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1.
Sci Total Environ ; : 157546, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1967102

ABSTRACT

Although SARS-CoV-2 can cause severe illness and death, a percentage of the infected population is asymptomatic. This, along with other factors, such as insufficient diagnostic testing and underreporting due to self-testing, contributes to the silent transmission of SARS-CoV-2 and highlights the importance of implementing additional surveillance tools. The fecal shedding of the virus from infected individuals enables its detection in community wastewater, and this has become a valuable public health tool worldwide as it allows the monitoring of the disease on a populational scale. Here, we monitored the presence of SARS-CoV-2 and its dynamic genomic changes in wastewater sampled from two metropolitan areas in Arkansas during major surges of COVID-19 cases and assessed how the viral titers in these samples related to the clinical case counts between late April 2020 and January 2022. The levels of SARS-CoV-2 RNA were quantified by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) using a set of TaqMan assays targeting three different viral genes (encoding ORF1ab polyprotein, surface glycoprotein, and nucleocapsid phosphoprotein). An allele-specific RT-qPCR approach was used to screen the samples for SARS-CoV-2 mutations. The identity and genetic diversity of the virus were further investigated through amplicon-based RNA sequencing, and SARS-CoV-2 variants of concern were detected in wastewater samples throughout the duration of this study. Our data show how changes in the virus genome can affect the sensitivity of specific RT-qPCR assays used in COVID-19 testing with the surge of new variants. A significant association was observed between viral titers in wastewater and recorded number of COVID-19 cases in the areas studied, except when assays failed to detect targets due to the presence of particular variants. These findings support the use of wastewater surveillance as a reliable complementary tool for monitoring SARS-CoV-2 and its genetic variants at the community level.

2.
Int J Infect Dis ; 2022 Aug 03.
Article in English | MEDLINE | ID: covidwho-1966626

ABSTRACT

BACKGROUND: We performed exhaled breath (EB) and nasopharyngeal (NP) qPCR and NP rapid antigen testing (RAT) throughout SARS-CoV-2 infections with different variants. METHODS: We recruited immuno-naïve alpha-infected (n=11) and partly boosted omicron-infected patients (n=8) as high-risk contacts. We compared peak NP and EB qPCR cycle time (CT) values between cohorts (Wilcoxon-Mann-Whitney test). Test positivity was compared for three infection phases (Cochran Q test). RESULTS: Peak median NP CT was 11.5 (IQR 10.1-12.1) for alpha and 12.2 (IQR 11.1-15.3) for omicron infections. Peak median EB CT was 25.2 (IQR 24.5-26.9) and 28.3 (IQR 26.4-30.8), respectively. Distributions did not differ between cohorts for NP (p = 0.19) or EB (p = 0.09). SARS-CoV-2 shedding peaked on day 1 in EB (CI 0.0 - 4.5) and day 3 in NP (CI 1.5 - 6.0). EB qPCR positivity equaled NP qPCR positivity on D0-D1 (p=0.44) and D2-D6 (p=1.0). It superseded NP RAT positivity on D0-D1 (p=0.003) and D2-D6 (p=0.008). It was inferior to both on D7-D10 (p<0.001). CONCLUSIONS: Peak exhaled breath and nasopharynx shedding were comparable across variants. EB qPCR positivity matched NP qPCR and superseded NP RAT in the first week of infection.

3.
Emerg Infect Dis ; 28(9)2022 Jul 22.
Article in English | MEDLINE | ID: covidwho-1963355

ABSTRACT

Wastewater monitoring of SARS-CoV-2 enables early detection and monitoring of the COVID-19 disease burden in communities and can track specific variants of concern. We determined proportions of the Omicron and Delta variants across 30 municipalities covering >75% of the province of Alberta (population 4.5 million), Canada, during November 2021-January 2022. Larger cities Calgary and Edmonton exhibited more rapid emergence of Omicron than did smaller and more remote municipalities. Notable exceptions were Banff, a small international resort town, and Fort McMurray, a medium-sized northern community that has many workers who fly in and out regularly. The integrated wastewater signal revealed that the Omicron variant represented close to 100% of SARS-CoV-2 burden by late December, before the peak in newly diagnosed clinical cases throughout Alberta in mid-January. These findings demonstrate that wastewater monitoring offers early and reliable population-level results for establishing the extent and spread of SARS-CoV-2 variants.

