COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Virology".

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 197333

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Department Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Viale Brambilla 74, 27100 Pavia, Italy
Interests: development and validation of molecular tools for diagnosis and monitoring of viral infections; study of mechanisms of resistance to antiviral drugs; study of pathogenesis of virus infection in immunocompetent and immunocompromised hosts; diagnosis and treatment of opportunistic infections in transplant recipients; study of virus evolution and quasispecies development, surveillance of emerging and reemerging virus infections

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Guest Editor
Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia/Infectious Diseases Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Interests: viral infections; treatment; clinical impact; antiviral drugs; clinical picture
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Special Issue Information

Dear Colleagues, 

We are all personally involved this very moment in history in the largest outbreak outside China of COVID-19; as such, I am positive that the more data we can gather and the more we know about this new clinical entity, the better equipped the scientific and medical community will be to fight back.

Thus, I believe that the readership of Microorganisms will greatly appreciate a collection of updated epidemiologic, virologic, and clinically-oriented papers on the many obscure aspects of this new pandemic.

In more detail, these are some of the most pressing questions in this topic:

  1. Epidemiologic aspects: i) Is the infection kinetics the same in different countries? ii) What is the impact of different demographic composition on lethality and mortality rate? iii) What is the impact of different countermeasures on the SARS-CoV2 spread? v) Seroprevalence? vi) R0 and Rt in different countries?
  2. Virology: i) Innovative molecular assays? ii) What is the impact of serologic assays on rapid diagnostics? iii) Drug susceptibility? iv) Genetic variability? v) Humoral and T-cell response kinetics?
  3. Clinical: i) What is the Sars-CoV2 load and disease progression? ii) What is the effect of experimental drugs on virologic and clinical recovery? iii) NT levels and disease progression? iv) progression scores? v) COVID-associated clinical pictures? vi) risk factors for disease progression and death?

Dr. Fausto Baldanti
Dr. Raffaele Bruno
Guest Editors

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Keywords

  • COVID-19
  • SARS-CoV-2
  • epidemics
  • diagnosis
  • antiviral treatment
  • clinical presentation
  • molecular epidemiology
  • outbreak
  • risk factors
  • prognostic parameters
  • pathogenesis
  • immune response
  • sequencing

Published Papers (42 papers)

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16 pages, 1521 KiB  
Article
Unique Evolution of SARS-CoV-2 in the Second Large Cruise Ship Cluster in Japan
by Haruka Abe, Yuri Ushijima, Murasaki Amano, Yasuteru Sakurai, Rokusuke Yoshikawa, Takaaki Kinoshita, Yohei Kurosaki, Katsunori Yanagihara, Koichi Izumikawa, Kouichi Morita, Shigeru Kohno and Jiro Yasuda
Microorganisms 2022, 10(1), 99; https://doi.org/10.3390/microorganisms10010099 - 04 Jan 2022
Cited by 2 | Viewed by 2687
Abstract
In the initial phase of the novel coronavirus disease (COVID-19) pandemic, a large-scale cluster on the cruise ship Diamond Princess (DP) emerged in Japan. Genetic analysis of the DP strains has provided important information for elucidating the possible transmission process of severe acute [...] Read more.
In the initial phase of the novel coronavirus disease (COVID-19) pandemic, a large-scale cluster on the cruise ship Diamond Princess (DP) emerged in Japan. Genetic analysis of the DP strains has provided important information for elucidating the possible transmission process of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a cruise ship. However, genome-based analyses of SARS-CoV-2 detected in large-scale cruise ship clusters other than the DP cluster have rarely been reported. In the present study, whole-genome sequences of 94 SARS-CoV-2 strains detected in the second large cruise ship cluster, which emerged on the Costa Atlantica (CA) in Japan, were characterized to understand the evolution of the virus in a crowded and confined place. Phylogenetic and haplotype network analysis indicated that the CA strains were derived from a common ancestral strain introduced on the CA cruise ship and spread in a superspreading event-like manner, resulting in several mutations that might have affected viral characteristics, including the P681H substitution in the spike protein. Moreover, there were significant genetic distances between CA strains and other strains isolated in different environments, such as cities under lockdown. These results provide new insights into the unique evolution patterns of SARS-CoV-2 in the CA cruise ship cluster. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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11 pages, 3149 KiB  
Article
Characterization of IgG Antibody Response against SARS-CoV-2 (COVID-19) in the Cypriot Population
by George Krashias, Elie Deeba, Astero Constantinou, Maria Hadjiagapiou, Dana Koptides, Jan Richter, Christina Tryfonos, Stavros Bashiardes, Anastasia Lambrianides, Maria A. Loizidou, Andreas Hadjisavvas, Mihalis I. Panayiotidis and Christina Christodoulou
Microorganisms 2022, 10(1), 85; https://doi.org/10.3390/microorganisms10010085 - 31 Dec 2021
Cited by 2 | Viewed by 1638
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has hit its second year and continues to damage lives and livelihoods across the globe. There continues to be a global effort to present serological data on SARS-CoV-2 antibodies in different individuals. As such, [...] Read more.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has hit its second year and continues to damage lives and livelihoods across the globe. There continues to be a global effort to present serological data on SARS-CoV-2 antibodies in different individuals. As such, this study aimed to characterize the seroprevalence of SARS-CoV-2 antibodies in the Cypriot population for the first time since the pandemic started. Our results show that a majority of people infected with SARS-CoV-2 developed IgG antibodies against the virus, whether anti-NP, anti-S1RBD, or both, at least 20 days after their infection. Additionally, the percentage of people with at least one antibody against SARS-CoV-2 in the group of volunteers deemed SARS-CoV-2 negative via RT-PCR or who remain untested/undetermined (14.43%) is comparable to other reported percentages worldwide, ranging anywhere from 0.2% to 24%. We postulate that these percentages reflect the underreporting of true infections in the population, and also show the steady increase of herd immunity. Additionally, we showed a significantly marked decrease in anti-NP IgG antibodies in contrast to relatively stable levels of anti-S1RBD IgG antibodies in previously infected individuals across time. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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11 pages, 1544 KiB  
Article
The Combined Use of Cytokine Serum Values with Laboratory Parameters Improves Mortality Prediction of COVID-19 Patients: The Interleukin-15-to-Albumin Ratio
by Salma A. Rizo-Téllez, Lucia A. Méndez-García, Ana C. Rivera-Rugeles, Marcela Miranda-García, Aarón N. Manjarrez-Reyna, Rebeca Viurcos-Sanabria, Helena Solleiro-Villavicencio, Enrique Becerril-Villanueva, José D. Carrillo-Ruíz, Julian M. Cota-Arce, Angélica Álvarez-Lee, Marco A. De León-Nava and Galileo Escobedo
Microorganisms 2021, 9(10), 2159; https://doi.org/10.3390/microorganisms9102159 - 16 Oct 2021
Cited by 4 | Viewed by 2489
Abstract
Laboratory parameters display limited accuracy in predicting mortality in coronavirus disease 2019 (COVID-19) patients, as with serum albumin. Emerging evidence suggests that cytokine serum values may enhance the predictive capacity of albumin, especially interleukin (IL)-15. We thus investigated whether the use of the [...] Read more.
Laboratory parameters display limited accuracy in predicting mortality in coronavirus disease 2019 (COVID-19) patients, as with serum albumin. Emerging evidence suggests that cytokine serum values may enhance the predictive capacity of albumin, especially interleukin (IL)-15. We thus investigated whether the use of the IL-15-to-albumin ratio enables improving mortality prediction at hospital admission in a large group of COVID-19 patients. In this prospective cross-sectional study, we enrolled and followed up three hundred and seventy-eight patients with a COVID-19 diagnosis until hospital discharge or death. Two hundred and fifty-five patients survived, whereas one hundred and twenty-three died. Student’s T-test revealed that non-survivors had a significant two-fold increase in the IL-15-to-albumin ratio compared to survivors (167.3 ± 63.8 versus 74.2 ± 28.5), a difference that was more evident than that found for IL-15 or albumin separately. Likewise, mortality prediction considerably improved when using the IL-15-to-albumin ratio with a cut-off point > 105.4, exhibiting an area under the receiver operating characteristic curve of 0.841 (95% Confidence Interval, 0.725–0.922, p < 0.001). As we outlined here, this is the first study showing that combining IL-15 serum values with albumin improves mortality prediction in COVID-19 patients. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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9 pages, 218 KiB  
Communication
In Vitro Rapid Antigen Test Performance with the SARS-CoV-2 Variants of Concern B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta)
by Sabrina Jungnick, Bernhard Hobmaier, Lena Mautner, Mona Hoyos, Maren Haase, Armin Baiker, Heidi Lahne, Ute Eberle, Clara Wimmer, Sabrina Hepner, Annika Sprenger, Carola Berger, Alexandra Dangel, Siegfried Ippisch, Sonja Hahner, Manfred Wildner, Bernhard Liebl, Nikolaus Ackermann, Andreas Sing and Volker Fingerle
Microorganisms 2021, 9(9), 1967; https://doi.org/10.3390/microorganisms9091967 - 16 Sep 2021
Cited by 17 | Viewed by 3026
Abstract
Rapid antigen tests (RATs) are an integral part of SARS-CoV-2 containment strategies. As emerging variants of concern (VOCs) displace the initially circulating strains, it is crucial that RATs do not fail to detect these new variants. In this study, four RATs for nasal [...] Read more.
