2023

Jump to: 2022, 2021, 2020

12 pages, 275 KiB

Open AccessArticle

The Detection of SARS-CoV-2 Antibodies in an Exposed Human Population Is Biased by the Immunoassay Used: Implications in Serosurveillance

by Francisco Llorente, Elisa Pérez-Ramírez, Mayte Pérez-Olmeda, Desirée Dafouz-Bustos, Jovita Fernández-Pinero, Mercedes Martínez-Cortés and Miguel Ángel Jiménez-Clavero

Pathogens 2023, 12(11), 1360; https://doi.org/10.3390/pathogens12111360 - 16 Nov 2023

Viewed by 833

Abstract

The presence of SARS-CoV-2 antibodies was examined over 7 months in a population of essential service workers exposed during the first epidemic wave in Madrid (Spain). Results obtained with different serological assays were compared. Firstly, serum samples obtained in April 2020 were analyzed [...] Read more.

The presence of SARS-CoV-2 antibodies was examined over 7 months in a population of essential service workers exposed during the first epidemic wave in Madrid (Spain). Results obtained with different serological assays were compared. Firstly, serum samples obtained in April 2020 were analyzed using eleven SARS-CoV-2 antibody detection methods, including seven ELISAs, two CLIAs and two LFAs. While all of the ELISA tests and the Roche eCLIA method showed good performance, it was poorer for the Abbott CLIA and LFA tests. Sera from 115 workers with serologically positive results in April were collected 2 and 7 months after the first sampling and were analyzed using five of the tests previously assessed. The results showed that while some ELISA tests consistently detected the presence of anti-SARS-CoV-2 antibodies even 7 months after first detection, other methods, such as the Abbott CLIA test, showed an important reduction in sensitivity for these mature antibodies. The sensitivity increased after establishing new cut-off values, calculated taking into account both recent and old infections, suggesting that an adjustment of assay parameters may improve the detection of individuals exposed to the infection. Full article

13 pages, 2573 KiB

Open AccessBrief Report

Oral Epithelial Cells Expressing Low or Undetectable Levels of Human Angiotensin-Converting Enzyme 2 Are Susceptible to SARS-CoV-2 Virus Infection In Vitro

by Laith Ebraham, Chuan Xu, Annie Wang, Cyril Hernandez, Nicholas Siclari, Divino Rajah, Lewins Walter, Salvatore A. E. Marras, Sanjay Tyagi, Daniel H. Fine, Carlo Amorin Daep and Theresa L. Chang

Pathogens 2023, 12(6), 843; https://doi.org/10.3390/pathogens12060843 - 19 Jun 2023

Cited by 2 | Viewed by 1297

Abstract

The oral cavity is thought to be one of the portals for SARS-CoV-2 entry, although there is limited evidence of active oral infection by SARS-CoV-2 viruses. We assessed the capacity of SARS-CoV-2 to infect and replicate in oral epithelial cells. Oral gingival epithelial [...] Read more.

The oral cavity is thought to be one of the portals for SARS-CoV-2 entry, although there is limited evidence of active oral infection by SARS-CoV-2 viruses. We assessed the capacity of SARS-CoV-2 to infect and replicate in oral epithelial cells. Oral gingival epithelial cells (hTERT TIGKs), salivary gland epithelial cells (A-253), and oral buccal epithelial cells (TR146), which occupy different regions of the oral cavity, were challenged with replication-competent SARS-CoV-2 viruses and with pseudo-typed viruses expressing SARS-CoV-2 spike proteins. All oral epithelial cells expressing undetectable or low levels of human angiotensin-converting enzyme 2 (hACE2) but high levels of the alternative receptor CD147 were susceptible to SARS-CoV-2 infection. Distinct viral dynamics were seen in hTERT TIGKs compared to A-253 and TR146 cells. For example, levels of viral transcripts were sustained in hTERT TIGKs but were significantly decreased in A-253 and TR146 cells on day 3 after infection. Analysis of oral epithelial cells infected by replication-competent SARS-CoV-2 viruses expressing GFP showed that the GFP signal and SARS-CoV-2 mRNAs were not evenly distributed. Furthermore, we found cumulative SARS-CoV-2 RNAs from released viruses in the media from oral epithelial cells on day 1 and day 2 after infection, indicating productive viral infection. Taken together, our results demonstrated that oral epithelial cells were susceptible to SARS-CoV-2 viruses despite low or undetectable levels of hACE2, suggesting that alternative receptors contribute to SARS-CoV-2 infection and may be considered for the development of future vaccines and therapeutics. Full article

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2022

Jump to: 2023, 2021, 2020

13 pages, 681 KiB

Open AccessArticle

High Seroprevalence of Anti-SARS-CoV-2 Antibodies in Children in Vietnam: An Observational, Hospital-Based Study

by Dien Minh Tran, Uyen Tu Thi Vu, Canh Ngoc Hoang, Ha Thu Thi Nguyen, Phu Huy Nguyen, Mai Chi Thi Tran, Anh Ngoc Chu and Phuc Huu Phan

Pathogens 2022, 11(12), 1442; https://doi.org/10.3390/pathogens11121442 - 30 Nov 2022

Viewed by 1602

Abstract

Background: The robustness of sero-surveillance has delineated the high burden of SARS-CoV-2 infection in children; however, these existing data showed wide variation. This study aimed to identify the serostatus of antibodies against SARS-CoV-2 and associated factors among children following the fourth pandemic wave [...] Read more.

Background: The robustness of sero-surveillance has delineated the high burden of SARS-CoV-2 infection in children; however, these existing data showed wide variation. This study aimed to identify the serostatus of antibodies against SARS-CoV-2 and associated factors among children following the fourth pandemic wave in Vietnam. Methods: A cross-sectional study was conducted at Vietnam National Children’s Hospital (VNCH) between March 13 and April 3, 2022. Thus, 4032 eligible children seeking medical care for any medical condition not related to acute COVID-19 infection were tested for IgG SARS-CoV-2 antibodies by ADVIA Centaur^® SARS-CoV-2 IgG (sCOVG) assay using the residuals of routine blood samples. Results: The median age of enrolled children was 39 (IQR = 14–82) months. The overall seropositive prevalence was 59.2% (95%CI = 57.6–60.7) and the median antibody titer was 4.78 (IQR 2.38–9.57) UI/mL. The risk of seropositivity and the median antibody titer were not related to gender (58.6% versus 60.1%, 4.9 versus 4.6 UI/mL, all p > 0.05). Children aged ≤12 months were likely to be seropositive compared to children aged 36 to <60 months (59.2% versus 57.5%, p = 0.49) and those aged ≥144 months (59.2% versus 65.5%, p = 0.16). Children aged ≥144 months exhibited a significantly higher titer of protective COVID-19 antibodies than other age groups (p < 0.001). In multivariate logistic regression, we observed independent factors associated with SARS-CoV-2 seropositivity, including the age 13 to <36 months (OR = 1.29, 95%CI = 1.06–1.56, p = 0.01), 60 to <144 months (OR = 0.79, 95%CI = 0.67–0.95, p = 0.01), ≥144 months (OR = 1.84, 95%CI = 1.21–2.8, p = 0.005), the presence of infected household members (OR = 2.36, 95%CI = 2.06–2.70, p < 0.001), participants from Hanoi (OR = 1.54, 95%CI = 1.34–1.77, p < 0.001), underlying conditions (OR = 0.71, 95%CI = 0.60–0.85, p ≤ 0.001), and using corticosteroids or immunosuppressants (OR = 0.64, 95%CI = 0.48–0.86, p = 0.003). Conclusions: This study highlights a high seroprevalence of antibodies against SARS-CoV-2 among children seeking medical care for non-acute COVID-19-related conditions in a tertiary children’s hospital in Hanoi, Vietnam. In the context of reopening in-person schools and future emerging COVID-19 variants, this point will also be a key message about the necessity of “rush-out” immunization coverage for children, especially those under the age of five years. Full article

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14 pages, 3122 KiB

Open AccessArticle

Effectiveness of Household Disinfection Techniques to Remove SARS-CoV-2 from Cloth Masks

by Maria Angélica Monteiro Mello Mares-Guia, Anne Aline Pereira Paiva, Vinicius Motta Mello, Cristiane M. Eller, Andreza Lemos Salvio, Felipe F. Nascimento, Emanuelle S. R. F. Silva, Vinicius Tadeu Martins Guerra Campos, Ygara da Silva Mendes, Elba Regina Sampaio Lemos, Ivanildo P. Sousa, Jr. and Marco Aurélio Pereira Horta

Pathogens 2022, 11(8), 916; https://doi.org/10.3390/pathogens11080916 - 15 Aug 2022

Cited by 2 | Viewed by 1599

Abstract

To assess the efficacy of washing cloth masks, we simulated SARS-CoV-2 contamination in tricoline fabric and tested decontaminants to reduce viral particles. Viral suspensions using two variants (B.1.1.28 and P.1) were inoculated in these fabrics, and the inactivation kinetics were evaluated after washing [...] Read more.

To assess the efficacy of washing cloth masks, we simulated SARS-CoV-2 contamination in tricoline fabric and tested decontaminants to reduce viral particles. Viral suspensions using two variants (B.1.1.28 and P.1) were inoculated in these fabrics, and the inactivation kinetics were evaluated after washing with various household disinfection products (Soap powder, Lysoform^®, Hypochlorite sodium and 70% Alcohol), rinse numbers, and exposure times. Afterward, the fabrics were washed in sterile water, and viral RNA was extracted and amplified using RT-qPCR. Finally, viral replication in cell cultures was examined. Our findings show that all biocidal treatments successfully disinfected the tissue tested. Some products showed less reduction in viral loads, such as soap powder (1.60 × 10⁴, 1.04 × 10³), soap powder and Lysoform^® (1.60 × 10⁴, 1.04 × 10³), and alcohol 70% (1.02 × 10³, 5.91 × 10¹), respectively. However, when sodium hypochlorite was used, this reduction was significantly increased (viral inactivation in 100% of the washes). After the first wash, the reduction in the number of viral particles was greater for the P.1 variant than for the B.1.1.28 variant (W = 51,759, p < 0.05). In conclusion, the role of sodium hypochlorite in cloth mask disinfection may also have implications for future health emergencies as well as recommendation by WHO. Full article

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45 pages, 9398 KiB

Open AccessSystematic Review

Heterogeneity and Risk of Bias in Studies Examining Risk Factors for Severe Illness and Death in COVID-19: A Systematic Review and Meta-Analysis

by Abraham Degarege, Zaeema Naveed, Josiane Kabayundo and David Brett-Major

Pathogens 2022, 11(5), 563; https://doi.org/10.3390/pathogens11050563 - 10 May 2022

Cited by 5 | Viewed by 4046

Abstract

This systematic review and meta-analysis synthesized the evidence on the impacts of demographics and comorbidities on the clinical outcomes of COVID-19, as well as the sources of the heterogeneity and publication bias of the relevant studies. Two authors independently searched the literature from [...] Read more.