4.
Int J Mol Sci ; 23(12)2022 Jun 20.
Article in English | MEDLINE | ID: covidwho-1963995

ABSTRACT

The SARS-CoV-2 pandemic remains a major public health threat, especially due to newly emerging SARS-CoV-2 Variants of Concern (VoCs), which are more efficiently transmitted, more virulent, and more able to escape naturally acquired and vaccine-induced immunity. Recently, the protease inhibitor Paxlovid® and the polymerase inhibitor molnupiravir, both targeting mutant-prone viral components, were approved for high-risk COVID-19 patients. Nevertheless, effective therapeutics to treat COVID-19 are urgently needed, especially small molecules acting independently of VoCs and targeting genetically stable cellular pathways which are crucial for viral replication. Pamapimod is a selective inhibitor of p38 Mitogen-Activated Protein Kinase alpha (p38 MAPKα) that has been extensively clinically evaluated for the treatment of rheumatoid arthritis. Signaling via p38 has recently been described as a key pathway for the replication of SARS-CoV-2. Here, we reveal that the combination of pamapimod with pioglitazone, an anti-inflammatory and approved drug for the treatment of type 2 diabetes, possesses potent and synergistic activity to inhibit SARS-CoV-2 replication in vitro. Both drugs showed similar antiviral potency across several cultured cell types and similar antiviral activity against SARS-CoV-2 Wuhan type, and the VoCs Alpha, Beta, Gamma, Delta, and Omicron. These data support the combination of pamapimod and pioglitazone as a potential therapy to reduce duration and severity of disease in COVID-19 patients, an assumption currently evaluated in an ongoing phase II clinical study.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Humans , Pioglitazone/pharmacology , Pioglitazone/therapeutic use , Pyridones , Pyrimidines , SARS-CoV-2
5.
Transpl Infect Dis ; : e13914, 2022 Jul 28.
Article in English | MEDLINE | ID: covidwho-1961997

ABSTRACT

BACKGROUND: The continuing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with decreased susceptibility to neutralizing antibodies is of clinical importance. Several spike mutations associated with immune escape have evolved independently in association with different variants of concern (VOCs). How and when these mutations arise is still unclear. We hypothesized that such mutations might arise in the context of persistent viral replication in immunosuppressed hosts. METHODS: Nasopharyngeal specimens were collected longitudinally from two immunosuppressed patients with persistent SARS-CoV-2 infection. Plasma was collected from these same patients late in disease course. SARS-CoV-2 whole genome sequencing was performed to assess the emergence and frequency of mutations over time. Select Spike mutations were assessed for their impact on viral entry and antibody neutralization in vitro. RESULTS: Our sequencing results revealed the intrahost emergence of spike mutations that are associated with circulating VOCs in both immunosuppressed patients (del241-243 and E484Q in one patient, and E484K in the other). These mutations decreased antibody-mediated neutralization of pseudotyped virus particles in cell culture, but also decreased efficiency of spike-mediated cell entry. CONCLUSIONS: These observations demonstrate the de novo emergence of SARS-CoV-2 spike mutations with enhanced immune evasion in immunosuppressed patients with persistent infection. These data suggest one potential mechanism for the evolution of VOCs and emphasize the importance of continued efforts to develop antiviral drugs for suppression of viral replication in hospitalized settings.

