Viruses

Editorial

10 pages, 299 KiB

Open AccessEditorial

SARS-CoV-2 Variants: A Synopsis of In Vitro Efficacy Data of Convalescent Plasma, Currently Marketed Vaccines, and Monoclonal Antibodies

by Daniele Focosi, Marco Tuccori, Andreina Baj and Fabrizio Maggi

Viruses 2021, 13(7), 1211; https://doi.org/10.3390/v13071211 - 23 Jun 2021

Cited by 31 | Viewed by 5606

Abstract

We summarize here in vitro evidences of efficacy for convalescent plasma, currently approved vaccines and monoclonal antibodies against SARS-CoV-2 variants of concern (VOC: B.1.1.7, B.1.351, P.1, and B.1.617.2), variants of interest (VOI: B.1.427/B.1.429, P.2, B.1.525, P.3, B.1.526, and B.1.671.1), and other strains (B.1.1.298 [...] Read more.

We summarize here in vitro evidences of efficacy for convalescent plasma, currently approved vaccines and monoclonal antibodies against SARS-CoV-2 variants of concern (VOC: B.1.1.7, B.1.351, P.1, and B.1.617.2), variants of interest (VOI: B.1.427/B.1.429, P.2, B.1.525, P.3, B.1.526, and B.1.671.1), and other strains (B.1.1.298 and B.1.258delta). While waiting from real world clinical efficacy, these data provide guidance for the treating physician. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

Research

Jump to: Editorial, Review, Other

13 pages, 1447 KiB

Open AccessArticle

In Vitro Diagnostic Assay to Detect SARS-CoV-2-Neutralizing Antibody in Patient Sera Using Engineered ACE-2 Mini-Protein

by Bruna Andersen Pereira de Jesus, Anderson Albino Gomes, Alex E. Clark, Tayse Andrade Rodrigues, Melissa Ledgerwood-Lee, Westley Van Zant, Howard Brickner, Meiqiao Wang, David L. Blum, Maria B. Cassera, Aaron F. Carlin, Eliah S. Aronoff-Spencer, Gustavo Felippe da Silva, Maria de Lourdes Borba Magalhães and Partha Ray

Viruses 2022, 14(12), 2823; https://doi.org/10.3390/v14122823 - 18 Dec 2022

Cited by 1 | Viewed by 3367

Abstract

The recent development and mass administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines allowed for disease control, reducing hospitalizations and mortality. Most of these vaccines target the SARS-CoV-2 Spike (S) protein antigens, culminating with the production of neutralizing antibodies (NAbs) that [...] Read more.

The recent development and mass administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines allowed for disease control, reducing hospitalizations and mortality. Most of these vaccines target the SARS-CoV-2 Spike (S) protein antigens, culminating with the production of neutralizing antibodies (NAbs) that disrupt the attachment of the virus to ACE2 receptors on the host cells. However, several studies demonstrated that the NAbs typically rise within a few weeks after vaccination but quickly reduce months later. Thus, multiple booster administration is recommended, leading to vaccination hesitancy in many populations. Detecting serum anti-SARS-CoV-2 NAbs can instruct patients and healthcare providers on correct booster strategies. Several in vitro diagnostics kits are available; however, their high cost impairs the mass NAbs diagnostic testing. Recently, we engineered an ACE2 mimetic that interacts with the Receptor Binding Domain (RBD) of the SARS-2 S protein. Here we present the use of this engineered mini-protein (p-deface2 mut) to develop a detection assay to measure NAbs in patient sera using a competitive ELISA assay. Serum samples from twenty-one patients were tested. Nine samples (42.8%) tested positive, and twelve (57.1%) tested negative for neutralizing sera. The data correlated with the result from the standard commercial assay that uses human ACE2 protein. This confirmed that p-deface2 mut could replace human ACE2 in ELISA assays. Using bacterially expressed p-deface2 mut protein is cost-effective and may allow mass SARS-CoV-2 NAbs detection, especially in low-income countries where economical diagnostic testing is crucial. Such information will help providers decide when a booster is required, reducing risks of reinfection and preventing the administration before it is medically necessary. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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Graphical abstract

13 pages, 5162 KiB

Open AccessArticle

Comparison of a Prototype SARS-CoV-2 Lateral Flow IMMUNOASSAY with the BinaxNOW^TM COVID-19 Antigen CARD

by Haydon J. Hill, Timsy Uppal, Derrick Hau, Sujata G. Pandit, Jose Arias-Umana, Abigail J. Foster, Andrew Gorzalski, Kathryn J. Pflughoeft, Amanda R. Burnham-Marusich, Dana E. Reed, Marcellene A. Gates-Hollingsworth, Lynette Gumbleton, Subhash C. Verma and David P. AuCoin

Viruses 2022, 14(12), 2609; https://doi.org/10.3390/v14122609 - 23 Nov 2022

Viewed by 3187

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the COVID-19 pandemic. From the onset of the pandemic, rapid antigen tests have quickly proved themselves to be an accurate and accessible diagnostic platform. The initial (and still most commonly used [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the COVID-19 pandemic. From the onset of the pandemic, rapid antigen tests have quickly proved themselves to be an accurate and accessible diagnostic platform. The initial (and still most commonly used antigen tests) for COVID-19 diagnosis were constructed using monoclonal antibodies (mAbs) specific to severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid protein (NP). These mAbs are able to bind SARS-CoV-2 NP due to high homology between the two viruses. However, since first being identified in 2019, SARS-CoV-2 has continuously mutated, and a multitude of variants have appeared. These mutations have an elevated risk of leading to possible diagnostic escape when using tests produced with SARS-CoV-derived mAbs. Here, we established a library of 18 mAbs specific to SARS-CoV-2 NP and used two of these mAbs (1CV7 and 1CV14) to generate a prototype antigen-detection lateral flow immunoassay (LFI). A side-by-side analysis of the 1CV7/1CV14 LFI and the commercially available BinaxNOW^TM COVID-19 Antigen CARD was performed. Results indicated the 1CV7/1CV14 LFI outperformed the BinaxNOW^TM test in the detection of BA.2, BA.2.12.1, and BA.5 Omicron sub-variants when testing remnant RT-PCR positive patient nasopharyngeal swabs diluted in viral transport media. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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10 pages, 2661 KiB

Open AccessArticle

Comparison and Harmonization of Different Semi-Automated and Automated qRT-PCR Assays in the Assessment of SARS-CoV-2

by Sascha Dierks, Karin Thiele, Wolfgang Bohne, Raimond Lugert, Michael Weig, Uwe Groß, Nicolas von Ahsen, Julie Schanz, Andreas Fischer and Moritz Schnelle

Viruses 2022, 14(10), 2239; https://doi.org/10.3390/v14102239 - 12 Oct 2022

Cited by 2 | Viewed by 2032

Abstract

In SARS-CoV-2 diagnostics, cycle threshold (Ct) values from qRT-PCRs semi-quantitatively estimate a patient’s viral load. However, relevant analytical differences between qRT-PCR assays are often neglected. This study was designed (i) to identify such differences between five commonly used assays and (ii) to demonstrate [...] Read more.

