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1.
Microbiol Spectr ; : e0213322, 2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2108227

ABSTRACT

The genome of the Omicron variant of concern (VOC) contains more than 50 mutations, many of which have been associated with increased transmissibility, differing disease severity, and the potential to elute immune responses acquired after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination or infection with previous VOCs. Due to a better tropism for the upper respiratory tract, it was suggested that the detection of the Omicron variant could be preferred in saliva, compared to nasopharyngeal swabs (NPS). Our objective was to compare the SARS-CoV-2 levels in saliva fluid and NPS to estimated Ct values, according to the main SARS-CoV-2 variants circulating in France since the beginning of 2021. We analyzed 1,289 positive reverse transcription-polymerase chain reaction (RT-PCR) results during the three major waves: Alpha, Delta, and Omicron. NPS and saliva sampling were performed for 909 (71%) and 380 (29%) cases, respectively. The Ct values were significantly lower in the NPS samples than in the saliva samples for the three main VOCs. Still, the difference was less pronounced with the Omicron variant than for the Alpha and Delta variants. In contrast, in the saliva samples, Ct values were significantly lower for the Omicron variant than for the Delta (difference of -2.7 Ct) and the Alpha (difference of -3.0 Ct) variants, confirming a higher viral load in saliva. To conclude, the higher viral load in saliva was evidenced for the Omicron variant, compared to the Alpha and Delta variants, suggesting that established diagnostic methods might require revalidation with the emergence of novel variants. IMPORTANCE Established methods for SARS-CoV-2 diagnostics might require revalidation with the emergence of novel variants. This is important for screening strategy programs and for the investigation of the characteristics of new variants in terms of tropism modification and increased viral burden leading to its spread. SARS-CoV-2 RT-PCR screening on saliva samples reported lower but acceptable performance, compared to nasopharyngeal samples. Due to a better tropism for the upper respiratory tract, it was suggested that the detection of the Omicron variant could be preferred in saliva, compared to nasopharyngeal swabs. Our study analyzed 1,289 positive RT-PCR results during the three major waves in France: Alpha, Delta, and Omicron. Our findings also showed a higher viral load in saliva for the Omicron variant, compared to the Alpha and Delta variants.

2.
J Virol ; : e0125022, 2022 Nov 09.
Article in English | MEDLINE | ID: covidwho-2108211

ABSTRACT

The appearance of new dominant variants of concern (VOC) of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) threatens the global response to the coronavirus disease 2019 (COVID-19) pandemic. Of these, the alpha variant (also known as B.1.1.7), which appeared initially in the United Kingdom, became the dominant variant in much of Europe and North America in the first half of 2021. The spike (S) glycoprotein of alpha acquired seven mutations and two deletions compared to the ancestral virus, including the P681H mutation adjacent to the polybasic cleavage site, which has been suggested to enhance S cleavage. Here, we show that the alpha spike protein confers a level of resistance to beta interferon (IFN-ß) in human lung epithelial cells. This correlates with resistance to an entry restriction mediated by interferon-induced transmembrane protein 2 (IFITM2) and a pronounced infection enhancement by IFITM3. Furthermore, the P681H mutation is essential for resistance to IFN-ß and context-dependent resistance to IFITMs in the alpha S. P681H reduces dependence on endosomal cathepsins, consistent with enhanced cell surface entry. However, reversion of H681 does not reduce cleaved spike incorporation into particles, indicating that it exerts its effect on entry and IFN-ß downstream of furin cleavage. Overall, we suggest that, in addition to adaptive immune escape, mutations associated with VOC may well also confer a replication and/or transmission advantage through adaptation to resist innate immune mechanisms. IMPORTANCE Accumulating evidence suggests that variants of concern (VOC) of SARS-CoV-2 evolve to evade the human immune response, with much interest focused on mutations in the spike protein that escape from antibodies. However, resistance to the innate immune response is essential for efficient viral replication and transmission. Here, we show that the alpha (B.1.1.7) VOC of SARS-CoV-2 is substantially more resistant to type I interferons than the parental Wuhan-like virus. This correlates with resistance to the antiviral protein IFITM2 and enhancement by its paralogue IFITM3. The key determinant of this is a proline-to-histidine change at position 681 in S adjacent to the furin cleavage site, which in the context of the alpha spike modulates cell entry pathways of SARS-CoV-2. Reversion of the mutation is sufficient to restore interferon and IFITM2 sensitivity, highlighting the dynamic nature of the SARS CoV-2 as it adapts to both innate and adaptive immunity in the humans.