6.
J Travel Med ; 2022 Jul 28.
Article in English | MEDLINE | ID: covidwho-1961107

ABSTRACT

BACKGROUND: Covaxin/BBV152 is one of the most widely used vaccines against SARS-CoV-2 infection and one of the few vaccines used extensively in low- and middle-income countries (LMIC). METHODS: We investigated the effect of Covaxin on the SARS-CoV-2 specific IgG and IgA and neutralizing antibody (NAb) levels at baseline (M0) and at months 1 (M1), 2 (M2), 3 (M3), 4 (M4), 6 (M6) and 12 (M12) following vaccination in health care workers. In addition, we also examined the NAb levels against variant lineages of B.1.617.2 (Delta, India), B.1.617.2.1 (Delta Plus, India), B.1.351 (Beta, SA), B.1.1.7 (Alpha, UK) and B.1.1.529 (Omicron).Results: Covaxin induces enhanced SARS-CoV-2 binding antibodies of IgG and IgA responses against both spike (S) and nucleocapsid (N) antigens at M1, M2, M3, M4, M6 and M12 in comparison to M0. Our data also reveal that NAb levels against the ancestral strain (Wuhan, Wild type) are elevated and sustained at M1, M2, M3, M4, M6 and M12 in comparison to M0 and against variant lineages of B.1.617.2 (Delta, India), B.1.617.2.1 (Delta Plus, India), B.1.351 (Beta, SA), B.1.1.7 (Alpha, UK) are elevated at M3, M6 and M12 in comparison to M0. However, NAb levels against B.1.1.529 (Omicron) was consistently below the limit of detection except at M12. CONCLUSION: Thus, Covaxin induces an enhanced humoral immune response, with persistence till at least 12 months post-vaccination against most SARS-CoV-2 variants.

7.
Proc Natl Acad Sci U S A ; 119(32): e2203760119, 2022 Aug 09.
Article in English | MEDLINE | ID: covidwho-1960625

ABSTRACT

The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis, and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity or neutralizing antibody evasion may drive the emergence of these novel variants, studies documenting a critical role for interferon responses in the early control of SARS-CoV-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence SARS-CoV-2 evolution. Here, we compared the potency of 17 different human interferons against multiple viral lineages sampled during the course of the global outbreak, including ancestral and five major variants of concern that include the B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), B.1.617.2 (delta), and B.1.1.529 (omicron) lineages. Our data reveal that relative to ancestral isolates, SARS-CoV-2 variants of concern exhibited increased interferon resistance, suggesting that evasion of innate immunity may be a significant, ongoing driving force for SARS-CoV-2 evolution. These findings have implications for the increased transmissibility and/or lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections.


Subject(s)
Antiviral Agents , COVID-19 , Interferons , SARS-CoV-2 , Antibodies, Neutralizing , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/immunology , COVID-19/prevention & control , COVID-19/transmission , Humans , Interferons/pharmacology , Interferons/therapeutic use , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics
8.
J Med Virol ; 2022 Jul 28.
Article in English | MEDLINE | ID: covidwho-1958809

ABSTRACT

SARS-CoV-2 vaccines have contributed to the control of COVID-19 in some parts of the world. However, the constant emergence of variants of concern (VOCs) challenges the effectiveness of SARS-CoV-2 vaccines over time. In particular, Omicron contains a high number of mutations in the spike (S) protein gene, on which most vaccines were developed. In this study, we quantitated neutralizing antibodies in vaccine recipients at various times postvaccination using S protein-based pseudoviruses derived from wild type (WT) SARS-CoV-2 and five VOCs including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529). We found that two-dose mRNA-1273 and BNT162b2 vaccines elicited robust neutralizing antibodies against WT, Alpha, Beta, Gamma, and Delta, but wanned after 6 months with a faster decline observed for BNT162b2. Both mRNA-1273 and BNT162b2 elicited weak neutralizing antibodies against Omicron. One dose of Ad26.COV2.S vaccine induced weaker neutralizing antibodies against WT and most VOCs than mRNA-1273 and BNT162b2 did but moderate neutralizing antibodies against Delta and Omicron, which lasted for 6 months. These results support current recommendations of the Centers for Disease Control and Prevention for a booster 5 months after full immunization with an mRNA-based vaccine and the use of an mRNA-based vaccine 2 months after Ad26.COV2.S vaccination.