In SARS-CoV-2 diagnostics, cycle threshold (Ct) values from qRT-PCRs semi-quantitatively estimate a patient’s viral load. However, relevant analytical differences between qRT-PCR assays are often neglected. This study was designed (i) to identify such differences between five commonly used assays and (ii) to demonstrate a straightforward strategy to harmonize them. QRT-PCRs for SARS-CoV-2 were carried out in 85 oropharyngeal swab samples using three fully automated (Alinity m, cobas^®6800 and GeneXpert) and two semi-automated (genesig^® and RIDA^®GENE) assays. Qualitative results (positive/negative) showed excellent comparability between the fully automated assays, but not between the Alinity m and semi-automated methods. Ct values significantly varied between all the methods, with the median values ranging from 22.76 (Alinity m) to 30.89 (RIDA^®GENE) and 31.50 (genesig^®), indicating the lowest sensitivity for semi-automated methods. Passing–Bablok analysis further revealed systemic biases. Assay-specific viral load concentration calculations—based on generated individual standard curves—resulted in much better comparability between the assays. Applying these calculations, significant differences were no longer detectable. This study highlights relevant analytical differences between SARS-CoV-2 qRT-PCR assays, leading to divergent decisions about the mandatory isolation of infected individuals. Secondly, we propose a strategy to harmonize qRT-PCR assays to achieve better comparability. Our findings are of particular interest for laboratories utilizing different assays. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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17 pages, 3934 KiB

Open AccessArticle

Nasal Mucosa Exploited by SARS-CoV-2 for Replicating and Shedding during Reinfection

by Heng Li, Xin Zhao, Jing Li, Huiwen Zheng, Yurong Zhao, Jinling Yang, Jingxian Zhou, Fengmei Yang, Yanli Chen, Yuanyuan Zuo, Qingrun Lai, Haiting Long, Yanyan Li, Weihua Jin, Haijing Shi and Longding Liu

Viruses 2022, 14(8), 1608; https://doi.org/10.3390/v14081608 - 23 Jul 2022

Cited by 2 | Viewed by 1900

Abstract

Reinfection risk is a great concern with regard to the COVID-19 pandemic because a large proportion of the population has recovered from an initial infection, and previous reports found that primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques without viral presence [...] Read more.

Reinfection risk is a great concern with regard to the COVID-19 pandemic because a large proportion of the population has recovered from an initial infection, and previous reports found that primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques without viral presence and pathological injury; however, a high possibility for reinfection at the current stage of the pandemic has been proven. We found the reinfection of SARS-CoV-2 in Syrian hamsters with continuous viral shedding in the upper respiratory tracts and few injuries in the lung, and nasal mucosa was exploited by SARS-CoV-2 for replication and shedding during reinfection; meanwhile, no viral replication or enhanced damage was observed in the lower respiratory tracts. Consistent with the mild phenotype in the reinfection, increases in mRNA levels in cytokines and chemokines in the nasal mucosa but only slight increases in the lung were found. Notably, the high levels of neutralizing antibodies in serum could not prevent reinfection in hamsters but may play roles in benefitting the lung recovery and symptom relief of COVID-19. In summary, Syrian hamsters could be reinfected by SARS-CoV-2 with mild symptoms but with obvious viral shedding and replication, and both convalescent and vaccinated patients should be wary of the transmission and reinfection of SARS-CoV-2. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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19 pages, 2229 KiB

Open AccessArticle

Proper Selection of In Vitro Cell Model Affects the Characterization of the Neutralizing Antibody Response against SARS-CoV-2

by Elena Criscuolo, Benedetta Giuliani, Davide Ferrari, Roberto Ferrarese, Roberta A. Diotti, Massimo Clementi, Nicasio Mancini and Nicola Clementi

Viruses 2022, 14(6), 1232; https://doi.org/10.3390/v14061232 - 7 Jun 2022

Cited by 3 | Viewed by 3023

Abstract

(1) Background: Our aim is the evaluation of the neutralizing activity of BNT162b2 mRNA vaccine-induced antibodies in different in vitro cellular models, as this still represents one of the surrogates of protection against SARS-CoV-2 viral variants. (2) Methods: The entry mechanisms of SARS-CoV-2 [...] Read more.

(1) Background: Our aim is the evaluation of the neutralizing activity of BNT162b2 mRNA vaccine-induced antibodies in different in vitro cellular models, as this still represents one of the surrogates of protection against SARS-CoV-2 viral variants. (2) Methods: The entry mechanisms of SARS-CoV-2 in three cell lines (Vero E6, Vero E6/TMPRSS2 and Calu-3) were evaluated with both pseudoviruses and whole virus particles. The neutralizing capability of sera collected from vaccinated subjects was characterized through cytopathic effects and Real-Time RT PCR. (3) Results: In contrast to Vero E6 and Vero E6/TMPRSS2, Calu-3 allowed the evaluation of both viral entry mechanisms, resembling what occurs during natural infection. The choice of an appropriate cellular model can decisively influence the determination of the neutralizing activity of antibodies against SARS-CoV-2 variants. Indeed, the lack of correlation between neutralizing data in Calu-3 and Vero E6 demonstrated that testing the antibody inhibitory activity by using a single cell model possibly results in an inaccurate characterization. (4) Conclusions: Cellular systems allowing only one of the two viral entry pathways may not fully reflect the neutralizing activity of vaccine-induced antibodies moving increasingly further away from possible correlates of protection from SARS-CoV-2 infection. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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11 pages, 3439 KiB

Open AccessArticle

Vaccination with BNT162b2 and ChAdOx1 nCoV-19 Induces Cross-Reactive Anti-RBD IgG against SARS-CoV-2 Variants including Omicron

by Daniela Gerges, Sebastian Kapps, Esperanza Hernández-Carralero, Raimundo Freire, Monika Aiad, Sophie Schmidt, Wolfgang Winnicki, Thomas Reiter, Sahra Pajenda, Alice Schmidt, Gere Sunder-Plassmann and Ludwig Wagner

Viruses 2022, 14(6), 1181; https://doi.org/10.3390/v14061181 - 28 May 2022

Cited by 3 | Viewed by 2617

Abstract

SARS-CoV-2 variants of concern (VOCs) have caused a significant increase in infections worldwide. Despite high vaccination rates in industrialized countries, the fourth VOC, Omicron, has outpaced the Delta variant and is causing breakthrough infections in individuals with two booster vaccinations. While the magnitude [...] Read more.