Rapid antigen tests (RATs) are an integral part of SARS-CoV-2 containment strategies. As emerging variants of concern (VOCs) displace the initially circulating strains, it is crucial that RATs do not fail to detect these new variants. In this study, four RATs for nasal swab testing were investigated using cultured strains of B.1.1 (non-VOC), B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta). Based on dilution series in cell culture medium and pooled saliva, the limit of detection of these RATs was determined in a laboratory setting. Further investigations on cross-reactivity were conducted using recombinant N-protein from seasonal human coronaviruses (hCoVs). RATs evaluated showed an overall comparable performance with cultured strains of the non-VOC B.1.1 and the VOCs Alpha, Beta, Gamma, and Delta. No cross-reactivity was detected with recombinant N-protein of the hCoV strains HKU1, OC43, NL63, and 229E. A continuous evaluation of SARS-CoV-2 RAT performance is required, especially with regard to evolving mutations. Moreover, cross-reactivity and interference with pathogens and other substances on the test performance of RATs should be consistently investigated to ensure suitability in the context of SARS-CoV-2 containment. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
18 pages, 1576 KiB  
Article
Liver Involvement in Children with COVID-19 and Multisystem Inflammatory Syndrome: A Single-Center Bulgarian Observational Study
by Snezhina Lazova, Tea Alexandrova, Nadzhie Gorelyova-Stefanova, Kalin Atanasov, Iren Tzotcheva and Tsvetelina Velikova
Microorganisms 2021, 9(9), 1958; https://doi.org/10.3390/microorganisms9091958 - 15 Sep 2021
Cited by 14 | Viewed by 4413
Abstract
SARS-CoV-2 infection may precede and cause various autoimmune and inflammatory diseases, including multisystem inflammatory syndrome in children (MIS-C). Therefore, we aimed to observe the clinical presentation and laboratory, instrumental and other constellations in children with MIS-C, including liver involvement. We present the outcomes [...] Read more.
SARS-CoV-2 infection may precede and cause various autoimmune and inflammatory diseases, including multisystem inflammatory syndrome in children (MIS-C). Therefore, we aimed to observe the clinical presentation and laboratory, instrumental and other constellations in children with MIS-C, including liver involvement. We present the outcomes from a single-center prospective observational study in which 89 children was included (60 with proven COVID-19, 10 symptomatic with confirmed COVID-19 contact and 19 diagnosed with MIS-C). Laboratory, instrumental, immunological, and clinical investigations were performed. Only 12% (n = 4) from the COVID-19 group (except the ICU cases), we found elevated AST and/or ALT (up to 100). All of the children with elevated transaminase were overweight or obese, presenting along with moderate COVID-19 pneumonia. The majority of children with MIS-C showed typical laboratory constellations with higher levels of IL-6 (120.36 ± 35.56 ng/mL). About half of the children in the MIS-C group (52%, n = 11) showed elevated transaminases. Eleven children (57.9%) presented with abdominal pain, eight (42.1%) with ascites, two (10.5%) with hepatosplenomegaly, and four (21.1%) with symptoms such as diarrhea. Mesenteric lymphadenitis was observed more often in patients with elevated LDH (327.83 ± 159.39, p = 0.077). Ascites was associated with lymphopenia (0.86 ± 0.80, p = 0.029) and elevated LDH. Hepato-splenomegaly was also more frequent in children with lymphopenia (0.5 ± 0.14, p = 0.039), higher troponin (402.00 ± 101.23, p = 0.004) and low ESR. Diarrhea was more frequent in patients with lower CRP (9.00 ± 3.44 vs. 22.25 ± 2.58, p = 0.04), and higher AST and ALT (469.00 ± 349.59 vs. and 286.67 ± 174.91, respectively, p = 0.010), and D-dimer (4516.66 ± 715.83, p = 0.001). Our data suggest that the liver can also be involved in MIS-C, presenting with typical laboratory and instrumental outcomes. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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12 pages, 396 KiB  
Article
Sensitivity of Rapid Antigen Testing and RT-PCR Performed on Nasopharyngeal Swabs versus Saliva Samples in COVID-19 Hospitalized Patients: Results of a Prospective Comparative Trial (RESTART)
by Antonios Kritikos, Giorgia Caruana, René Brouillet, John-Paul Miroz, Samia Abed-Maillard, Geraldine Stieger, Onya Opota, Antony Croxatto, Peter Vollenweider, Pierre-Alexandre Bart, Jean-Daniel Chiche and Gilbert Greub
Microorganisms 2021, 9(9), 1910; https://doi.org/10.3390/microorganisms9091910 - 09 Sep 2021
Cited by 23 | Viewed by 3479
Abstract
Saliva sampling could serve as an alternative non-invasive sample for SARS-CoV-2 diagnosis while rapid antigen tests (RATs) might help to mitigate the shortage of reagents sporadically encountered with RT-PCR. Thus, in the RESTART study we compared antigen and RT-PCR testing methods on nasopharyngeal [...] Read more.
Saliva sampling could serve as an alternative non-invasive sample for SARS-CoV-2 diagnosis while rapid antigen tests (RATs) might help to mitigate the shortage of reagents sporadically encountered with RT-PCR. Thus, in the RESTART study we compared antigen and RT-PCR testing methods on nasopharyngeal (NP) swabs and salivary samples. We conducted a prospective observational study among COVID-19 hospitalized patients between 10 December 2020 and 1 February 2021. Paired saliva and NP samples were investigated by RT-PCR (Cobas 6800, Roche-Switzerland, Basel, Switzerland) and by two rapid antigen tests: One Step Immunoassay Exdia® COVID-19 Ag (Precision Biosensor, Daejeon, Korea) and Standard Q® COVID-19 Rapid Antigen Test (Roche-Switzerland). A total of 58 paired NP-saliva specimens were collected. A total of 32 of 58 (55%) patients were hospitalized in the intensive care unit, and the median duration of symptoms was 11 days (IQR 5-19). NP and salivary RT-PCR exhibited sensitivity of 98% and 69% respectively, whereas the specificity of these RT-PCRs assays was 100%. The NP RATs exhibited much lower diagnostic performance, with sensitivities of 35% and 41% for the Standard Q® and Exdia® assays, respectively, when a wet-swab approach was used (i.e., when the swab was diluted in the viral transport medium (VTM) before testing). The sensitivity of the dry-swab approach was slightly better (47%). These antigen tests exhibited very low sensitivity (4% and 8%) when applied to salivary swabs. Nasopharyngeal RT-PCR is the most accurate test for COVID-19 diagnosis in hospitalized patients. RT-PCR on salivary samples may be used when nasopharyngeal swabs are contraindicated. RATs are not appropriate for hospitalized patients. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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10 pages, 892 KiB  
Article
Impact of Full Vaccination with mRNA BNT162b2 on SARS-CoV-2 Infection: Genomic and Subgenomic Viral RNAs Detection in Nasopharyngeal Swab and Saliva of Health Care Workers
by Michela Deiana, Antonio Mori, Chiara Piubelli, Francesca Perandin, Davide Treggiari, Davide Martini, Fabio Chesini, Andrea Angheben, Francesco Bonfante, Calogero Terregino, Zeno Bisoffi and Elena Pomari
Microorganisms 2021, 9(8), 1738; https://doi.org/10.3390/microorganisms9081738 - 14 Aug 2021
Cited by 2 | Viewed by 2694
Abstract
SARS-CoV-2 infection was monitored in 1898 health care workers (HCWs) after receiving full vaccination with BNT162b2. Untill 30 June 2021, 10 HCWs tested positive for SARS-CoV-2 using real time RT-PCR, resulting in a 4-month cumulative incidence of 0.005%. The infection was mildly symptomatic [...] Read more.
SARS-CoV-2 infection was monitored in 1898 health care workers (HCWs) after receiving full vaccination with BNT162b2. Untill 30 June 2021, 10 HCWs tested positive for SARS-CoV-2 using real time RT-PCR, resulting in a 4-month cumulative incidence of 0.005%. The infection was mildly symptomatic in six (60%) and asymptomatic in four (40%) individuals. Among the infected HCWs, eight consenting individuals provided paired NPS and saliva during the course of infection, for the purpose of the analysis performed in the present study. Genomic and subgenomic viral RNAs were investigated using real-time RT-PCR in both biological specimens. The temporal profile of viral load was measured using ddPCR. Viral mutations were also analysed. Subgenomic viral RNA was detected in 8/8 (100%) NPS and in 6/8 (75%) saliva specimens at the baseline. The expression of subgenomic RNA was observed for up to 7 days in 3/8 (38%) symptomatic cases. Moreover, concordance was observed between NPS and saliva in the detection of viral mutations, and both N501Y and 69/70del (associated with the B.1.1.7 variant) were detected in the majority 6/8 (75%) of subjects, while the K417T mutation (associated with the P.1-type variants) was detected in 2/8 (25%) individuals. Overall, our findings report a low frequency of infected HCWs after full vaccination. It is, therefore, important to monitor the vaccinees in order to identify asymptomatic infected individuals. Saliva can be a surrogate for SARS-CoV-2 surveillance, particularly in social settings such as hospitals. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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9 pages, 552 KiB  
Article
Post-COVID-19 Syndrome: Nine Months after SARS-CoV-2 Infection in a Cohort of 354 Patients: Data from the First Wave of COVID-19 in Nord Franche-Comté Hospital, France
by Souheil Zayet, Hajer Zahra, Pierre-Yves Royer, Can Tipirdamaz, Julien Mercier, Vincent Gendrin, Quentin Lepiller, Solène Marty-Quinternet, Molka Osman, Nabil Belfeki, Lynda Toko, Pauline Garnier, Alix Pierron, Julie Plantin, Louise Messin, Marc Villemain, Kevin Bouiller and Timothée Klopfenstein
Microorganisms 2021, 9(8), 1719; https://doi.org/10.3390/microorganisms9081719 - 12 Aug 2021
Cited by 33 | Viewed by 5055
Abstract
(1) Background. Post-COVID-19 syndrome is defined as the persistence of symptoms after confirmed SARS-CoV-2 infection. (2) Methods. ANOSVID is an observational retrospective study in Nord Franche-Comté Hospital in France that included adult COVID-19 patients confirmed by RT-PCR from 1 March 2020 to 31 May [...] Read more.