This systematic review and meta-analysis synthesized the evidence on the impacts of demographics and comorbidities on the clinical outcomes of COVID-19, as well as the sources of the heterogeneity and publication bias of the relevant studies. Two authors independently searched the literature from PubMed, Embase, Cochrane library, and CINAHL on 18 May 2021; removed duplicates; screened the titles, abstracts, and full texts by using criteria; and extracted data from the eligible articles. The variations among the studies were examined by using Cochrane, Q.; I², and meta-regression. Out of 11,975 articles that were obtained from the databases and screened, 559 studies were abstracted, and then, where appropriate, were analyzed by meta-analysis (n = 542). COVID-19-related severe illness, admission to the ICU, and death were significantly correlated with comorbidities, male sex, and an age older than 60 or 65 years, although high heterogeneity was present in the pooled estimates. The study design, the study country, the sample size, and the year of publication contributed to this. There was publication bias among the studies that compared the odds of COVID-19-related deaths, severe illness, and admission to the ICU on the basis of the comorbidity status. While an older age and chronic diseases were shown to increase the risk of developing severe illness, admission to the ICU, and death among the COVID-19 patients in our analysis, a marked heterogeneity was present when linking the specific risks with the outcomes. Full article

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14 pages, 319 KiB

Open AccessReview

The Prevalence and Impact of Coinfection and Superinfection on the Severity and Outcome of COVID-19 Infection: An Updated Literature Review

by Samya A. Omoush and Jihad A. M. Alzyoud

Pathogens 2022, 11(4), 445; https://doi.org/10.3390/pathogens11040445 - 07 Apr 2022

Cited by 24 | Viewed by 4406

Abstract

Patients with viral illness are at higher risk of secondary infections—whether bacterial, viral, or parasitic—that usually lead to a worse prognosis. In the setting of Corona Virus Disease 2019 (COVID-19), the Severe Acute Respiratory Syndrome Coronavirus-type 2 (SARS-CoV-2) infection may be preceded by [...] Read more.

Patients with viral illness are at higher risk of secondary infections—whether bacterial, viral, or parasitic—that usually lead to a worse prognosis. In the setting of Corona Virus Disease 2019 (COVID-19), the Severe Acute Respiratory Syndrome Coronavirus-type 2 (SARS-CoV-2) infection may be preceded by a prior microbial infection or has a concurrent or superinfection. Previous reports documented a significantly higher risk of microbial coinfection in SARS-CoV-2-positive patients. Initial results from the United States (U.S.) and Europe found a significantly higher risk of mortality and severe illness among hospitalized patients with SARS-CoV-2 and bacterial coinfection. However, later studies found contradictory results concerning the impact of coinfection on the outcomes of COVID-19. Thus, we conducted the present literature review to provide updated evidence regarding the prevalence of coinfection and superinfection amongst patients with SARS-CoV-2, possible mechanisms underlying the higher risk of coinfection and superinfection in SARS-CoV-2 patients, and the impact of coinfection and superinfection on the outcomes of patients with COVID-19. Full article

11 pages, 758 KiB

Open AccessPerspective

Superantigens and SARS-CoV-2

by Adam Hamdy and Anthony Leonardi

Pathogens 2022, 11(4), 390; https://doi.org/10.3390/pathogens11040390 - 23 Mar 2022

Cited by 12 | Viewed by 48249

Abstract

It has been posited SARS-CoV-2 contains at least one unique superantigen-like motif not found in any other SARS or endemic coronaviruses. Superantigens are potent antigens that can send the immune system into overdrive. SARS-CoV-2 causes many of the biological and clinical consequences of [...] Read more.

It has been posited SARS-CoV-2 contains at least one unique superantigen-like motif not found in any other SARS or endemic coronaviruses. Superantigens are potent antigens that can send the immune system into overdrive. SARS-CoV-2 causes many of the biological and clinical consequences of a superantigen, and, in the context of reinfection and waning immunity, it is important to better understand the impact of a widely circulating, airborne pathogen that may be a superantigen, superantigen-like or trigger a superantigenic host response. Urgent research is needed to better understand the long-term risks being taken by governments whose policies enable widespread transmission of a potential superantigenic pathogen, and to more clearly define the vaccination and public health policies needed to protect against the consequences of repeat exposure to the pathogen. Full article

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12 pages, 1335 KiB

Open AccessArticle

Evaluation of Betacoronavirus OC43 and SARS-CoV-2 Elimination by Zefero Air Sanitizer Device in a Novel Laboratory Recirculation System

by Marco Sebastiano Nicolò, Maria Giovanna Rizzo, Nicoletta Palermo, Concetta Gugliandolo, Salvatore Cuzzocrea and Salvatore P. P. Guglielmino

Pathogens 2022, 11(2), 221; https://doi.org/10.3390/pathogens11020221 - 08 Feb 2022

Cited by 4 | Viewed by 2354

Abstract

Indoor air sanitizers contrast airborne diseases and particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/Coronavirus disease 2019 (COVID-19). The commercial air sanitizer Zefero (Cf7 S.r.l., San Giovanni La Punta, Italy) works alternatively using a set of integrated disinfecting technologies (namely Photocatalysis/UV mode) or [...] Read more.

Indoor air sanitizers contrast airborne diseases and particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/Coronavirus disease 2019 (COVID-19). The commercial air sanitizer Zefero (Cf7 S.r.l., San Giovanni La Punta, Italy) works alternatively using a set of integrated disinfecting technologies (namely Photocatalysis/UV mode) or by generating ozone (Ozone mode). Here we evaluated the virucidal efficacy of Zefero setup modes against human Betacoronavirus OC43 and SARS-CoV-2. For this purpose, we designed a laboratory test system in which each virus, as aerosol, was treated with Photocatalysis/UV or Ozone mode and returned into a recirculation plexiglass chamber. Aerosol samples were collected after different times of exposure, corresponding to different volumes of air treated. The viral RNA concentration was determined by qRT-PCR. In Photocatalysis/UV mode, viral RNA of OC43 or SARS-CoV-2 was not detected after 120 or 90 min treatment, respectively, whereas in Ozone mode, viruses were eliminated after 30 or 45 min, respectively. Our results indicated that the integrated technologies used in the air sanitizer Zefero are effective in eliminating both viruses. As a reliable experimental system, the recirculation chamber developed in this study represents a suitable apparatus for effectively comparing the disinfection capacity of different air sanitizers. Full article

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2021

Jump to: 2023, 2022, 2020

17 pages, 3453 KiB

Open AccessArticle

Methodological Development of a Multi-Readout Assay for the Assessment of Antiviral Drugs against SARS-CoV-2

by Friedrich Hahn, Sigrun Häge, Alexandra Herrmann, Christina Wangen, Jintawee Kicuntod, Doris Jungnickl, Julia Tillmanns, Regina Müller, Kirsten Fraedrich, Klaus Überla, Hella Kohlhof, Armin Ensser and Manfred Marschall

Pathogens 2021, 10(9), 1076; https://doi.org/10.3390/pathogens10091076 - 25 Aug 2021

Cited by 7 | Viewed by 3024

Abstract

Currently, human infections with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are accelerating the ongoing spread of the pandemic. Several innovative types of vaccines have already been developed, whereas effective options of antiviral treatments still await a scientific implementation. The development [...] Read more.

Currently, human infections with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are accelerating the ongoing spread of the pandemic. Several innovative types of vaccines have already been developed, whereas effective options of antiviral treatments still await a scientific implementation. The development of novel anti-SARS-CoV-2 drug candidates demands skillful strategies and analysis systems. Promising results have been achieved with first generation direct-acting antivirals targeting the viral polymerase RdRp or the protease 3CL^pro. Such recently approved or investigational drugs like remdesivir and GC376 represent a basis for further development and optimization. Here, we establish a multi-readout assay (MRA) system that enables the antiviral assessment and mechanistic characterization of novel test compounds, drug repurposing and combination treatments. Our SARS-CoV-2-specific MRA combines the quantitative measurement of several parameters of virus infection, such as the intracellular production of proteins and genomes, enzymatic activities and virion release, as well as the use of reporter systems. In this regard, the antiviral efficacy of remdesivir and GC376 has been investigated in human Caco-2 cells. The readouts included the use of spike- and double-strand RNA-specific monoclonal antibodies for in-cell fluorescence imaging, a newly generated recombinant SARS-CoV-2 reporter virus d6YFP, the novel 3CL^pro-based FRET CFP::YFP and the previously reported FlipGFP reporter assays, as well as viral genome-specific RT-qPCR. The data produced by our MRA confirm the high antiviral potency of these two drugs in vitro. Combined, this MRA approach may be applied for broader analyses of SARS-CoV-2-specific antivirals, including compound screenings and the characterization of selected drug candidates. Full article

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35 pages, 1505 KiB

Open AccessReview

Sewage Systems Surveillance for SARS-CoV-2: Identification of Knowledge Gaps, Emerging Threats, and Future Research Needs

by Fatemeh Amereh, Masoud Negahban-Azar, Siavash Isazadeh, Hossein Dabiri, Najmeh Masihi, Mahsa Jahangiri-rad and Mohammad Rafiee

Pathogens 2021, 10(8), 946; https://doi.org/10.3390/pathogens10080946 - 28 Jul 2021

Cited by 16 | Viewed by 4323

Abstract

The etiological agent for novel coronavirus (COVID-19, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), not only affects the human respiratory system, but also the gastrointestinal tract resulting in gastrointestinal manifestations. The high rate of asymptomatic infected individuals has challenged the estimation of infection [...] Read more.