SARS-CoV-2 variants of concern (VOCs) have caused a significant increase in infections worldwide. Despite high vaccination rates in industrialized countries, the fourth VOC, Omicron, has outpaced the Delta variant and is causing breakthrough infections in individuals with two booster vaccinations. While the magnitude of morbidity and lethality is lower in Omicron, the infection rate and global spread are rapid. Using a specific IgG multipanel-ELISA with the spike protein’s receptor-binding domain (RBD) from recombinant Alpha, Gamma, Delta, and Omicron variants, sera from health-care workers from the Medical University of Vienna were tested pre-pandemic and post-vaccination (BNT162b2; ChAdOx1 nCoV-19). The cohort was continuously monitored by SARS-CoV-2 testing and commercial nucleocapsid IgG ELISA. RBD IgG ELISA showed significantly lower reactivity against the Omicron-RBD compared to the Alpha variant in all individuals (p < 0.001). IgG levels were independent of sex, but were significantly higher in BNT162b2 recipients <45 years of age for Alpha, Gamma, and Delta (p < 0.001; p = 0.040; p = 0.004, respectively). Pre-pandemic cross-reactive anti-Omicron IgG was detected in 31 individuals and was increased 8.78-fold after vaccination, regardless of vaccine type. The low anti-RBD Omicron IgG level could explain the breakthrough infections and their presence could also contribute to a milder COVID-19 course by cross-reactivity and broadening the adaptive immunity. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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18 pages, 6912 KiB

Open AccessArticle

Palmitoylethanolamide (PEA) Inhibits SARS-CoV-2 Entry by Interacting with S Protein and ACE-2 Receptor

by Rossella Fonnesu, Venkata Bala Sai Chaitanya Thunuguntla, Ganesh Kumar Veeramachaneni, Jayakumar Singh Bondili, Veronica La Rocca, Carolina Filipponi, Pietro Giorgio Spezia, Maria Sidoti, Erika Plicanti, Paola Quaranta, Giulia Freer, Mauro Pistello, Michael Lee Mathai and Michele Lai

Viruses 2022, 14(5), 1080; https://doi.org/10.3390/v14051080 - 17 May 2022

Cited by 23 | Viewed by 5933

Abstract

Lipids play a crucial role in the entry and egress of viruses, regardless of whether they are naked or enveloped. Recent evidence shows that lipid involvement in viral infection goes much further. During replication, many viruses rearrange internal lipid membranes to create niches [...] Read more.

Lipids play a crucial role in the entry and egress of viruses, regardless of whether they are naked or enveloped. Recent evidence shows that lipid involvement in viral infection goes much further. During replication, many viruses rearrange internal lipid membranes to create niches where they replicate and assemble. Because of the close connection between lipids and inflammation, the derangement of lipid metabolism also results in the production of inflammatory stimuli. Due to its pivotal function in the viral life cycle, lipid metabolism has become an area of intense research to understand how viruses seize lipids and to design antiviral drugs targeting lipid pathways. Palmitoylethanolamide (PEA) is a lipid-derived peroxisome proliferator-activated receptor-α (PPAR-α) agonist that also counteracts SARS-CoV-2 entry and its replication. Our work highlights for the first time the antiviral potency of PEA against SARS-CoV-2, exerting its activity by two different mechanisms. First, its binding to the SARS-CoV-2 S protein causes a drop in viral infection of ~70%. We show that this activity is specific for SARS-CoV-2, as it does not prevent infection by VSV or HSV-2, other enveloped viruses that use different glycoproteins and entry receptors to mediate their entry. Second, we show that in infected Huh-7 cells, treatment with PEA dismantles lipid droplets, preventing the usage of these vesicular bodies by SARS-CoV-2 as a source of energy and protection against innate cellular defenses. This is not surprising since PEA activates PPAR-α, a transcription factor that, once activated, generates a cascade of events that leads to the disruption of fatty acid droplets, thereby bringing about lipid droplet degradation through β-oxidation. In conclusion, the present work demonstrates a novel mechanism of action for PEA as a direct and indirect antiviral agent against SARS-CoV-2. This evidence reinforces the notion that treatment with this compound might significantly impact the course of COVID-19. Indeed, considering that the protective effects of PEA in COVID-19 are the current objectives of two clinical trials (NCT04619706 and NCT04568876) and given the relative lack of toxicity of PEA in humans, further preclinical and clinical tests will be needed to fully consider PEA as a promising adjuvant therapy in the current COVID-19 pandemic or against emerging RNA viruses that share the same route of replication as coronaviruses. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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10 pages, 2218 KiB

Open AccessArticle

Epipharyngeal Abrasive Therapy (EAT) Has Potential as a Novel Method for Long COVID Treatment

by Kazuaki Imai, Takafumi Yamano, Soichiro Nishi, Ryushiro Nishi, Tatsuro Nishi, Hiroaki Tanaka, Toshiyuki Tsunoda, Shohei Yoshimoto, Ayaki Tanaka, Kenji Hiromatsu, Senji Shirasawa, Takashi Nakagawa and Kensuke Nishi

Viruses 2022, 14(5), 907; https://doi.org/10.3390/v14050907 - 27 Apr 2022

Cited by 14 | Viewed by 23613

Abstract

COVID-19 often causes sequelae after initial recovery, referred to collectively as long COVID. Long COVID is considered to be caused by the persistence of chronic inflammation after acute COVID-19 infection. We found that all long COVID patients had residual inflammation in the epipharynx, [...] Read more.

