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1.
Emerg Infect Dis ; 29(7): 1386-1396, 2023 07.
Article in English | MEDLINE | ID: covidwho-20237258

ABSTRACT

Isolating and characterizing emerging SARS-CoV-2 variants is key to understanding virus pathogenesis. In this study, we isolated samples of the SARS-CoV-2 R.1 lineage, categorized as a variant under monitoring by the World Health Organization, and evaluated their sensitivity to neutralizing antibodies and type I interferons. We used convalescent serum samples from persons in Canada infected either with ancestral virus (wave 1) or the B.1.1.7 (Alpha) variant of concern (wave 3) for testing neutralization sensitivity. The R.1 isolates were potently neutralized by both the wave 1 and wave 3 convalescent serum samples, unlike the B.1.351 (Beta) variant of concern. Of note, the R.1 variant was significantly more resistant to type I interferons (IFN-α/ß) than was the ancestral isolate. Our study demonstrates that the R.1 variant retained sensitivity to neutralizing antibodies but evolved resistance to type I interferons. This critical driving force will influence the trajectory of the pandemic.


Subject(s)
COVID-19 , Interferon Type I , Humans , SARS-CoV-2/genetics , Interferon Type I/genetics , Antibodies, Neutralizing , COVID-19 Serotherapy , Canada/epidemiology , Antibodies, Viral , Spike Glycoprotein, Coronavirus
2.
Inflammopharmacology ; 31(4): 1779-1788, 2023 Aug.
Article in English | MEDLINE | ID: covidwho-2325971

ABSTRACT

The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 responsible for the global COVID-19 pandemic has caused almost 760 million confirmed cases and 7 million deaths worldwide, as of end-February 2023. Since the beginning of the first COVID-19 case, several virus variants have emerged: Alpha (B1.1.7), Beta (B135.1), Gamma (P.1), Delta (B.1.617.2) and then Omicron (B.1.1.529) and its sublineages. All variants have diversified in transmissibility, virulence, and pathogenicity. All the newly emerging SARS-CoV-2 variants appear to contain some similar mutations associated with greater "evasiveness" of the virus to immune defences. From early 2022 onward, several Omicron subvariants named BA.1, BA.2, BA.3, BA.4, and BA.5, with comparable mutation forms, have followed. After the wave of contagions caused by Omicron BA.5, a new Indian variant named Centaurus BA.2.75 and its new subvariant BA.2.75.2, a second-generation evolution of the Omicron variant BA.2, have recently been identified. From early evidence, it appears that this new variant has higher affinity for the cell entry receptor ACE-2, making it potentially able to spread very fast. According to the latest studies, the BA.2.75.2 variant may be able to evade more antibodies in the bloodstream generated by vaccination or previous infection, and it may be more resistant to antiviral and monoclonal antibody drug treatments. In this manuscript, the authors highlight and describe the latest evidences and critical issues have emerged on the new SARS-CoV-2 variants.

3.
Front Public Health ; 11: 1085020, 2023.
Article in English | MEDLINE | ID: covidwho-2313721

ABSTRACT

Background: The coronavirus disease (COVID-19) pandemic is slowing down, and countries are discussing whether preventive measures have remained effective or not. This study aimed to investigate a particular property of the trend of COVID-19 that existed and if its variants of concern were cointegrated, determining its possible transformation into an endemic. Methods: Biweekly expected new cases by variants of COVID-19 for 48 countries from 02 May 2020 to 29 August 2022 were acquired from the GISAID database. While the case series was tested for homoscedasticity with the Breusch-Pagan test, seasonal decomposition was used to obtain a trend component of the biweekly global new case series. The percentage change of trend was then tested for zero-mean symmetry with the one-sample Wilcoxon signed rank test and zero-mean stationarity with the augmented Dickey-Fuller test to confirm a random COVID trend globally. Vector error correction models with the same seasonal adjustment were regressed to obtain a variant-cointegrated series for each country. They were tested by the augmented Dickey-Fuller test for stationarity to confirm a constant long-term stochastic intervariant interaction within the country. Results: The trend series of seasonality-adjusted global COVID-19 new cases was found to be heteroscedastic (p = 0.002), while its rate of change was indeterministic (p = 0.052) and stationary (p = 0.024). Seasonal cointegration relationships between expected new case series by variants were found in 37 out of 48 countries (p < 0.05), reflecting a constant long-term stochastic trend in new case numbers contributed from different variants of concern within most countries. Conclusion: Our results indicated that the new case long-term trends were random on a global scale and stable within most countries; therefore, the virus was unlikely to be eliminated but containable. Policymakers are currently in the process of adapting to the transformation of the pandemic into an endemic.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/epidemiology , Pandemics , Research Design
4.
Biomedicines ; 11(4)2023 Apr 10.
Article in English | MEDLINE | ID: covidwho-2299941