9.
Vaccines (Basel) ; 10(7)2022 Jul 21.
Article in English | MEDLINE | ID: covidwho-1957463

ABSTRACT

The emergence of SARS-CoV-2 Omicron subvariants prompted countries to call for accelerated booster vaccinations to limit disease and transmission. Here, we characterized correlates of protection over time after the second booster or after Omicron BA.1 infection comparing variants of concern (VOCs). Sera from subjects before and two and seven weeks after the second booster or after Omicron infection were examined for the level of Spike receptor-binding-domain (RBD)-specific antibodies. Furthermore, neutralizing antibodies (nABs) were characterized in in vitro neutralization assays comparing the variants of concern Alpha, Beta, Delta, and Omicron BA.1 and BA.2 against the ancestral strain B.1. Here, the second booster resulted in an increase in anti-RBD-IgG-antibodies, remaining nearly constant over time, accompanied by an increase in nABs against B.1 and the VOCs Alpha, Beta, Delta, and Omicron BA.1 and BA.2. However, compared to B.1, the neutralizing capacity against the Omicron subvariants remained low and was limited after the second booster vaccination. This indicates that antibody-mediated protection against infection with this VOC is unlikely, as evidenced by the fact that three individuals of our study cohort became infected with Omicron BA.1 after the second booster. T cell activation was measured by interferon-gamma release assays in a subgroup of subjects and was increased in all subjects tested after the second booster vaccination, correlating with the amount of Spike-specific antibodies. In subjects with Omicron BA.1 breakthrough infection, a significant increase in nABs to all VOCs studied was observed independently of booster vaccinations. Taken together, our data indicate that a second booster or Omicron BA.1 infection mediate a substantial increase in anti-Spike IgG antibodies; however, infection with Omicron BA.1 induced a stronger increase in neutralizing antibodies against the different VOCs.

10.
Int J Mol Sci ; 23(15)2022 Jul 25.
Article in English | MEDLINE | ID: covidwho-1957347

ABSTRACT

Mutations in the spike protein of SARS-CoV-2 can lead to evasion from neutralizing antibodies and affect the efficacy of passive and active immunization strategies. Immunization of mice harboring an entire set of human immunoglobulin variable region gene segments allowed to identify nine neutralizing monoclonal antibodies, which either belong to a cluster of clonally related RBD or NTD binding antibodies. To better understand the genetic barrier to emergence of SARS-CoV-2 variants resistant to these antibodies, escape mutants were selected in cell culture to one antibody from each cluster and a combination of the two antibodies. Three independently derived escape mutants to the RBD antibody harbored mutations in the RBD at the position T478 or S477. These mutations impaired the binding of the RBD antibodies to the spike protein and conferred resistance in a pseudotype neutralization assay. Although the binding of the NTD cluster antibodies were not affected by the RBD mutations, the RBD mutations also reduced the neutralization efficacy of the NTD cluster antibodies. The mutations found in the escape variants to the NTD antibody conferred resistance to the NTD, but not to the RBD cluster antibodies. A variant resistant to both antibodies was more difficult to select and only emerged after longer passages and higher inoculation volumes. VOC carrying the same mutations as the ones identified in the escape variants were also resistant to neutralization. This study further underlines the rapid emergence of escape mutants to neutralizing monoclonal antibodies in cell culture and indicates the need for thorough investigation of escape mutations to select the most potent combination of monoclonal antibodies for clinical use.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Animals , Antibodies, Monoclonal , Antibodies, Viral , Humans , Mice , Mutation , Neutralization Tests , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry
11.
J Food Biochem ; : e14354, 2022 Jul 27.
Article in English | MEDLINE | ID: covidwho-1956771