COVID-19 often causes sequelae after initial recovery, referred to collectively as long COVID. Long COVID is considered to be caused by the persistence of chronic inflammation after acute COVID-19 infection. We found that all long COVID patients had residual inflammation in the epipharynx, an important site of coronavirus replication, and some long COVID symptoms are similar to those associated with chronic epipharyngitis. Epipharyngeal abrasive therapy (EAT) is a treatment for chronic epipharyngitis in Japan that involves applying zinc chloride as an anti-inflammatory agent to the epipharyngeal mucosa. In this study, we evaluated the efficacy of EAT for the treatment of long COVID. The subjects in this study were 58 patients with long COVID who were treated with EAT in the outpatient department once a week for one month (mean age = 38.4 ± 12.9 years). The intensities of fatigue, headache, and attention disorder, which are reported as frequent symptoms of long COVID, were assessed before and after EAT using the visual analog scale (VAS). EAT reduced inflammation in the epipharynx and significantly improved the intensity of fatigue, headache, and attention disorder, which may be related to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These results suggest that EAT has potential as a novel method for long COVID treatment. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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12 pages, 1304 KiB

Open AccessArticle

Clinical Picture and Risk Factors of Severe Respiratory Symptoms in COVID-19 in Children

by Anna Mania, Kamil Faltin, Katarzyna Mazur-Melewska, Paweł Małecki, Katarzyna Jończyk-Potoczna, Karol Lubarski, Zuzanna Lewandowska, Agnieszka Cwalińska, Jowita Rosada-Kurasińska, Alicja Bartkowska-Śniatkowska and Magdalena Figlerowicz

Viruses 2021, 13(12), 2366; https://doi.org/10.3390/v13122366 - 25 Nov 2021

Cited by 13 | Viewed by 3395

Abstract

Children with COVID-19 develop moderate symptoms in most cases. Thus, a proportion of children requires hospital admission. The study aimed to assess the history, clinical and laboratory parameters in children with COVID-19 concerning the severity of respiratory symptoms. The study included 332 children [...] Read more.

Children with COVID-19 develop moderate symptoms in most cases. Thus, a proportion of children requires hospital admission. The study aimed to assess the history, clinical and laboratory parameters in children with COVID-19 concerning the severity of respiratory symptoms. The study included 332 children (median age 57 months) with COVID-19. History data, clinical findings, laboratory parameters, treatment, and outcome, were evaluated. Children were compared in the groups that varied in the severity of symptoms of respiratory tract involvement. Children who required oxygen therapy represented 8.73%, and intensive care 1.5% of the whole cohort. Comorbidities were present in 126 patients (37.95%). Factors increasing the risk of oxygen therapy included comorbidities (odds ratio (OR) = 92.39; 95% confidence interval (95% CI) = (4.19; 2036.90); p < 0.00001), dyspnea (OR = 45.81; 95% CI (4.05; 518.21); p < 0.00001), auscultation abnormalities (OR = 34.33; 95% CI (2.59; 454.64); p < 0.00001). Lactate dehydrogenase (LDH) > 280 IU/L and creatinine kinase > 192 IU/L were parameters with a good area under the curve (0.804-LDH) and a positive predictive value (42.9%-CK). The clinical course of COVID-19 was mild to moderate in most patients. Children with comorbidities, dyspnea, or abnormalities on auscultation are at risk of oxygen therapy. Laboratory parameters potentially useful in patients evaluated for the severe course are LDH > 200 IU/L and CK > 192 IU/L. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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8 pages, 1216 KiB

Open AccessCommunication

Antibody-Mediated Neutralization of Authentic SARS-CoV-2 B.1.617 Variants Harboring L452R and T478K/E484Q

by Alexander Wilhelm, Tuna Toptan, Christiane Pallas, Timo Wolf, Udo Goetsch, Rene Gottschalk, Maria J. G. T. Vehreschild, Sandra Ciesek and Marek Widera

Viruses 2021, 13(9), 1693; https://doi.org/10.3390/v13091693 - 26 Aug 2021

Cited by 67 | Viewed by 3882

Abstract

The capacity of convalescent and vaccine-elicited sera and monoclonal antibodies (mAb) to neutralize SARS-CoV-2 variants is currently of high relevance to assess the protection against infections. We performed a cell culture-based neutralization assay focusing on authentic SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.427/B.1.429 [...] Read more.

The capacity of convalescent and vaccine-elicited sera and monoclonal antibodies (mAb) to neutralize SARS-CoV-2 variants is currently of high relevance to assess the protection against infections. We performed a cell culture-based neutralization assay focusing on authentic SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.427/B.1.429 (Epsilon), all harboring the spike substitution L452R. We found that authentic SARS-CoV-2 variants harboring L452R had reduced susceptibility to convalescent and vaccine-elicited sera and mAbs. Compared to B.1, Kappa and Delta showed a reduced neutralization by convalescent sera by a factor of 8.00 and 5.33, respectively, which constitutes a 2-fold greater reduction when compared to Epsilon. BNT2b2 and mRNA1273 vaccine-elicited sera were less effective against Kappa, Delta, and Epsilon compared to B.1. No difference was observed between Kappa and Delta towards vaccine-elicited sera, whereas convalescent sera were 1.51-fold less effective against Delta, respectively. Both B.1.617 variants Kappa (+E484Q) and Delta (+T478K) were less susceptible to either casirivimab or imdevimab. In conclusion, in contrast to the parallel circulating Kappa variant, the neutralization efficiency of convalescent and vaccine-elicited sera against Delta was moderately reduced. Delta was resistant to imdevimab, which, however, might be circumvented by combination therapy with casirivimab together. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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11 pages, 405 KiB

Open AccessArticle

Characteristics and Clinical Outcomes of 116,539 Patients Hospitalized with COVID-19—Poland, March–December 2020

by Mariusz Gujski, Mateusz Jankowski, Daniel Rabczenko, Paweł Goryński and Grzegorz Juszczyk