3.
Drug Resist Updat ; 65: 100882, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2104805

ABSTRACT

WHO-defined SARS-CoV-2 variants of concern (VOC) drive therapeutics and vaccine development. The Omicron VOC is dominating the arena since November 2021, but the number of its sublineages is growing in complexity. Omicron represent a galaxy with a myriad of stars that suddenly rise and expand before collapsing into apparent extinction when a more fit sublineage appears. This has already happened with BA.1, BA.2, and BA.4/5 and is happening with BA.2.75. We review here the current PANGO phylogeny, focusing on sublineages with Spike mutations, and show how frequently xxxxxxxx convergent evolution has occurred in these sublineages. We finally summarize how Omicron evolution has progressively defeated the anti-Spike monoclonal antibodies authorized so far, leaving clinicians to again fall back on COVID19 convalescent plasma from vaccinated donors as the only antibody-based therapy available.


Subject(s)
Antineoplastic Agents, Immunological , COVID-19 , Humans , Antibodies, Monoclonal/genetics , Antibodies, Monoclonal/therapeutic use , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Antibodies, Viral , Antibodies, Neutralizing
4.
Atmosphere ; 13(10), 2022.
Article in English | Web of Science | ID: covidwho-2099316

ABSTRACT

The current pandemic of the SARS-CoV-2 virus requires measures to reduce the risk of infection. In addition to the usual hygiene measures, air cleaners are a recommended solution to decrease the viral load in rooms. Suitable technologies range from pure filters to inactivating units, such as cold plasma or UVC irradiation. Such inactivating air cleaners, partly combined with filter technology, are available on the market in various designs, dimensions and technical specifications. Since it is not always clear whether they may produce undesirable by-products, and the suitability for particular applications cannot be assessed on the basis of the principle of operation, the effectivity of six inactivating devices was investigated in a near-real environment. The investigations were based on a standard method published by the VDI. The procedure was extended in such a way that a permanent virus source was simulated, which corresponds to the presence of a person suffering from COVID-19 in a room. The study addresses the difference of the mere presence of viruses to the determination of the virulence. As a result, a deep understanding is provided between the behavior of a virus as a pure aerosolized particle and its real infectivity in order to enable the assessment of suitable air cleaners.

5.
Immunol Rev ; 310(1): 61-75, 2022 09.
Article in English | MEDLINE | ID: covidwho-2097773

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has shifted our paradigms about B cell immunity and the goals of vaccination for respiratory viruses. The development of population immunity, through responses directed to highly immunogenic regions of this virus, has been a strong driving force in the emergence of progressively mutated variants. This review highlights how the strength of the existing global virology and immunology networks built for HIV vaccine research enabled rapid adaptation of techniques, assays, and skill sets, to expeditiously respond to the SARS-CoV-2 pandemic. Allying real-time genomic surveillance to immunological platforms enabled the characterization of immune responses elicited by infection with distinct variants, in sequential epidemic waves, as well as studies of vaccination and hybrid immunity (combination of infection- and vaccination-induced immunity). These studies have shown that consecutive variants of concern have steadily diminished the ability of vaccines to prevent infection, but that increasing levels of hybrid immunity result in higher frequencies of cross-reactive responses. Ultimately, this rapid pivot from HIV to SARS-CoV-2 enabled a depth of understanding of the SARS-CoV-2 antigenic vulnerabilities as population immunity expanded and diversified, providing key insights for future responses to the SARS-CoV-2 pandemic.