ABSTRACT

During the COVID-19 pandemic, different SARS-CoV-2 variants of concern (VOC) with specific characteristics have emerged and spread worldwide. At the same time, clinicians routinely evaluate the results of certain blood tests upon patient admission as well as during hospitalization to assess disease severity and the overall patient status. In the present study, we searched for significant cell blood count and biomarker differences among patients affected with the Alpha, Delta and Omicron VOCs at admission. Data from 330 patients were retrieved regarding age, gender, VOC, cell blood count results (WBC, Neut%, Lymph%, Ig%, PLT), common biomarkers (D-dimers, urea, creatinine, SGOT, SGPT, CRP, IL-6, suPAR), ICU admission and death. Statistical analyses were performed using ANOVA, the Kruskal-Wallis test, two-way ANOVA, Chi-square, T-test, the Mann-Whitney test and logistic regression was performed where appropriate using SPSS v.28 and STATA 14. Age and VOC were significantly associated with hospitalization, whereas significant differences among VOC groups were found for WBC, PLT, Neut%, IL-6, creatinine, CRP, D-dimers and suPAR. Our analyses showed that throughout the current pandemic, not only the SARS-CoV-2 VOCs but also the laboratory parameters that are used to evaluate the patient's status at admission are subject to changes.

5.
Viruses ; 15(4)2023 03 27.
Article in English | MEDLINE | ID: covidwho-2298279

ABSTRACT

Genetic variant(s) of concern (VoC) of SARS-CoV-2 have been emerging worldwide due to mutations in the gene encoding spike glycoprotein. We performed comprehensive analyses of spike protein mutations in the significant variant clade of SARS-CoV-2, using the data available on the Nextstrain server. We selected various mutations, namely, A222V, N439K, N501Y, L452R, Y453F, E484K, K417N, T478K, L981F, L212I, N856K, T547K, G496S, and Y369C for this study. These mutations were chosen based on their global entropic score, emergence, spread, transmission, and their location in the spike receptor binding domain (RBD). The relative abundance of these mutations was mapped with global mutation D614G as a reference. Our analyses suggest the rapid emergence of newer global mutations alongside D614G, as reported during the recent waves of COVID-19 in various parts of the world. These mutations could be instrumentally imperative for the transmission, infectivity, virulence, and host immune system's evasion of SARS-CoV-2. The probable impact of these mutations on vaccine effectiveness, antigenic diversity, antibody interactions, protein stability, RBD flexibility, and accessibility to human cell receptor ACE2 was studied in silico. Overall, the present study can help researchers to design the next generation of vaccines and biotherapeutics to combat COVID-19 infection.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Humans , Spike Glycoprotein, Coronavirus/genetics , SARS-CoV-2/genetics , Mutation , Protein Binding
6.
Sci Total Environ ; 881: 163292, 2023 Jul 10.
Article in English | MEDLINE | ID: covidwho-2295246