Viruses 2021, 13(8), 1458; https://doi.org/10.3390/v13081458 - 27 Jul 2021

Cited by 21 | Viewed by 3273

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19). This study aimed to characterize patients hospitalized with COVID-19 in Poland between March and December 2020, as well as to identify factors associated with COVID 19–related risk of in-hospital death. [...] Read more.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19). This study aimed to characterize patients hospitalized with COVID-19 in Poland between March and December 2020, as well as to identify factors associated with COVID 19–related risk of in-hospital death. This retrospective analysis was based on data from the hospital discharge reports on COVID-19 patients hospitalized in Poland between March and December 2020. A total of 116,539 discharge reports on patients hospitalized with COVID-19 were analyzed. Among patients with COVID-19, 21,490 (18.4%) died during hospitalization. Patients over 60 years of age (OR = 7.74; 95%CI: 7.37–8.12; p < 0.001), men (OR = 1.42; 95%CI: 1.38–1.47; p < 0.001) as well as those with cardiovascular diseases (OR = 1.51; 95%CI: 1.46–1.56; p < 0.001) or disease of the genitourinary system (OR = 1.39; 95%CI: 1.31–1.47; p < 0.001) had much higher odds of COVID 19–related risk of in-hospital death. The presence of at least one comorbidity more than doubled the COVID 19–related risk of in-hospital death (OR = 2.23; 95%CI: 2.14–2.32; p < 0.01). The following predictors of admission to ICU were found in multivariable analysis: age over 60 years (OR: 2.03; 95%CI: 1.90–2.16), male sex (OR: 1.79; 95%CI: 1.69–1.89), presence of at least one cardiovascular disease (OR: 1.26; 95%CI: 1.19–1.34), presence of at least one endocrine, nutritional and metabolic disease (OR: 1.17; 95%CI: 1.07–1.28). Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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Review

Jump to: Editorial, Research, Other

15 pages, 1210 KiB

Open AccessReview

Use of Antiandrogens as Therapeutic Agents in COVID-19 Patients

by Efstathios S. Giotis, Emine Cil and Greg N. Brooke

Viruses 2022, 14(12), 2728; https://doi.org/10.3390/v14122728 - 7 Dec 2022

Cited by 3 | Viewed by 2841

Abstract

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), is estimated to have caused over 6.5 million deaths worldwide. The emergence of fast-evolving SARS-CoV-2 variants of concern alongside increased transmissibility and/or virulence, as well as immune and vaccine escape capabilities, [...] Read more.

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), is estimated to have caused over 6.5 million deaths worldwide. The emergence of fast-evolving SARS-CoV-2 variants of concern alongside increased transmissibility and/or virulence, as well as immune and vaccine escape capabilities, highlight the urgent need for more effective antivirals to combat the disease in the long run along with regularly updated vaccine boosters. One of the early risk factors identified during the COVID-19 pandemic was that men are more likely to become infected by the virus, more likely to develop severe disease and exhibit a higher likelihood of hospitalisation and mortality rates compared to women. An association exists between SARS-CoV-2 infectiveness and disease severity with sex steroid hormones and, in particular, androgens. Several studies underlined the importance of the androgen-mediated regulation of the host protease TMPRSS2 and the cell entry protein ACE2, as well as the key role of these factors in the entry of the virus into target cells. In this context, modulating androgen signalling is a promising strategy to block viral infection, and antiandrogens could be used as a preventative measure at the pre- or early hospitalisation stage of COVID-19 disease. Different antiandrogens, including commercial drugs used to treat metastatic castration-sensitive prostate cancer and other conditions, have been tested as antivirals with varying success. In this review, we summarise the most recent updates concerning the use of antiandrogens as prophylactic and therapeutic options for COVID-19. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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12 pages, 601 KiB

Open AccessReview

A Critical Analysis of the Use of Cilgavimab plus Tixagevimab Monoclonal Antibody Cocktail (Evusheld™) for COVID-19 Prophylaxis and Treatment

by Daniele Focosi and Arturo Casadevall

Viruses 2022, 14(9), 1999; https://doi.org/10.3390/v14091999 - 9 Sep 2022

Cited by 44 | Viewed by 12410

Abstract

Evusheld^® (tixagevimab + cilgavimab; AZD7442) was the first anti-Spike monoclonal antibody (mAb) cocktail designed not only for treatment but also with pre-exposure prophylaxis in mind. The immunoglobulins were engineered for prolonged half-life by modifying the Fc fragment, thus creating a long-acting antibody [...] Read more.

Evusheld^® (tixagevimab + cilgavimab; AZD7442) was the first anti-Spike monoclonal antibody (mAb) cocktail designed not only for treatment but also with pre-exposure prophylaxis in mind. The immunoglobulins were engineered for prolonged half-life by modifying the Fc fragment, thus creating a long-acting antibody (LAAB). We review here preclinical development, baseline and treatment-emergent resistance, clinical efficacy from registration trials, and real-world post-marketing evidence. The combination was initially approved for pre-exposure prophylaxis at the time of the SARS-CoV-2 Delta VOC wave based on a trial conducted in unvaccinated subjects when the Alpha VOC was dominant. Another trial also conducted at the time of the Alpha VOC wave proved efficacy as early treatment in unvaccinated patients and led to authorization at the time of the BA.4/5 VOC wave. Tixagevimab was ineffective against any Omicron sublineage, so cilgavimab has so far been the ingredient which has made a difference. Antibody monotherapy has a high risk of selecting for immune escape variants in immunocompromised patients with high viral loads, which nowadays represent the main therapeutic indication for antibody therapies. Among Omicron sublineages, cilgavimab was ineffective against BA.1, recovered efficacy against BA.2 and BA.2.12.1, but lost efficacy again against BA.4/BA.5 and BA.2.75. Our analysis indicated that Evusheld^® has been used during the Omicron VOC phase without robust clinical data of efficacy against this variant and suggested that several regulatory decisions regarding its use lacked consistency. There is an urgent need for new randomized controlled trials in vaccinated, immunocompromised subjects, using COVID-19 convalescent plasma as a control arm. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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10 pages, 406 KiB

Open AccessReview

Strategies That Facilitate Extraction-Free SARS-CoV-2 Nucleic Acid Amplification Tests

by David J. Delgado-Diaz, Dhanasekaran Sakthivel, Hanh H. T. Nguyen, Khashayar Farrokzhad, William Hopper, Charles A. Narh and Jack S. Richards

Viruses 2022, 14(6), 1311; https://doi.org/10.3390/v14061311 - 15 Jun 2022

Cited by 10 | Viewed by 4251

Abstract

The COVID-19 pandemic has resulted in an unprecedented global demand for in vitro diagnostic reagents. Supply shortages and hoarding have impacted testing capacity which has led to inefficient COVID-19 case identification and transmission control, predominantly in developing countries. Traditionally, RNA extraction is a [...] Read more.