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several vaccines against SARS-CoV-2 have been approved; however, variants of concern (VOCs) can evade vaccine protection. Therefore, developing small compound drugs that directly block the interaction between the viral spike glycoprotein and ACE2 is urgently needed to provide a complementary or alternative treatment for COVID-19 patients. We developed a viral infection assay to screen a library of approximately 126 small molecules and showed that peimine inhibits VOCs viral infections. In addition, a fluorescence resonance energy transfer (FRET) assay showed that peimine suppresses the interaction of spike and ACE2. Molecular docking analysis revealed that peimine exhibits a higher binding affinity for variant spike proteins and is able to form hydrogen bonds with N501Y in the spike protein. These results suggest that peimine, a compound isolated from Fritillaria, may be a potent inhibitor of SARS-CoV-2 variant infection. PRACTICAL APPLICATIONS: In this study, we identified a naturally derived compound of peimine, a major bioactive alkaloid extracted from Fritillaria, that could inhibit SARS-CoV-2 variants of concern (VOCs) viral infection in 293T/ACE2 and Calu-3 lung cells. In addition, peimine blocks viral entry through interruption of spike and ACE2 interaction. Moreover, molecular docking analysis demonstrates that peimine has a higher binding affinity on N501Y in the spike protein. Furthermore, we found that Fritillaria significantly inhibits SARS-CoV-2 viral infection. These results suggested that peimine and Fritillaria could be a potential functional drug and food for COVID-19 patients.

12.
Int J Biol Sci ; 18(12): 4781-4791, 2022.
Article in English | MEDLINE | ID: covidwho-1954684

ABSTRACT

Rapid development and successful use of vaccines against SARS-CoV-2 might hold the key to curb the ongoing pandemic of COVID-19. Emergence of vaccine-evasive SARS-CoV-2 variants of concern (VOCs) has posed a new challenge to vaccine design and development. One urgent need is to determine what types of variant-specific and bivalent vaccines should be developed. Here, we compared homotypic and heterotypic protection against SARS-CoV-2 infection of hamsters with monovalent and bivalent whole-virion inactivated vaccines derived from representative VOCs. In addition to the ancestral SARS-CoV-2 Wuhan strain, Delta (B.1.617.2; δ) and Theta (P.3; θ) variants were used in vaccine preparation. Additional VOCs including Omicron (B.1.1.529) and Alpha (B.1.1.7) variants were employed in the challenge experiment. Consistent with previous findings, Omicron variant exhibited the highest degree of immune evasion, rendering all different forms of inactivated vaccines substantially less efficacious. Notably, monovalent and bivalent Delta variant-specific inactivated vaccines provided optimal protection against challenge with Delta variant. Yet, some cross-variant protection against Omicron and Alpha variants was seen with all monovalent and bivalent inactivated vaccines tested. Taken together, our findings support the notion that an optimal next-generation inactivated vaccine against SARS-CoV-2 should contain the predominant VOC in circulation. Further investigations are underway to test whether a bivalent vaccine for Delta and Omicron variants can serve this purpose.


Subject(s)
COVID-19 , Viral Vaccines , Animals , COVID-19/prevention & control , COVID-19 Vaccines , Cricetinae , Humans , SARS-CoV-2 , Vaccines, Combined , Vaccines, Inactivated
13.
Front Med (Lausanne) ; 9: 851861, 2022.
Article in English | MEDLINE | ID: covidwho-1952374