(1) Background. Post-COVID-19 syndrome is defined as the persistence of symptoms after confirmed SARS-CoV-2 infection. (2) Methods. ANOSVID is an observational retrospective study in Nord Franche-Comté Hospital in France that included adult COVID-19 patients confirmed by RT-PCR from 1 March 2020 to 31 May 2020. The aim was to describe patients with post-COVID-19 syndrome with persistent symptoms (PS group) and to compare them with the patients without persistent symptoms (no-PS group). (3) Results. Of the 354 COVID-19 patients, 35.9% (n = 127) reported persistence of at least one symptom after a mean of 289.1 ± 24.5 days after symptom onset. Moreover, 115 patients reported a recurrence of symptoms after recovery, and only 12 patients reported continuous symptoms. The mean age of patients was 48.6 years (19–93) ± 19.4, and 81 patients (63.8%) were female. Patients in the PS group had a longer duration of symptoms of initial acute SARS-CoV-2 infection than patients in the no-PS group (respectively, 57.1 ± 82.1 days versus 29.7 ± 42.1 days, p < 0.001). A majority of patients (n = 104, 81.9%) reported three or more symptoms. The most prevalent persistent symptoms were loss of smell (74.0%, n = 94), fatigue (53.5%, n = 68), loss of taste (31.5%, n = 40), and dyspnea (30.7%, n = 39). These were followed by pain symptoms (26.8% (n = 34), 26.0% (n = 33), 24.4% (n = 31); headache, arthralgia, and myalgia, respectively). More than half of patients reporting persistent symptoms (58%, n = 73) were healthcare workers (HCWs). Among outpatients, this population was more present in the PS group than the no-PS group ((86.6%) n = 71/82 versus (72.2%) n = 109/151, p = 0.012). Post-COVID-19 syndrome was more frequent in patients with a past history of chronic rhinosinusitis (8.7% (n = 11%) versus 1.3% (n = 3), p < 0.001). No significant difference was found regarding clinical characteristics and outcome, laboratory, imaging findings, and treatment received in the two groups. (4) Conclusions. More than a third of our COVID-19 patients presented persistent symptoms after SARS-CoV-2 infection, particularly through loss of smell, loss of taste, fatigue, and dyspnea, with a high prevalence in HCWs among COVID-19 outpatients. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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15 pages, 5498 KiB  
Article
Molecular Epidemiology of SARS-CoV-2 in Diverse Environmental Samples Globally
by Ariful Islam, Md. Abu Sayeed, Md. Abul Kalam, Jinnat Ferdous, Md. Kaisar Rahman, Josefina Abedin, Shariful Islam, Shahanaj Shano, Otun Saha, Tahmina Shirin and Mohammad Mahmudul Hassan
Microorganisms 2021, 9(8), 1696; https://doi.org/10.3390/microorganisms9081696 - 10 Aug 2021
Cited by 10 | Viewed by 3640
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has swamped the global environment greatly in the current pandemic. Wastewater-based epidemiology (WBE) effectively forecasts the surge of COVID-19 cases in humans in a particular region. To understand the genomic characteristics/footprints and diversity of SARS-CoV-2 [...] Read more.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has swamped the global environment greatly in the current pandemic. Wastewater-based epidemiology (WBE) effectively forecasts the surge of COVID-19 cases in humans in a particular region. To understand the genomic characteristics/footprints and diversity of SARS-CoV-2 in the environment, we analyzed 807 SARS-CoV-2 sequences from 20 countries deposited in GISAID till 22 May 2021. The highest number of sequences (n = 638) were reported in Austria, followed by the Netherlands, China, and Bangladesh. Wastewater samples were highest (40.0%) to successfully yield the virus genome followed by a 24 h composite wastewater sample (32.6%) and sewage (18.5%). Phylogenetic analysis revealed that SARS-CoV-2 environmental strains are a close congener with the strains mostly circulating in the human population from the same region. Clade GRY (32.7%), G (29.2%), GR (25.3%), O (7.2%), GH (3.4%), GV (1.4%), S (0.5%), and L (0.4%) were found in environmental samples. Various lineages were identified in environmental samples; nevertheless, the highest percentages (49.4%) of the alpha variant (B.1.1.7) were detected in Austria, Liechtenstein, Slovenia, Czech Republic, Switzerland, Germany, and Italy. Other prevalent lineages were B.1 (18.2%), B.1.1 (9.2%), and B.1.160 (3.9%). Furthermore, a significant number of amino acid substitutions were found in environmental strains where the D614G was found in 83.8% of the sequences. However, the key mutations—N501Y (44.6%), S982A (44.4%), A570D (43.3%), T716I (40.4%), and P681H (40.1%) were also recorded in spike protein. The identification of the environmental belvedere of SARS-CoV-2 and its genetic signature is crucial to detect outbreaks, forecast pandemic harshness, and prepare with the appropriate tools to control any impending pandemic. We recommend genomic environmental surveillance to trace the emerging variants and diversity of SARS-CoV-2 viruses circulating in the community. Additionally, proper disposal and treatment of wastewater, sewage, and medical wastes are important to prevent environmental contamination. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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11 pages, 2652 KiB  
Article
SARS-CoV-2 Spike Mutations, L452R, T478K, E484Q and P681R, in the Second Wave of COVID-19 in Maharashtra, India
by Sarah Cherian, Varsha Potdar, Santosh Jadhav, Pragya Yadav, Nivedita Gupta, Mousumi Das, Partha Rakshit, Sujeet Singh, Priya Abraham, Samiran Panda and NIC Team
Microorganisms 2021, 9(7), 1542; https://doi.org/10.3390/microorganisms9071542 - 20 Jul 2021
Cited by 446 | Viewed by 13124
Abstract
As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being used to investigate its transmission and evolution. Against the backdrop of the global emergence of “variants of concern” (VOCs) during December 2020 and [...] Read more.
As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being used to investigate its transmission and evolution. Against the backdrop of the global emergence of “variants of concern” (VOCs) during December 2020 and an upsurge in a state in the western part of India since January 2021, whole genome sequencing and analysis of spike protein mutations using sequence and structural approaches were undertaken to identify possible new variants and gauge the fitness of the current circulating strains. Phylogenetic analysis revealed that newly identified lineages B.1.617.1 and B.1.617.2 were predominantly circulating. The signature mutations possessed by these strains were L452R, T478K, E484Q, D614G and P681R in the spike protein, including within the receptor-binding domain (RBD). Of these, the mutations at residue positions 452, 484 and 681 have been reported in other globally circulating lineages. The structural analysis of RBD mutations L452R, T478K and E484Q revealed that these may possibly result in increased ACE2 binding while P681R in the furin cleavage site could increase the rate of S1-S2 cleavage, resulting in better transmissibility. The two RBD mutations, L452R and E484Q, indicated decreased binding to select monoclonal antibodies (mAbs) and may affect their neutralization potential. Further in vitro/in vivo studies would help confirm the phenotypic changes of the mutant strains. Overall, the study revealed that the newly emerged variants were responsible for the second wave of COVID-19 in Maharashtra. Lineage B.1.617.2 has been designated as a VOC delta and B.1.617.1 as a variant of interest kappa, and they are being widely reported in the rest of the country as well as globally. Continuous monitoring of these and emerging variants in India is essential. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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9 pages, 903 KiB  
Communication
Combination of rRT-PCR and Anti-Nucleocapsid/Anti-Spike Antibodies to Characterize Specimens with Very Low Viral SARs-CoV-2 Load: A Real-Life Experience
by Zoe Florou, Meropi Zigra, Philippos Kartalidis, Katerina Tsilipounidaki, Georgia Papadamou, Aikaterini Belia, George C. Fthenakis and Efthymia Petinaki
Microorganisms 2021, 9(6), 1263; https://doi.org/10.3390/microorganisms9061263 - 10 Jun 2021
Viewed by 2030
Abstract
The objective of the present study was to evaluate the true positivity among people, whose results of initial testing of nasopharyngeal swabs (NPS) showed a very low viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Seventy-seven people detected with low viral [...] Read more.
The objective of the present study was to evaluate the true positivity among people, whose results of initial testing of nasopharyngeal swabs (NPS) showed a very low viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Seventy-seven people detected with low viral loads of SARs-CoV-2 in nasopharyngeal samples (Ct ≥ 35) were enrolled in the study. For this purpose, a second NPS was collected for rRT-PCR (real-time reverse transcription polymerase chain reaction) combined with a pair of serum samples for detection of anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies. In 8 people, subsequent examinations indicated an increase in viral loads, thereafter, followed by an increase of anti-N and anti-S antibodies, findings compatible with an early stage of COVID-19 infection. In 9 people, who already had increased anti-N antibodies, subsequent examination showed a decrease or absence of viral load and an increase in antibodies, indicative of a late stage of COVID-19 infection. In 60 people, subsequent examination showed absence of infection (as indicated by absence of viral load and antibodies). We propose that the combination of a second NPS and one serum-specimen, both taken three days after the first NPS, helps significantly to avoid false-positive results. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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13 pages, 3154 KiB  
Article
Molecular Analysis of SARS-CoV-2 Circulating in Bangladesh during 2020 Revealed Lineage Diversity and Potential Mutations
by Rokshana Parvin, Sultana Zahura Afrin, Jahan Ara Begum, Salma Ahmed, Mohammed Nooruzzaman, Emdadul Haque Chowdhury, Anne Pohlmann and Shyamal Kumar Paul
Microorganisms 2021, 9(5), 1035; https://doi.org/10.3390/microorganisms9051035 - 12 May 2021
Cited by 7 | Viewed by 2813
Abstract
Virus evolution and mutation analyses are crucial for tracing virus transmission, the potential variants, and other pathogenic determinants. Despite continuing circulation of the SARS-CoV-2, very limited studies have been conducted on genetic evolutionary analysis of the virus in Bangladesh. In this study, a [...] Read more.