The COVID-19 pandemic has resulted in an unprecedented global demand for in vitro diagnostic reagents. Supply shortages and hoarding have impacted testing capacity which has led to inefficient COVID-19 case identification and transmission control, predominantly in developing countries. Traditionally, RNA extraction is a prerequisite for conducting SARS-CoV-2 nucleic acid amplification tests (NAAT); however, simplified methods of sample processing have been successful at bypassing typical nucleic acid extraction steps, enabling extraction-free SARS-CoV-2 NAAT workflows. These methods involve chemical and physical approaches that are inexpensive and easily accessible alternatives to overcome extraction kit supply shortages, while offering acceptable test performance. Here we provide an overview of three main sample preparation strategies that have been shown to facilitate extraction-free SARS-CoV-2 NAATs. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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13 pages, 976 KiB

Open AccessReview

Recombination in Coronaviruses, with a Focus on SARS-CoV-2

by Daniele Focosi and Fabrizio Maggi

Viruses 2022, 14(6), 1239; https://doi.org/10.3390/v14061239 - 7 Jun 2022

Cited by 73 | Viewed by 4551

Abstract

Recombination is a common evolutionary tool for RNA viruses, and coronaviruses are no exception. We review here the evidence for recombination in SARS-CoV-2 and reconcile nomenclature for recombinants, discuss their origin and fitness, and speculate how recombinants could make a difference in the [...] Read more.

Recombination is a common evolutionary tool for RNA viruses, and coronaviruses are no exception. We review here the evidence for recombination in SARS-CoV-2 and reconcile nomenclature for recombinants, discuss their origin and fitness, and speculate how recombinants could make a difference in the future of the COVID-19 pandemics. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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17 pages, 2054 KiB

Open AccessReview

Gastrointestinal Involvement in SARS-CoV-2 Infection

by Tsung-Hsien Chen, Ming-Tse Hsu, Ming-Yang Lee and Chu-Kuang Chou

Viruses 2022, 14(6), 1188; https://doi.org/10.3390/v14061188 - 30 May 2022

Cited by 27 | Viewed by 6756

Abstract

SARS-CoV-2 has evolved into a virus that primarily results in mild or asymptomatic disease, making its transmission more challenging to control. In addition to the respiratory tract, SARS-CoV-2 also infects the digestive tract. Some gastrointestinal symptoms occur with or before respiratory symptoms in [...] Read more.

SARS-CoV-2 has evolved into a virus that primarily results in mild or asymptomatic disease, making its transmission more challenging to control. In addition to the respiratory tract, SARS-CoV-2 also infects the digestive tract. Some gastrointestinal symptoms occur with or before respiratory symptoms in patients with COVID-19. Respiratory infections are known to cause intestinal immune impairment and gastrointestinal symptoms. When the intestine is inflamed, cytokines affect the lung immune response and inflammation through blood circulation. The gastrointestinal microbiome may be a modifiable factor in determining the risk of SARS-CoV-2 infection and disease severity. The development of oral SARS-CoV-2 vaccine candidates and the maintenance of gut microbiota profiles may contribute to the early control of COVID-19 outbreaks. To this end, this review summarizes information on the gastrointestinal complications caused by SARS-CoV-2, SARS-CoV-2 infection, the gastrointestinal–lung axis immune response, potential control strategies for oral vaccine candidates and maintaining intestinal microbiota homeostasis. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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15 pages, 518 KiB

Open AccessReview

Mucosal Vaccines, Sterilizing Immunity, and the Future of SARS-CoV-2 Virulence

by Daniele Focosi, Fabrizio Maggi and Arturo Casadevall

Viruses 2022, 14(2), 187; https://doi.org/10.3390/v14020187 - 19 Jan 2022

Cited by 58 | Viewed by 12981

Abstract

Sterilizing immunity after vaccination is desirable to prevent the spread of infection from vaccinees, which can be especially dangerous in hospital settings while managing frail patients. Sterilizing immunity requires neutralizing antibodies at the site of infection, which for respiratory viruses such as SARS-CoV-2 [...] Read more.

Sterilizing immunity after vaccination is desirable to prevent the spread of infection from vaccinees, which can be especially dangerous in hospital settings while managing frail patients. Sterilizing immunity requires neutralizing antibodies at the site of infection, which for respiratory viruses such as SARS-CoV-2 implies the occurrence of neutralizing IgA in mucosal secretions. Systemic vaccination by intramuscular delivery induces no or low-titer neutralizing IgA against vaccine antigens. Mucosal priming or boosting, is needed to provide sterilizing immunity. On the other side of the coin, sterilizing immunity, by zeroing interhuman transmission, could confine SARS-CoV-2 in animal reservoirs, preventing spontaneous attenuation of virulence in humans as presumably happened with the endemic coronaviruses. We review here the pros and cons of each vaccination strategy, the current mucosal SARS-CoV-2 vaccines under development, and their implications for public health. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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12 pages, 494 KiB

Open AccessReview

COVID-19 Convalescent Plasma Is More than Neutralizing Antibodies: A Narrative Review of Potential Beneficial and Detrimental Co-Factors

by Daniele Focosi, Massimo Franchini, Liise-anne Pirofski, Thierry Burnouf, DeLisa Fairweather, Michael J. Joyner and Arturo Casadevall

Viruses 2021, 13(8), 1594; https://doi.org/10.3390/v13081594 - 11 Aug 2021

Cited by 31 | Viewed by 4190

Abstract

COVID-19 convalescent plasma (CCP) is currently under investigation for both treatment and post-exposure prophylaxis. The active component of CCP mediating improved outcome is commonly reported as specific antibodies, particularly neutralizing antibodies, with clinical efficacy characterized according to the level or antibody affinity. In [...] Read more.

