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Viral Markers and the Diagnosis of COVID-19

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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "SARS-CoV-2 and COVID-19".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 51818

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Special Issue Editors

Prof. Dr. Bertram Flehmig

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Guest Editor

Childrens Hospital, University of Tübingen, Tübingen, Germany
Interests: hepatitis viruses A, B, C, D, E; influenza viruses; clinical virology diagnostics and vaccine research; SARS-CoV-2

Prof. Dr. Karin Klingel

E-Mail Website
Guest Editor

Cardiopathology, Institute for Pathology and Neuropathology, University Hospital Tuebingen, Tuebingen, Germany
Interests: hepatitis viruses; influenza viruses; human papillomaviruses; COVID-19
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Since the detection of SARS-CoV-2 as the causative agent of COVID-19, enormous scientific activity occurred in the scientific community regarding the development of diagnostic test systems.

Besides the detection of viral RNA by RT-PCR, many of these assay systems have focused on the detection of antibodies in human sera to the SARS-CoV-2 S1 (RBD) protein and the nucleocapsid protein to diagnose this infection. Despite this progress, many open questions have to be answered to define serological markers for the severity of the COVID-19 disease, the long-term follow up of the immune response and the long-term complications of COVID-19.

A new thread for human populations is the newly emerged variants of SARS-CoV-2 having mutations in the Spike S1 protein with the unforeseeable effects of immune escape variants, and variants having the characteristics of higher transmissibility, higher infectivity, higher virulence and pathogenicity, and persistence with longer excretion of the virus.

The measurement of the immune response with various test systems has, to date, mostly been performed semiquantitatively by measuring the S and N proteins. However, in the future, a quantitative determination of the immune response also involving the SARS-CoV-2 M and E proteins and the nonstructural proteins will be desirable, especially in vaccinated persons.

In this Special Issue, manuscripts are welcome that focus on diagnostic test systems, markers for the outcomes of COVID-19, epidemiology, new variants of SARS-CoV-2, transmissibility, and pathogenicity as well as the immune response to the new variants and the immune response after vaccination.

Prof. Dr. Bertram Flehmig
Prof. Dr. Karin Klingel
Guest Editors

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Keywords

SARS-CoV-2
COVID-19
diagnostic test systems
markers epidemiology
new variants
transmissibility
pathogenicity
immune response
vaccination

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Published Papers (12 papers)

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Research

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9 pages, 927 KiB

Open AccessArticle

Long-Term Humoral Immune Response against SARS-CoV-2 after Natural Infection and Subsequent Vaccination According to WHO International Binding Antibody Units (BAU/mL)

by Natalia Ruetalo, Bertram Flehmig, Michael Schindler, Lutz Pridzun, Angelika Haage, Marija Reichenbächer, Thomas Kirchner, Teresa Kirchner, Karin Klingel, Michael B. Ranke and Andrea Normann

Viruses 2021, 13(12), 2336; https://doi.org/10.3390/v13122336 - 23 Nov 2021

Cited by 11 | Viewed by 3037

Abstract

The new WHO reference standard allows for the definition of serum antibodies against various SARS-CoV-2 antigens in terms of binding antibody units (BAU/mL) and thus to compare the results of different ELISA systems. In this study, the concentration of antibodies (ABs) against both the S- and the N-protein of SARS-CoV-2 as well as serum neutralization activity were evaluated in three patients after a mild course of COVID-19. Serum samples were collected frequently during a period of over one year. Furthermore, in two individuals, the effects of an additional vaccination with a mRNA vaccine containing the S1-RBD sequence on these antibodies were examined. After natural infection, the antibodies (IgA, IgG) against the S1-protein remained elevated above the established cut-off to positivity (S-IgA 60 BAU/mL and S-IgG 50 BAU/mL, respectively) for over a year in all patients, while this was not the case for ABs against the N-protein (cut-off N-IgG 40 BAU/mL, N-IgA 256 BAU/mL). Sera from all patients retained the ability to neutralize SARS-CoV-2 for more than a year. Vaccination resulted in a rapid boost of antibodies to S1-protein but, as expected, not to the N-protein. Most likely, the wide use of the WHO reference preparation will be very useful in determining the individual immune status of patients after an infection with SARS-CoV-2 or after vaccination. Full article

(This article belongs to the Special Issue Viral Markers and the Diagnosis of COVID-19)