Virus evolution and mutation analyses are crucial for tracing virus transmission, the potential variants, and other pathogenic determinants. Despite continuing circulation of the SARS-CoV-2, very limited studies have been conducted on genetic evolutionary analysis of the virus in Bangladesh. In this study, a total of 791 complete genome sequences of SARS-CoV-2 from Bangladesh deposited in the GISAID database during March 2020 to January 2021 were analyzed. Phylogenetic analysis revealed circulation of seven GISAID clades G, GH, GR, GRY, L, O, and S or five Nextstrain clades 20A, 20B, 20C, 19A, and 19B in the country during the study period. The GISAID clade GR or the Nextstrain clade 20B or lineage B.1.1.25 is predominant in Bangladesh and closely related to the sequences from India, USA, Canada, UK, and Italy. The GR clade or B.1.1.25 lineage is likely to be responsible for the widespread community transmission of SARS-CoV-2 in the country during the first wave of infection. Significant amino acid diversity was observed among Bangladeshi SARS-CoV-2 isolates, where a total of 1023 mutations were detected. In particular, the D614G mutation in the spike protein (S_D614G) was found in 97% of the sequences. However, the introduction of lineage B.1.1.7 (UK variant/S_N501Y) and S_E484K mutation in lineage B.1.1.25 in a few sequences reported in late December 2020 is of particular concern. The wide genomic diversity indicated multiple introductions of SARS-CoV-2 into Bangladesh through various routes. Therefore, a continuous and extensive genome sequence analysis would be necessary to understand the genomic epidemiology of SARS-CoV-2 in Bangladesh. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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19 pages, 1120 KiB  
Article
A Phase II Study on the Use of Convalescent Plasma for the Treatment of Severe COVID-19- A Propensity Score-Matched Control Analysis
by Vasiliki Pappa, Anthi Bouchla, Evangelos Terpos, Thomas P. Thomopoulos, Margherita Rosati, Dimitris Stellas, Anastasia Antoniadou, Andreas Mentis, Sotirios G. Papageorgiou, Marianna Politou, Anastasia Kotanidou, Ioannis Kalomenidis, Garyfalia Poulakou, Edison Jahaj, Eleni Korompoki, Sotiria Grigoropoulou, Xintao Hu, Jenifer Bear, Sevasti Karaliota, Robert Burns, Maria Pagoni, Ioannis Trontzas, Elisavet Grouzi, Stavroula Labropoulou, Kostantinos Stamoulis, Aristotelis Bamias, Sotirios Tsiodras, Barbara K. Felber, George N. Pavlakis and Meletios- Athanasios Dimopoulosadd Show full author list remove Hide full author list
Microorganisms 2021, 9(4), 806; https://doi.org/10.3390/microorganisms9040806 - 11 Apr 2021
Cited by 9 | Viewed by 2949
Abstract
COVID-19 is a global pandemic associated with increased morbidity and mortality. Convalescent plasma (CP) infusion is a strategy of potential therapeutic benefit. We conducted a multicenter phase II study to evaluate the efficacy and safety of CP in patients with COVID-19, grade 4 [...] Read more.
COVID-19 is a global pandemic associated with increased morbidity and mortality. Convalescent plasma (CP) infusion is a strategy of potential therapeutic benefit. We conducted a multicenter phase II study to evaluate the efficacy and safety of CP in patients with COVID-19, grade 4 or higher. To evaluate the efficacy of CP, a matched propensity score analysis was used comparing the intervention (n = 59) to a control group (n = 59). Sixty patients received CP within a median time of 7 days from symptom onset. During a median follow-up of 28.5 days, 56/60 patients fully recovered and 1 patient remained in the ICU. The death rate in the CP group was 3.4% vs. 13.6% in the control group. By multivariate analysis, CP recipients demonstrated a significantly reduced risk of death [HR: 0.04 (95% CI: 0.004–0.36), p: 0.005], significantly better overall survival by Kaplan–Meir analysis (p < 0.001), and increased probability of extubation [OR: 30.3 (95% CI: 2.64–348.9), p: 0.006]. Higher levels of antibodies in the CP were independently associated with significantly reduced risk of death. CP infusion was safe with only one grade 3 adverse event (AE), which easily resolved. CP used early may be a safe and effective treatment for patients with severe COVID-19 (trial number NCT04408209). Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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13 pages, 2723 KiB  
Article
Implementing SARS-CoV-2 Rapid Antigen Testing in the Emergency Ward of a Swiss University Hospital: The INCREASE Study
by Giorgia Caruana, Antony Croxatto, Eleftheria Kampouri, Antonios Kritikos, Onya Opota, Maryline Foerster, René Brouillet, Laurence Senn, Reto Lienhard, Adrian Egli, Giuseppe Pantaleo, Pierre-Nicolas Carron and Gilbert Greub
Microorganisms 2021, 9(4), 798; https://doi.org/10.3390/microorganisms9040798 - 10 Apr 2021
Cited by 44 | Viewed by 7715
Abstract
Following the Swiss Federal Office of Public Health (FOPH) authorization of the rapid antigen test (RAT), we implemented the use of the RAT in the emergency ward of our university hospital for patients’ cohorting. RAT triaging in association with RT-PCR allowed us to [...] Read more.
Following the Swiss Federal Office of Public Health (FOPH) authorization of the rapid antigen test (RAT), we implemented the use of the RAT in the emergency ward of our university hospital for patients’ cohorting. RAT triaging in association with RT-PCR allowed us to promptly isolate positive patients and save resources. Among 532 patients, overall sensitivities were 48.3% for Exdia and 41.2% for Standard Q®, PanbioTM and BD Veritor™. All RATs exhibited specificity above 99%. Sensitivity increased to 74.6%, 66.2%, 66.2% and 64.8% for Exdia, Standard Q®, PanbioTM and BD Veritor™, respectively, for viral loads above 105 copies/mL, to 100%, 97.8%, 96.6% and 95.6% for viral loads above 106 copies/mL and 100% for viral loads above 107 copies/mL. Sensitivity was significantly higher for patients with symptoms onset within four days (74.3%, 69.2%, 69.2% and 64%, respectively) versus patients with the evolution of symptoms longer than four days (36.8%, 21.1%, 21.1% and 23.7%, respectively). Among COVID-19 asymptomatic patients, sensitivity was 33%. All Immunoglobulin-A-positive patients resulted negative for RAT. The RAT might represent a useful resource in selected clinical settings as a complementary tool in RT-PCR for rapid patient triaging, but the lower sensitivity, especially in late presenters and COVID-19 asymptomatic subjects, must be taken into account. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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12 pages, 5927 KiB  
Communication
Persistence of Anti-SARS-CoV-2 Antibodies Depends on the Analytical Kit: A Report for Up to 10 Months after Infection
by Julien Favresse, Christine Eucher, Marc Elsen, Constant Gillot, Sandrine Van Eeckhoudt, Jean-Michel Dogné and Jonathan Douxfils
Microorganisms 2021, 9(3), 556; https://doi.org/10.3390/microorganisms9030556 - 08 Mar 2021
Cited by 44 | Viewed by 4186
Abstract
Several studies have described the long-term kinetics of anti-SARS-CoV-2 antibodies but long-term follow-up data, i.e., >6 months, are still sparse. Additionally, the literature is inconsistent regarding the waning effect of the serological response. The aim of this study was to explore the temporal [...] Read more.
Several studies have described the long-term kinetics of anti-SARS-CoV-2 antibodies but long-term follow-up data, i.e., >6 months, are still sparse. Additionally, the literature is inconsistent regarding the waning effect of the serological response. The aim of this study was to explore the temporal dynamic changes of the immune response after SARS-CoV-2 infection in hospitalized and non-hospitalized symptomatic patients over a period of 10 months. Six different analytical kits for SARS-CoV-2 antibody detection were used. Positivity rates, inter-assay agreement and kinetic models were determined. A high inter-individual and an inter-methodology variability was observed. Assays targeting total antibodies presented higher positivity rates and reached the highest positivity rates sooner compared with assays directed against IgG. The inter-assay agreement was also higher between these assays. The stratification by disease severity showed a much-elevated serological response in hospitalized versus non-hospitalized patients in all assays. In this 10-month follow-up study, serological assays showed a clinically significant difference to detect past SARS-CoV-2 infection with total antibody assays presenting the highest positivity rates. The waning effect reported in several studies should be interpreted with caution because it could depend on the assay considered. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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10 pages, 856 KiB  
Article
Detection of SARS-CoV-2 and Other Infectious Agents in Lower Respiratory Tract Samples Belonging to Patients Admitted to Intensive Care Units of a Tertiary-Care Hospital, Located in an Epidemic Area, during the Italian Lockdown
by Adriana Calderaro, Mirko Buttrini, Sara Montecchini, Giovanna Piccolo, Monica Martinelli, Maria Loretana Dell'Anna, Alan Di Maio, Maria Cristina Arcangeletti, Clara Maccari, Flora De Conto and Carlo Chezzi
Microorganisms 2021, 9(1), 185; https://doi.org/10.3390/microorganisms9010185 - 16 Jan 2021
Cited by 8 | Viewed by 2111
Abstract
The aim of this study was the detection of infectious agents from lower respiratory tract (LRT) samples in order to describe their distribution in patients with severe acute respiratory failure and hospitalized in intensive care units (ICU) in an Italian tertiary-care hospital. LRT [...] Read more.