COVID-19 convalescent plasma (CCP) is currently under investigation for both treatment and post-exposure prophylaxis. The active component of CCP mediating improved outcome is commonly reported as specific antibodies, particularly neutralizing antibodies, with clinical efficacy characterized according to the level or antibody affinity. In this review, we highlight the potential role of additional factors in CCP that can be either beneficial (e.g., AT-III, alpha-1 AT, ACE2+ extracellular vesicles) or detrimental (e.g., anti-ADAMTS13, anti-MDA5 or anti-interferon autoantibodies, pro-coagulant extracellular vesicles). Variations in these factors in CCP may contribute to varied outcomes in patients with COVID-19 and undergoing CCP therapy. We advise careful, retrospective investigation of such co-factors in randomized clinical trials that use fresh frozen plasma in control arms. Nevertheless, it might be difficult to establish a causal link between these components and outcome, given that CCP is generally safe and neutralizing antibody effects may predominate. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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11 pages, 1408 KiB

Open AccessReview

Convalescent Plasma for Pregnant Women with COVID-19: A Systematic Literature Review

by Massimo Franchini, Federico Prefumo, Gianpaolo Grisolia, Valentino Bergamini, Claudia Glingani, Marlene Pisello, Francesca Presti and Marco Zaffanello

Viruses 2021, 13(7), 1194; https://doi.org/10.3390/v13071194 - 22 Jun 2021

Cited by 9 | Viewed by 3046

Abstract

The treatment of COVID-19 is particularly critical in pregnant women, considering the potential teratogenic effects of antiviral agents and the immune-depression related with pregnancy. The aim of this review is to systematically examine the current evidence on the clinical use of convalescent plasma [...] Read more.

The treatment of COVID-19 is particularly critical in pregnant women, considering the potential teratogenic effects of antiviral agents and the immune-depression related with pregnancy. The aim of this review is to systematically examine the current evidence on the clinical use of convalescent plasma during pregnancy. The electronic databases Medline PubMed Advanced Search Builder, Scopus, Web Of Science and Google Scholar were searched (until 1 January 2021). Inclusion criteria were pregnant women with COVID-19 (or SARS-CoV-2 infection), in whom convalescent plasma (or hyperimmune plasma) was used as treatment. We searched clinical trial registries (censored 5 January 2021) for eligible studies under way. After elimination of duplications, the initial search yielded 79 potentially relevant records, of which 67 were subsequently excluded. The 12 remaining records were case reports involving 12 pregnancies. Six of the mothers were reported to be well, two were reported to have preeclampsia, and in one case each the maternal outcome was described as survival, clinical improvement, discharged with oxygen and rehabilitation. With regard to the neonates, two were declared to be well, four had transient morbidity, two were critically ill and one died; normal ongoing pregnancies, but no post-delivery information, were reported for the remaining three cases. Clinical trials under way or planned to investigate the use of convalescent plasma for COVID-19 during pregnancy are lacking. This is the first systematic review of the literature regarding the treatment of COVID-19 in pregnancy. The published literature data seem to indicate that convalescent plasma administered to pregnant women with severe COVID-19 provides benefits for both the mother and the fetus. The quality of the available studies is, however, very limited since they are all case reports and thus suffer from relevant reporting bias. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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13 pages, 429 KiB

Open AccessReview

Convalescent Plasma Transfusion for the Treatment of COVID-19 in Adults: A Global Perspective

by Saly Kanj and Basem Al-Omari

Viruses 2021, 13(5), 849; https://doi.org/10.3390/v13050849 - 7 May 2021

Cited by 7 | Viewed by 3343

Abstract

More than one year into the novel coronavirus disease 2019 (COVID-19) pandemic, healthcare systems across the world continue to be overwhelmed with soaring daily cases. The treatment spectrum primarily includes ventilation support augmented with repurposed drugs and/or convalescent plasma transfusion (CPT) from recovered [...] Read more.

More than one year into the novel coronavirus disease 2019 (COVID-19) pandemic, healthcare systems across the world continue to be overwhelmed with soaring daily cases. The treatment spectrum primarily includes ventilation support augmented with repurposed drugs and/or convalescent plasma transfusion (CPT) from recovered COVID-19 patients. Despite vaccine variants being recently developed and administered in several countries, challenges in global supply chain logistics limit their timely availability to the wider world population, particularly in developing countries. Given the measured success of conventional CPT in treating several infections over the past decade, recent studies have reported its effectiveness in decreasing the duration and severity of COVID-19 symptoms. In this review, we conduct a literature search of published studies investigating the use of CPT to treat COVID-19 patients from January 2020 to January 2021. The literature search identified 181 records of which 39 were included in this review. A random-effects model was used to aggregate data across studies, and mortality rates of 17 vs. 32% were estimated for the CPT and control patient groups, respectively, with an odds ratio (OR) of 0.49. The findings indicate that CPT shows potential in reducing the severity and duration of COVID-19 symptoms. However, early intervention (preferably within 3 days), recruitment of donors, and plasma potency introduce major challenges for its scaled-up implementation. Given the low number of existing randomized clinical trials (RCTs, four with a total of 319 patients), unanticipated risks to CPT recipients are highlighted and discussed. Nevertheless, CPT remains a promising COVID-19 therapeutic option that merits internationally coordinated RCTs to achieve a scientific risk–benefit consensus. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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8 pages, 1460 KiB

Open AccessBrief Report

SARS-CoV-2 N-Antigen Quantification in Respiratory Tract, Plasma and Urine: Kinetics and Association with RT-qPCR Results

by Delphine Parraud, Anne-Lise Maucotel, Maude Bouscambert, Florence Morfin, Laurent Bitker, Christian Chidiac, Nathalie De Castro, Emilie Frobert, Alexandre Gaymard and on behalf of the French COVID Cohort Study Group

Viruses 2023, 15(5), 1041; https://doi.org/10.3390/v15051041 - 24 Apr 2023

Cited by 1 | Viewed by 1271

Abstract

Qualitative SARS-CoV-2 antigen assays based on immunochromatography are useful for mass diagnosis of COVID-19, even though their sensitivity is poor in comparison with RT-PCR assays. In addition, quantitative assays could improve antigenic test performance and allow testing with different specimens. Using quantitative assays, [...] Read more.

Qualitative SARS-CoV-2 antigen assays based on immunochromatography are useful for mass diagnosis of COVID-19, even though their sensitivity is poor in comparison with RT-PCR assays. In addition, quantitative assays could improve antigenic test performance and allow testing with different specimens. Using quantitative assays, we tested 26 patients for viral RNA and N-antigen in respiratory samples, plasma and urine. This allowed us to compare the kinetics between the three compartments and to compare RNA and antigen concentrations in each. Our results showed the presence of N-antigen in respiratory (15/15, 100%), plasma (26/59, 44%) and urine (14/54, 28.9%) samples, whereas RNA was only detected in respiratory (15/15, 100%) and plasma (12/60, 20%) samples. We detected N-antigen in urine and plasma samples until the day 9 and day 13 post-inclusion, respectively. The antigen concentration was found to correlate with RNA levels in respiratory (p < 0.001) and plasma samples (p < 0.001). Finally, urinary antigen levels correlated with plasma levels (p < 0.001). Urine N-antigen detection could be part of the strategy for the late diagnosis and prognostic evaluation of COVID-19, given the ease and painlessness of sampling and the duration of antigen excretion in this biological compartment. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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7 pages, 263 KiB

Open AccessPerspective

Molnupiravir: From Hope to Epic Fail?

by Daniele Focosi

Viruses 2022, 14(11), 2560; https://doi.org/10.3390/v14112560 - 19 Nov 2022

Cited by 20 | Viewed by 6401

Abstract

Molnupiravir has been the first oral antiviral authorized for COVID-19 outpatients, reporting extraordinary sales and preserved in vitro efficacy against Omicron sublineages so far. However, it has recently been associated with very poor clinical efficacy, the risk of creating novel SARS-CoV-2 variants of [...] Read more.