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11 pages, 672 KiB

Open AccessArticle

Feasibility and Effectiveness Assessment of SARS-CoV-2 Antigenic Tests in Mass Screening of a Pediatric Population and Correlation with the Kinetics of Viral Loads

by Marcello Lanari, Giovanni Battista Biserni, Matteo Pavoni, Eva Caterina Borgatti, Marta Leone, Ilaria Corsini and Tiziana Lazzarotto

Viruses 2021, 13(10), 2071; https://doi.org/10.3390/v13102071 - 14 Oct 2021

Cited by 9 | Viewed by 2527

Abstract

The gold standard for diagnosis of SARS-CoV-2 infection has been nucleic acid amplification tests (NAAT). However, rapid antigen detection kits (Ag-RDTs), may offer advantages over NAAT in mass screening, generating results in minutes, both as laboratory-based test or point-of-care (POC) use for clinicians, at a lower cost. We assessed two different POC Ag-RDTs in mass screening versus NAAT for SARS-CoV-2 in a cohort of pediatric patients admitted to the Pediatric Emergency Unit of IRCCS—Polyclinic of Sant’Orsola, Bologna (from November 2020 to April 2021). All patients were screened with nasopharyngeal swabs for the detection of SARS-CoV-2-RNA and for antigen tests. Results were obtained from 1146 patients. The COVID-19 Ag FIA kit showed a baseline sensitivity of 53.8% (CI 35.4–71.4%), baseline specificity 99.7% (CI 98.4–100%) and overall accuracy of 80% (95% CI 0.68–0.91); the AFIAS COVID-19 Ag kit, baseline sensitivity of 86.4% (CI 75.0–93.9%), baseline specificity 98.3% (CI 97.1–99.1%) and overall accuracy of 95.3% (95% CI 0.92–0.99). In both tests, some samples showed very low viral load and negative Ag-RDT. This disagreement may reflect the positive inability of Ag-RDTs of detecting antigen in late phase of infection. Among all cases with positive molecular test and negative antigen test, none showed viral loads > 10⁶ copies/mL. Finally, we found one false Ag-RDTs negative result (low cycle thresholds; 9 × 10⁵ copies/mL). Our results suggest that both Ag-RDTs showed good performances in detection of high viral load samples, making it a feasible and effective tool for mass screening in actively infected children. Full article

(This article belongs to the Special Issue Viral Markers and the Diagnosis of COVID-19)

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7 pages, 700 KiB

Open AccessCommunication

Development of a Multiplex Tandem PCR (MT-PCR) Assay for the Detection of Emerging SARS-CoV-2 Variants

by Richard Hale, Peter Crowley, Samir Dervisevic, Lindsay Coupland, Penelope R. Cliff, Saidat Ebie, Luke B. Snell, Joel Paul, Cheryl Williams, Paul Randell, Marcus Pond and Keith Stanley

Viruses 2021, 13(10), 2028; https://doi.org/10.3390/v13102028 - 8 Oct 2021

Cited by 17 | Viewed by 4238

Abstract

The emergence of variants of SARS-CoV-2 has created challenges for the testing infrastructure. Although large-scale genome sequencing of SARS-CoV-2 has facilitated hospital and public health responses, access to sequencing facilities globally is variable and turnaround times can be significant, so there is a requirement for rapid and cost-effective alternatives. Applying a polymerase chain reaction (PCR)-based single nucleotide polymorphism (SNP) approach enables rapid (<4 h) identification of SARS-CoV-2 lineages from nucleic acid extracts, through the presence or absence of a panel of defined of genomic polymorphisms. For example, the B.1.1.7 lineage (“UK”, “Alpha”, or “Kent” variant) is characterised by 23 mutations compared to the reference strain, and the most biologically significant of these are found in the S gene. We have developed a SARS-CoV-2 typing assay focused on five positions in the S gene (HV69/70, N501, K417, E484 and P681). This configuration can identify a range of variants, including all the “Variants of Concern” currently designated by national and international public health bodies. The panel has been evaluated using a range of clinical isolates and standardised control materials at four UK hospitals and shows excellent concordance with the known lineage information derived from full sequence analysis. The assay has a turnaround time of about three hours for a set of up to 24 samples and has been utilised to identify emerging variants in a clinical setting. Full article

(This article belongs to the Special Issue Viral Markers and the Diagnosis of COVID-19)