ABSTRACT

SARS-CoV-2 variants of concern (VOC) and interest (VOI) present mutations in reference to the original virus, being more transmissible. We implemented a rapid strategy for the screening of SARS-CoV-2 VOC/VOIs using real time RT-PCR and performed monitoring and surveillance of the variants in our region. Consecutive real-time RT-PCRs for detection of the relevant mutations/deletions present in the Spike protein in VOC/VOIs (TaqMan™ SARS-CoV-2 Mutation Panel, Applied Biosystems) were implemented. A total of 6,640 SARS-CoV-2 RNA samples (Cts < 30) from infected individuals in Central Argentina during 2021 were analyzed using different algorithms that were gradually adapted to the changing scenarios of local variant circulation. The strategy developed allowed the early detection and the identification of VOC/VOIs that circulated through the year, with a 100% of concordance with the WGS. The analyses of the samples showed introductions of VOCs Alpha and Gamma in February and March 2021, respectively. Gamma showed an exponential increase, with a peak of detection in July (72%), being responsible of the second wave of COVID19 in Argentina. Since VOC Delta entered into the region, it increased gradually, together with VOI Lambda, replacing VOC Gamma, until being the main variant (84.9%) on November. By December, these variants were replaced by the emergent VOC Omicron in a term of 2 weeks, producing the third wave. We report a useful tool for VOC/VOI detection, capable to quickly and cost-effectively monitor currently recognized variants in resource-limited settings, which allowed to track the recent expansion of Omicron in our region, and contributed to the implementation of public health measures to control the disease spread.

15.
Infection ; 2022 May 20.
Article in English | MEDLINE | ID: covidwho-1943482

ABSTRACT

PURPOSE: Omicron is rapidly spreading as a new SARS-CoV-2 variant of concern (VOC). The question whether this new variant has an impact on SARS-CoV-2 rapid antigen test (RAT) performance is of utmost importance. To obtain an initial estimate regarding differences of RATs in detecting omicron and delta, seven commonly used SARS-CoV-2 RATs from different manufacturers were analysed using cell culture supernatants and clinical specimens. METHODS: For this purpose, cell culture-expanded omicron and delta preparations were serially diluted in Dulbecco's modified Eagle's Medium (DMEM) and the Limit of Detection (LoD) for both VOCs was determined. Additionally, clinical specimens stored in viral transport media or saline (n = 51) were investigated to complement in vitro results with cell culture supernatants. Ct values and RNA concentrations were determined via quantitative reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: The in vitro determination of the LoD showed no obvious differences in detection of omicron and delta for the RATs examined. The LoD in this study was at a dilution level of 1:1,000 (corresponding to 3.0-5.6 × 106 RNA copies/mL) for tests I-V and at a dilution level of 1:100 (corresponding to 3.7-4.9 × 107 RNA copies/mL) for tests VI and VII. Based on clinical specimens, no obvious differences were observed between RAT positivity rates when comparing omicron to delta in this study setting. Overall positivity rates varied between manufacturers with 30-81% for omicron and 42-71% for delta. Test VII was only conducted in vitro with cell culture supernatants for feasibility reasons. In the range of Ct < 23, positivity rates were 50-100% for omicron and 67-93% for delta. CONCLUSION: In this study, RATs from various manufacturers were investigated, which displayed no obvious differences in terms of analytical LoD in vitro and RAT positivity rates based on clinical samples comparing the VOCs omicron and delta. However, differences between tests produced by various manufacturers were detected. In terms of clinical samples, a focus of this study was on specimens with high virus concentrations. Further systematic, clinical and laboratory studies utilizing large datasets are urgently needed to confirm reliable performance in terms of sensitivity and specificity for all individual RATs and SARS-CoV-2 variants.