Subject(s)
COVID-19 , HIV Infections , Viral Vaccines , Antibodies, Viral , Humans , SARS-CoV-2 , South Africa , Vaccination
6.
Viruses ; 14(11)2022 Oct 27.
Article in English | MEDLINE | ID: covidwho-2090360

ABSTRACT

COVID-19 has been associated with a broad range of long-term sequelae, commonly referred to as "long-COVID" or "post-COVID-19" syndrome. Despite an increasing body of literature, long COVID remains poorly characterized. We retrospectively analysed data from electronic medical records of patients admitted to the post-COVID-19 outpatient service of the Infectious and Tropical Diseases Unit, Careggi University Hospital, Florence, Italy, between June 2020 and June 2021, 4-12 weeks after hospital discharge. A total of 428 patients, 41% women, median age 64 years, underwent a follow-up visit a median 53 days after hospital discharge. Overall, 76% patients reported at least one persistent symptom, including dyspnoea (37%), chronic fatigue (36%), insomnia (16%), visual disorders (13%) and brain fog (13%). Increasing oxygen support (OR 1.4, 95% CI 1.1-1.8), use of immunosuppressants (OR 6.4, 95% CI 1.5-28) and female sex (OR 1.8, 95% CI 1.1-2.9) were associated with a higher risk of long COVID symptoms. Comparison between symptomatic patients infected in the period March-December 2020 (prevalent circulation of wild-type SARS-CoV-2) with those infected in the period January-April 2021 (prevalent circulation of B.1.1.7 Alpha variant) showed a significant modification in the pattern of symptoms belonging to the neurological and cognitive/emotional categories. Our findings confirmed shortness of breath and chronic fatigue as the most frequent long COVID manifestations, while female sex and severe COVID-19 course were the main risk factors for developing lingering symptoms. SARS-CoV-2 variants may induce different long COVID phenotypes, possibly due to changes in cell tropism and differences in viral-host interaction.


Subject(s)
COVID-19 , Fatigue Syndrome, Chronic , Female , Humans , Male , COVID-19/epidemiology , Fatigue Syndrome, Chronic/complications , Pandemics , Phenotype , Retrospective Studies , SARS-CoV-2/genetics , Middle Aged
7.
Microbiol Spectr ; : e0138622, 2022 Oct 27.
Article in English | MEDLINE | ID: covidwho-2088429

ABSTRACT

Nonpharmaceutical interventions (NPIs) to contain the SARS-CoV-2 pandemic drastically reduced human-to-human interactions, decreasing the circulation of other respiratory viruses, as well. Consequently, influenza virus circulation, which is normally responsible for 3 to 5 million hospitalizations per year globally, was significantly reduced. With the downscaling of the NPI countermeasures, there is a concern for increased influenza disease, particularly in individuals suffering from postacute effects of SARS-CoV-2 infection. To investigate this, we performed a sequential influenza H1N1 infection 4 weeks after an initial SARS-CoV-2 infection in ferrets. Upon H1N1 infection, ferrets that were previously infected with SARS-CoV-2 showed an increased tendency to develop clinical signs, compared to the control H1N1-infected animals. A histopathological analysis indicated only a slight increase for type II pneumocyte hyperplasia and bronchitis. Thus, the effects of the sequential infection appeared minor. However, ferrets were infected with B.1.351-SARS-CoV-2, the beta variant of concern, which replicated poorly in our model. The histopathology of the respiratory organs was mostly resolved 4 weeks after the SARS-CoV-2 infection, with only reminiscent histopathological features in the upper respiratory tract. Nevertheless, SARS-CoV-2 specific cellular and humoral responses were observed, confirming an established infection. On account of a modest trend toward the enhancement of the influenza disease, even upon a mild SARS-CoV-2 infection, our findings suggest that a stronger SARS-CoV-2 infection and its consequent, long-term effects could have a greater impact on the outcome of disease after a sequential influenza infection. Hence, the influenza vaccination of individuals suffering from postacute SARS-CoV-2 infection effects may be considered an avertible measure for such a scenario. IMPORTANCE During the COVID-19 pandemic, the use of face masks, social distancing, and isolation were effective not only in decreasing the circulation of SARS-CoV-2 but also in reducing other respiratory viruses, such as influenza. With fewer restrictions currently in place, influenza is slowly returning. In the meantime, people who are still suffering from long-COVID could be more vulnerable to an influenza virus infection and could develop a more severe influenza disease. This study provides directions to the effect of a previous SARS-CoV-2 exposure on influenza disease severity in a ferret model. This model is highly valuable to test sequential infections under controlled settings for translation to humans. We could not induce clear long-term COVID-19 effects, as the SARS-CoV-2 infections in the ferrets were mild. However, we still observed a slight increase in influenza disease severity compared to ferrets that had not encountered SARS-CoV-2 before. Therefore, it may be advisable to include long-COVID patients as a risk group for influenza vaccination.