The etiological agent for novel coronavirus (COVID-19, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), not only affects the human respiratory system, but also the gastrointestinal tract resulting in gastrointestinal manifestations. The high rate of asymptomatic infected individuals has challenged the estimation of infection spread based on patients’ surveillance, and thus alternative approaches such as wastewater-based epidemiology (WBE) have been proposed. Accordingly, the number of publications on this topic has increased substantially. The present systematic review thus aimed at providing state-of-the-knowledge on the occurrence and existing methods for sampling procedures, detection/quantification of SARS-CoV-2 in sewage samples, as well as anticipating challenges and providing future research direction to improve the current scientific knowledge. Articles were collected from three scientific databases. Only studies reporting measurements of virus in stool, urine, and wastewater samples were included. Results showed that improving the scientific community’s understanding in these avenues is essential if we are to develop appropriate policy and management tools to address this pandemic pointing particularly towards WBE as a new paradigm in public health. It was also evident that standardized protocols are needed to ensure reproducibility and comparability of outcomes. Areas that require the most improvements are sampling procedures, concentration/enrichment, detection, and quantification of virus in wastewater, as well as positive controls. Results also showed that selecting the most accurate population estimation method for WBE studies is still a challenge. While the number of people infected in an area could be approximately estimated based on quantities of virus found in wastewater, these estimates should be cross-checked by other sources of information to draw a more comprehensive conclusion. Finally, wastewater surveillance can be useful as an early warning tool, a management tool, and/or a way for investigating vaccination efficacy and spread of new variants. Full article

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6 pages, 1414 KiB

Open AccessBrief Report

Presence of SARS-CoV-2 in a Cornea Transplant

by Myriem Otmani Idrissi, Jean-Pierre Baudoin, Anne-Line Chateau, Sarah Aherfi, Marielle Bedotto-Buffet, Alain Latil, Hubert Lepidi, Jacques Chiaroni, Christophe Picard, Jean-Louis Mege, Bernard La Scola and Soraya Mezouar

Pathogens 2021, 10(8), 934; https://doi.org/10.3390/pathogens10080934 - 24 Jul 2021

Cited by 2 | Viewed by 2626

Abstract

Background: The SARS-CoV-2 pandemic has impacted tissue transplantation procedures since conjunctivas were found to be associated with coronavirus infection. Here, we investigated infection of a cornea graft from a COVID-19-positive donor. Methods: In order to evaluate the presence of SARS-CoV-2 in the cornea [...] Read more.

Background: The SARS-CoV-2 pandemic has impacted tissue transplantation procedures since conjunctivas were found to be associated with coronavirus infection. Here, we investigated infection of a cornea graft from a COVID-19-positive donor. Methods: In order to evaluate the presence of SARS-CoV-2 in the cornea graft we first carried out a qRT-PCR and then we investigated the presence of SARS-CoV-2 by fluorescence and electron microscopy. Conclusions: Although the cornea graft was found to be negative by qRT-PCR, we were able to show the presence of SARS-CoV-2 in corneal cells expressing the SARS-CoV-2 receptor, ACE2. Taken together, our findings may have important implications for the use of corneal tissue in graft indications and open the debate on SARS-CoV-2 transmissibility. Full article

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10 pages, 3716 KiB

Open AccessCommunication

Antibodies Targeting Two Epitopes in SARS-CoV-2 Neutralize Pseudoviruses with the Spike Proteins from Different Variants

by Chee-Hing Yang, Hui-Chun Li, Wen-Han Lee and Shih-Yen Lo

Pathogens 2021, 10(7), 869; https://doi.org/10.3390/pathogens10070869 - 09 Jul 2021

Cited by 2 | Viewed by 2779

Abstract

The COVID-19 pandemic was caused by SARS-CoV-2 infection. To prevent the spread of SARS-CoV-2, an effective vaccine is required. Two linear peptides from potential B-cell epitopes in the spike protein of SARS-CoV-2 (a.a. 440–460; a.a. 494–506) were synthesized and used to immunize rabbits. [...] Read more.

The COVID-19 pandemic was caused by SARS-CoV-2 infection. To prevent the spread of SARS-CoV-2, an effective vaccine is required. Two linear peptides from potential B-cell epitopes in the spike protein of SARS-CoV-2 (a.a. 440–460; a.a. 494–506) were synthesized and used to immunize rabbits. High-titer antibodies of IgG were produced, purified, and verified by Western blot analysis. Antibodies against these two epitopes could effectively neutralize SARS-CoV-2 pseudoviral particles with the spike proteins from not only the original strain (basal; wild-type), but also a strain with a single point mutation (D614G), and two other emerging variants (the Alpha and Beta variants) prevalent around the world, but not from SARS-CoV. In conclusion, antibodies against these two epitopes are protective. This information is important for the development of vaccines against SARS-CoV-2. Full article

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15 pages, 17543 KiB

Open AccessEditor’s ChoiceArticle

Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation

by Jeffrey E. Gold, Ramazan A. Okyay, Warren E. Licht and David J. Hurley

Pathogens 2021, 10(6), 763; https://doi.org/10.3390/pathogens10060763 - 17 Jun 2021

Cited by 185 | Viewed by 91633

Abstract

Coronavirus disease 2019 (COVID-19) patients sometimes experience long-term symptoms following resolution of acute disease, including fatigue, brain fog, and rashes. Collectively these have become known as long COVID. Our aim was to first determine long COVID prevalence in 185 randomly surveyed COVID-19 patients [...] Read more.

Coronavirus disease 2019 (COVID-19) patients sometimes experience long-term symptoms following resolution of acute disease, including fatigue, brain fog, and rashes. Collectively these have become known as long COVID. Our aim was to first determine long COVID prevalence in 185 randomly surveyed COVID-19 patients and, subsequently, to determine if there was an association between occurrence of long COVID symptoms and reactivation of Epstein–Barr virus (EBV) in 68 COVID-19 patients recruited from those surveyed. We found the prevalence of long COVID symptoms to be 30.3% (56/185), which included 4 initially asymptomatic COVID-19 patients who later developed long COVID symptoms. Next, we found that 66.7% (20/30) of long COVID subjects versus 10% (2/20) of control subjects in our primary study group were positive for EBV reactivation based on positive titers for EBV early antigen-diffuse (EA-D) IgG or EBV viral capsid antigen (VCA) IgM. The difference was significant (p < 0.001, Fisher’s exact test). A similar ratio was observed in a secondary group of 18 subjects 21–90 days after testing positive for COVID-19, indicating reactivation may occur soon after or concurrently with COVID-19 infection. These findings suggest that many long COVID symptoms may not be a direct result of the SARS-CoV-2 virus but may be the result of COVID-19 inflammation-induced EBV reactivation. Full article

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8 pages, 1103 KiB

Open AccessArticle

Rapid Inactivation In Vitro of SARS-CoV-2 in Saliva by Black Tea and Green Tea

by Eriko Ohgitani, Masaharu Shin-Ya, Masaki Ichitani, Makoto Kobayashi, Takanobu Takihara, Masaya Kawamoto, Hitoshi Kinugasa and Osam Mazda

Pathogens 2021, 10(6), 721; https://doi.org/10.3390/pathogens10060721 - 08 Jun 2021

Cited by 18 | Viewed by 15573

Abstract

Saliva plays major roles in the human-to-human transmission of SARS-CoV-2. If the virus in saliva in SARS-CoV-2-infected individuals can be rapidly and efficiently inactivated by a beverage, the ingestion of the beverage may attenuate the spread of virus infection within a population. Recently, [...] Read more.

Saliva plays major roles in the human-to-human transmission of SARS-CoV-2. If the virus in saliva in SARS-CoV-2-infected individuals can be rapidly and efficiently inactivated by a beverage, the ingestion of the beverage may attenuate the spread of virus infection within a population. Recently, we reported that SARS-CoV-2 was significantly inactivated by treatment with black tea, green tea, roasted green tea and oolong tea, as well as their constituents, (-) epigallocatechin gallate (EGCG), theasinensin A (TSA), and galloylated theaflavins. However, it remains unclear to what extent tea inactivates the virus present in saliva, because saliva contains various proteins, nitrogenous products, electrolytes, and so on, which could influence the antivirus effect of tea. Here, we assessed whether tea inactivated the SARS-CoV-2 which was added in human saliva. A virus was added in healthy human saliva in vitro, and after treatment with black tea or green tea, the infectivity of the virus was evaluated by TCID₅₀ assays. The virus titer fell below the detectable level or less than 1/100 after treatment with black tea or green tea for 10 s. The black tea-treated virus less remarkably replicated in cells compared with the untreated virus. These findings suggest the possibility that the ingestion of tea may inactivate SARS-CoV-2 in saliva in infected individuals, although clinical studies are required to determine the intensity and duration of the anti-viral effect of tea in saliva in humans. Full article

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9 pages, 1092 KiB

Open AccessArticle

Performance of the LIAISON^® SARS-CoV-2 Antigen Assay vs. SARS-CoV-2-RT-PCR

by Melanie Fiedler, Caroline Holtkamp, Ulf Dittmer and Olympia E. Anastasiou

Pathogens 2021, 10(6), 658; https://doi.org/10.3390/pathogens10060658 - 26 May 2021

Cited by 7 | Viewed by 4065

Abstract

We aimed to evaluate the LIAISON^® SARS-CoV-2 antigen assay (DiaSorin), comparing its performance to real-time polymerase chain reaction (RT-PCR) for the detection of SARS-CoV-2 RNA. 182 (110 PCR-positive and 72 PCR-negative) nasopharyngeal swab samples were taken for the detection of SARS-CoV-2. RT-PCR [...] Read more.

We aimed to evaluate the LIAISON^® SARS-CoV-2 antigen assay (DiaSorin), comparing its performance to real-time polymerase chain reaction (RT-PCR) for the detection of SARS-CoV-2 RNA. 182 (110 PCR-positive and 72 PCR-negative) nasopharyngeal swab samples were taken for the detection of SARS-CoV-2. RT-PCR and antigen assay were performed using the same material. The sensitivity and specificity of the antigen assay were calculated for different cut-offs, with RT-PCR serving as the reference method. Stored clinical samples that were positive for other respiratory viruses were tested to evaluate cross-reactivity. One third (33/110, 30%) were falsely classified as negative, while no false positives were found using the 200 TCID₅₀/mL cut-off for the SARS-CoV-2 antigen as proposed by the manufacturer. This corresponded to a sensitivity of 70% (60–78%) and a specificity of 100% (94–100%). Lowering the cut-off for positivity of the antigen assay to 22.79 or 57.68 TCID₅₀/mL increased the sensitivity of the method, reaching a sensitivity of 92% (85–96%) vs. 79% (70–86%) and a specificity of 81% (69–89%) vs. 99% (91–100%), respectively. The antigen assay reliably detected samples with high SARS-CoV-2 viral loads (≥10⁶ copies SARS-CoV-2/mL), while it cannot differentiate between negative and low positive samples. Cross-reactivity toward other respiratory viruses was not detected. Full article

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21 pages, 1635 KiB

Open AccessReview

Fundamental and Advanced Therapies, Vaccine Development against SARS-CoV-2

by Nikola Hudakova, Simona Hricikova, Amod Kulkarni, Mangesh Bhide, Eva Kontsekova and Dasa Cizkova

Pathogens 2021, 10(6), 636; https://doi.org/10.3390/pathogens10060636 - 21 May 2021

Cited by 2 | Viewed by 4049

Abstract

Coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus has been affecting the world since the end of 2019. The severity of the disease can range from an asymptomatic or mild course to acute respiratory distress syndrome (ARDS) with respiratory failure, which may lead [...] Read more.

Coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus has been affecting the world since the end of 2019. The severity of the disease can range from an asymptomatic or mild course to acute respiratory distress syndrome (ARDS) with respiratory failure, which may lead to death. Since the outbreak of the pandemic, scientists around the world have been studying the genome and molecular mechanisms of SARS-CoV-2 infection to develop effective therapies and prevention. In this review, we summarize the progressive development of various treatments and vaccines as they have emerged, a year after the outbreak of the pandemic. Initially for COVID-19, patients were recommended drugs with presumed antiviral, anti-inflammatory, and antimicrobial effects that were previously used to treat other diseases. Thereafter, therapeutic interventions were supplemented with promising approaches based on antibodies, peptides, and stem cells. However, licensed COVID-19 vaccines remain the most effective weapon in combating the pandemic. While there is an enormous effort to enhance the vaccination rate to increase the entire population immunity, the production and delivery of vaccines is becoming limited in several countries. In this regard, there are new challenges needing to be addressed by combining non-pharmacological intervention with effective therapies until vaccination is accessible to all. Full article

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6 pages, 893 KiB

Open AccessCase Report

Mild Symptomatic SARS-CoV-2 P.1 (B.1.1.28) Infection in a Fully Vaccinated 83-Year-Old Man

by Marco Fabiani, Katia Margiotti, Antonella Viola, Alvaro Mesoraca and Claudio Giorlandino

Pathogens 2021, 10(5), 614; https://doi.org/10.3390/pathogens10050614 - 17 May 2021

Cited by 9 | Viewed by 2604

Abstract

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) and the associated coronavirus disease 2019 (COVID-19) continue to spread throughout the world, causing more than 120 million infections. Several variants of concern (VOCs) have emerged and spread with implications for vaccine efficacy, therapeutic antibody [...] Read more.

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) and the associated coronavirus disease 2019 (COVID-19) continue to spread throughout the world, causing more than 120 million infections. Several variants of concern (VOCs) have emerged and spread with implications for vaccine efficacy, therapeutic antibody treatments, and possible reinfections. On 17 March 2021, several VOCs were detected, including lineage B.1.1.7, first identified in the UK, B.1.351 in South Africa, Lineage P.1 (B.1.1.28.1) in Brazil, and novel Sub-Lineage A (A.23.1), reported in Uganda, and B.1.525, reported in Nigeria. Here, we describe an 83-year-old man infected with the SARS-CoV-2 P.1 variant after two doses of the BNT162b2 mRNA COVID-19 vaccine. Full article

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14 pages, 1031 KiB

Open AccessEditor’s ChoiceReview

Neonatal SARS-CoV-2 Infection: Practical Tips

by Cinzia Auriti, Domenico Umberto De Rose, Vito Mondì, Ilaria Stolfi, Chryssoula Tzialla and on behalf of the Study Group of Neonatal Infectious Diseases

Pathogens 2021, 10(5), 611; https://doi.org/10.3390/pathogens10050611 - 17 May 2021

Cited by 16 | Viewed by 3937

Abstract

The recent viral pandemic in Wuhan, Hubei, China has led to the identification of a new species of beta-coronavirus, able to infect humans, the 2019-nCoV, later named SARS-CoV-2. SARS-CoV-2 causes a clinical syndrome named COVID-19, which presents with a spectrum of symptoms ranging [...] Read more.

The recent viral pandemic in Wuhan, Hubei, China has led to the identification of a new species of beta-coronavirus, able to infect humans, the 2019-nCoV, later named SARS-CoV-2. SARS-CoV-2 causes a clinical syndrome named COVID-19, which presents with a spectrum of symptoms ranging from mild upper respiratory tract infection to severe pneumonia, with acute respiratory distress syndrome and frequent death. All age groups are susceptible to the infection, but children, especially infants, seem to be partially spared, having a more favorable clinical course than other age groups. There is currently no clear evidence showing vertical transmission and intrauterine SARS-CoV-2 infection in fetuses of women developing COVID-19 pneumonia in late pregnancy, and even if transmission is possible, the SARS-CoV2 positivity of the mother does not require delivery by caesarean section, does not contraindicate the management of the infant in rooming-in and allows breastfeeding. This review provides an overview on the biology of the virus, on the pathogenesis of the infection, with particular attention to pregnancy and neonatal age, on the clinical presentation of infection in newborns and young infants and summarizes the international recommendations currently available on the clinical care of neonates with SARS-CoV2 infection or at risk of catching the virus. The main objective of the review is to provide an update especially focused to the clinical management of COVID-19 infection in the perinatal and neonatal age. Full article

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11 pages, 273 KiB

Open AccessReview

Endothelial Dysfunction and SARS-CoV-2 Infection: Association and Therapeutic Strategies

by Hai Deng, Ting-Xuan Tang, Deng Chen, Liang-Sheng Tang, Xiang-Ping Yang and Zhao-Hui Tang

Pathogens 2021, 10(5), 582; https://doi.org/10.3390/pathogens10050582 - 11 May 2021

Cited by 17 | Viewed by 3603

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has been recently considered a systemic disorder leading to the procoagulant state. Preliminary studies have shown that SARS-CoV-2 can infect endothelial cells, and extensive evidence of inflammation and endothelial dysfunction has [...] Read more.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has been recently considered a systemic disorder leading to the procoagulant state. Preliminary studies have shown that SARS-CoV-2 can infect endothelial cells, and extensive evidence of inflammation and endothelial dysfunction has been found in advanced COVID-19. Endothelial cells play a critical role in many physiological processes, such as controlling blood fluidity, leukocyte activation, adhesion, platelet adhesion and aggregation, and transmigration. Therefore, it is reasonable to think that endothelial dysfunction leads to vascular dysfunction, immune thrombosis, and inflammation associated with COVID-19. This article summarizes the association of endothelial dysfunction and SARS-CoV-2 infection and its therapeutic strategies. Full article

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25 pages, 901 KiB

Open AccessReview

Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

by Ali A. Rabaan, Shamsah H. Al-Ahmed, Mohammed A. Garout, Ayman M. Al-Qaaneh, Anupam A Sule, Raghavendra Tirupathi, Abbas Al Mutair, Saad Alhumaid, Abdulkarim Hasan, Manish Dhawan, Ruchi Tiwari, Khan Sharun, Ranjan K. Mohapatra, Saikat Mitra, Talha Bin Emran, Muhammad Bilal, Rajendra Singh, Salem A. Alyami, Mohammad Ali Moni and Kuldeep Dhama

Pathogens 2021, 10(5), 565; https://doi.org/10.3390/pathogens10050565 - 07 May 2021

Cited by 55 | Viewed by 7128

Abstract

The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for the disease has not been discovered. Recent [...] Read more.

The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for the disease has not been discovered. Recent investigations and research studies primarily focus on the immunopathology of the disease. A healthy immune system responds immediately after viral entry, causing immediate viral annihilation and recovery. However, an impaired immune system causes extensive systemic damage due to an unregulated immune response characterized by the hypersecretion of chemokines and cytokines. The elevated levels of cytokine or hypercytokinemia leads to acute respiratory distress syndrome (ARDS) along with multiple organ damage. Moreover, the immune response against SARS-CoV-2 has been linked with race, gender, and age; hence, this viral infection’s outcome differs among the patients. Many therapeutic strategies focusing on immunomodulation have been tested out to assuage the cytokine storm in patients with severe COVID-19. A thorough understanding of the diverse signaling pathways triggered by the SARS-CoV-2 virus is essential before contemplating relief measures. This present review explains the interrelationships of hyperinflammatory response or cytokine storm with organ damage and the disease severity. Furthermore, we have thrown light on the diverse mechanisms and risk factors that influence pathogenesis and the molecular pathways that lead to severe SARS-CoV-2 infection and multiple organ damage. Recognition of altered pathways of a dysregulated immune system can be a loophole to identify potential target markers. Identifying biomarkers in the dysregulated pathway can aid in better clinical management for patients with severe COVID-19 disease. A special focus has also been given to potent inhibitors of proinflammatory cytokines, immunomodulatory and immunotherapeutic options to ameliorate cytokine storm and inflammatory responses in patients affected with COVID-19. Full article

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10 pages, 4100 KiB

Open AccessCase Report

Myopericarditis Associated with COVID-19 in a Pediatric Patient with Kidney Failure Receiving Hemodialysis

by Marcela Daniela Ionescu, Mihaela Balgradean, Catalin Gabriel Cirstoveanu, Ioana Balgradean, Loredana Ionela Popa, Carmen Pavelescu, Andrei Capitanescu, Elena Camelia Berghea and Cristina Filip

Pathogens 2021, 10(4), 486; https://doi.org/10.3390/pathogens10040486 - 17 Apr 2021

Cited by 4 | Viewed by 2460

Abstract

The outbreak of COVID-19 can be associated with cardiac and pulmonary involvement and is emerging as one of the most significant and life-threatening complications in patients with kidney failure receiving hemodialysis. Here, we report a critically ill case of a 13-year-old female patient [...] Read more.

The outbreak of COVID-19 can be associated with cardiac and pulmonary involvement and is emerging as one of the most significant and life-threatening complications in patients with kidney failure receiving hemodialysis. Here, we report a critically ill case of a 13-year-old female patient with acute pericarditis and bilateral pleurisy, screened positive for SARS-CoV-2 RT-PCR, presented with high fever, frequent dry cough, and dyspnea with tachypnea. COVID-19-induced myopericarditis has been noted to be a complication in patients with concomitant kidney failure with replacement therapy (KFRT). This article brings information in the light of our case experience, suggesting that the direct effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on cardiac tissue was a significant contributor to myopericarditis in our patient. Further studies in this direction are required, as such associations have thus far been reported. Full article

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7 pages, 220 KiB

Open AccessOpinion

Why Does SARS-CoV-2 Infection Induce Autoantibody Production?

by Ales Macela and Klara Kubelkova

Pathogens 2021, 10(3), 380; https://doi.org/10.3390/pathogens10030380 - 22 Mar 2021

Cited by 3 | Viewed by 2390

Abstract

SARS-CoV-2 infection induces the production of autoantibodies, which is significantly associated with complications during hospitalization and a more severe prognosis in COVID-19 patients. Such a response of the patient’s immune system may reflect (1) the dysregulation of the immune response or (2) it [...] Read more.