16.
Microbiol Spectr ; : e0115722, 2022 Jul 12.
Article in English | MEDLINE | ID: covidwho-1950017

ABSTRACT

Large-scale head-to-head assessment of the performance of lateral-flow tests (LFTs) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen is required in the context of the continuous emergence of new viral variants. The aim of this study was to evaluate the performance of 22 rapid LFTs for the detection of SARS-CoV-2 antigens. The clinical performance of 22 LFTs was evaluated in 1,157 samples collected in the Greater Paris area. The 8 best-performing LFTs were further assessed for their ability to detect 4 variants of concern (VOC), including the alpha, beta, delta, and omicron (BA.1) variants. The specificity of SARS-CoV-2 LFTs was generally high (100% for 15 of them) but was insufficient (<75%) for 3 tests. Sensitivity of the LFTs varied from 30.0% to 79.7% compared to nucleic acid amplification testing (NAAT). Using a cycle threshold (CT) cutoff of ≤25, sensitivity of the assays ranged from 59.7% to 100%. The 8 best-performing assays had a sensitivity of ≥80% for the detection of the 4 VOC when the CT was ≤25. Falsely negative SARS-CoV-2 antigen LFT results were observed with omicron, due to the occurrence of low viral loads (CT > 30 in 32% of samples) during the two first days following symptom onset. Several LFTs exhibited satisfactory sensitivity and specificity, whereas a few others yielded an unacceptable proportion of false-positive results and/or lacked sensitivity. The sensitivity of the best-performing assays was not influenced by VOC, including alpha, beta, delta, and omicron variants. The ability of LFTs to detect the omicron variant could be reduced during the first days following symptom onset due to lower viral loads than with other variants. IMPORTANCE The use of lateral-flow tests (LFTs) to detect SARS-CoV-2 has expanded worldwide. LFTs detect SARS-CoV-2 viral antigen and are less sensitive than nucleic acid amplification testing (NAAT). Their performance must be evaluated independently of the manufacturers. Our study assessed the performance of 22 SARS-CoV-2 antigen LFTs in large panels of well-characterized samples. The majority of LFTs tested exhibited satisfactory sensitivity and specificity, while some assays yielded unacceptable proportions of false-positive results, and others lacked sensitivity for samples containing large amounts of virus. The sensitivity of the best-performing assays did not vary according to the VOC, including the alpha, beta, delta, and omicron variants.

17.
Rhythmos ; 17(3):46-52, 2022.
Article in English | Academic Search Complete | ID: covidwho-1940113

ABSTRACT

A recent surge of COVID-19 reinfections has been ascribed to new variants of concern (VOCs) with increased transmissibility, such as the Omicron variant, but also to laxity in compliance with measures of prophylaxis, incomplete or lack of vaccination, the Peltzman effect where people tend to increase their risky behavior when safety measures are mandated, weaker antibody responses after booster immunization in some individuals and/or immunocompromised patients, and increased antigen variability in VOCs. The latter impairs humoral and cellular immunity post-infection rendering COVID-19 convalescents more vulnerable and at risk of re-infection with VOCs. Unfortunately, COVID-19 disease is here to stay demanding observance of measures of prophylaxis, expansion of vaccination programs and continued vigilance;there is still a dire need for the development of durably effective vaccines against SARS-CoV-2 but also against its emerging variants. [ FROM AUTHOR] Copyright of Rhythmos is the property of Evagelismos General Hospital of Athens and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

18.
Comput Methods Programs Biomed ; 224: 107029, 2022 Jul 16.
Article in English | MEDLINE | ID: covidwho-1936219

ABSTRACT

BACKGROUND: In Italy, the administration of COVID-19 vaccines began in late 2020. In the early stages, the number of available doses was limited. To maximize the effectiveness of the vaccine campaign, the national health agency assigned priority access to at-risk individuals, such as health care workers and the elderly. Current vaccination campaign strategies do not take full advantage of the latest mathematical models, which capture many subtle nuances, allowing different territorial situations to be analyzed aiming to make context-specific decisions. OBJECTIVES: The main objective is the definition of an agent-based model using open data and scientific literature to assess and optimize the impact of vaccine campaigns for an Italian region. Specifically, the aim is twofold: (i) estimate the reduction in the number of infections and deaths attributable to vaccines, and (ii) assess the performances of alternative vaccine allocation strategies. METHODS: The COVID-19 Agent-based simulator Covasim has been employed to build an agent-based model by considering the Lombardy region as case study. The model has been tailored by leveraging open data and knowledge from the scientific literature. Dynamic mobility restrictions and the presence of Variant of Concern have been explicitly represented. Free parameters have been calibrated using the grid search methodology. RESULTS: The model mimics the COVID-19 wave that hit Lombardy from September 2020 to April 2021. It suggests that 168,492 cumulative infections 2,990 cumulative deaths have been avoided due to the vaccination campaign in Lombardy from January 1 to April 30, 2021. Without vaccines, the number of deaths would have been 66% greater in the 80-89 age group and 114% greater for those over 90. The best vaccine allocation strategy depends on the goal. To minimize infections, the best policy is related to dose availability. If at least 1/3 of the population can be covered in 4 months, targeting at-risk individuals and the elderly first is recommended; otherwise, the youngest people should be vaccinated first. To minimize overall deaths, priority is best given to at-risk groups and the elderly in all scenarios. CONCLUSIONS: This work proposes a methodological approach that leverages open data and scientific literature to build a model of COVID-19 capable of assessing and optimizing the impact of vaccine campaigns. This methodology can help national institutions to design regional mathematical models that can support pandemic-related decision-making processes.