8.
Gene Rep ; 29: 101703, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2086235

ABSTRACT

The genetic variability of SARS-CoV-2 (genus Betacoronavirus, family Coronaviridae) has been scrutinized since its first detection in December 2019. Although the role of structural variants, particularly deletions, in virus evolution is little explored, these genome changes are extremely frequent. They are associated with relevant processes, including immune escape and attenuation. Deletions commonly occur in accessory ORFs and might even lead to the complete loss of one or more ORFs. This scenario poses an interesting question about the origin and spreading of extreme structural rearrangements that persist without compromising virus viability. Here, we analyze the genome of SARS-CoV-2 in late 2021 in Uruguay and identify a Delta lineage (AY.20) that experienced a large deletion (872 nucleotides according to the reference Wuhan strain) that removes the 7a, 7b, and 8 ORFs. Deleted viruses coexist with wild-type (without deletion) AY.20 and AY.43 strains. The Uruguayan deletion is like those identified in Delta strains from Poland and Japan but occurs in a different Delta clade. Besides providing proof of the circulation of this large deletion in America, we infer that the 872-deletion arises by the consecutive occurrence of a 6-nucleotide deletion, characteristic of delta strains, and an 866-nucleotide deletion that arose independently in the AY.20 Uruguayan lineage. The largest deletion occurs adjacent to transcription regulatory sequences needed to synthesize the nested set of subgenomic mRNAs that serve as templates for transcription. Our findings support the role of transcription sequences as a hotspot for copy-choice recombination and highlight the remarkable dynamic of SARS-CoV-2 genomes.

9.
Cureus Journal of Medical Science ; 14(7), 2022.
Article in English | Web of Science | ID: covidwho-2083138

ABSTRACT

Background The coronavirus disease 2019 (COVID-19) pandemic had and is still having a tremendous impact on people all over the world, but it has been particularly harsh in South America. Nine out of 13 South American countries are among the 50 countries with the highest COVID-19 death rates. The gamma severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant that emerged by the end of 2020 in the Brazilian Amazon quickly spread throughout the country causing the harsh COVID-19 second wave. This variant displayed high viral loads, high transmissibility, and increased virulence as compared to previous variants. Aims The aim of this retrospective study is to revisit and analyse the epidemiology of the COVID-19 second wave in the state of Sao Paulo, the most populous Brazilian state. In addition to examining the possible factors that led to the emergence and propagation of the gamma variant, measures that could have prevented its spread and that of other highly virulent variants were also investigated. Materials and methods Data from Sao Paulo's official sources on morbidity, mortality, age distribution, and testing prior to and during the COVID-19 second wave (February - June 2021) and data regarding the distribution of SARS-CoV-2 variants in the country were parsed, analyzed, and compared to the period that anteceded the eruption of the second COVID-19 wave. Results In the state of Sao Paulo, the toll of the COVID-19 second wave surpassed that of the first 11 months of the pandemic (from March 2020 to January 2021), as 56% of the deaths occurred in the five months of the second wave between February and June 2021. The mean age of COVID-19 victims, which was already below life expectancy in the state dropped even further in the pandemic's second wave, reaching an average of 60 years of age. The years of life lost per death per month doubled and the case-fatality rate (CFR) of young adults (20-39 years old) more than trebled during this period. A number of hypotheses have been raised that might explain the emergence and spread of the gamma variant and the measures that could have been taken to prevent it and minimise its impact on the population. Conclusions Over 142,000 people died as a result of the SARS-CoV-2 gamma variant sweep in Sao Paulo in the first semester of 2021. Due to its high viral load, the gamma variant displayed high transmissibility and a high degree of virulence resulting in increased case fatality rates across most age tiers. Notably, this second wave was marked by a very significant increase in deaths among young adults. This increase was at least partially due to a deterioration in general health provoked by non-pharmaceutical interventions. In hindsight, a safer and more effective measure might have been to allow the free spread of the virus among the young and healthy in the first wave, thus conferring immunity against more virulent variants that emerged later on.