ABSTRACT

Wastewater-based surveillance has become an effective tool around the globe for indirect monitoring of COVID-19 in communities. Variants of Concern (VOCs) have been detected in wastewater by use of reverse transcription polymerase chain reaction (RT-PCR) or whole genome sequencing (WGS). Rapid, reliable RT-PCR assays continue to be needed to determine the relative frequencies of VOCs and sub-lineages in wastewater-based surveillance programs. The presence of multiple mutations in a single region of the N-gene allowed for the design of a single amplicon, multiple probe assay, that can distinguish among several VOCs in wastewater RNA extracts. This approach which multiplexes probes designed to target mutations associated with specific VOC's along with an intra-amplicon universal probe (non-mutated region) was validated in singleplex and multiplex. The prevalence of each mutation (i.e. VOC) is estimated by comparing the abundance of the targeted mutation with a non-mutated and highly conserved region within the same amplicon. This is advantageous for the accurate and rapid estimation of variant frequencies in wastewater. The N200 assay was applied to monitor frequencies of VOCs in wastewater extracts from several communities in Ontario, Canada in near real time from November 28, 2021 to January 4, 2022. This includes the period of the rapid replacement of the Delta variant with the introduction of the Omicron variant in these Ontario communities in early December 2021. The frequency estimates using this assay were highly reflective of clinical WGS estimates for the same communities. This style of qPCR assay, which simultaneously measures signal from a non-mutated comparator probe and multiple mutation-specific probes contained within a single qPCR amplicon, can be applied to future assay development for rapid and accurate estimations of variant frequencies.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Wastewater , Ontario
7.
Viruses ; 15(4)2023 04 19.
Article in English | MEDLINE | ID: covidwho-2293766

ABSTRACT

The unprecedented pandemic of COVID-19, caused by a novel coronavirus, SARS-CoV-2, and its highly transmissible variants, led to massive human suffering, death, and economic devastation worldwide. Recently, antibody-evasive SARS-CoV-2 subvariants, BQ and XBB, have been reported. Therefore, the continued development of novel drugs with pan-coronavirus inhibition is critical to treat and prevent infection of COVID-19 and any new pandemics that may emerge. We report the discovery of several highly potent small-molecule inhibitors. One of which, NBCoV63, showed low nM potency against SARS-CoV-2 (IC50: 55 nM), SARS-CoV-1 (IC50: 59 nM), and MERS-CoV (IC50: 75 nM) in pseudovirus-based assays with excellent selectivity indices (SI > 900), suggesting its pan-coronavirus inhibition. NBCoV63 showed equally effective antiviral potency against SARS-CoV-2 mutant (D614G) and several variants of concerns (VOCs) such as B.1.617.2 (Delta), B.1.1.529/BA.1 and BA.4/BA.5 (Omicron), and K417T/E484K/N501Y (Gamma). NBCoV63 also showed similar efficacy profiles to Remdesivir against authentic SARS-CoV-2 (Hong Kong strain) and two of its variants (Delta and Omicron), SARS-CoV-1, and MERS-CoV by plaque reduction in Calu-3 cells. Additionally, we show that NBCoV63 inhibits virus-mediated cell-to-cell fusion in a dose-dependent manner. Furthermore, the absorption, distribution, metabolism, and excretion (ADME) data of NBCoV63 demonstrated drug-like properties.


Subject(s)
COVID-19 , Middle East Respiratory Syndrome Coronavirus , Humans , SARS-CoV-2 , Anti-Retroviral Agents , Spike Glycoprotein, Coronavirus/genetics
8.
Microb Genom ; 9(4)2023 04.
Article in English | MEDLINE | ID: covidwho-2291995

ABSTRACT

Wastewater-based epidemiology has been used extensively throughout the COVID-19 (coronavirus disease 19) pandemic to detect and monitor the spread and prevalence of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and its variants. It has proven an excellent, complementary tool to clinical sequencing, supporting the insights gained and helping to make informed public-health decisions. Consequently, many groups globally have developed bioinformatics pipelines to analyse sequencing data from wastewater. Accurate calling of mutations is critical in this process and in the assignment of circulating variants; yet, to date, the performance of variant-calling algorithms in wastewater samples has not been investigated. To address this, we compared the performance of six variant callers (VarScan, iVar, GATK, FreeBayes, LoFreq and BCFtools), used widely in bioinformatics pipelines, on 19 synthetic samples with known ratios of three different SARS-CoV-2 variants of concern (VOCs) (Alpha, Beta and Delta), as well as 13 wastewater samples collected in London between the 15th and 18th December 2021. We used the fundamental parameters of recall (sensitivity) and precision (specificity) to confirm the presence of mutational profiles defining specific variants across the six variant callers. Our results show that BCFtools, FreeBayes and VarScan found the expected variants with higher precision and recall than GATK or iVar, although the latter identified more expected defining mutations than other callers. LoFreq gave the least reliable results due to the high number of false-positive mutations detected, resulting in lower precision. Similar results were obtained for both the synthetic and wastewater samples.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/epidemiology , Wastewater-Based Epidemiological Monitoring , Wastewater , Algorithms
9.
Curr Top Med Chem ; 2023 Apr 11.
Article in English | MEDLINE | ID: covidwho-2304070