19.
Vaccines (Basel) ; 10(7)2022 Jul 14.
Article in English | MEDLINE | ID: covidwho-1939050

ABSTRACT

During the COVID-19 pandemic, several SARS-CoV-2 variants of concern (VOC) emerged, bringing with them varying degrees of health and socioeconomic burdens. In particular, the Omicron VOC displayed distinct features of increased transmissibility accompanied by antigenic drift in the spike protein that partially circumvented the ability of pre-existing antibody responses in the global population to neutralize the virus. However, T cell immunity has remained robust throughout all the different VOC transmission waves and has emerged as a critically important correlate of protection against SARS-CoV-2 and its VOCs, in both vaccinated and infected individuals. Therefore, as SARS-CoV-2 VOCs continue to evolve, it is crucial that we characterize the correlates of protection and the potential for immune escape for both B cell and T cell human immunity in the population. Generating the insights necessary to understand T cell immunity, experimentally, for the global human population is at present a critical but a time consuming, expensive, and laborious process. Further, it is not feasible to generate global or universal insights into T cell immunity in an actionable time frame for potential future emerging VOCs. However, using computational means we can expedite and provide early insights into the correlates of T cell protection. In this study, we generated and revealed insights on the T cell epitope landscape for the five main SARS-CoV-2 VOCs observed to date. We demonstrated using a unique AI prediction platform, a significant conservation of presentable T cell epitopes across all mutated peptides for each VOC. This was modeled using the most frequent HLA alleles in the human population and covers the most common HLA haplotypes in the human population. The AI resource generated through this computational study and associated insights may guide the development of T cell vaccines and diagnostics that are even more robust against current and future VOCs, and their emerging subvariants.

20.
J Biomol Struct Dyn ; : 1-13, 2022 Jul 18.
Article in English | MEDLINE | ID: covidwho-1937553

ABSTRACT

The Spike protein's structure of the SARS-CoV-2 provides a unique opportunity to consider perturbations at the atomic level. We used the cryo-electron microscopy structure of the open conformation of the Spike protein to assess the impact of the mutations observed in the variants of concern at the molecular level. Molecular dynamics were subsequently performed with both the wt and the mutated forms to compare the flexibility and variation data for each residue of the three-dimensional fluctuations in the region associated with each alpha carbon. Additionally, protein-protein docking was used to investigate the interaction of each mutated profile with the ACE-2 receptor. After the molecular dynamics, the results show that the mutations increased the stability of the trimeric protein, with greater stability observed in the Gamma variant harboring the 10 characteristic mutations. The results of molecular dynamics, as shown by RMSF demonstrated for the residues that comprise the binding domain receptor (RBD), exhibited a reduction in flexibility, which was more pronounced in the Gamma variant. Finally, protein-protein docking experiments revealed an increase in the number of hydrophobic interactions and hydrogen bonds in the Gamma variant against the ACE-2 receptor, as opposed to the other variants. Taken together, these in silico experiments suggest that the evolution of the mutations favored the increased stability of Spike protein while potentially improving its interaction with the ACE-2 receptor, which in turn may indicate putative structural outcomes of the selection of these mutations in the convergent adaptive evolution as it has been observed for SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

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