memory and central memory A2/S269+CD8+ T-cells rather than effector memory populations suggests that SARS-CoV2 infection may be compromising CD8+ T-cell activation. Priming with an appropriate vaccine may thus have great value for optimizing protective CD8+ T-cell immunity in COVID-19.
Subject(s)
COVID-19ABSTRACT
There is an urgent need for a safe and protective vaccine to control the global spread of SARS-CoV-2 and prevent COVID-19. Here, we report the immunogenicity and protective efficacy of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length SARS-CoV-2 spike (S) glycoprotein stabilized in the prefusion conformation. Cynomolgus macaques (Macaca fascicularis) immunized with NVX-CoV2373 and the saponin-based Matrix-M adjuvant induced anti-S antibody that was neutralizing and blocked binding to the human angiotensin-converting enzyme 2 (hACE2) receptor. Following intranasal and intratracheal challenge with SARS-CoV-2, immunized macaques were protected against upper and lower infection and pulmonary disease. These results support ongoing phase 1/2 clinical studies of the safety and immunogenicity of NVX-CoV2327 vaccine (NCT04368988). HighlightsO_LIFull-length SARS-CoV-2 prefusion spike with Matrix-M1 (NVX-CoV2373) vaccine. C_LIO_LIInduced hACE2 receptor blocking and neutralizing antibodies in macaques. C_LIO_LIVaccine protected against SARS-CoV-2 replication in the nose and lungs. C_LIO_LIAbsence of pulmonary pathology in NVX-CoV2373 vaccinated macaques. C_LI
Subject(s)
COVID-19 , Lung DiseasesABSTRACT
Individual decision-making about social distancing, self-quarantine and self-isolation is crucial in managing the COVID-19 pandemic. In the rapidly evolving pandemic, little is known about how different government communication strategies may systematically affect people’s attitudes to staying home or going out, nor the extent to which people perceive and process the risk of different scenarios. In this study, we report results from a sample of 581 participants (residing in the United Kingdom), and we examine the degree to which participants’ attitudes regarding the permissibility of leaving one’s home are (1) sensitive to different levels of risk of viral transmission in specific scenarios, (2) sensitive to communication framings that are either imperative or that invite reasoning about scenarios, or (3) creating “loopholes” for themselves when scenarios are framed with reference to the participants themselves rather than in general terms. We find that participants’ attitudes to social distancing are sensitive to the level of risk of transmission, and that when scenarios are framed in imperative terms, rather than when their reasoning is encouraged, participants have more impermissive attitudes to going out in Minimal Risk scenarios, with a trend of decreased permissiveness more generally; for self-loopholes, more research is needed to determine if participants make exceptions for themselves. Thus, subject to the limitations of this study, during phases where it is important to promote self-isolation for all scenarios, including those perceived to be low risk, imperative communication may be best.
Subject(s)
COVID-19ABSTRACT
Background The ability of global health systems to cope with increasing numbers of COVID-19 cases is of major concern. In readiness for this challenge, Australia has drawn on clinical pathway models developed over many years in preparation for influenza pandemics. These models have been used to estimate health care requirements for COVID-19 patients, in the context of broader public health measures. Methods An age and risk stratified transmission model of COVID-19 infection was used to simulate an unmitigated epidemic with parameter ranges reflecting uncertainty in current estimates of transmissibility and severity. Overlaid public health measures included case isolation and quarantine of contacts, and broadly applied social distancing. Clinical presentations and patient flows through the Australian health care system were simulated, including expansion of available intensive care capacity and alternative clinical assessment pathways. Findings An unmitigated COVID-19 epidemic would dramatically exceed the capacity of the Australian health system, over a prolonged period. Case isolation and contact quarantine alone will be insufficient to constrain case presentations within a feasible level of expansion of health sector capacity. Overlaid social restrictions will need to be applied at some level over the course of the epidemic to ensure that systems do not become overwhelmed, and that essential health sector functions, including care of COVID-19 patients, can be maintained. Attention to the full pathway of clinical care is needed to ensure access to critical care. Interpretation Reducing COVID-19 morbidity and mortality will rely on a combination of measures to strengthen and extend public health and clinical capacity, along with reduction of overall infection transmission in the community. Ongoing attention to maintaining and strengthening the capacity of health care systems and workers to manage cases is needed.
Subject(s)
COVID-19 , InfectionsABSTRACT
SARS-Cov-2 (severe acute respiratory disease coronavirus 2), which causes Coronavirus Disease 2019 (COVID19) was first detected in China in late 2019 and has since then caused a global pandemic. While molecular assays to directly detect the viral genetic material are available for the diagnosis of acute infection, we currently lack serological assays suitable to specifically detect SARS-CoV-2 antibodies. Here we describe serological enzyme-linked immunosorbent assays (ELISA) that we developed using recombinant antigens derived from the spike protein of SARS-CoV-2. Using negative control samples representing pre-COVID 19 background immunity in the general adult population as well as samples from COVID19 patients, we demonstrate that these assays are sensitive and specific, allowing for screening and identification of COVID19 seroconverters using human plasma/serum as early as two days post COVID19 symptoms onset. Importantly, these assays do not require handling of infectious virus, can be adjusted to detect different antibody types and are amendable to scaling. Such serological assays are of critical importance to determine seroprevalence in a given population, define previous exposure and identify highly reactive human donors for the generation of convalescent serum as therapeutic. Sensitive and specific identification of coronavirus SARS-Cov-2 antibody titers may, in the future, also support screening of health care workers to identify those who are already immune and can be deployed to care for infected patients minimizing the risk of viral spread to colleagues and other patients.