10.
International Journal of Life Science and Pharma Research ; 12(5):L206-L220, 2022.
Article in English | Web of Science | ID: covidwho-2082683

ABSTRACT

Deadly COVID-19 viruses have raised a pandemic situation in the year 2019, causing serious and contagious respiratory infections in humans. SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is the main causative agent for this disease outbreak. The pandemic created a critical impact on the global economy. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis that lasted about 11 months. Since, late 2020, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations. This resulted so far, in over 2.7 million deaths and near about 122 million infection cases. Most mutations in the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) genome are either deleterious and swiftly purged or relatively neutral. As far as the concern is the variants it impacts the virus characteristics, including antigenicity and transmissibility in response to the modification of the human immune profile. In recent days, COVID-19 affected cases are rapidly increasing and it became difficult to inhibit this virus as they are continuously mutated in the host cell forming various new strains like B.1.1.7, B.1.351, P.1, P.2, B.1.1.529, etc. These monitoring, surveillance of variation, and sequencing efforts within the SARS-CoV-2 genome enabled the rapid identification of the first some of Variants of Concern (VOCs) in late 2020, where genome changes became the most observable impact on virus biology and disease transmission. In this review article, we tried to focus and spot the light on the genetic diversification of various strains, their nature, similarities and dissimilarities, mechanism of action, and the prophylactic interventions which could prevent this life-threatening disease in the long run.

11.
Biomedicines ; 10(10)2022 Oct 16.
Article in English | MEDLINE | ID: covidwho-2071222

ABSTRACT

The latest SARS-CoV-2 variant of concern (VOC), Omicron (B.1.1.529), has diversified into more than 300 sublineages. With an expanding number of newly emerging sublineages, the mutation profile is also becoming complicated. There exist mutually exclusive and revertant mutations in different sublineages. Omicron sublineages share some common mutations with previous VOCs (Alpha, Beta, Gamma, and Delta), indicating an evolutionary relationship between these VOCs. A diverse mutation profile at the spike-antibody interface, flexibility of the regions harboring mutations, mutation types, and coexisting mutations suggest that SARS-CoV-2's evolution is far from over.

12.
Expert Rev Vaccines ; 21(12): 1831-1841, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2070019

ABSTRACT

BACKGROUND: This meta-analysis aims to assess the effectiveness of the current Sars-Cov2 vaccine regimens against Omicron infection. A secondary endpoint aims to investigate the waning effectiveness of primary vaccination against symptomatic infection and related hospitalization. RESEARCH DESIGN AND METHODS: The systematic review started on 1 December 2021 and was concluded on 1 March 2022. Random-effects frequentist meta-analyses and multiple meta-regressions were performed. RESULTS: In total, 15 studies are included in the quantitative synthesis. According to the meta-analysis results, the overall risk of Sars-Cov2 infection in vaccinated individuals is on average 31 · 5% lower than the infection risk in unvaccinated while vaccinated with one booster dose have a 70 · 4% risk reduction of Omicron infection compared to unvaccinated. In particular, one booster dose significantly decreases by 69% the risk of symptomatic Omicron infection with respect to unvaccinated. Six months after the primary vaccination, the average risk reduction declines to 22% against symptomatic infection and to 55% against hospitalization. CONCLUSIONS: Primary vaccination does not provide sufficient protection against symptomatic Omicron infection. Although the effectiveness of the primary vaccination against hospitalization due to Omicron remains significantly above 50% after 3 months, it dramatically fades after 6 months.