SARS-CoV-2 infection induces the production of autoantibodies, which is significantly associated with complications during hospitalization and a more severe prognosis in COVID-19 patients. Such a response of the patient’s immune system may reflect (1) the dysregulation of the immune response or (2) it may be an attempt to regulate itself in situations where the non-infectious self poses a greater threat than the infectious non-self. Of significance may be the primary virus-host cell interaction where the surface-bound ACE2 ectoenzyme plays a critical role. Here, we present a brief analysis of recent findings concerning the immune recognition of SARS-CoV-2, which, we believe, favors the second possibility as the underlying reason for the production of autoantibodies during COVID-19. Full article

14 pages, 3541 KiB

Open AccessArticle

Evaluation of “Caterina assay”: An Alternative Tool to the Commercialized Kits Used for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Identification

by Germano Orrù, Alessandra Scano, Sara Fais, Miriam Loddo, Mauro Giovanni Carta, Giorgio Carlo Steri, Simonetta Santus, Riccardo Cappai, Maria Laura Ferrando and Ferdinando Coghe

Pathogens 2021, 10(3), 325; https://doi.org/10.3390/pathogens10030325 - 10 Mar 2021

Cited by 2 | Viewed by 2719

Abstract

Here we describe the first molecular test developed in the early stage of the pandemic to diagnose the first cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Sardinian patients in February–March 2020, when diagnostic certified methodology had not yet been [...] Read more.

Here we describe the first molecular test developed in the early stage of the pandemic to diagnose the first cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Sardinian patients in February–March 2020, when diagnostic certified methodology had not yet been adopted by clinical microbiology laboratories. The “Caterina assay” is a SYBR^®Green real-time reverse-transcription polymerase chain reaction (rRT-PCR), designed to detect the nucleocapsid phosphoprotein (N) gene that exhibits high discriminative variation RNA sequence among bat and human coronaviruses. The molecular method was applied to detect SARS-CoV-2 in nasal swabs collected from 2110 suspected cases. The study article describes the first molecular test developed in the early stage of the declared pandemic to identify the coronavirus disease 2019 (COVID-19) in Sardinian patients in February–March 2020, when a diagnostic certified methodology had not yet been adopted by clinical microbiology laboratories. The assay presented high specificity and sensitivity (with a detection limit ≥50 viral genomes/μL). No false-positives were detected, as confirmed by the comparison with two certified commercial kits. Although other validated molecular methods are currently in use, the Caterina assay still represents a valid and low-cost detection procedure that could be applied in countries with limited economic resources. Full article

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14 pages, 2289 KiB

Open AccessArticle

Molecular Epidemiology Surveillance of SARS-CoV-2: Mutations and Genetic Diversity One Year after Emerging

by Alejandro Flores-Alanis, Armando Cruz-Rangel, Flor Rodríguez-Gómez, James González, Carlos Alberto Torres-Guerrero, Gabriela Delgado, Alejandro Cravioto and Rosario Morales-Espinosa

Pathogens 2021, 10(2), 184; https://doi.org/10.3390/pathogens10020184 - 09 Feb 2021

Cited by 26 | Viewed by 5273

Abstract

In December 2019, the first cases of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were identified in the city of Wuhan, China. Since then, it has spread worldwide with new mutations being reported. The aim of the present study was to [...] Read more.

In December 2019, the first cases of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were identified in the city of Wuhan, China. Since then, it has spread worldwide with new mutations being reported. The aim of the present study was to monitor the changes in genetic diversity and track non-synonymous substitutions (dN) that could be implicated in the fitness of SARS-CoV-2 and its spread in different regions between December 2019 and November 2020. We analyzed 2213 complete genomes from six geographical regions worldwide, which were downloaded from GenBank and GISAID databases. Although SARS-CoV-2 presented low genetic diversity, there has been an increase over time, with the presence of several hotspot mutations throughout its genome. We identified seven frequent mutations that resulted in dN substitutions. Two of them, C14408T>P323L and A23403G>D614G, located in the nsp12 and Spike protein, respectively, emerged early in the pandemic and showed a considerable increase in frequency over time. Two other mutations, A1163T>I120F in nsp2 and G22992A>S477N in the Spike protein, emerged recently and have spread in Oceania and Europe. There were associations of P323L, D614G, R203K and G204R substitutions with disease severity. Continuous molecular surveillance of SARS-CoV-2 will be necessary to detect and describe the transmission dynamics of new variants of the virus with clinical relevance. This information is important to improve programs to control the virus. Full article

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28 pages, 1110 KiB

Open AccessReview

Host Diversity and Potential Transmission Pathways of SARS-CoV-2 at the Human-Animal Interface

by Hayden D. Hedman, Eric Krawczyk, Yosra A. Helmy, Lixin Zhang and Csaba Varga

Pathogens 2021, 10(2), 180; https://doi.org/10.3390/pathogens10020180 - 08 Feb 2021

Cited by 28 | Viewed by 6115

Abstract

Emerging infectious diseases present great risks to public health. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has become an urgent public health issue of global concern. It is speculated that the virus first emerged through a [...] Read more.

Emerging infectious diseases present great risks to public health. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has become an urgent public health issue of global concern. It is speculated that the virus first emerged through a zoonotic spillover. Basic research studies have suggested that bats are likely the ancestral reservoir host. Nonetheless, the evolutionary history and host susceptibility of SARS-CoV-2 remains unclear as a multitude of animals has been proposed as potential intermediate or dead-end hosts. SARS-CoV-2 has been isolated from domestic animals, both companion and livestock, as well as in captive wildlife that were in close contact with human COVID-19 cases. Currently, domestic mink is the only known animal that is susceptible to a natural infection, develop severe illness, and can also transmit SARS-CoV-2 to other minks and humans. To improve foundational knowledge of SARS-CoV-2, we are conducting a synthesis review of its host diversity and transmission pathways. To mitigate this COVID-19 pandemic, we strongly advocate for a systems-oriented scientific approach that comprehensively evaluates the transmission of SARS-CoV-2 at the human and animal interface. Full article

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11 pages, 948 KiB

Open AccessArticle

Psychophysical Evaluation of the Olfactory Function: European Multicenter Study on 774 COVID-19 Patients

by Luigi Angelo Vaira, Jerome R. Lechien, Mohamad Khalife, Marzia Petrocelli, Stephane Hans, Lea Distinguin, Giovanni Salzano, Marco Cucurullo, Piero Doneddu, Francesco Antonio Salzano, Federico Biglioli, Fabrice Journe, Andrea Fausto Piana, Giacomo De Riu and Sven Saussez

Pathogens 2021, 10(1), 62; https://doi.org/10.3390/pathogens10010062 - 12 Jan 2021

Cited by 41 | Viewed by 2883

Abstract

Background: The objective evaluation of the olfactory function of coronavirus disease 2019 patients is difficult because of logistical and operator-safety problems. For this reason, in the literature, the data obtained from psychophysical tests are few and based on small case series. Methods: A [...] Read more.

Background: The objective evaluation of the olfactory function of coronavirus disease 2019 patients is difficult because of logistical and operator-safety problems. For this reason, in the literature, the data obtained from psychophysical tests are few and based on small case series. Methods: A multicenter, cohort study conducted in seven European hospitals between March 22 and August 20, 2020. The Sniffin-Sticks test and the Connecticut Chemosensory Clinical Research Center orthonasal olfaction test were used to objectively evaluate the olfactory function. Results: This study included 774 patients, of these 481 (62.1%) presented olfactory dysfunction (OD): 280 were hyposmic and 201 were anosmic. There was a significant difference between self-reported anosmia/hyposmia and psychophysical test results (p = 0.006). Patients with gastroesophageal disorders reported a significantly higher probability of presenting hyposmia (OR 1.86; p = 0.015) and anosmia (OR 2.425; p < 0.001). Fever, chest pain, and phlegm significantly increased the likelihood of having hyposmia but not anosmia or an olfactory disturbance. In contrast, patients with dyspnea, dysphonia, and severe-to-critical COVID-19 were significantly more likely to have no anosmia, while these symptoms had no effect on the risk of developing hyposmia or an OD. Conclusions: Psychophysical assessment represents a significantly more accurate assessment tool for olfactory function than patient self-reported clinical outcomes. Olfactory disturbances appear to be largely independent from the epidemiological and clinical characteristics of the patients. The non-association with rhinitis symptoms and the high prevalence as a presenting symptom make olfactory disturbances an important symptom in the differential diagnosis between COVID-19 and common flu. Full article

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2020

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10 pages, 238 KiB

Open AccessArticle

Clinical Presentation, Course, and Risk Factors Associated with Mortality in a Severe Outbreak of COVID-19 in Rhode Island, USA, April–June 2020

by Eleftheria Atalla, Raina Zhang, Fadi Shehadeh, Evangelia K. Mylona, Maria Tsikala-Vafea, Saisanjana Kalagara, Laura Henseler, Philip A. Chan and Eleftherios Mylonakis

Pathogens 2021, 10(1), 8; https://doi.org/10.3390/pathogens10010008 - 24 Dec 2020

Cited by 15 | Viewed by 3574

Abstract

Long-term care facilities (LTCFs) have had a disproportionally high mortality rate due to COVID-19. We describe a rapidly escalating COVID-19 outbreak among 116 LTCF residents in Rhode Island, USA. Overall, 111 (95.6%) residents tested positive and, of these, 48 (43.2%) died. The most [...] Read more.