The aim of this study was the detection of infectious agents from lower respiratory tract (LRT) samples in order to describe their distribution in patients with severe acute respiratory failure and hospitalized in intensive care units (ICU) in an Italian tertiary-care hospital. LRT samples from 154 patients admitted to ICU from 27 February to 10 May 2020 were prospectively examined for respiratory viruses, including SARS-CoV-2, bacteria and/or fungi. SARS-CoV-2 was revealed in 90 patients (58.4%, 72 males, mean age 65 years). No significant difference was observed between SARS-CoV-2 positives and SARS-CoV-2 negatives with regard to sex, age and bacterial and/or fungal infections. Nonetheless, fungi were more frequently detected among SARS-CoV-2 positives (44/54, 81.4%, p = 0.0053). Candida albicans was the overall most frequently isolated agent, followed by Enterococcus faecalis among SARS-CoV-2 positives and Staphylococcus aureus among SARS-CoV-2 negatives. Overall mortality rate was 40.4%, accounting for 53 deaths: 37 among SARS-CoV-2 positives (mean age 69 years) and 16 among SARS-CoV-2 negatives (mean age 63 years). This study highlights the different patterns of infectious agents between the two patient categories: fungi were prevalently involved among SARS-CoV-2-positive patients and bacteria among the SARS-CoV-2-negative patients. The different therapies and the length of the ICU stay could have influenced these different patterns of infectious agents. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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11 pages, 1727 KiB  
Article
Performance of a Point-of-Care Test for the Rapid Detection of SARS-CoV-2 Antigen
by Annabelle Strömer, Ruben Rose, Miriam Schäfer, Frieda Schön, Anna Vollersen, Thomas Lorentz, Helmut Fickenscher and Andi Krumbholz
Microorganisms 2021, 9(1), 58; https://doi.org/10.3390/microorganisms9010058 - 28 Dec 2020
Cited by 55 | Viewed by 7020
Abstract
The rapid detection of infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is necessary in the ongoing pandemic. Antigen-specific point-of-care tests (POCT) may be useful for this purpose. Here, such a POCT (SARS-CoV-2 NADAL® COVID-19 Ag) was compared to [...] Read more.
The rapid detection of infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is necessary in the ongoing pandemic. Antigen-specific point-of-care tests (POCT) may be useful for this purpose. Here, such a POCT (SARS-CoV-2 NADAL® COVID-19 Ag) was compared to a laboratory-developed triplex real-time polymerase chain reaction (RT-PCR) designed for the detection of viral nucleoprotein gene and two control targets. This RT-PCR served as a reference to investigate POCT sensitivity by re-testing upper respiratory tract (URT) samples (n = 124) exhibiting different SARS-CoV-2 loads in terms of RT-PCR threshold cycle (Ct) values. The optical intensities of the antigen bands were compared to the Ct values of the RT-PCR. The infectivity of various virus loads was estimated by inoculating Vero cells with URT samples (n = 64, Ct 17-34). POCT sensitivity varied from 100% (Ct < 25) to 73.1% (Ct ≤ 30); higher SARS-CoV-2 loads correlated with higher band intensities. All samples with a Ct > 30 were negative; among SARS-CoV-2 free samples (n = 10) no false-positives were detected. A head-to-head comparison with another POCT (Abbott, Panbio™ COVID-19 Ag Rapid Test) yielded similar results. Isolation of SARS-CoV-2 in cell-culture was successful up to a Ct value of 29. The POCT reliably detects high SARS-CoV-2 loads and rapidly identifies infectious individuals. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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12 pages, 244 KiB  
Article
Higher Mortality and Intensive Care Unit Admissions in COVID-19 Patients with Liver Enzyme Elevations
by Lucia Taramasso, Antonio Vena, Francesca Bovis, Federica Portunato, Sara Mora, Chiara Dentone, Emanuele Delfino, Malgorzata Mikulska, Daniele Roberto Giacobbe, Andrea De Maria, Laura Magnasco, Mauro Giacomini, Antonio Di Biagio and Matteo Bassetti
Microorganisms 2020, 8(12), 2010; https://doi.org/10.3390/microorganisms8122010 - 16 Dec 2020
Cited by 8 | Viewed by 2035
Abstract
The aim of the present study is to evaluate if an independent association exists between liver enzyme elevations (LEE) and the risk of mortality or intensive care unit (ICU) admissions in patients with COVID-19. This was a single-center observational study, recruiting all consecutive [...] Read more.
The aim of the present study is to evaluate if an independent association exists between liver enzyme elevations (LEE) and the risk of mortality or intensive care unit (ICU) admissions in patients with COVID-19. This was a single-center observational study, recruiting all consecutive adults with COVID-19. The elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) to the highest level between COVID-19 diagnosis and hospital discharge was categorized according to a standardized toxicity grade scale. In total, 799 patients were included in this study, 39% of which were female, with a mean age of 69.9 (±16.0) years. Of these patients, 225 (28.1%) developed LEE of grade ≥2 after a median of three days (interquartile range (IQR): 0–8 days) from the diagnosis of COVID-19, and they were estimated to have a higher hazard of death or ICU admission (adjusted hazard ratio (aHR): 1.46, 95% confidence interval (CI): 1.14–1.88). The clinical and laboratory variables associated with the development of LEE were male sex, higher respiratory rate, higher gamma glutamyl transpeptidase (GGT) and lower albumin levels at baseline. Among the analyzed treatments, steroids, tocilizumab and darunavir/ritonavir correlated with LEE. In conclusion, LEE were associated with mortality and ICU admission among COVID-19 patients. While the origin of LEE is probably multifactorial, LEE evaluation could add information to the clinical and laboratory variables that are commonly evaluated during the course of COVID-19. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
14 pages, 5365 KiB  
Article
Transcriptional Profiling of Immune and Inflammatory Responses in the Context of SARS-CoV-2 Fungal Superinfection in a Human Airway Epithelial Model
by Claire Nicolas de Lamballerie, Andrés Pizzorno, Julien Fouret, Lea Szpiro, Blandine Padey, Julia Dubois, Thomas Julien, Aurélien Traversier, Victoria Dulière, Pauline Brun, Bruno Lina, Manuel Rosa-Calatrava and Olivier Terrier
Microorganisms 2020, 8(12), 1974; https://doi.org/10.3390/microorganisms8121974 - 11 Dec 2020
Cited by 5 | Viewed by 2454
Abstract
An increasing amount of evidence indicates a relatively high prevalence of superinfections associated with coronavirus disease 2019 (COVID-19), including invasive aspergillosis, but the underlying mechanisms remain to be characterized. In the present study, to better understand the biological impact of superinfection, we determine [...] Read more.
An increasing amount of evidence indicates a relatively high prevalence of superinfections associated with coronavirus disease 2019 (COVID-19), including invasive aspergillosis, but the underlying mechanisms remain to be characterized. In the present study, to better understand the biological impact of superinfection, we determine and compare the host transcriptional response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) versus Aspergillus superinfection, using a model of reconstituted human airway epithelium. Our analyses reveal that both simple infection and superinfection induce strong deregulation of core components of innate immune and inflammatory responses, with a stronger response to superinfection in the bronchial epithelial model compared to its nasal counterpart. Our results also highlight unique transcriptional footprints of SARS-CoV-2 Aspergillus superinfection, such as an imbalanced type I/type III IFN, and an induction of several monocyte and neutrophil associated chemokines, that could be useful for the understanding of Aspergillus-associated COVID-19 and also the management of severe forms of aspergillosis in this specific context. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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12 pages, 814 KiB  
Article
Eosinopenia in COVID-19 Patients: A Retrospective Analysis
by Narcisse Ndieugnou Djangang, Lorenzo Peluso, Marta Talamonti, Antonio Izzi, Pierre Alain Gevenois, Alessandra Garufi, Jean-Christophe Goffard, Sophie Henrard, Paolo Severgnini, Jean-Louis Vincent, Jacques Creteur and Fabio Silvio Taccone
Microorganisms 2020, 8(12), 1929; https://doi.org/10.3390/microorganisms8121929 - 04 Dec 2020
Cited by 7 | Viewed by 3306
Abstract
Objectives: The aim of this study was to assess the diagnostic role of eosinophils count in COVID-19 patients. Methods: Retrospective analysis of patients admitted to our hospital with suspicion of COVID-19. Demographic, clinical and laboratory data were collected on admission. Eosinopenia [...] Read more.
Objectives: The aim of this study was to assess the diagnostic role of eosinophils count in COVID-19 patients. Methods: Retrospective analysis of patients admitted to our hospital with suspicion of COVID-19. Demographic, clinical and laboratory data were collected on admission. Eosinopenia was defined as eosinophils < 100 cells/mm3. The outcomes of this study were the association between eosinophils count on admission and positive real-time reverse transcription polymerase chain reaction (rRT-PCR) test and with suggestive chest computerized tomography (CT) of COVID-19 pneumonia. Results: A total of 174 patients was studied. Of those, 54% had positive rRT-PCR for SARS-CoV-2. A chest CT-scan was performed in 145 patients; 71% showed suggestive findings of COVID-19. Eosinophils on admission had a high predictive accuracy for positive rRT-PCR and suggestive chest CT-scan (area under the receiver operating characteristic—ROC curve, 0.84 (95% CIs 0.78–0.90) and 0.84 (95% CIs 0.77–0.91), respectively). Eosinopenia and high LDH were independent predictors of positive rRT-PCR, whereas eosinopenia, high body mass index and hypertension were predictors for suggestive CT-scan findings. Conclusions: Eosinopenia on admission could predict positive rRT-PCR test or suggestive chest CT-scan for COVID-19. This laboratory finding could help to identify patients at high-risk of COVID-19 in the setting where gold standard diagnostic methods are not available. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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19 pages, 1765 KiB  
Article
Anti–SARS-CoV-2 Antibody Responses in Convalescent Plasma Donors Are Increased in Hospitalized Patients; Subanalyses of a Phase 2 Clinical Study
by Evangelos Terpos, Marianna Politou, Theodoros N. Sergentanis, Andreas Mentis, Margherita Rosati, Dimitris Stellas, Jenifer Bear, Xintao Hu, Barbara K. Felber, Vassiliki Pappa, Maria Pagoni, Elisavet Grouzi, Stavroula Labropoulou, Ioanna Charitaki, Ioannis Ntanasis-Stathopoulos, Dimitra Moschandreou, Anthi Bouhla, Stylianos Saridakis, Eleni Korompoki, Chara Giatra, Tina Bagratuni, Angelos Pefanis, Sotirios Papageorgiou, Alexandros Spyridonidis, Anastasia Antoniadou, Anastasia Kotanidou, Konstantinos Syrigos, Konstantinos Stamoulis, George Panayiotakopoulos, Sotirios Tsiodras, Leonidas Alexopoulos, Meletios A. Dimopoulos and George N. Pavlakisadd Show full author list remove Hide full author list
Microorganisms 2020, 8(12), 1885; https://doi.org/10.3390/microorganisms8121885 - 28 Nov 2020
Cited by 37 | Viewed by 4775
Abstract
We evaluated the antibody responses in 259 potential convalescent plasma donors for Covid-19 patients. Different assays were used: a commercial ELISA detecting antibodies against the recombinant spike protein (S1); a multiplex assay detecting total and specific antibody isotypes against three SARS-CoV-2 antigens (S1, [...] Read more.