ABSTRACT

The Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths and threatens public health and safety. Nowadays, modern society has faced a new challenging problem, the emergence of novel SARS-CoV-2 variants of concern (VOCs). In this context, the Omicron (B.1.1.529) variant, having more than 60 mutations when compared to its ancestral wild-type virus, has infected many individuals around the world. It is rapidly spread person-to-person due to its increased transmissibility. Additionally, it was demonstrated that this newest variant and its subvariants have the capability of evading the host immune system, being resistant to neutralizing antibodies. Moreover, it has been proven to be resistant to monoclonal antibodies and several different vaccines. This ability is associated with a huge number of mutations associated with its spike (S) glycoprotein, which presents at least 15 mutations. These mutations are able to modify the way how this virus interacts with the host angiotensin-converting enzyme 2 (ACE2), increasing its infectivity and making the therapeutic alternatives more ineffective. Concerning its chymotrypsin-like picornavirus 3C-like protease (3CLpro) and RNA-dependent RNA polymerase (RdRp), it has been seen that some compounds can be active against different SARS-CoV-2 variants, in a similar mode than its wild-type precursor. This broad spectrum of action for some drugs could be attributed to the fact that the currently identified mutations found in 3CLpro and RNA proteins being localized near the catalytic binding site, conserving their activities. Herein this review, we provide a great and unprecedented compilation of all identified and/or repurposed compounds/drugs against this threatening variant, Omicron. The main targets for those compounds are the protein-protein interface (PPI) of S protein with ACE2, 3CLpro, RdRp, and Nucleocapsid (N) protein. Some of these studies have presented only in silico data, having a lack of experimental results to prove their findings. However, these should be considered here since other research teams can use their observations to design and investigate new potential agents. Finally, we believe that our review will contribute to several studies that are in progress worldwide, compiling several interesting aspects about VOCs associated with SARS-CoV2, as well as describing the results for different chemical classes of compounds that could be promising as prototypes for designing new and more effective antiviral agents.

10.
Aerosol Science and Engineering ; 2023.
Article in English | Scopus | ID: covidwho-2284514

ABSTRACT

The current study examines the air quality trends in response to Covid-19-induced lockdowns at various locations in Delhi. The primary pollutants like NO2, CO, and PM10 have shown reductions during the lockdown phase, but the magnitude varied significantly in different places. Also, during the lockdown, air quality in some areas of Delhi exceeded National Ambient Air Quality Standards. Secondary pollutants like O3 have shown mixed trends due to complex atmospheric processes and dependence on relative proportions of VOC and NOx levels. A total of six sites, including traffic, industrial, and residential sites, have been studied. The diurnal behavior of pollutants also differed significantly around different places. During the lockdown, Ashok Vihar, a traffic-influenced area, showed a decrease in O3 (~ 40%), while at DTU (Traffic site), O3 levels increased (~ 48%). The industrial sites Okhla and Wazirpur also showed different trends during the lockdown;O3 in Wazirpur decreased by 50%, whereas Okhla increased by 25%. NOx concentration was lesser in 2020 at all the stations compared to 2019, indicating the positive impact of the lockdown on air pollution due to vehicular emissions. The Approximate Envelope Method estimates the secondary fraction of PM2.5. This fraction of PM is dominated in the lockdown year in the residential site, while it remains unchanged in the traffic site and increased by 11% in the industrial area. Despite being not so far from each other, these sites show very different patterns of pollutants during lockdown episodes. © 2023, The Author(s) under exclusive licence to Institute of Earth Environment, Chinese Academy Sciences.