Long-term care facilities (LTCFs) have had a disproportionally high mortality rate due to COVID-19. We describe a rapidly escalating COVID-19 outbreak among 116 LTCF residents in Rhode Island, USA. Overall, 111 (95.6%) residents tested positive and, of these, 48 (43.2%) died. The most common comorbidities were hypertension (84.7%) and cardiovascular disease (84.7%). A small percentage (9%) of residents were asymptomatic, while 33.3% of residents were pre-symptomatic, with progression to symptoms within a median of three days following the positive test. While typical symptoms of fever (80.2%) and cough (43.2%) were prevalent, shortness of breath (14.4%) was rarely found despite common hypoxemia (95.5%). The majority of patients demonstrated atypical symptoms with the most common being loss of appetite (61.3%), lethargy (42.3%), diarrhea (37.8%), and fatigue (32.4%). Many residents had increased agitation (38.7%) and anxiety (5.4%), potentially due to the restriction measures or the underlying mental illness. The fever curve was characterized by an intermittent low-grade fever, often the first presenting symptom. Mortality was associated with a disease course beginning with a loss of appetite and lethargy, as well as one more often involving fever greater than 38 °C, loss of appetite, altered mental status, diarrhea, and respiratory distress. Interestingly, no differences in age or comorbidities were noted between survivors and non-survivors. Taking demographic factors into account, treatment with anticoagulation was still associated with reduced mortality (adjusted OR 0.16; 95% C.I. 0.06–0.39; p < 0.001). Overall, the clinical features of the disease in this population can be subtle and the symptoms are commonly atypical. However, clinical decline among those who did not survive was often rapid with patients expiring within 10 days from disease detection. Further studies are needed to better explain the variability in clinical course of COVID-19 among LTCF residents, specifically the factors affecting mortality, the differences observed in symptom presentation, and rate of clinical decline. Full article

22 pages, 744 KiB

Open AccessEditor’s ChoiceArticle

Hand Hygiene Behaviors in a Representative Sample of Polish Adolescents in Regions Stratified by COVID-19 Morbidity and by Confounding Variables (PLACE-19 Study): Is There Any Association?

by Dominika Skolmowska, Dominika Głąbska and Dominika Guzek

Pathogens 2020, 9(12), 1011; https://doi.org/10.3390/pathogens9121011 - 01 Dec 2020

Cited by 24 | Viewed by 3041

Abstract

The hand hygiene may possibly influence the course of the COVID-19 pandemic, but the multifactorial influence on hand hygiene knowledge and behaviors is proven. The aim of the study was to analyze hand hygiene behaviors in a national representative sample of Polish adolescents [...] Read more.

The hand hygiene may possibly influence the course of the COVID-19 pandemic, but the multifactorial influence on hand hygiene knowledge and behaviors is proven. The aim of the study was to analyze hand hygiene behaviors in a national representative sample of Polish adolescents in regions stratified by COVID-19 morbidity, while taking socioeconomic status of the region, as well rural or urban environment, into account as possible interfering factors. The study was conducted Polish Adolescents’ COVID-19 Experience (PLACE-19) Study population (n = 2323) that was recruited based on a random sampling of schools, while the pair-matching procedure was applied within schools and age, in order to obtain adequate number of boys and girls, representative for the general Polish population (n = 1222). The participants were asked about their handwashing habits while using Handwashing Habits Questionnaire (HHQ) and about applied procedure of washing hands. The results were compared in subgroups that were stratified by region for COVID-19 morbidity, socioeconomic status of the region, and rural/urban environment. In regions of low COVID-19 morbidity, a higher share of adolescents, than in regions of high morbidity, declared washing their hands before meals (p = 0.0196), after meals (p = 0.0041), after preparing meals (p = 0.0297), before using the restroom (p = 0.0068), after using the restroom (p = 0.0014), after combing their hair (p = 0.0298), after handshaking (p = 0.0373), after touching animals (p = 0.0007), after contacting babies (p = 0.0278), after blowing nose (p = 0.0435), after touching sick people (p = 0.0351), and after cleaning home (p = 0.0234). For the assessed steps of the handwashing procedure, in regions of low COVID-19 morbidity, a higher share of adolescents included them to their daily handwashing, than in regions of high morbidity, that was stated for removing watch and bracelets (p = 0.0052), removing rings (p = 0.0318), and drying hands with towel (p = 0.0031). For the comparison in regions stratified by Gross Domestic Product, the differences were only minor and inconsistent. For the comparison in place of residence stratified by number of residents in city, there were some minor differences indicating better hand hygiene behaviors in the case of villages and small towns when compared with medium and large cities (p < 0.05). It may be concluded that, in a population-based sample of Polish adolescents, individuals from regions of low COVID-19 morbidity presented more beneficial hand hygiene habits than those from regions of high COVID-19 morbidity. Full article

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18 pages, 1091 KiB

Open AccessEditor’s ChoiceReview

Antibody-Based Immunotherapeutic Strategies for COVID-19

by Jamal Hussen, Mahmoud Kandeel, Maged Gomaa Hemida and Abdullah I. A. Al-Mubarak

Pathogens 2020, 9(11), 917; https://doi.org/10.3390/pathogens9110917 - 05 Nov 2020

Cited by 12 | Viewed by 3314

Abstract

Global efforts to contain the coronavirus disease-2019 (COVID-19) include the development of novel preventive vaccines and effective therapeutics. Passive antibody therapies using convalescent plasma, SARS-CoV-2 (Severe-Acute-Respiratory-Syndrome-Corona-Virus-2)-specific neutralizing antibodies (NAbs), and the development of monoclonal antibodies (MAbs) are among the most promising strategies for [...] Read more.

Global efforts to contain the coronavirus disease-2019 (COVID-19) include the development of novel preventive vaccines and effective therapeutics. Passive antibody therapies using convalescent plasma, SARS-CoV-2 (Severe-Acute-Respiratory-Syndrome-Corona-Virus-2)-specific neutralizing antibodies (NAbs), and the development of monoclonal antibodies (MAbs) are among the most promising strategies for prophylaxis and treatment of SARS-CoV-2 infections. In addition, several immunomodulatory antibodies acting via several mechanisms to boost the host immune defense against SARS-CoV-2 infection as well as to avoid the harmful overreaction of the immune system are currently under clinical trial. Our main objective is to present the current most up-to-date progress in some clinical trials registered at ClinicalTrials.gov. We highlight the pros and pitfalls of several SARS-CoV-2 antibody-based immunotherapeutics. Full article

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32 pages, 4779 KiB

Open AccessReview

Threading the Pieces Together: Integrative Perspective on SARS-CoV-2

by Akshay Kanakan, Neha Mishra, Janani Srinivasa Vasudevan, Shweta Sahni, Azka Khan, Sachin Sharma and Rajesh Pandey

Pathogens 2020, 9(11), 912; https://doi.org/10.3390/pathogens9110912 - 04 Nov 2020

Cited by 7 | Viewed by 4609

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has challenged the research community globally to innovate, interact, and integrate findings across hierarchies. Research on SARS-CoV-2 has produced an abundance of data spanning multiple parallels, including clinical data, SARS-CoV-2 genome architecture, host response [...] Read more.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has challenged the research community globally to innovate, interact, and integrate findings across hierarchies. Research on SARS-CoV-2 has produced an abundance of data spanning multiple parallels, including clinical data, SARS-CoV-2 genome architecture, host response captured through transcriptome and genetic variants, microbial co-infections (metagenome), and comorbidities. Disease phenotypes in the case of COVID-19 present an intriguing complexity that includes a broad range of symptomatic to asymptomatic individuals, further compounded by a vast heterogeneity within the spectrum of clinical symptoms displayed by the symptomatic individuals. The clinical outcome is further modulated by the presence of comorbid conditions at the point of infection. The COVID-19 pandemic has produced an expansive wealth of literature touching many aspects of SARS-CoV-2 ranging from causal to outcome, predisposition to protective (possible), co-infection to comorbidity, and differential mortality globally. As challenges provide opportunities, the current pandemic’s challenge has underscored the need and opportunity to work for an integrative approach that may be able to thread together the multiple variables. Through this review, we have made an effort towards bringing together information spanning across different domains to facilitate researchers globally in pursuit of their response to SARS-CoV-2. Full article

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18 pages, 2666 KiB

Open AccessEditor’s ChoiceArticle

Predictive Accuracy of COVID-19 World Health Organization (WHO) Severity Classification and Comparison with a Bayesian-Method-Based Severity Score (EPI-SCORE)

by Christophe de Terwangne, Jabber Laouni, Lionel Jouffe, Jerome R. Lechien, Vincent Bouillon, Sammy Place, Lucio Capulzini, Shahram Machayekhi, Antonia Ceccarelli, Sven Saussez, Antonio Sorgente and on behalf of EPIBASE TEAM

Pathogens 2020, 9(11), 880; https://doi.org/10.3390/pathogens9110880 - 24 Oct 2020

Cited by 30 | Viewed by 4825

Abstract

Objectives: Assess the predictive accuracy of the WHO COVID-19 severity classification on COVID-19 hospitalized patients. The secondary aim was to compare its predictive power with a new prediction model, named COVID-19 EPI-SCORE, based on a Bayesian network analysis. Methods: We retrospectively analyzed a [...] Read more.

Objectives: Assess the predictive accuracy of the WHO COVID-19 severity classification on COVID-19 hospitalized patients. The secondary aim was to compare its predictive power with a new prediction model, named COVID-19 EPI-SCORE, based on a Bayesian network analysis. Methods: We retrospectively analyzed a population of 295 COVID-19 RT-PCR positive patients hospitalized at Epicura Hospital Center, Belgium, admitted between March 1st and April 30th, 2020. Results: Our cohort’s median age was 73 (62–83) years, and the female proportion was 43%. All patients were classified following WHO severity classification at admission. In total, 125 (42.4%) were classified as Moderate, 69 (23.4%) as Severe, and 101 (34.2%) as Critical. Death proportions through these three classes were 11.2%, 33.3%, and 67.3%, respectively, and the proportions of critically ill patients (dead or needed Invasive Mechanical Ventilation) were 11.2%, 34.8%, and 83.2%, respectively. A Bayesian network analysis was used to create a model to analyze predictive accuracy of the WHO severity classification and to create the EPI-SCORE. The six variables that have been automatically selected by our machine learning algorithm were the WHO severity classification, acute kidney injury, age, Lactate Dehydrogenase Levels (LDH), lymphocytes and activated prothrombin time (aPTT). Receiver Operation Characteristic (ROC) curve indexes hereby obtained were 83.8% and 91% for the models based on WHO classification only and our EPI-SCORE, respectively. Conclusions: Our study shows that the WHO severity classification is reliable in predicting a severe outcome among COVID-19 patients. The addition to this classification of a few clinical and laboratory variables as per our COVID-19 EPI-SCORE has demonstrated to significantly increase its accuracy. Full article

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19 pages, 3958 KiB

Open AccessArticle

Genomic Diversity and Hotspot Mutations in 30,983 SARS-CoV-2 Genomes: Moving Toward a Universal Vaccine for the “Confined Virus”?

by Tarek Alouane, Meriem Laamarti, Abdelomunim Essabbar, Mohammed Hakmi, El Mehdi Bouricha, M. W. Chemao-Elfihri, Souad Kartti, Nasma Boumajdi, Houda Bendani, Rokia Laamarti, Fatima Ghrifi, Loubna Allam, Tarik Aanniz, Mouna Ouadghiri, Naima El Hafidi, Rachid El Jaoudi, Houda Benrahma, Jalil El Attar, Rachid Mentag, Laila Sbabou, Chakib Nejjari, Saaid Amzazi, Lahcen Belyamani and Azeddine Ibrahimi Show full author list Hide full author list

Pathogens 2020, 9(10), 829; https://doi.org/10.3390/pathogens9100829 - 10 Oct 2020

Cited by 41 | Viewed by 7327

Abstract

The COVID-19 pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. Understanding and monitoring the genetic evolution of the virus, its geographical characteristics, and its stability are particularly important for controlling the spread of the disease and especially [...] Read more.