We evaluated the antibody responses in 259 potential convalescent plasma donors for Covid-19 patients. Different assays were used: a commercial ELISA detecting antibodies against the recombinant spike protein (S1); a multiplex assay detecting total and specific antibody isotypes against three SARS-CoV-2 antigens (S1, basic nucleocapsid (N) protein and receptor-binding domain (RBD)); and an in-house ELISA detecting antibodies to complete spike, RBD and N in 60 of these donors. Neutralizing antibodies (NAb) were also evaluated in these 60 donors. Analyzed samples were collected at a median time of 62 (14–104) days from the day of first symptoms or positive PCR (for asymptomatic patients). Anti-SARS-CoV-2 antibodies were detected in 88% and 87.8% of donors using the ELISA and the multiplex assay, respectively. The multivariate analysis showed that age ≥50 years (p < 0.001) and need for hospitalization (p < 0.001) correlated with higher antibody titers, while asymptomatic status (p < 0.001) and testing >60 days after symptom onset (p = 0.001) correlated with lower titers. Interestingly, pseudotype virus-neutralizing antibodies (PsNAbs) significantly correlated with spike and with RBD antibodies by ELISA. Sera with high PsNAb also showed a strong ability to neutralize active SARS-CoV-2 virus, with hospitalized patients showing higher titers. Therefore, convalescent plasma donors can be selected based on the presence of high RBD antibody titers. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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15 pages, 1465 KiB  
Article
New Insights in Laboratory Testing for COVID-19 Patients: Looking for the Role and Predictive Value of Human epididymis secretory protein 4 (HE4) and the Innate Immunity of the Oral Cavity and Respiratory Tract
by Annalisa Schirinzi, Angela Pia Cazzolla, Roberto Lovero, Lorenzo Lo Muzio, Nunzio Francesco Testa, Domenico Ciavarella, Giuseppe Palmieri, Pietro Pozzessere, Vito Procacci, Francesca Di Serio and Luigi Santacroce
Microorganisms 2020, 8(11), 1718; https://doi.org/10.3390/microorganisms8111718 - 02 Nov 2020
Cited by 31 | Viewed by 3204
Abstract
COVID-19 is a viral pandemic caused by the new coronavirus SARS-CoV-2, an enveloped positive stranded RNA virus. The mechanisms of innate immunity, considered as the first line of antiviral defense, is essential towards viruses. A significant role in host defense of the lung, [...] Read more.
COVID-19 is a viral pandemic caused by the new coronavirus SARS-CoV-2, an enveloped positive stranded RNA virus. The mechanisms of innate immunity, considered as the first line of antiviral defense, is essential towards viruses. A significant role in host defense of the lung, nasal and oral cavities is played by Human epididymis secretory protein 4 (HE4) HE4 has been demonstrated to be serum inflammatory biomarker and to show a role in natural immunity at the level of oral cavity, nasopharynx and respiratory tract with both antimicrobial/antiviral and anti-inflammatory activity. Several biomarkers like IL-6, presepsin (PSP), procalcitonin (PCT), CRP, D-Dimer have showed a good function as predictor factors for the clinical evolution of COVID-19 patients (mild, severe and critical). The aim of this study was to correlate the blood levels of CRP, IL-6, PSP, PCT, D-Dimer with He4, to identify the predictive values of these biomarkers for the evolution of the disease and to evaluate the possible role of HE4 in the defense mechanisms of innate immunity at the level of oral cavity, nasopharynx and respiratory tract. Of 134 patients admitted at COVID hospital of Policlinico—University of Bari, 86 (58 men age 67.6 ± 12.4 and 28 women age 65.7 ± 15.4) fulfilled the inclusion criteria: in particular, 80 patients (93%) showed prodromal symptoms (smell and/or taste dysfunctions) and other typical clinical manifestations and 19 died (13 men age 73.4 ± 7.7 and 6 women age 74.8 ± 6.7). 48 patients were excluded because 13 finished chemotherapy and 6 radiotherapy recently, 5 presented suspected breast carcinoma, 5 suspected lung carcinoma, 6 suspected ovarian carcinoma or ovary cyst, 1 cystic fibrosis, 3 renal fibrosis and 9 were affected by autoimmune diseases in treatment with monoclonal antibodies. The venous sample was taken for each patient on the admission and during the hospital stay. For each patient, six measurements relating to considered parameters were performed. Significant correlations between He4 and IL-6 levels (r = 0.797), between He4 and PSP (r = 0.621), between He4 and PCT (r = 0.447), between He4 and D-Dimer (r = 0.367), between He4 and RCP (r = 0.327) have been found. ROC curves analysis showed an excellent accuracy for He4 (AUC = 0.92) and IL-6 (AUC = 0.91), a very good accuracy for PSP (AUC = 0.81), a good accuracy for PCT (AUC = 0.701) and D-Dimer (AUC = 0.721) and sufficient accuracy for RCP (AUC = 0.616). These results demonstrated the important correlation between He4, IL6 and PSP, an excellent accuracy of He4 and IL6 and showed a probable role of He4 in the innate immunity in particularly at the level of oral cavity, nasopharynx and respiratory tract. Besides He4 together with IL6 might be involved in the onset of smell and/or taste disorders and it might be used as innovative biomarker to monitor clinical evolution of COVID-19 because He4 could indicate a multi-organ involvement. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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12 pages, 2307 KiB  
Article
Kinetics of Nucleo- and Spike Protein-Specific Immunoglobulin G and of Virus-Neutralizing Antibodies after SARS-CoV-2 Infection
by Annabelle Strömer, Ruben Rose, Olaf Grobe, Franziska Neumann, Helmut Fickenscher, Thomas Lorentz and Andi Krumbholz
Microorganisms 2020, 8(10), 1572; https://doi.org/10.3390/microorganisms8101572 - 13 Oct 2020
Cited by 30 | Viewed by 4175
Abstract
Kinetics of neutralizing antibodies and immunoglobulin G (IgG) against the nucleo (N) or spike (S) proteins of severe acute respiratory syndrome coronavirus type2 (SARS-CoV-2) were studied in patients up to 165 days after PCR diagnosis of infection. Two immunoassays were selected out [...] Read more.
Kinetics of neutralizing antibodies and immunoglobulin G (IgG) against the nucleo (N) or spike (S) proteins of severe acute respiratory syndrome coronavirus type2 (SARS-CoV-2) were studied in patients up to 165 days after PCR diagnosis of infection. Two immunoassays were selected out of eight IgG or total antibody tests by comparing their specificities and sensitivities. Sensitivities were calculated with convalescent sera from 26 PCR-confirmed cases, of which 76.9% had neutralizing antibodies (>1:10). Stored sera collected during the summer 2018 (N = 50) and winter seasons 2018/2019 (N = 50) were included to demonstrate the test specificities. IgG kinetics, avidities, and virus-neutralizing capacities were recorded over up to 165 days in eleven patients and five individuals from routine diagnostics. Sensitivities, specificities, and diagnostic accuracies ranged between 80.8–96.3%, 96.0–100%, and 93.7–99.2%, respectively. Nearly all results were confirmed with two different SARS-CoV-2-specific immunoblots. Six (54.4%) patients exhibited stable N-specific IgG indices over 120 days and longer; three of them developed IgG of high avidity. The S-specific IgG response was stable in ten (91.0%) patients, and eight (72.7%) had neutralizing antibodies. However, the titers were relatively low, suggesting that sustained humoral immunity is uncertain, especially after outpatient SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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17 pages, 1599 KiB  
Article
The Neutrophil-to-Monocyte Ratio and Lymphocyte-to-Neutrophil Ratio at Admission Predict In-Hospital Mortality in Mexican Patients with Severe SARS-CoV-2 Infection (Covid-19)
by Salma A. Rizo-Téllez, Lucia A. Méndez-García, Cruz Flores-Rebollo, Fernando Alba-Flores, Raúl Alcántara-Suárez, Aarón N. Manjarrez-Reyna, Neyla Baltazar-López, Verónica A. Hernández-Guzmán, José I. León-Pedroza, Rogelio Zapata-Arenas, Antonio González-Chávez, Joselín Hernández-Ruíz, José D. Carrillo-Ruíz, Raúl Serrano-Loyola, Guadalupe M. L. Guerrero-Avendaño and Galileo Escobedo
Microorganisms 2020, 8(10), 1560; https://doi.org/10.3390/microorganisms8101560 - 10 Oct 2020
Cited by 41 | Viewed by 4333
Abstract
There is a deep need for mortality predictors that allow clinicians to quickly triage patients with severe coronavirus disease 2019 (Covid-19) into intensive care units at the time of hospital admission. Thus, we examined the efficacy of the lymphocyte-to-neutrophil ratio (LNR) and neutrophil-to-monocyte [...] Read more.