11.
Problemy Osobo Opasnykh Infektsii ; - (3):164-169, 2022.
Article in Russian | Scopus | ID: covidwho-2281217

ABSTRACT

The aim of the work was to study the pathogenicity of newly emerging variants of SARS-CoV-2 on the model of the Syrian golden hamster. Materials and methods. We used the strains of SARS-CoV-2 virus related to the VOC circulating in the territory of the Russian Federation. The experiments were carried out on outbreed Syrian hamsters obtained from the nursery of the SSC VB "Vector”. The infectious titer of coronavirus in tissue samples collected from infected laboratory animals was determined on a Vero E6 cell culture. The Ct in RT-PCR was considered an additional parameter for monitoring the viral load in the samples. The severity of lung tissue damage in Syrian hamsters with COVID-19 was assessed by histological preparations. Results and discussion. 50 % infecting doses in case of the intranasal infection have been determined, histological analysis of lung tissues performed. The pathogenicity of various variants of the SARS-CoV-2 virus for the Syrian hamster has been evaluated, differences in infecting doses and pathological changes in the lungs have been revealed. SARS-CoV-2 viruses belonging to Beta genetic variant have the highest virulence, while Alpha variant has the lowest one when comparing the studied strains by the ID50 value. The Delta and Omicron variants have a matched ability to cause specific damage to the tissues of the respiratory tract, while being inferior only to the Beta variant. It has been demonstrated that Syrian hamsters are an adequate model for assessing the pathogenicity of the SARS-CoV-2 virus variants of concern. Variants of SARS-CoV-2 virus during intranasal infection has shown different degree of pathogenicity in the Syrian hamster model. © 2022 Russian Research Anti-Plague Institute. All rights reserved.

12.
Viral, Parasitic, Bacterial, and Fungal Infections: Antimicrobial, Host Defense, and Therapeutic Strategies ; : 237-262, 2022.
Article in English | Scopus | ID: covidwho-2255077

ABSTRACT

The clinical outcomes in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection include asymptomatic disease or mild disease with influenza-like symptoms or severe disease condition following death by pneumonia and acute respiratory distress syndrome (ARDS). The current mRNA- and vector-based vaccines successfully addressed the antigenic challenges of the parental SARS-CoV-2 strain. However, recent concerns are being raised against some SARS-CoV-2 variants, which have the potential to escape natural immunity and vaccine-induced immune recognition partially, leading to a possible increase in transmissibility and disease severity. The coronavirus disease-19 (COVID-19)-induced rapid changes in human immune profiles might be instigating the evolution of SARS-CoV-2 with a higher propensity. Therefore, we require critical surveillance on the genomic sequence and structural conformation of the evolving variants and phenotypic impacts of the accumulating mutations on the host-immune response for possible updates in the booster vaccine sequence, if required. Here, we will highlight the role of accumulating mutations in SARS-CoV-2 genomic sequences leading to the host-immune escape by regulating the T cell- and B cell-mediated responses in infected, unvaccinated, and vaccinated individuals. © 2023 Elsevier Inc. All rights reserved.

13.
53rd Annual Meeting of the Italian Electronics Society, SIE 2022 ; 1005 LNEE:111-116, 2023.
Article in English | Scopus | ID: covidwho-2253916

ABSTRACT

The COVID-19 pandemic outbreak, declared in March 2020, has led to several behavioral changes in the general population, such as social distancing and mask usage among others. Furthermore, the sanitary emergency has stressed health system weaknesses in terms of disease prevention, diagnosis, and cure. Thus, smart technologies allowing for early and quick detection of diseases are called for. In this framework, the development of point-of-care devices can provide new solutions for sanitary emergencies management. This work focuses on the development of useful tools for early disease diagnosis based on nanomaterials on cotton substrates, to obtain a low-cost and easy-to-use detector of breath volatiles as disease markers. Specifically, we report encouraging experimental results concerning acetone detection through impedance measurements. Such findings can pave the way to the implementation of VOCs (Volatile Organic Compounds) sensors into smart and user friendly diagnostic devices. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