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10 pages, 1571 KiB

Open AccessArticle

A Reverse Transcription Recombinase-Aided Amplification Method for Rapid and Point-of-Care Detection of SARS-CoV-2, including Variants

by Fengyun Li, Ping He, Dongyan Xiong, Yakun Lou, Qiaosheng Pu, Haixia Zhang, Huige Zhang and Junping Yu

Viruses 2021, 13(9), 1875; https://doi.org/10.3390/v13091875 - 19 Sep 2021

Cited by 5 | Viewed by 2771

Abstract

The worldwide pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its emergence of variants needs rapid and point-of-care testing methods for a broad diagnosis. The regular RT-qPCR is time-consuming and limited in central laboratories, so a broad and large-scale screening requirement calls for rapid and in situ methods. In this regard, a reverse transcription recombinase-aided amplification (RT-RAA) is proposed here for the rapid and point-of-care detection of SARS-CoV-2. A set of highly conserved primers and probes targeting more than 98% of SARS-CoV-2 strains, including currently circulating variants (four variants of concerns (VOCs) and three variants of interest (VOIs)), was used in this study. With the preferred primers, the RT-RAA assay showed a 100% specificity to SARS-CoV-2 from eight other respiratory RNA viruses. Moreover, the assay here is of a high sensitivity and 0.48 copies/μL can be detected within 25 min at a constant temperature (42 °C), which can be realized on portable equipment. Furthermore, the RT-RAA assay demonstrated its high agreement for the detection of SARS-CoV-2 in clinical specimens compared with RT-qPCR. The rapid, simple and point-of-care RT-RAA method is expected to be an appealing detection tool to detect SARS-CoV-2, including variants, in clinical diagnostic applications. Full article

(This article belongs to the Special Issue Viral Markers and the Diagnosis of COVID-19)

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9 pages, 1282 KiB

Open AccessArticle

Efficacy of Unsupervised Self-Collected Mid-Turbinate FLOQSwabs for the Diagnosis of Coronavirus Disease 2019 (COVID-19)

by Egildo Luca D’Andrea, Alessia Maria Cossu, Marianna Scrima, Vincenzo Messina, Pasquale Iuliano, Felice Di Perna, Marco Pizza, Fabio Pizza, Nicola Coppola, Luca Rinaldi, Anna Maria Bellizzi, Chiara Pelosi, Carmen Cocca, Angelo Frieri, Fabio Lo Calzo, Giovambattista Capasso, Santina Castriciano, Paolo Maggi, Alessandra Fucci and Michele Caraglia

Viruses 2021, 13(8), 1663; https://doi.org/10.3390/v13081663 - 22 Aug 2021

Cited by 4 | Viewed by 3850

Abstract

Context: The Global Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic has resulted in explosive patterns of transmission in most countries. Nasopharyngeal swabs were the specimen’s collection tools recommended for the diagnosis of SARS-CoV-2 infection, and for monitoring infection outbreaks in communities. Our objective was to report the quality and efficacy of unsupervised self-collected mid turbinate “dry FLOQSwabs” (MT FLOQSwabs) (56380CS01, Copan). There were 111 specimens collected for the study: 36 by health care personnel, from themselves, to verify the quality and efficacy of mid-turbinate swabs; 75 to compare and assess the diagnostic performance, among health care personnel, of nasopharyngeal swabs and self-collected mid-turbinate FLOQSwabs. A collection of 51 specimens was enrolled to define the efficacy of the Testami program (validation). Our analyses demonstrate that self-collected mid-turbinate dry swabs ensure an accuracy of 97.3%, as compared to the standard nasopharyngeal swabs collected by health care workers. Furthermore, the mid-turbinate FLOQSwabs can be stored without medium for six days at room temperature without affecting the molecular diagnosis of the SARS-CoV-2 virus infection. Self-collection of diagnostic specimens at home could offer an avenue to increase testing availability for SARS-CoV-2 infection without asking people to travel to a clinic or a laboratory, thus reducing people’s exposure to infection. Our findings demonstrate that unsupervised self-collection swabs, transported dry, are sensitive, practical and easy-to-use tools and should be considered for diagnosis of SARS-COV-2 and coronavirus disease 2019 (COVID-19) surveillance. Full article

(This article belongs to the Special Issue Viral Markers and the Diagnosis of COVID-19)

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15 pages, 2556 KiB

Open AccessArticle

Cell Population Data and Serum Polyclonal Immunoglobulin Free Light Chains in the Assessment of COVID-19 Severity

by Milena Małecka-Giełdowska, Maria Fołta, Agnieszka Wiśniewska, Emilia Czyżewska and Olga Ciepiela