There is a deep need for mortality predictors that allow clinicians to quickly triage patients with severe coronavirus disease 2019 (Covid-19) into intensive care units at the time of hospital admission. Thus, we examined the efficacy of the lymphocyte-to-neutrophil ratio (LNR) and neutrophil-to-monocyte ratio (NMR) as predictors of in-hospital death at admission in patients with severe Covid-19. A total of 54 Mexican adult patients with Covid-19 that met hospitalization criteria were retrospectively enrolled, followed-up daily until hospital discharge or death, and then assigned to survival or non-survival groups. Clinical, demographic, and laboratory parameters were recorded at admission. A total of 20 patients with severe Covid-19 died, and 75% of them were men older than 62.90 ± 14.18 years on average. Type 2 diabetes, hypertension, and coronary heart disease were more prevalent in non-survivors. As compared to survivors, LNR was significantly fourfold decreased while NMR was twofold increased. LNR ≤ 0.088 predicted in-hospital mortality with a sensitivity of 85.00% and a specificity of 74.19%. NMR ≥ 17.75 was a better independent risk factor for mortality with a sensitivity of 89.47% and a specificity of 80.00%. This study demonstrates for the first time that NMR and LNR are accurate predictors of in-hospital mortality at admission in patients with severe Covid-19. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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9 pages, 389 KiB  
Communication
Healthcare-Associated SARS-CoV-2 Transmission—Experiences from a German University Hospital
by Carlos L. Correa-Martínez, Vera Schwierzeck, Alexander Mellmann, Marc Hennies and Stefanie Kampmeier
Microorganisms 2020, 8(9), 1378; https://doi.org/10.3390/microorganisms8091378 - 08 Sep 2020
Cited by 12 | Viewed by 2423
Abstract
During the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, healthcare systems worldwide have to prevent nosocomial SARS-CoV-2 transmission while maintaining duty of care. In our study, we characterize the transmission dynamic of SARS-CoV-2 in inpatients and healthcare workers (HCWs) at the [...] Read more.
During the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, healthcare systems worldwide have to prevent nosocomial SARS-CoV-2 transmission while maintaining duty of care. In our study, we characterize the transmission dynamic of SARS-CoV-2 in inpatients and healthcare workers (HCWs) at the University Hospital Münster (UHM) in northwest Germany. We identified 27 cases of healthcare-associated SARS-CoV-2 infections (4 inpatients and 23 HCWs) who had contact with patients and/or HCWs without the use of adequate PPE. The contacts of these index cases were followed up for SARS-CoV-2 infection after unprotected exposure and a quantitative measure of probability of becoming infected, the attack rate, was calculated. In addition, transmission was evaluated in the context of infection control measures established during the pandemic and we compared the epidemiological data of all index cases, including symptoms and Ct values of virology test results. The overall attack rate in the hospital setting was 1.3% (inpatients 0.9%, HCWs 1.6%). However, during an outbreak, the attack rate was 25.5% (inpatients 20.0%, HCWs 29.6%). For both scenarios, HCWs had a higher attack rate illustrating their role in healthcare-associated SARS-CoV-2 transmission. Taken together, our experiences demonstrate how infection control measures can minimize the transmission of SARS-CoV-2 in the healthcare setting. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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10 pages, 1576 KiB  
Communication
A Novel Multiplex qRT-PCR Assay to Detect SARS-CoV-2 Infection: High Sensitivity and Increased Testing Capacity
by Sara Petrillo, Giovanna Carrà, Paolo Bottino, Elisa Zanotto, Maria Chiara De Santis, Jean Piero Margaria, Alessandro Giorgio, Giorgia Mandili, Miriam Martini, Rossana Cavallo, Davide Barberio and Fiorella Altruda
Microorganisms 2020, 8(7), 1064; https://doi.org/10.3390/microorganisms8071064 - 17 Jul 2020
Cited by 34 | Viewed by 5815
Abstract
Rapid and sensitive screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential to limit the spread of the global pandemic we are facing. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) is currently used for the clinical diagnosis of SARS-CoV-2 infection using [...] Read more.
Rapid and sensitive screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential to limit the spread of the global pandemic we are facing. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) is currently used for the clinical diagnosis of SARS-CoV-2 infection using nasopharyngeal swabs, tracheal aspirates, or bronchoalveolar lavage (BAL) samples. Despite the high sensitivity of the qRT-PCR method, false negative outcomes might occur, especially in patients with a low viral load. Here, we developed a multiplex qRT-PCR methodology for the simultaneous detection of SARS-CoV-2 genome (N gene) and of the human RNAse P gene as internal control. We found that multiplex qRT-PCR was effective in detecting SARS-Cov-2 infection in human specimens with 100% sensitivity. Notably, patients with few copies of SARS-CoV-2 RNA (<5 copies/reaction) were successfully detected by the novel multiplex qRT-PCR method. Finally, we assessed the efficacy of multiplex qRT-PCR on human nasopharyngeal swabs without RNA extraction. Collectively, our results provide evidence of a novel and reliable tool for SARS-CoV-2 RNA detection in human specimens, which allows the testing capacity to be expanded and the RNA extraction step to be bypassed. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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12 pages, 1362 KiB  
Communication
SARS-CoV-2 Virologic and Immunologic Correlates in Patients with Olfactory and Taste Disorders
by Marco Benazzo, Irene Cassaniti, Eugenia Maiorano, Anna Calastri, Federica Novazzi, Alice Bonetti, Antonella Sarasini, Raffaele Bruno and Fausto Baldanti
Microorganisms 2020, 8(7), 1052; https://doi.org/10.3390/microorganisms8071052 - 15 Jul 2020
Cited by 7 | Viewed by 4704
Abstract
The main object of the study was to investigate the SARS-CoV-2 molecular and serological pattern in patients with mild symptoms including anosmia and ageusia. A cohort of 69 patients with olfactory and taste disorders (OTDs) were enrolled and prospectively monitored. Serological and molecular [...] Read more.
The main object of the study was to investigate the SARS-CoV-2 molecular and serological pattern in patients with mild symptoms including anosmia and ageusia. A cohort of 69 patients with olfactory and taste disorders (OTDs) were enrolled and prospectively monitored. Serological and molecular assays for the characterization of SARS-CoV-2 IgG and SARS-CoV-2 RNA, respectively, were performed at the time of enrolment and after 7 and 14 days. Patients were stratified according to the symptoms’ onset. A total of 52 patients (75.4%) were diagnosed as COVID-19 positive being SARS-CoV-2 RNA and/or SARS-CoV-2 IgG positive. The remaining 17 (24.6%) were negative for COVID-19 and excluded from the analysis. We reported that only 34 out of 52 patients (65.4%) were positive for SARS-CoV-2 RNA. Moreover, the median time from onset of symptoms and enrolment was significantly higher in those patients with negative SARS-CoV-2 RNA in nasal swabs, suggesting that symptoms might last longer than SARS-CoV-2 replication. The great majority of patients (80%) developed SARS-CoV-2 IgG at three weeks after symptoms’ onset while the detectability of SARS-CoV-2 RNA dramatically decreased over time, suggesting the crucial role of combination of molecular and serological assays for the diagnosis of COVID-19 in those patients reporting mild symptoms. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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10 pages, 237 KiB  
Communication
Calcineurin Inhibitor-Based Immunosuppression and COVID-19: Results from a Multidisciplinary Cohort of Patients in Northern Italy
by Lorenzo Cavagna, Elena Seminari, Giovanni Zanframundo, Marilena Gregorini, Angela Di Matteo, Teresa Rampino, Carlomaurizio Montecucco, Stefano Pelenghi, Barbara Cattadori, Eleonora Francesca Pattonieri, Patrizio Vitulo, Alessandro Bertani, Gianluca Sambataro, Carlo Vancheri, Alessandro Biglia, Emanuele Bozzalla-Cassione, Valentina Bonetto, Maria Cristina Monti, Elena Ticozzelli, Annalisa Turco, Tiberio Oggionni, Angelo Corsico, Francesco Bertuccio, Valentina Zuccaro, Veronica Codullo, Monica Morosini, Carlo Marena, Massimiliano Gnecchi, Carlo Pellegrini and Federica Meloniadd Show full author list remove Hide full author list
Microorganisms 2020, 8(7), 977; https://doi.org/10.3390/microorganisms8070977 - 30 Jun 2020
Cited by 42 | Viewed by 3392
Abstract
The role of immunosuppression in SARS-CoV-2-related disease (COVID-19) is a matter of debate. We here describe the course and the outcome of COVID-19 in a cohort of patients undergoing treatment with calcineurin inhibitors. In this monocentric cohort study, data were collected from the [...] Read more.
The role of immunosuppression in SARS-CoV-2-related disease (COVID-19) is a matter of debate. We here describe the course and the outcome of COVID-19 in a cohort of patients undergoing treatment with calcineurin inhibitors. In this monocentric cohort study, data were collected from the COVID-19 outbreak in Italy up to 28 April 2020. Patients were followed at our hospital for solid organ transplantation or systemic rheumatic disorders (RMDs) and were on calcineurin inhibitor (CNI)-based therapy. Selected patients were referred from the North of Italy. The aim of our study was to evaluate the clinical course of COVID-19 in this setting. We evaluated 385 consecutive patients (220 males, 57%; median age 61 years, IQR 48–69); 331 (86%) received solid organ transplantation and 54 (14%) had a RMD. CNIs were the only immunosuppressant administered in 47 patients (12%). We identified 14 (4%) COVID-19 patients, all transplanted, mainly presenting with fever (86%) and diarrhea (71%). Twelve patients were hospitalized and two of them died, both with severe comorbidities. No patients developed acute respiratory distress syndrome or infectious complications. The surviving 10 patients are now fully recovered. The clinical course of COVID-19 patients on CNIs is generally mild, and the risk of superinfection seems low. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
12 pages, 822 KiB  
Article
Tocilizumab for Treatment of Severe COVID-19 Patients: Preliminary Results from SMAtteo COvid19 REgistry (SMACORE)
by Marta Colaneri, Laura Bogliolo, Pietro Valsecchi, Paolo Sacchi, Valentina Zuccaro, Fabio Brandolino, Carlomaurizio Montecucco, Francesco Mojoli, Emanuele Maria Giusti, Raffaele Bruno and the COVID IRCCS San Matteo Pavia Task Force
Microorganisms 2020, 8(5), 695; https://doi.org/10.3390/microorganisms8050695 - 09 May 2020
Cited by 167 | Viewed by 13352
Abstract
Objective: This study aimed to assess the role of Tocilizumab therapy (TCZ) in terms of ICU admission and mortality rate of critically ill patients with severe COVID-19 pneumonia. Design: Patients with COVID-19 pneumonia were prospectively enrolled in SMAtteo COvid19 REgistry (SMACORE). A retrospective [...] Read more.
