Topical Collection "SARS-CoV Infections"

A topical collection in Pathogens (ISSN 2076-0817). This collection belongs to the section "Viral Pathogens".

Editor

Dr. Lisa Gralinski
E-Mail Website
Collection Editor
Department of Epidemiology, University of North Carolina (UNC) at Chapel Hill, Chapel Hill, NC, USA
Interests: host genetic variation; severity of respiratory virus infection; SARS-CoV; Influenza virus.

Topical Collection Information

Dear Colleagues,

SARS Coronavirus (CoV) caused the first epidemic of the 21st century. The zoonotic emergence of SARS-CoV highlights the risk of rapid global spread of a highly infectious, novel pathogen. Disease ranged from mild respiratory symptoms to development of acute respiratory distress syndrome (ARDS) and death; ultimately the virus infected over 8,000 people with a 10% mortality rate. While SARS-CoV was contained by effective public health measures, a number of highly related zoonotic viruses have been found in bats that are fully capable of infecting human cells.

In the 16 years since SARS-CoV was identified, much has been learned about its emergence, replication and resulting disease. Several reverse genetics systems have allowed for investigation of the role of viral genes in both in vitro and in vivo infections while development of small animal models has allowed examination of the role of the host immune response following infection. Recent advances in structural biology have provided critical insights into how the viral spike protein binds to its cellular receptor, Ace2.

We would like to invite you to contribute to a Topical Collection on SARS-CoV Infections. In this Special Issue we welcome the coronavirus community to submit a research article, review or short communication focused on SARS-CoV emergence, replication, disease pathogenesis and protection, host immune response modulation, structural insights or anti-viral therapeutics.

We look forward to your contribution.

Dr. Lisa Gralinski
Collection Editor

Circulating bat viruses and emerging coronaviruses, recent structure advances, reverse genetics systems, immune mediated disease, 1st epidemic of 21st century

Manuscript Submission Information

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Keywords

  • coronavirus
  • SARS-CoV
  • respiratory virus
  • viral pathogenesis
  • immune response
  • zoonosis

Published Papers (34 papers)

2021

Jump to: 2020

Review
Sewage Systems Surveillance for SARS-CoV-2: Identification of Knowledge Gaps, Emerging Threats, and Future Research Needs
Pathogens 2021, 10(8), 946; https://doi.org/10.3390/pathogens10080946 - 28 Jul 2021
Viewed by 222
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. Thus, this systematic review 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 wastewater-based epidemiology 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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Brief Report
Presence of SARS-CoV-2 in a Cornea Transplant
Pathogens 2021, 10(8), 934; https://doi.org/10.3390/pathogens10080934 - 24 Jul 2021
Viewed by 335
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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Communication
Antibodies Targeting Two Epitopes in SARS-CoV-2 Neutralize Pseudoviruses with the Spike Proteins from Different Variants
Pathogens 2021, 10(7), 869; https://doi.org/10.3390/pathogens10070869 - 09 Jul 2021
Viewed by 454
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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Article
Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation
Pathogens 2021, 10(6), 763; https://doi.org/10.3390/pathogens10060763 - 17 Jun 2021
Viewed by 15975
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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Article
Rapid Inactivation In Vitro of SARS-CoV-2 in Saliva by Black Tea and Green Tea
Pathogens 2021, 10(6), 721; https://doi.org/10.3390/pathogens10060721 - 08 Jun 2021
Viewed by 1927
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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Article
Performance of the LIAISON® SARS-CoV-2 Antigen Assay vs. SARS-CoV-2-RT-PCR
Pathogens 2021, 10(6), 658; https://doi.org/10.3390/pathogens10060658 - 26 May 2021
Viewed by 851
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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Review
Fundamental and Advanced Therapies, Vaccine Development against SARS-CoV-2
Pathogens 2021, 10(6), 636; https://doi.org/10.3390/pathogens10060636 - 21 May 2021
Viewed by 977
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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Case Report
Mild Symptomatic SARS-CoV-2 P.1 (B.1.1.28) Infection in a Fully Vaccinated 83-Year-Old Man
Pathogens 2021, 10(5), 614; https://doi.org/10.3390/pathogens10050614 - 17 May 2021
Viewed by 742
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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Review
Neonatal SARS-CoV-2 Infection: Practical Tips
Pathogens 2021, 10(5), 611; https://doi.org/10.3390/pathogens10050611 - 17 May 2021
Viewed by 732
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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Review
Endothelial Dysfunction and SARS-CoV-2 Infection: Association and Therapeutic Strategies
Pathogens 2021, 10(5), 582; https://doi.org/10.3390/pathogens10050582 - 11 May 2021
Cited by 1 | Viewed by 736
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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Graphical abstract

Review
Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses
Pathogens 2021, 10(5), 565; https://doi.org/10.3390/pathogens10050565 - 07 May 2021
Cited by 3 | Viewed by 1608
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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Case Report
Myopericarditis Associated with COVID-19 in a Pediatric Patient with Kidney Failure Receiving Hemodialysis
Pathogens 2021, 10(4), 486; https://doi.org/10.3390/pathogens10040486 - 17 Apr 2021
Viewed by 571
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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Opinion
Why Does SARS-CoV-2 Infection Induce Autoantibody Production?
Pathogens 2021, 10(3), 380; https://doi.org/10.3390/pathogens10030380 - 22 Mar 2021
Viewed by 580
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
Article
Evaluation of “Caterina assay”: An Alternative Tool to the Commercialized Kits Used for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Identification
Pathogens 2021, 10(3), 325; https://doi.org/10.3390/pathogens10030325 - 10 Mar 2021
Viewed by 620
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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Article
Molecular Epidemiology Surveillance of SARS-CoV-2: Mutations and Genetic Diversity One Year after Emerging
Pathogens 2021, 10(2), 184; https://doi.org/10.3390/pathogens10020184 - 09 Feb 2021
Cited by 5 | Viewed by 1137
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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Review
Host Diversity and Potential Transmission Pathways of SARS-CoV-2 at the Human-Animal Interface
Pathogens 2021, 10(2), 180; https://doi.org/10.3390/pathogens10020180 - 08 Feb 2021
Cited by 2 | Viewed by 1899
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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Article
Psychophysical Evaluation of the Olfactory Function: European Multicenter Study on 774 COVID-19 Patients
Pathogens 2021, 10(1), 62; https://doi.org/10.3390/pathogens10010062 - 12 Jan 2021
Cited by 9 | Viewed by 708
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