The COVID-19 pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. Understanding and monitoring the genetic evolution of the virus, its geographical characteristics, and its stability are particularly important for controlling the spread of the disease and especially for the development of a universal vaccine covering all circulating strains. From this perspective, we analyzed 30,983 complete SARS-CoV-2 genomes from 79 countries located in the six continents and collected from 24 December 2019, to 13 May 2020, according to the GISAID database. Our analysis revealed the presence of 3206 variant sites, with a uniform distribution of mutation types in different geographic areas. Remarkably, a low frequency of recurrent mutations has been observed; only 169 mutations (5.27%) had a prevalence greater than 1% of genomes. Nevertheless, fourteen non-synonymous hotspot mutations (>10%) have been identified at different locations along the viral genome; eight in ORF1ab polyprotein (in nsp2, nsp3, transmembrane domain, RdRp, helicase, exonuclease, and endoribonuclease), three in nucleocapsid protein, and one in each of three proteins: Spike, ORF3a, and ORF8. Moreover, 36 non-synonymous mutations were identified in the receptor-binding domain (RBD) of the spike protein with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike protein to the human ACE2 receptor. These results along with intra-genomic divergence of SARS-CoV-2 could indicate that unlike the influenza virus or HIV viruses, SARS-CoV-2 has a low mutation rate which makes the development of an effective global vaccine very likely. Full article

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9 pages, 234 KiB

Open AccessEditor’s ChoiceArticle

Statin Use Is Associated with Decreased Risk of Invasive Mechanical Ventilation in COVID-19 Patients: A Preliminary Study

by Sophia L. Song, Sarah B. Hays, Constance E. Panton, Evangelia K. Mylona, Markos Kalligeros, Fadi Shehadeh and Eleftherios Mylonakis

Pathogens 2020, 9(9), 759; https://doi.org/10.3390/pathogens9090759 - 17 Sep 2020

Cited by 41 | Viewed by 4166

Abstract

COVID-19 disproportionately affects patients with medical comorbidities such as cardiovascular disease (CVD). Patients with CVD are widely prescribed 3-hydroxy-3-methyl-glutayl-CoA (HMG-CoA) reductase inhibitors (statins), a class of lipid-lowering medications known for their pleiotropic anti-inflammatory and immunomodulatory effects. However, the relationship between statin use and [...] Read more.

COVID-19 disproportionately affects patients with medical comorbidities such as cardiovascular disease (CVD). Patients with CVD are widely prescribed 3-hydroxy-3-methyl-glutayl-CoA (HMG-CoA) reductase inhibitors (statins), a class of lipid-lowering medications known for their pleiotropic anti-inflammatory and immunomodulatory effects. However, the relationship between statin use and COVID-19 outcomes is not fully understood. In this preliminary study, we explored the association between statin use and severe COVID-19 outcomes in hospitalized patients, including intensive care unit (ICU) admission, the need for invasive mechanical ventilation (IMV), and in-hospital death. We performed a retrospective cohort study of 249 patients hospitalized with COVID-19 from 3 March 2020 to 10 April 2020 in Rhode Island, USA. Patient demographics, past medical history, current medications, and hospital course were recorded and analyzed. A multivariate logistic regression analysis was conducted to examine associations. After adjusting for age, sex, race, cardiovascular disease, chronic pulmonary disease, diabetes, and obesity, statin use was significantly associated with decreased risk for IMV (adjusted Odds Ratio (aOR) = 0.45, 95% Confidence Interval (CI): 0.20–0.99). Our results support the continued use of statins among COVID-19 patients and could have implications for future prospective studies on the management of COVID-19. Full article

19 pages, 927 KiB

Open AccessReview

Immune Response to COVID-19: Can We Benefit from the SARS-CoV and MERS-CoV Pandemic Experience?

by Emilia Sinderewicz, Wioleta Czelejewska, Katarzyna Jezierska-Wozniak, Joanna Staszkiewicz-Chodor and Wojciech Maksymowicz

Pathogens 2020, 9(9), 739; https://doi.org/10.3390/pathogens9090739 - 09 Sep 2020

Cited by 8 | Viewed by 5723

Abstract

The global range and high fatality rate of the newest human coronavirus (HCoV) pandemic has made SARS-CoV-2 the focus of the scientific world. Next-generation sequencing of the viral genome and a phylogenetic analysis have shown the high homology of SARS-CoV-2 to other HCoVs [...] Read more.

The global range and high fatality rate of the newest human coronavirus (HCoV) pandemic has made SARS-CoV-2 the focus of the scientific world. Next-generation sequencing of the viral genome and a phylogenetic analysis have shown the high homology of SARS-CoV-2 to other HCoVs that have led to local epidemics in the past. The experience acquired in SARS and MERS epidemics may prove useful in understanding the SARS-CoV-2 pathomechanism and lead to effective treatment and potential vaccine development. This study summarizes the immune response to SARS-CoV, MERS-CoV, and SARS-CoV-2 and focuses on T cell response, humoral immunity, and complement system activation in different stages of HCoVs infections. The study also presents the quantity and frequency of T cell responses, particularly CD4⁺ and CD8⁺; the profile of cytokine production and secretion; and its relation to T cell type, disease severity, and utility in prognostics of the course of SARS, MERS, and COVID-19 outbreaks. The role of interferons in the therapy of these infections is also discussed. Moreover, the kinetics of specific antibody production, the correlation between humoral and cellular immune response and the immunogenicity of the structural HCoVs proteins and their utility in the development of a vaccine against SARS, MERS, and COVID-19 has been updated. Full article

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26 pages, 3806 KiB

Open AccessReview

SARS-CoV-2 ORF8 and SARS-CoV ORF8ab: Genomic Divergence and Functional Convergence

by Sameer Mohammad, Abderrezak Bouchama, Bothina Mohammad Alharbi, Mamoon Rashid, Tanveer Saleem Khatlani, Nusaibah S. Gaber and Shuja Shafi Malik

Pathogens 2020, 9(9), 677; https://doi.org/10.3390/pathogens9090677 - 20 Aug 2020

Cited by 39 | Viewed by 9327

Abstract

The COVID-19 pandemic, in the first seven months, has led to more than 15 million confirmed infected cases and 600,000 deaths. SARS-CoV-2, the causative agent for COVID-19, has proved to be a great challenge for its ability to spread in asymptomatic stages and [...] Read more.

The COVID-19 pandemic, in the first seven months, has led to more than 15 million confirmed infected cases and 600,000 deaths. SARS-CoV-2, the causative agent for COVID-19, has proved to be a great challenge for its ability to spread in asymptomatic stages and the diverse disease spectrum it has generated. This has created a challenge of unimaginable magnitude, not only affecting human health and life but also potentially generating a long-lasting socioeconomic impact. Both medical sciences and biomedical research have also been challenged, consequently leading to a large number of clinical trials and vaccine initiatives. While known proteins of pathobiological importance are targets for these therapeutic approaches, it is imperative to explore other factors of viral significance. Accessory proteins are one such trait that have diverse roles in coronavirus pathobiology. Here, we analyze certain genomic characteristics of SARS-CoV-2 accessory protein ORF8 and predict its protein features. We have further reviewed current available literature regarding its function and comparatively evaluated these and other features of ORF8 and ORF8ab, its homolog from SARS-CoV. Because coronaviruses have been infecting humans repeatedly and might continue to do so, we therefore expect this study to aid in the development of holistic understanding of these proteins. Despite low nucleotide and protein identity and differentiating genome level characteristics, there appears to be significant structural integrity and functional proximity between these proteins pointing towards their high significance. There is further need for comprehensive genomics and structural-functional studies to lead towards definitive conclusions regarding their criticality and that can eventually define their relevance to therapeutics development. Full article

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14 pages, 4534 KiB

Open AccessEditor’s ChoiceArticle

Genetic Diversity Among SARS-CoV2 Strains in South America may Impact Performance of Molecular Detection

by Juan David Ramírez, Marina Muñoz, Carolina Hernández, Carolina Flórez, Sergio Gomez, Angelica Rico, Lisseth Pardo, Esther C. Barros and Alberto E. Paniz-Mondolfi

Pathogens 2020, 9(7), 580; https://doi.org/10.3390/pathogens9070580 - 17 Jul 2020

Cited by 30 | Viewed by 6069

Abstract

Since its emergence in Wuhan (China) on December 2019, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide. After its arrival in South America in February 2020, the virus has expanded throughout the region, infecting over 900,000 individuals with approximately [...] Read more.

Since its emergence in Wuhan (China) on December 2019, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide. After its arrival in South America in February 2020, the virus has expanded throughout the region, infecting over 900,000 individuals with approximately 41,000 reported deaths to date. In response to the rapidly growing number of cases, a number of different primer-probe sets have been developed. However, despite being highly specific, most of these primer-probe sets are known to exhibit variable sensitivity. Currently, there are more than 300 SARS-CoV2 whole genome sequences deposited in databases from Brazil, Chile, Ecuador, Colombia, Uruguay, Peru, and Argentina. To test how regional viral diversity may impact oligo binding sites and affect test performance, we reviewed all available primer-probe sets targeting the E, N, and RdRp genes against available South American SARS-CoV-2 genomes checking for nucleotide variations in annealing sites. Results from this in silico analysis showed no nucleotide variations on the E-gene target region, in contrast to the N and RdRp genes which showed massive nucleotide variations within oligo binding sites. In lines with previous data, our results suggest that the E-gene stands as the most conserved and reliable target when considering single-gene target testing for molecular diagnosis of SARS-CoV-2 in South America. Full article

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16 pages, 2197 KiB

Open AccessEditor’s ChoiceArticle

Mutational Frequencies of SARS-CoV-2 Genome during the Beginning Months of the Outbreak in USA

by Neha Kaushal, Yogita Gupta, Mehendi Goyal, Svetlana F. Khaiboullina, Manoj Baranwal and Subhash C. Verma

Pathogens 2020, 9(7), 565; https://doi.org/10.3390/pathogens9070565 - 13 Jul 2020

Cited by 55 | Viewed by 6707

Abstract

SARS-CoV-2 has spread very quickly from its first reported case on 19 January 2020 in the United Stated of America, leading WHO to declare pandemic by 11 March 2020. RNA viruses accumulate mutations following replication and passage in human population, which prompted us [...] Read more.