13.
Viruses ; 14(10)2022 09 29.
Article in English | MEDLINE | ID: covidwho-2066546

ABSTRACT

From a country with one of the highest SARS-CoV-2 morbidity and mortality rates, Brazil has implemented one of the most successful vaccination programs. Brazil's first model city vaccination program was performed by the CoronaVac vaccine (Sinovac Biotech) in the town of Serrana, São Paulo State. To evaluate the vaccination effect on the SARS-CoV-2 molecular dynamics and clinical outcomes, we performed SARS-CoV-2 molecular surveillance on 4375 complete genomes obtained between June 2020 and April 2022 in this location. This study included the period between the initial SARS-CoV-2 introduction and during the vaccination process. We observed that the SARS-CoV-2 substitution dynamics in Serrana followed the viral molecular epidemiology in Brazil, including the initial identification of the ancestral lineages (B.1.1.28 and B.1.1.33) and epidemic waves of variants of concern (VOC) including the Gamma, Delta, and, more recently, Omicron. Most probably, as a result of the immunization campaign, the mortality during the Gamma and Delta VOC was significantly reduced compared to the rest of Brazil, which was also related to lower morbidity. Our phylogenetic analysis revealed the evolutionary history of the SARS-CoV-2 in this location and showed that multiple introduction events have occurred over time. The evaluation of the COVID-19 clinical outcome revealed that most cases were mild (88.9%, 98.1%, 99.1% to Gamma, Delta, and Omicron, respectively) regardless of the infecting VOC. In conclusion, we observed that vaccination was responsible for reducing the death toll rate and related COVID-19 morbidity, especially during the gamma and Delta VOC; however, it does not prevent the rapid substitution rate and morbidity of the Omicron VOC.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Brazil/epidemiology , Phylogeny , COVID-19/epidemiology , COVID-19/prevention & control , Vaccination
14.
Int J Mol Sci ; 23(19)2022 Oct 06.
Article in English | MEDLINE | ID: covidwho-2066139

ABSTRACT

SARS-CoV-2 is the cause of the COVID-19 pandemic which has claimed more than 6.5 million lives worldwide, devastating the economy and overwhelming healthcare systems globally. The development of new drug molecules and vaccines has played a critical role in managing the pandemic; however, new variants of concern still pose a significant threat as the current vaccines cannot prevent all infections. This situation calls for the collaboration of biomedical scientists and healthcare workers across the world. Repurposing approved drugs is an effective way of fast-tracking new treatments for recently emerged diseases. To this end, we have assembled and curated a database consisting of 7817 compounds from the Compounds Australia Open Drug collection. We developed a set of eight filters based on indicators of efficacy and safety that were applied sequentially to down-select drugs that showed promise for drug repurposing efforts against SARS-CoV-2. Considerable effort was made to evaluate approximately 14,000 assay data points for SARS-CoV-2 FDA/TGA-approved drugs and provide an average activity score for 3539 compounds. The filtering process identified 12 FDA-approved molecules with established safety profiles that have plausible mechanisms for treating COVID-19 disease. The methodology developed in our study provides a template for prioritising drug candidates that can be repurposed for the safe, efficacious, and cost-effective treatment of COVID-19, long COVID, or any other future disease. We present our database in an easy-to-use interactive interface (CoviRx that was also developed to enable the scientific community to access to the data of over 7000 potential drugs and to implement alternative prioritisation and down-selection strategies.


Subject(s)
COVID-19 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Drug Repositioning , Humans , Pandemics , SARS-CoV-2
15.
Front Med (Lausanne) ; 9: 1001022, 2022.
Article in English | MEDLINE | ID: covidwho-2065583

ABSTRACT

Countries around the world are gearing for the transition of the coronavirus disease 2019 (COVID-19) from pandemic to endemic phase but the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants could lead to a prolonged pandemic. SARS-CoV-2 has continued to evolve as it optimizes its adaptation to the human host and the successive waves of COVID-19 have been linked to the explosion of particular variant of concern. As the genetic diversity and epidemiological landscape of SARS-CoV-2 differ from country to country, this study aims to provide insights into the variants that are circulating in Malaysia. Whole genome sequencing was performed for 204 SARS-CoV-2 from COVID-19 cases and an additional 18,667 SARS-CoV-2 genome sequences were retrieved from the GISAID EpiCoV database for clade, lineage and genetic variation analyses. Complete genome sequences with high coverage were then used for phylogeny investigation and the resulting phylogenetic tree was constructed from 8,716 sequences. We found that the different waves of COVID-19 in Malaysia were dominated by different clades with the L and O clade for first and second wave, respectively, whereas the progressive replacement by G, GH, and GK of the GRA clade were observed in the subsequence waves. Continuous monitoring of the genetic diversity of SARS-CoV-2 is important to identify the emergence and dominance of new variant in different locality so that the appropriate countermeasures can be taken to effectively contain the spread of SARS-CoV-2.