Jump to: 2021

Article
Clinical Presentation, Course, and Risk Factors Associated with Mortality in a Severe Outbreak of COVID-19 in Rhode Island, USA, April–June 2020
Pathogens 2021, 10(1), 8; https://doi.org/10.3390/pathogens10010008 - 24 Dec 2020
Cited by 1 | Viewed by 1165
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
Article
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?
Pathogens 2020, 9(12), 1011; https://doi.org/10.3390/pathogens9121011 - 01 Dec 2020
Cited by 6 | Viewed by 807
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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Review
Antibody-Based Immunotherapeutic Strategies for COVID-19
Pathogens 2020, 9(11), 917; https://doi.org/10.3390/pathogens9110917 - 05 Nov 2020
Cited by 5 | Viewed by 1261
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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Review
Threading the Pieces Together: Integrative Perspective on SARS-CoV-2
Pathogens 2020, 9(11), 912; https://doi.org/10.3390/pathogens9110912 - 04 Nov 2020
Cited by 1 | Viewed by 1104
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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Article
Predictive Accuracy of COVID-19 World Health Organization (WHO) Severity Classification and Comparison with a Bayesian-Method-Based Severity Score (EPI-SCORE)
Pathogens 2020, 9(11), 880; https://doi.org/10.3390/pathogens9110880 - 24 Oct 2020
Cited by 3 | Viewed by 1448
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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Article
Genomic Diversity and Hotspot Mutations in 30,983 SARS-CoV-2 Genomes: Moving Toward a Universal Vaccine for the “Confined Virus”?
Pathogens 2020, 9(10), 829; https://doi.org/10.3390/pathogens9100829 - 10 Oct 2020
Cited by 18 | Viewed by 2479
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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Article
Statin Use Is Associated with Decreased Risk of Invasive Mechanical Ventilation in COVID-19 Patients: A Preliminary Study
Pathogens 2020, 9(9), 759; https://doi.org/10.3390/pathogens9090759 - 17 Sep 2020
Cited by 17 | Viewed by 1219
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
Review
Immune Response to COVID-19: Can We Benefit from the SARS-CoV and MERS-CoV Pandemic Experience?
Pathogens 2020, 9(9), 739; https://doi.org/10.3390/pathogens9090739 - 09 Sep 2020
Viewed by 1701
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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Review
SARS-CoV-2 ORF8 and SARS-CoV ORF8ab: Genomic Divergence and Functional Convergence
Pathogens 2020, 9(9), 677; https://doi.org/10.3390/pathogens9090677 - 20 Aug 2020
Cited by 15 | Viewed by 2402
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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Article
Genetic Diversity Among SARS-CoV2 Strains in South America may Impact Performance of Molecular Detection
Pathogens 2020, 9(7), 580; https://doi.org/10.3390/pathogens9070580 - 17 Jul 2020
Cited by 14 | Viewed by 3076
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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Article
Mutational Frequencies of SARS-CoV-2 Genome during the Beginning Months of the Outbreak in USA
Pathogens 2020, 9(7), 565; https://doi.org/10.3390/pathogens9070565 - 13 Jul 2020
Cited by 18 | Viewed by 2132
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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Review
SARS-CoV-2, ACE2, and Hydroxychloroquine: Cardiovascular Complications, Therapeutics, and Clinical Readouts in the Current Settings
Pathogens 2020, 9(7), 546; https://doi.org/10.3390/pathogens9070546 - 07 Jul 2020
Cited by 18 | Viewed by 2732
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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Review
Coronavirus Disease Pandemic (COVID-19): Challenges and a Global Perspective
Pathogens 2020, 9(7), 519; https://doi.org/10.3390/pathogens9070519 - 28 Jun 2020
Cited by 40 | Viewed by 5579
Abstract
The technology-driven world of the 21st 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 21st 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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Review
Emerging Prevention and Treatment Strategies to Control COVID-19
Pathogens 2020, 9(6), 501; https://doi.org/10.3390/pathogens9060501 - 23 Jun 2020
Cited by 10 | Viewed by 4560
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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Review
Coronavirus Disease 2019 (COVID–19): A Short Review on Hematological Manifestations
Pathogens 2020, 9(6), 493; https://doi.org/10.3390/pathogens9060493 - 20 Jun 2020
Cited by 44 | Viewed by 2766
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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Review
A Review on SARS-CoV-2 Virology, Pathophysiology, Animal Models, and Anti-Viral Interventions
Pathogens 2020, 9(6), 426; https://doi.org/10.3390/pathogens9060426 - 29 May 2020
Cited by 21 | Viewed by 4139
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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Review
SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far
Pathogens 2020, 9(3), 231; https://doi.org/10.3390/pathogens9030231 - 20 Mar 2020
Cited by 224 | Viewed by 30495
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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