14.
Med Microbiol Immunol ; 2022 Nov 12.
Article in English | MEDLINE | ID: covidwho-2275137

ABSTRACT

During 2022, the COVID-19 pandemic has been dominated by the variant of concern (VoC) Omicron (B.1.1.529) and its rapidly emerging subvariants, including Omicron-BA.1 and -BA.2. Rapid antigen tests (RATs) are part of national testing strategies to identify SARS-CoV-2 infections on site in a community setting or to support layman's diagnostics at home. We and others have recently demonstrated an impaired RAT detection of infections caused by Omicron-BA.1 compared to Delta. Here, we evaluated the performance of five SARS-CoV-2 RATs in a single-centre laboratory study examining a total of 140 SARS-CoV-2 PCR-positive respiratory swab samples, 70 Omicron-BA.1 and 70 Omicron-BA.2, as well as 52 SARS-CoV-2 PCR-negative swabs collected from March 8th until April 10th, 2022. One test did not meet minimal criteria for specificity. In an assessment of the analytical sensitivity in clinical specimen, the 50% limit of detection (LoD50) ranged from 4.2 × 104 to 9.2 × 105 RNA copies subjected to the RAT for Omicron-BA.1 compared to 1.3 × 105 to 1.5 × 106 for Omicron-BA.2. Overall, intra-assay differences for the detection of Omicron-BA.1-containing and Omicron-BA.2-containing samples were non-significant, while a marked overall heterogeneity among the five RATs was observed. To score positive in these point-of-care tests, up to 22-fold (LoD50) or 68-fold (LoD95) higher viral loads were required for the worst performing compared to the best performing RAT. The rates of true-positive test results for these Omicron subvariant-containing samples in the highest viral load category (Ct values < 25) ranged between 44.7 and 91.1%, while they dropped to 8.7 to 22.7% for samples with intermediate Ct values (25-30). In light of recent reports on the emergence of two novel Omicron-BA.2 subvariants, Omicron-BA.2.75 and BJ.1, awareness must be increased for the overall reduced detection rate and marked differences in RAT performance for these Omicron subvariants.

15.
J Clin Virol Plus ; 2(4): 100109, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2273286

ABSTRACT

The Omicron emerged in November 2021 and became the predominant SARS-CoV-2 variant globally. It spreads more rapidly than ancestral lineages and its rapid detection is critical for the prevention of disease outbreaks. Antigen tests such as immunochromatographic assay (ICA) and chemiluminescent enzyme immunoassay (CLEIA) yield results more quickly than standard polymerase chain reaction (PCR). However, their utility for the detection of the Omicron variant remains unclear. We herein evaluated the performance of ICA and CLEIA in saliva from 51 patients with Omicron and 60 PCR negative individuals. The sensitivity and specificity of CLEIA were 98.0% (95%CI: 89.6-100.0%) and 100.0% (95%CI: 94.0-100.0%), respectively, with fine correlation with cycle threshold (Ct) values. The sensitivity and specificity of ICA were 58.8% (95%CI: 44.2-72.4%) and 100.0% (95%CI: 94.0-100.0%), respectively. The sensitivity of ICA was 100.0% (95%CI: 80.5-100.0%) when PCR Ct was less than 25. The Omicron can be efficiently detected in saliva by CLEIA. ICA also detects high viral load Omicron using saliva.

16.
Virol Sin ; 2022 Sep 24.
Article in English | MEDLINE | ID: covidwho-2258965

ABSTRACT

The continuously arising of SARS-CoV-2 variants has been posting a great threat to public health safety globally, from B.1.17 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta) to B.1.1.529 (Omicron). The emerging or re-emerging of the SARS-CoV-2 variants of concern is calling for the constant monitoring of their epidemics, pathogenicity and immune escape. In this study, we aimed to characterize replication and pathogenicity of the Alpha and Delta variant strains isolated from patients infected in Laos. The amino acid mutations within the spike fragment of the isolates were determined via sequencing. The more efficient replication of the Alpha and Delta isolates was documented than the prototyped SARS-CoV-2 in Calu-3 and Caco-2 â€‹cells, while such features were not observed in Huh-7, Vero E6 and HPA-3 â€‹cells. We utilized both animal models of human ACE2 (hACE2) transgenic mice and hamsters to evaluate the pathogenesis of the isolates. The Alpha and Delta can replicate well in multiple organs and cause moderate to severe lung pathology in these animals. In conclusion, the spike protein of the isolated Alpha and Delta variant strains was characterized, and the replication and pathogenicity of the strains in the cells and animal models were also evaluated.

17.
Microbiol Spectr ; : e0138622, 2022 Oct 27.
Article in English | MEDLINE | ID: covidwho-2256572

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.