Viruses 2021, 13(7), 1381; https://doi.org/10.3390/v13071381 - 15 Jul 2021

Cited by 6 | Viewed by 3018

Abstract

Distinguishing between severe and nonsevere COVID-19 to ensure adequate healthcare quality and efficiency is a challenge for the healthcare system. The aim of this study was to assess the usefulness of CBC parameters together with analysis of FLC serum concentration in risk stratification of COVID-19. Materials and methods: CBC was analyzed in 735 COVID ICU, COVID non-ICU, and non-COVID ICU cases. FLC concentration was analyzed in 133 of them. Results: COVID ICU had neutrophils and lymphocytes with the greatest size, granularity, and nucleic acid content. Significant differences in concentrations of κ and λ FLCs were shown between COVID ICU and COVID non-ICU. However, no difference was found in the κ/λ ratio between these groups, and the ratio stayed within the reference value, which indicates the presence of polyclonal FLCs. FLC κ measurement has significant power to distinguish between severe COVID-19 and nonsevere COVID-19 (AUC = 0.7669), with a sensitivity of 86.67% and specificity of 93.33%. The κ coefficients’ odds ratio of 3.0401 was estimated. Conclusion: It can be concluded that the results obtained from the measure of free light immunoglobulin concentration in serum are useful in distinguishing between severe and nonsevere COVID-19. Full article

(This article belongs to the Special Issue Viral Markers and the Diagnosis of COVID-19)

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17 pages, 958 KiB

Open AccessArticle

Long-Term Longitudinal Evaluation of Six Commercial Immunoassays for the Detection of IgM and IgG Antibodies against SARS CoV-2

by Iulia Nedelcu, Raluca Jipa, Roxana Vasilescu, Cristian Băicuș, Costin-Ioan Popescu, Eliza Manea, Laura E. Stoichițoiu, Larisa Pinte, Anca Damalan, Oana Simulescu, Irina Stoica, Madalina Stoica and Adriana Hristea

Viruses 2021, 13(7), 1244; https://doi.org/10.3390/v13071244 - 26 Jun 2021

Cited by 3 | Viewed by 2615

Abstract

The number of serological assays for SARS-CoV-2 has skyrocketed in the past year. Concerns have been raised regarding their performance characteristics, depending on the disease severity and the time of the analysis post-symptom onset (PSO). Thus, independent validations using an unbiased sample selection are required for meaningful serology data interpretation. We aimed to assess the clinical performance of six commercially available assays, the seroconversion, and the dynamics of the humoral response to SARS-CoV-2 infection. The study included 528 serum samples from 156 patients with follow-up visits up to six months PSO and 161 serum samples from healthy people. The IgG/total antibodies positive percentage increased and remained above 95% after six months when chemiluminescent immunoassay (CLIA) IgG antiS1/S2 and electro-chemiluminescent assay (ECLIA) total antiNP were used. At early time points PSO, chemiluminescent microparticle immunoassay (CMIA) IgM antiS achieved the best sensitivity. IgM and IgG appear simultaneously in most circumstances, and when performed in parallel the sensitivity increases. The severe and the moderate clinical forms were significantly associated with higher seropositivity percentage and antibody levels. High specificity was found in all evaluated assays, but the sensitivity was variable depending on the time PSO, severity of disease, detection method and targeted antigen. Full article

(This article belongs to the Special Issue Viral Markers and the Diagnosis of COVID-19)

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12 pages, 2111 KiB

Open AccessArticle

Fast Detection of SARS-CoV-2 RNA Directly from Respiratory Samples Using a Loop-Mediated Isothermal Amplification (LAMP) Test

by Olympia E. Anastasiou, Caroline Holtkamp, Miriam Schäfer, Frieda Schön, Anna Maria Eis-Hübinger and Andi Krumbholz