SARS-CoV-2 has spread very quickly from its first reported case on 19 January 2020 in the United Stated of America, leading WHO to declare pandemic by 11 March 2020. RNA viruses accumulate mutations following replication and passage in human population, which prompted us to determine the rate and the regions (hotspots) of the viral genome with high rates of mutation. We analyzed the rate of mutation accumulation over a period of 11 weeks (submitted between 19th January to 15 April 2020) in USA SARS-CoV-2 genome. Our analysis identified that majority of the viral genes accumulated mutations, although with varying rates and these included NSP2, NSP3, RdRp, helicase, Spike, ORF3a, ORF8, and Nucleocapsid protein. Sixteen mutations accumulated in Spike protein in which four mutations are located in the receptor binding domain. Intriguingly, we identified a fair number of viral proteins (NSP7, NSP9, NSP10, NSP11, Envelop, ORF6, and ORF7b proteins), which did not accumulate any mutation. Limited changes in these proteins may suggest that they have conserved functions, which are essential for virus propagation. This provides a basis for a better understanding of the genetic variation in SARS-CoV-2 circulating in the US, which could help in identifying potential therapeutic targets for controlling COVID-19. Full article

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35 pages, 1989 KiB

Open AccessReview

SARS-CoV-2, ACE2, and Hydroxychloroquine: Cardiovascular Complications, Therapeutics, and Clinical Readouts in the Current Settings

by Rajkumar Singh Kalra, Dhanendra Tomar, Avtar Singh Meena and Ramesh Kandimalla

Pathogens 2020, 9(7), 546; https://doi.org/10.3390/pathogens9070546 - 07 Jul 2020

Cited by 32 | Viewed by 6408

Abstract

The rapidly evolving coronavirus disease 2019 (COVID-19, caused by severe acute respiratory syndrome coronavirus 2- SARS-CoV-2), has greatly burdened the global healthcare system and led it into crisis in several countries. Lack of targeted therapeutics led to the idea of repurposing broad-spectrum drugs [...] Read more.

The rapidly evolving coronavirus disease 2019 (COVID-19, caused by severe acute respiratory syndrome coronavirus 2- SARS-CoV-2), has greatly burdened the global healthcare system and led it into crisis in several countries. Lack of targeted therapeutics led to the idea of repurposing broad-spectrum drugs for viral intervention. In vitro analyses of hydroxychloroquine (HCQ)’s anecdotal benefits prompted its widespread clinical repurposing globally. Reports of emerging cardiovascular complications due to its clinical prescription are revealing the crucial role of angiotensin-converting enzyme 2 (ACE2), which serves as a target receptor for SARS-CoV-2. In the present settings, a clear understanding of these targets, their functional aspects and physiological impact on cardiovascular function are critical. In an up-to-date format, we shed light on HCQ’s anecdotal function in stalling SARS-CoV-2 replication and immunomodulatory activities. While starting with the crucial role of ACE2, we here discuss the impact of HCQ on systemic cardiovascular function, its associated risks, and the scope of HCQ-based regimes in current clinical settings. Citing the extent of HCQ efficacy, the key considerations and recommendations for the use of HCQ in clinics are further discussed. Taken together, this review provides crucial insights into the role of ACE2 in SARS-CoV-2-led cardiovascular activity, and concurrently assesses the efficacy of HCQ in contemporary clinical settings. Full article

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30 pages, 2251 KiB

Open AccessEditor’s ChoiceReview

Coronavirus Disease Pandemic (COVID-19): Challenges and a Global Perspective

by Yashpal Singh Malik, Naveen Kumar, Shubhankar Sircar, Rahul Kaushik, Sudipta Bhat, Kuldeep Dhama, Parakriti Gupta, Kapil Goyal, Mini P Singh, Ujjala Ghoshal, Mohamed E. El Zowalaty, VinodhKumar O. R, Mohd Iqbal Yatoo, Ruchi Tiwari, Mamta Pathak, Shailesh Kumar Patel, Ranjit Sah, Alfonso J Rodriguez-Morales, Balasubramanian Ganesh, Prashant Kumar and Raj Kumar Singh Show full author list Hide full author list

Pathogens 2020, 9(7), 519; https://doi.org/10.3390/pathogens9070519 - 28 Jun 2020

Cited by 97 | Viewed by 16154

Abstract

The technology-driven world of the 21^st century is currently confronted with a major threat to humankind, represented by the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2). As of now, COVID-19 has affected more than 6 million [...] Read more.

The technology-driven world of the 21^st century is currently confronted with a major threat to humankind, represented by the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2). As of now, COVID-19 has affected more than 6 million confirmed cases and took 0.39 million human lives. SARS-CoV-2 spreads much faster than its two ancestors, SARS-CoV and Middle East respiratory syndrome-CoV (MERS-CoV), but has low fatality rates. Our analyses speculate that the efficient replication and transmission of SARS-CoV-2 might be due to the high-density basic amino acid residues, preferably positioned in close proximity at both the furin-like cleavage sites (S1/S2 and S2’) within the spike protein. Given the high genomic similarities of SARS-CoV-2 to bat SARS-like CoVs, it is likely that bats serve as a reservoir host for its progenitor. Women and children are less susceptible to SARS-CoV-2 infection, while the elderly and people with comorbidities are more prone to serious clinical outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. The cohesive approach amongst researchers across the globe has delivered high-end viral diagnostics. However, home-based point-of-care diagnostics are still under development, which may prove transformative in current COVID-19 pandemic containment. Similarly, vaccines and therapeutics against COVID-19 are currently in the pipeline for clinical trials. In this review, we discuss the noteworthy advancements, focusing on the etiological viral agent, comparative genomic analysis, population susceptibility, disease epidemiology and diagnosis, animal reservoirs, laboratory animal models, disease transmission, therapeutics, vaccine challenges, and disease mitigation measures. Full article

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16 pages, 1882 KiB

Open AccessEditor’s ChoiceReview

Emerging Prevention and Treatment Strategies to Control COVID-19

by Vipul K. Singh, Abhishek Mishra, Shubhra Singh, Premranjan Kumar, Manisha Singh, Chinnaswamy Jagannath and Arshad Khan

Pathogens 2020, 9(6), 501; https://doi.org/10.3390/pathogens9060501 - 23 Jun 2020

Cited by 19 | Viewed by 10924

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has now become a serious global threat after inflicting more than 8 million infections and 425,000 deaths in less than 6 months. Currently, no definitive treatment or prevention [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has now become a serious global threat after inflicting more than 8 million infections and 425,000 deaths in less than 6 months. Currently, no definitive treatment or prevention therapy exists for COVID-19. The unprecedented rise of this pandemic has rapidly fueled research efforts to discover and develop new vaccines and treatment strategies against this novel coronavirus. While hundreds of vaccines/therapeutics are still in the preclinical or early stage of clinical development, a few of them have shown promising results in controlling the infection. Here, in this review, we discuss the promising vaccines and treatment options for COVID-19, their challenges, and potential alternative strategies. Full article

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19 pages, 951 KiB

Open AccessEditor’s ChoiceReview

Coronavirus Disease 2019 (COVID–19): A Short Review on Hematological Manifestations

by Artur Słomka, Mariusz Kowalewski and Ewa Żekanowska

Pathogens 2020, 9(6), 493; https://doi.org/10.3390/pathogens9060493 - 20 Jun 2020

Cited by 72 | Viewed by 7461

Abstract

Infection with severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2) is a rapidly spreading and devastating global pandemic. Many researchers are attempting to clarify the mechanisms of infection and to develop a drug or vaccine against the virus, but there are still no proven [...] Read more.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2) is a rapidly spreading and devastating global pandemic. Many researchers are attempting to clarify the mechanisms of infection and to develop a drug or vaccine against the virus, but there are still no proven effective treatments. The present article reviews the common presenting hematological manifestations of coronavirus disease 2019 (COVID–19). Elucidating the changes in hematological parameters in SARS–CoV–2 infected patients could help to understand the pathophysiology of the disease and may provide early clues to diagnosis. Several studies have shown that hematological parameters are markers of disease severity and suggest that they mediate disease progression. Full article

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22 pages, 1089 KiB

Open AccessEditor’s ChoiceReview

A Review on SARS-CoV-2 Virology, Pathophysiology, Animal Models, and Anti-Viral Interventions

by Sabari Nath Neerukonda and Upendra Katneni

Pathogens 2020, 9(6), 426; https://doi.org/10.3390/pathogens9060426 - 29 May 2020

Cited by 43 | Viewed by 9228

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective antiviral therapy or vaccine currently exists, and supportive [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective antiviral therapy or vaccine currently exists, and supportive care remains to be the cornerstone treatment. Through previous lessons learned from SARS-CoV-1 and MERS-CoV studies, scientific groups worldwide have rapidly expanded the knowledge pertaining to SARS-CoV-2 virology that includes in vitro and in vivo models for testing of antiviral therapies and randomized clinical trials. In the present narrative, we review SARS-CoV-2 virology, clinical features, pathophysiology, and animal models with a specific focus on the antiviral and adjunctive therapies currently being tested or that require testing in animal models and randomized clinical trials. Full article

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14 pages, 3323 KiB

Open AccessEditor’s ChoiceReview

SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far

by Firas A. Rabi, Mazhar S. Al Zoubi, Ghena A. Kasasbeh, Dunia M. Salameh and Amjad D. Al-Nasser

Pathogens 2020, 9(3), 231; https://doi.org/10.3390/pathogens9030231 - 20 Mar 2020

Cited by 479 | Viewed by 141477

Abstract

In December 2019, a cluster of fatal pneumonia cases presented in Wuhan, China. They were caused by a previously unknown coronavirus. All patients had been associated with the Wuhan Wholefood market, where seafood and live animals are sold. The virus spread rapidly and [...] Read more.

In December 2019, a cluster of fatal pneumonia cases presented in Wuhan, China. They were caused by a previously unknown coronavirus. All patients had been associated with the Wuhan Wholefood market, where seafood and live animals are sold. The virus spread rapidly and public health authorities in China initiated a containment effort. However, by that time, travelers had carried the virus to many countries, sparking memories of the previous coronavirus epidemics, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and causing widespread media attention and panic. Based on clinical criteria and available serological and molecular information, the new disease was called coronavirus disease of 2019 (COVID-19), and the novel coronavirus was called SARS Coronavirus-2 (SARS-CoV-2), emphasizing its close relationship to the 2002 SARS virus (SARS-CoV). The scientific community raced to uncover the origin of the virus, understand the pathogenesis of the disease, develop treatment options, define the risk factors, and work on vaccine development. Here we present a summary of current knowledge regarding the novel coronavirus and the disease it causes. Full article

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