18.
Heliyon ; 9(2): e13382, 2023 Feb.
Article in English | MEDLINE | ID: covidwho-2271201

ABSTRACT

Introduction: This study aimed to perform mutation and phylogenetic analyses of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta variants and analyze the characteristic signs and symptoms of patients infected with SARS-CoV-2 Delta variant originated from Makassar during the Delta outbreak.Methods: We collected samples from patients who were infected with coronavirus disease 2019 (COVID-19) between June and October 2021. We selected the Quantitative Reverse Transcription-Polymerase Chain Reaction (PCR)-positive samples with a cycle threshold value of <30 for whole genome sequencing. Total viral ribonucleic acid (RNA) was isolated from 34 PCR-positive nasopharyngeal swab samples, and whole genome sequencing was performed using the Oxford Nanopore GridlON sequencer. Phylogenetic and maximum clade credibility analyses were performed using the Bayesian Markov chain Monte Carlo method. Results: It was found that 33 patients were infected with the SARS-CoV-2 Delta variant in this cohort study, among whom 63.6% (21) patients were female. According to the clinical data, 24 (72.7%), 7 (21.2%), and 2 (6.1%) patients had mild, moderate, and severe COVID-19 infections. Phylogenetic analysis based on the spike and RNA-dependent RNA polymerase (RdRp) genes showed that the collected samples were clustered in the main lineage of B.1.617.2 (Delta variant). The Delta variants had a high frequency of distinct mutations in the spike protein region, including T19R (94.12%), L452R (88.23%), T478K (91.17%), D614G (97%), P681R (97%), and D950 N (97%). Other unique mutations found in a smaller frequency in our samples were present in the N-terminal domain, including A27T (2.94%) and A222V (14.70%), and in the receptor-binding domain, including Q414K (5.88%), G446V (2.94%), and T470 N (2.94%). Conclusion: This study revealed the unique mutations in the S protein region of Delta variants. T19R, L452R, T478K/T478R, D614G, P681R, and D950 N were the most common substitutions in Makassar's Delta variant.

19.
Viruses ; 15(3)2023 03 21.
Article in English | MEDLINE | ID: covidwho-2270792

ABSTRACT

The SARS-CoV-2 pandemic has seriously affected the population in Turkey. Since the beginning, phylogenetic analysis has been necessary to monitor public health measures against COVID-19 disease. In any case, the analysis of spike (S) and nucleocapsid (N) gene mutations was crucial in determining their potential impact on viral spread. We screened S and N regions to detect usual and unusual substitutions, whilst also investigating the clusters among a patient cohort resident in Kahramanmaras city, in a restricted time span. Sequences were obtained by Sanger methods and genotyped by the PANGO Lineage tool. Amino acid substitutions were annotated comparing newly generated sequences to the NC_045512.2 reference sequence. Clusters were defined using phylogenetic analysis with a 70% cut-off. All sequences were classified as Delta. Eight isolates carried unusual mutations on the S protein, some of them located in the S2 key domain. One isolate displayed the unusual L139S on the N protein, while few isolates carried the T24I and A359S N substitutions able to destabilize the protein. Phylogeny identified nine monophyletic clusters. This study provided additional information about SARS-CoV-2 epidemiology in Turkey, suggesting local transmission of infection in the city by several transmission routes, and highlighting the necessity to improve the power of sequencing worldwide.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Turkey/epidemiology , COVID-19/epidemiology , Phylogeny , Cluster Analysis
20.
Respir Med Res ; 83: 100990, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2276566

ABSTRACT

This multicenter observational study included 171 COVID-19 adult patients hospitalized in the ICUs of nine hospitals in Lombardy (Northern Italy) from December, 1st 2021, to February, 9th 2022. During the study period, the Delta/Omicron variant ratio of cases decreased with a delay of two weeks in ICU patients compared to that in the community; a higher proportion of COVID-19 unvaccinated patients was infected by Delta than by Omicron whereas a higher rate of COVID-19 boosted patients was Omicron-infected. A higher number of comorbidities and a higher comorbidity score in ICU critically COVID-19 inpatients was positively associated with the Omicron infection as well in vaccinated individuals. Although people infected by Omicron have a lower risk of severe disease than those infected by Delta variant, the outcome, including the risk of ICU admission and the need for mechanical ventilation due to infection by Omicron versus Delta, remains uncertain. The continuous monitoring of the circulating SARS-CoV-2 variants remains a milestone to counteract this pandemic.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Humans , COVID-19/epidemiology , Inpatients , Intensive Care Units , Italy/epidemiology
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