16.
Trials ; 23(1): 865, 2022 Oct 08.
Article in English | MEDLINE | ID: covidwho-2064838

ABSTRACT

BACKGROUND: In the ongoing COVID-19 pandemic, advanced age is a risk factor for a severe clinical course of SARS-CoV-2 infection. Thus, older people may benefit in particular from booster doses with potent vaccines and research should focus on optimal vaccination schedules. In addition to each individual's medical history, immunosenescence warrants further research in this population. This study investigates vaccine-induced immune response over 1 year. METHODS/DESIGN: EU-COVAT-1-AGED is a randomised controlled, adaptive, multicentre phase II protocol evaluating different booster strategies in individuals aged ≥75 years (n=600) already vaccinated against SARS-CoV-2. The initial protocol foresaw a 3rd vaccination (1st booster) as study intervention. The present modified Part B of this trial foresees testing of mRNA-1273 (Spikevax®) vs. BNT162b2 (Comirnaty®) as 4th vaccination dose (2nd booster) for comparative assessment of their immunogenicity and safety against SARS-CoV-2 wild-type and variants. The primary endpoint of the trial is to assess the rate of 2-fold antibody titre increase 14 days after vaccination measured by quantitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA) against wild-type virus. Secondary endpoints include the changes in neutralising antibody titres (Virus Neutralisation Assay) against wild-type as well as against Variants of Concern (VOC) at 14 days and up to 12 months. T cell response measured by qPCR will be performed in subgroups at 14 days as exploratory endpoint. Biobanking samples are being collected for neutralising antibody titres against potential future VOC. Furthermore, potential correlates between humoral immune response, T cell response and neutralising capacity will be assessed. The primary endpoint analysis will be triggered as soon as for all patients the primary endpoint (14 days after the 4th vaccination dose) has been observed. DISCUSSION: The EU-COVAT-1-AGED trial Part B compares immunogenicity and safety of mRNA-1273 (Spikevax®) and BNT162b2 (Comirnaty®) as 4th SARS-CoV-2 vaccine dose in adults ≥75 years of age. The findings of this trial have the potential to optimise the COVID-19 vaccination strategy for this at-risk population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05160766 . Registered on 16 December 2021. PROTOCOL VERSION: V06_0: 27 July 2022.


Subject(s)
COVID-19 , Vaccines , Adult , Aged , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , Biological Specimen Banks , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Clinical Trials, Phase II as Topic , Humans , Pandemics/prevention & control , Randomized Controlled Trials as Topic , SARS-CoV-2
17.
J Allergy Clin Immunol Glob ; 2022 Oct 04.
Article in English | MEDLINE | ID: covidwho-2061406

ABSTRACT

Background & Objectives: SARS-CoV-2 infection leads to coronavirus disease 2019 (COVID-19), which can range from a mild illness to a severe phenotype characterised by acute respiratory distress, needing mechanical ventilation. Children with combined immunodeficiencies might be unable to mount a sufficient cellular and humoral immune response against Covid-19 and have persistent disease. The authors describe a child with combined immunodeficiency, with favorable post-HSCT course following a haploidentical haematopoietic stem cell transplant in the presence of persistent SARS-CoV-2 infection. Methods & results: A 13-month-old girl with MHC class II deficiency developed persistent pre-HSCT SARS-CoV-2 infection. Faced with a significant challenge of balancing the risk of progressive infection due to incompetent immune system with the danger of inflammatory pneumonitis peri-immune reconstitution post-HSCT, she underwent a maternal (with a recent history of Covid-19 infection) haploidentical haematopoietic stem cell transplant. The patient received Regdanvimab® (post stem cell infusion) and Remdesivir (pre and post stem cell infusion). We noted a gradual increase in the Ct (cycle threshold) values, implying reduction in viral RNA with concomitant expansion in the CD3 lymphocyte subset and clinical/radiological improvement. Conclusions: Combination of adoptive transfer of maternal CD45RO+ memory add-back T-lymphocytes after haploidentical HSCT, use of Regdanvimab® (SARS-CoV-2 neutralising monoclonal antibody) and Remdesivir may have led to the successful outcome in our patient with severe immunodeficiency, undergoing HSCT. Our case highlights the role of novel antiviral strategies (monoclonal antibodies and CD45RO+ memory T-lymphocytes) in contributing to viral clearance in a challenging clinical scenario.