Viruses 2021, 13(5), 801; https://doi.org/10.3390/v13050801 - 29 Apr 2021

Cited by 13 | Viewed by 3533

Abstract

The availability of simple SARS-CoV-2 detection methods is crucial to contain the COVID-19 pandemic. This study examined whether a commercial LAMP assay can reliably detect SARS-CoV-2 genomes directly in respiratory samples without having to extract nucleic acids (NA) beforehand. Nasopharyngeal swabs (NPS, n = 220) were tested by real-time reverse transcription (RT)-PCR and with the LAMP assay. For RT-PCR, NA were investigated. For LAMP, NA from 26 NPS in viral transport medium (VTM) were tested. The other 194 NPS were analyzed directly without prior NA extraction (140 samples in VTM; 54 dry swab samples stirred in phosphate buffered saline). Ten NPS were tested directly by LAMP using a sous-vide cooking unit. The isothermal assay demonstrated excellent specificity (100%) but moderate sensitivity (68.8%), with a positive predictive value of 1 and a negative predictive value of 0.65 for direct testing of NPS in VTM. The use of dry swabs, even without NA extraction, improved the analytical sensitivity; up to 6% of samples showed signs of inhibition. LAMP could be performed successfully with a sous-vide cooking unit. This technique is very fast, requires little laboratory resources, and can replace rapid antigen tests or verify reactive rapid tests on-site. Full article

(This article belongs to the Special Issue Viral Markers and the Diagnosis of COVID-19)

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12 pages, 2338 KiB

Open AccessArticle

Development and Clinical Evaluation of an Immunochromatography-Based Rapid Antigen Test (GenBody™ COVAG025) for COVID-19 Diagnosis

by Doyeong Kim, Jihoo Lee, Jyotiranjan Bal, Seul Ki Seo, Chom-Kyu Chong, Jong Ho Lee and Hyun Park

Viruses 2021, 13(5), 796; https://doi.org/10.3390/v13050796 - 29 Apr 2021

Cited by 20 | Viewed by 7222

Abstract

Antigen tests for SARS-CoV-2 diagnosis are simpler and faster than their molecular counterparts. Clinical validation of such tests is a prerequisite before their field applications. We developed and clinically evaluated an immunochromatographic immunoassay, GenBody™ COVAG025, for the rapid detection of SARS-CoV-2 nucleocapsid (NP) antigen in two different clinical studies. Retrospectively, 130 residual nasopharyngeal swabs transferred in viral transport medium (VTM), pre-examined for COVID-19 through emergency use authorization (EUA)-approved real-time RT-PCR assay and tested with GenBody™ COVAG025, revealed a sensitivity and specificity of 90.00% (27/30; 95% CI: 73.47% to 97.89%) and 98.00% (98/100; 95% CI: 92.96% to 99.76%), respectively, fulfilling WHO guidelines. Subsequently, the prospective examination of 200 symptomatic and asymptomatic nasopharyngeal swabs, collected on site and tested with GenBody™ COVAG025 and EUA-approved real-time RT-PCR assay simultaneously, revealed a significantly higher sensitivity and specificity of 94.00% (94/100; 95% CI: 87.40% to 97.77%) and 100.00% (100/100; 95% CI: 96.38% to 100.00%), respectively. Clinical sensitivity and specificity were significantly high for samples with Ct values ≤ 30 as well as within 3 days of symptom onset, justifying its dependency on the viral load. Thus, it is assumed this can help with the accurate diagnosis and timely isolation and treatment of patients with COVID-19, contributing to better control of the global pandemic. Full article

(This article belongs to the Special Issue Viral Markers and the Diagnosis of COVID-19)

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20 pages, 4809 KiB

Open AccessArticle

Accessible LAMP-Enabled Rapid Test (ALERT) for Detecting SARS-CoV-2

by Ali Bektaş, Michael F. Covington, Guy Aidelberg, Anibal Arce, Tamara Matute, Isaac Núñez, Julia Walsh, David Boutboul, Constance Delaugerre, Ariel B. Lindner, Fernán Federici and Anitha D. Jayaprakash