Molnupiravir has been the first oral antiviral authorized for COVID-19 outpatients, reporting extraordinary sales and preserved in vitro efficacy against Omicron sublineages so far. However, it has recently been associated with very poor clinical efficacy, the risk of creating novel SARS-CoV-2 variants of concern, and long-term risk for mutagenicity in humans. The latter two are severe concerns, especially in the indicated population, i.e., long-replicating, immunodeficient patients. We conclude that, at this point, alternative antivirals should be preferred over molnupiravir. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

8 pages, 788 KiB

Open AccessBrief Report

Detection of Torquetenovirus and Redondovirus DNA in Saliva Samples from SARS-CoV-2-Positive and -Negative Subjects

by Pietro Giorgio Spezia, Andreina Baj, Francesca Drago Ferrante, Sara Boutahar, Lorenzo Azzi, Angelo Genoni, Daniela Dalla Gasperina, Federica Novazzi, Francesco Dentali, Daniele Focosi and Fabrizio Maggi

Viruses 2022, 14(11), 2482; https://doi.org/10.3390/v14112482 - 9 Nov 2022

Cited by 8 | Viewed by 1855

Abstract

Objectives: Torquetenovirus (TTV) and Redondovirus (ReDoV) are the most prevalent viruses found in the human respiratory virome in viral metagenomics studies. A large-scale epidemiological study was performed to investigate their prevalence and loads in saliva samples according to SARS-CoV-2 status. Methods: Saliva samples [...] Read more.

Objectives: Torquetenovirus (TTV) and Redondovirus (ReDoV) are the most prevalent viruses found in the human respiratory virome in viral metagenomics studies. A large-scale epidemiological study was performed to investigate their prevalence and loads in saliva samples according to SARS-CoV-2 status. Methods: Saliva samples from 448 individuals (73% SARS-CoV-2 negative and 27% SARS-CoV-2 positive) aged 23–88 years were tested. SARS-CoV-2 and TTV were determined in saliva by specific qualitative and quantitative real-time PCRs, respectively. A sub-cohort of 377 subjects was additionally tested for the presence and load of ReDoV in saliva, and a different sub-cohort of 120 subjects for which paired saliva and plasma samples were available was tested for TTV and ReDoV viremia at the same timepoints as saliva. Results: TTV in saliva was 72% prevalent in the entire cohort, at a mean DNA load of 4.6 log copies/mL, with no difference regardless of SARS-CoV-2 status. ReDoV was found in saliva from 61% of the entire cohort and was more prevalent in the SARS-CoV-2-negative subgroup (65% vs. 52%, respectively). In saliva, the total mean load of ReDoV was very similar to the one of TTV, with a value of 4.4 log copies/mL. The mean viral loads in subjects infected with a single virus, namely, those infected with TTV or ReDoV alone, was lower than in dually infected samples, and Tukey’s multiple-comparison test showed that ReDoV single-infected samples resulted in the only true outlier (p = 0.004). Differently from TTV, ReDoV was not detected in any blood samples. Conclusions: This study establishes the prevalence and mean value of TTV and ReDoV in saliva samples and demonstrates the existence of differences between these two components of the human virome. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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9 pages, 1236 KiB

Open AccessBrief Report

OraSure InteliSwab^™ Rapid Antigen Test Performance with the SARS-CoV-2 Variants of Concern—Alpha, Beta, Gamma, Delta, and Omicron

by Zachary A. Weishampel, Janean Young, Mark Fischl, Robert J. Fischer, Irene Owusu Donkor, Jade C. Riopelle, Jonathan E. Schulz, Julia R. Port, Taylor A. Saturday, Neeltje van Doremalen, Jody D. Berry, Vincent J. Munster and Claude Kwe Yinda

Viruses 2022, 14(3), 543; https://doi.org/10.3390/v14030543 - 6 Mar 2022

Cited by 18 | Viewed by 3105

Abstract

The emergence of SARS-CoV-2 in the human population and the resulting COVID-19 pandemic have led to the development of various diagnostic tests. The OraSure InteliSwab^™ COVID-19 Rapid Test is a recently developed and FDA emergency use-authorized rapid antigen-detecting test that functions as [...] Read more.

The emergence of SARS-CoV-2 in the human population and the resulting COVID-19 pandemic have led to the development of various diagnostic tests. The OraSure InteliSwab^™ COVID-19 Rapid Test is a recently developed and FDA emergency use-authorized rapid antigen-detecting test that functions as a lateral flow device targeting the nucleocapsid protein. Due to SARS-CoV-2 evolution, there is a need to evaluate the sensitivity of rapid antigen-detecting tests for new variants, especially variants of concern such as Omicron. In this study, the sensitivity of the OraSure InteliSwab^™ Test was investigated using cultured strains of the known variants of concern (VOCs, Alpha, Beta, Gamma, Delta, and Omicron) and the ancestral lineage (lineage A). Based on dilution series in cell culture medium, an approximate limit of detection for each variant was determined. The OraSure InteliSwab^™ Test showed an overall comparable performance using recombinant nucleocapsid protein and different cultured variants, with recorded limits of detection ranging between 3.77 × 10⁵ and 9.13 × 10⁵ RNA copies/mL. Finally, the sensitivity was evaluated using oropharyngeal swabs from Syrian golden hamsters inoculated with the six VOCs. Ultimately, the OraSure InteliSwab^™ COVID-19 Rapid Test showed no decrease in sensitivity between the ancestral SARS-CoV-2 strain and any VOCs including Omicron. Full article

(This article belongs to the Special Issue SARS-CoV-2 inside and outside the Respiratory Tract: From Diagnostics to Therapies)

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