19.
Microbiol Spectr ; 10(5): e0056322, 2022 Oct 26.
Article in English | MEDLINE | ID: covidwho-2053135

ABSTRACT

The emergence of the SARS-CoV-2 B.1.617.2 lineage (Delta variant) in 2021 was associated with increased case numbers and test positivity rates, including a large number of infections in fully vaccinated individuals. Here, we describe the findings of an investigation conducted in Tompkins County, New York, to evaluate factors underlying a significant uptick in the number of coronavirus disease 2019 (COVID-19) cases observed in the months of July and August 2021. We performed genomic surveillance and genotyping as well as virological assessments to determine infectivity of the virus in a select number of clinical diagnostic samples. Genomic sequence analyses revealed complete replacement of the B.1.1.7 lineage (Alpha variant) with the B.1.617.2 lineage (Delta variant) between July 1 and August 4 2021. We observed a strong association between viral RNA loads detected by real-time reverse transcriptase PCR and infectious virus detected in respiratory secretions by virus titration. A marked increase in positive cases among fully vaccinated individuals was observed. The sequence divergence between two index Delta variant cases in April and May, and the cases after July 1st, revealed independent Delta variant introductions in Tompkins County. Contact tracing information enabled the detection of clusters of connected cases within closely related phylogenetic clusters. We also found evidence of transmission between vaccinated individuals and between vaccinated and unvaccinated individuals. This was confirmed by detection and isolation of infectious virus from a group of individuals within epidemiologically connected transmission clusters, confirming shedding of high viral loads and transmission of the virus by fully vaccinated individuals. IMPORTANCE The SARS-CoV-2 lineage B.1.617.2 (Delta variant) emerged in Asia and rapidly spread to other countries, becoming the dominant circulating lineage. Worldwide infections with B.1.617.2 peaked at a time in which vaccination rates were increasing. In this study, we present data characterizing the emergence of SARS-CoV-2 lineage B.1.617.2 (Delta variant) in Tompkins County, New York, which has one of the highest vaccination rates in the state. We present evidence demonstrating infection, replication, and transmission of SARS-CoV-2 lineage B.1.617.2 (Delta variant) between fully vaccinated individuals. Importantly, infectious virus loads were determined in a subset of samples and demonstrated shedding of high viral titers in respiratory secretions of vaccinated individuals.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , RNA, Viral/genetics , Phylogeny , COVID-19/epidemiology
20.
J Allergy Clin Immunol Glob ; 1(3): 112-121, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-2049362

ABSTRACT

Background: Adaptive immunity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is decisive for disease control. Delayed activation of T cells is associated with a worse outcome in coronavirus disease 2019 (COVID-19). Although convalescent individuals exhibit solid T-cell immunity, to date, long-term immunity to SARS-CoV-2 is still under investigation. Objectives: We aimed to characterize the specific T-cell response on the basis of the in vitro recall of IFN-γ-producing cells to in silico-predicted peptides in samples from SARS-CoV-2 convalescent individuals. Methods: The sequence of the SARS-CoV-2 genome was screened, leading to the identification of specific and promiscuous peptides predicted to be recognized by CD4+ and CD8+ T cells. Next, we performed an in vitro recall of specific T cells from PBMC samples from the participants. The results were analyzed according to clinical features of the cohort and HLA diversity. Results: Our results indicated heterogeneous T-cell responsiveness among the participants. Compared with patients who exhibited mild symptoms, hospitalized patients had a significantly higher magnitude of response. In addition, male and older patients showed a lower number of IFN-γ-producing cells. Analysis of samples collected after 180 days revealed a reduction in the number of specific circulating IFN-γ-producing T cells, suggesting decreased immunity against viral peptides. Conclusion: Our data are evidence that in silico-predicted peptides are highly recognized by T cells from convalescent individuals, suggesting a possible application for vaccine design. However, the number of specific T cells decreases 180 days after infection, which might be associated with reduced protection against reinfection over time.

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