Viruses 2021, 13(5), 742; https://doi.org/10.3390/v13050742 - 23 Apr 2021

Cited by 21 | Viewed by 6087

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has highlighted bottlenecks in large-scale, frequent testing of populations for infections. Polymerase chain reaction (PCR)-based diagnostic tests are expensive, reliant on centralized labs, can take days to deliver results, and are prone to backlogs and supply shortages. Antigen tests that bind and detect the surface proteins of a virus are rapid and scalable but suffer from high false negative rates. To address this problem, an inexpensive, simple, and robust 60-minute do-it-yourself (DIY) workflow to detect viral RNA from nasal swabs or saliva with high sensitivity (0.1 to 2 viral particles/μL) and specificity (>97% true negative rate) utilizing reverse transcription loop-mediated isothermal amplification (RT-LAMP) was developed. ALERT (Accessible LAMP-Enabled Rapid Test) incorporates the following features: (1) increased shelf-life and ambient temperature storage, compared to liquid reaction mixes, by using wax layers to isolate enzymes from other reagents; (2) improved specificity compared to other LAMP end-point reporting methods, by using sequence-specific QUASR (quenching of unincorporated amplification signal reporters); (3) increased sensitivity, compared to methods without purification through use of a magnetic wand to enable pipette-free concentration of sample RNA and cell debris removal; (4) quality control with a nasopharyngeal-specific mRNA target; and (5) co-detection of other respiratory viruses, such as influenza B, by multiplexing QUASR-modified RT-LAMP primer sets. The flexible nature of the ALERT workflow allows easy, at-home and point-of-care testing for individuals and higher-throughput processing for labs and hospitals. With minimal effort, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific primer sets can be swapped out for other targets to repurpose ALERT to detect other viruses, microorganisms, or nucleic acid-based markers. Full article

(This article belongs to the Special Issue Viral Markers and the Diagnosis of COVID-19)

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11 pages, 578 KiB

Open AccessReview

Utility of Routine Laboratory Biomarkers to Detect COVID-19: A Systematic Review and Meta-Analysis

by Jana Suklan, James Cheaveau, Sarah Hill, Samuel G. Urwin, Kile Green, Amanda Winter, Timothy Hicks, Anna E. Boath, Ashleigh Kernohan, D. Ashley Price, A. Joy Allen, Eoin Moloney and Sara Graziadio

Viruses 2021, 13(5), 803; https://doi.org/10.3390/v13050803 - 30 Apr 2021

Cited by 6 | Viewed by 3106

Abstract

No routine laboratory biomarkers perform well enough in diagnosing COVID-19 in isolation for them to be used as a standalone diagnostic test or to help clinicians prioritize patients for treatment. Instead, other diagnostic tests are needed. The aim of this work was to statistically summarise routine laboratory biomarker measurements in COVID-19-positive and -negative patients to inform future work. A systematic literature review and meta-analysis were performed. The search included names of commonly used, routine laboratory tests in the UK NHS, and focused on research papers reporting laboratory results of patients diagnosed with COVID-19. A random effects meta-analysis of the standardized mean difference between COVID-19-positive and -negative groups was conducted for each biomarker. When comparing reported laboratory biomarker results, we identified decreased white blood cell, neutrophil, lymphocyte, eosinophil, and platelet counts; while lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase were elevated in COVID-19-positive compared to COVID-19-negative patients. Differences were identified across a number of routine laboratory biomarkers between COVID-19-positive and -negative patients. Further research is required to identify whether routine laboratory biomarkers can be used in the development of a clinical scoring system to aid with triage of patients. Full article

(This article belongs to the Special Issue Viral Markers and the Diagnosis of COVID-19)

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15 pages, 2158 KiB

Open AccessBrief Report

Detection of SARS-CoV-2 Derived Small RNAs and Changes in Circulating Small RNAs Associated with COVID-19

by Claudius Grehl, Christoph Schultheiß, Katrin Hoffmann, Mascha Binder, Thomas Altmann, Ivo Grosse and Markus Kuhlmann

Viruses 2021, 13(8), 1593; https://doi.org/10.3390/v13081593 - 11 Aug 2021

Cited by 24 | Viewed by 4922

Abstract

Cleavage of double-stranded RNA is described as an evolutionary conserved host defense mechanism against viral infection. Small RNAs are the product and triggers of post transcriptional gene silencing events. Up until now, the relevance of this mechanism for SARS-CoV-2-directed immune responses remains elusive. Herein, we used high throughput sequencing to profile the plasma of active and convalescent COVID-19 patients for the presence of small circulating RNAs. The existence of SARS-CoV-2 derived small RNAs in plasma samples of mild and severe COVID-19 cases is described. Clusters of high siRNA abundance were discovered, homologous to the nsp2 3′-end and nsp4 virus sequence. Four virus-derived small RNA sequences have the size of human miRNAs, and a target search revealed candidate genes associated with ageusia and long COVID symptoms. These virus-derived small RNAs were detectable also after recovery from the disease. The additional analysis of circulating human miRNAs revealed differentially abundant miRNAs, discriminating mild from severe cases. A total of 29 miRNAs were reduced or absent in severe cases. Several of these are associated with JAK-STAT response and cytokine storm. Full article

(This article belongs to the Special Issue Viral Markers and the Diagnosis of COVID-19)

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