Objective: This study aimed to assess the role of Tocilizumab therapy (TCZ) in terms of ICU admission and mortality rate of critically ill patients with severe COVID-19 pneumonia. Design: Patients with COVID-19 pneumonia were prospectively enrolled in SMAtteo COvid19 REgistry (SMACORE). A retrospective analysis of patients treated with TCZ matched using propensity score to patients treated with Standard Of Care (SOC) was conducted. Setting: The study was conducted at IRCCS Policlinico San Matteo Hospital, Pavia, Italy, from March 14, 2020 to March 27, 2020. Participants: Patients with a confirmed diagnosis of COVID-19 hospitalized in our institution at the time of TCZ availability. Interventions: TCZ was administered to 21 patients. The first administration was 8 mg/kg (up to a maximum 800 mg per dose) of Tocilizumab intravenously, repeated after 12 h if no side effects were reported after the first dose. Main Outcomes and Measures: ICU admission and 7-day mortality rate. Secondary outcomes included clinical and laboratory data. Results: There were 112 patients evaluated (82 were male and 30 were female, with a median age of 63.55 years). Using propensity scores, the 21 patients who received TCZ were matched to 21 patients who received SOC (a combination of hydroxychloroquine, azithromycin and prophylactic dose of low weight heparin). No adverse event was detected following TCZ administration. This study found that treatment with TCZ did not significantly affect ICU admission (OR 0.11; 95% CI between 0.00 and 3.38; p = 0.22) or 7-day mortality rate (OR 0.78; 95% CI between 0.06 and 9.34; p = 0.84) when compared with SOC. Analysis of laboratory measures showed significant interactions between time and treatment regarding C-Reactive Protein (CRP), alanine aminotransferase (ALT), platelets and international normalized ratio (INR) levels. Variation in lymphocytes count was observed over time, irrespective of treatment. Conclusions: TCZ administration did not reduce ICU admission or mortality rate in a cohort of 21 patients. Additional data are needed to understand the effect(s) of TCZ in treating patients diagnosed with COVID-19. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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14 pages, 339 KiB  
Review
The Impact of Angiotensin-Converting Enzyme 2 (ACE2) Expression Levels in Patients with Comorbidities on COVID-19 Severity: A Comprehensive Review
by Rui Rodrigues and Sofia Costa de Oliveira
Microorganisms 2021, 9(8), 1692; https://doi.org/10.3390/microorganisms9081692 - 09 Aug 2021
Cited by 24 | Viewed by 2998
Abstract
Angiotensin-Converting Enzyme 2 (ACE2) has been proved to be the main host cell receptor for the binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic. The SARS-CoV-2 spike (S) protein binds to ACE2 to initiate [...] Read more.
Angiotensin-Converting Enzyme 2 (ACE2) has been proved to be the main host cell receptor for the binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic. The SARS-CoV-2 spike (S) protein binds to ACE2 to initiate the process of replication. This enzyme is widely present in human organ tissues, such as the heart and lung. The pathophysiology of ACE2 in SARS-CoV-2 infection is complex and may be associated with several factors and conditions that are more severe in COVID-19 patients, such as age, male gender, and comorbidities, namely, cardiovascular diseases, chronic respiratory diseases, obesity, and diabetes. Here we present a comprehensive review that aims to correlate the levels of expression of the ACE2 in patients with comorbidities and with a poor outcome in COVID-19 disease. Significantly higher levels of expression of ACE2 were observed in myocardial and lung tissues in heart failure and COPD patients, respectively. An age-dependent increase in SARS2-CoV-2 receptors in the respiratory epithelium may be also responsible for the increased severity of COVID-19 lung disease in elderly people. Although the role of ACE2 is highlighted regarding the damage that can arise upon the SARS-CoV-2 invasion, there was no association observed between renin-angiotensin-aldosterone system (RAAS) inhibitors and the severity of COVID-19. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
16 pages, 827 KiB  
Review
Cross-Reactive Immune Responses toward the Common Cold Human Coronaviruses and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Mini-Review and a Murine Study
by Robert E. Sealy and Julia L. Hurwitz
Microorganisms 2021, 9(8), 1643; https://doi.org/10.3390/microorganisms9081643 - 31 Jul 2021
Cited by 15 | Viewed by 3560
Abstract
While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes serious morbidity and mortality in humans (coronavirus disease 2019, COVID-19), there is an enormous range of disease outcomes following virus exposures. Some individuals are asymptomatic while others succumb to virus infection within days. Presently, [...] Read more.
While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes serious morbidity and mortality in humans (coronavirus disease 2019, COVID-19), there is an enormous range of disease outcomes following virus exposures. Some individuals are asymptomatic while others succumb to virus infection within days. Presently, the factors responsible for disease severity are not fully understood. One factor that may influence virus control is pre-existing immunity conferred by an individual’s past exposures to common cold human coronaviruses (HCoVs). Here, we describe previous literature and a new, murine study designed to examine cross-reactive immune responses between SARS-CoV-2 and common cold HCoVs (represented by prototypes OC43, HKU1, 229E, and NL63). Experimental results have been mixed. In SARS-CoV-2-unexposed humans, cross-reactive serum antibodies were identified toward nucleocapsid (N) and the spike subunit S2. S2-specific antibodies were in some cases associated with neutralization. SARS-CoV-2-unexposed humans rarely exhibited antibody responses to the SARS-CoV-2 spike subunit S1, and when naïve mice were immunized with adjuvanted S1 from either SARS-CoV-2 or common cold HCoVs, S1-specific antibodies were poorly cross-reactive. When humans were naturally infected with SARS-CoV-2, cross-reactive antibodies that recognized common cold HCoV antigens increased in magnitude. Cross-reactive T cells, like antibodies, were present in humans prior to SARS-CoV-2 exposures and increased following SARS-CoV-2 infections. Some studies suggested that human infections with common cold HCoVs afforded protection against disease caused by subsequent exposures to SARS-CoV-2. Small animal models are now available for the testing of controlled SARS-CoV-2 infections. Additionally, in the United Kingdom, a program of SARS-CoV-2 human challenge experiments has received regulatory approval. Future, controlled experimental challenge studies may better define how pre-existing, cross-reactive immune responses influence SARS-CoV-2 infection outcomes. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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19 pages, 1580 KiB  
Review
A Comprehensive Review of Detection Methods for SARS-CoV-2
by Aziz Eftekhari, Mahdieh Alipour, Leila Chodari, Solmaz Maleki Dizaj, Mohammadreza Ardalan, Mohammad Samiei, Simin Sharifi, Sepideh Zununi Vahed, Irada Huseynova, Rovshan Khalilov, Elham Ahmadian and Magali Cucchiarini
Microorganisms 2021, 9(2), 232; https://doi.org/10.3390/microorganisms9020232 - 22 Jan 2021
Cited by 80 | Viewed by 9425
Abstract
Recently, the outbreak of the coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, in China and its subsequent spread across the world has caused numerous infections and deaths and disrupted normal social activity. Presently, various techniques are used for the diagnosis of [...] Read more.
Recently, the outbreak of the coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, in China and its subsequent spread across the world has caused numerous infections and deaths and disrupted normal social activity. Presently, various techniques are used for the diagnosis of SARS-CoV-2 infection, with various advantages and weaknesses to each. In this paper, we summarize promising methods, such as reverse transcription-polymerase chain reaction (RT-PCR), serological testing, point-of-care testing, smartphone surveillance of infectious diseases, nanotechnology-based approaches, biosensors, amplicon-based metagenomic sequencing, smartphone, and wastewater-based epidemiology (WBE) that can also be utilized for the detection of SARS-CoV-2. In addition, we discuss principles, advantages, and disadvantages of these detection methods, and highlight the potential methods for the development of additional techniques and products for early and fast detection of SARS-CoV-2. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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33 pages, 3810 KiB  
Review
Drawing Comparisons between SARS-CoV-2 and the Animal Coronaviruses
by Souvik Ghosh and Yashpal S. Malik
Microorganisms 2020, 8(11), 1840; https://doi.org/10.3390/microorganisms8111840 - 23 Nov 2020
Cited by 14 | Viewed by 5748
Abstract
The COVID-19 pandemic, caused by a novel zoonotic coronavirus (CoV), SARS-CoV-2, has infected 46,182 million people, resulting in 1,197,026 deaths (as of 1 November 2020), with devastating and far-reaching impacts on economies and societies worldwide. The complex origin, extended human-to-human transmission, pathogenesis, host [...] Read more.
The COVID-19 pandemic, caused by a novel zoonotic coronavirus (CoV), SARS-CoV-2, has infected 46,182 million people, resulting in 1,197,026 deaths (as of 1 November 2020), with devastating and far-reaching impacts on economies and societies worldwide. The complex origin, extended human-to-human transmission, pathogenesis, host immune responses, and various clinical presentations of SARS-CoV-2 have presented serious challenges in understanding and combating the pandemic situation. Human CoVs gained attention only after the SARS-CoV outbreak of 2002–2003. On the other hand, animal CoVs have been studied extensively for many decades, providing a plethora of important information on their genetic diversity, transmission, tissue tropism and pathology, host immunity, and therapeutic and prophylactic strategies, some of which have striking resemblance to those seen with SARS-CoV-2. Moreover, the evolution of human CoVs, including SARS-CoV-2, is intermingled with those of animal CoVs. In this comprehensive review, attempts have been made to compare the current knowledge on evolution, transmission, pathogenesis, immunopathology, therapeutics, and prophylaxis of SARS-CoV-2 with those of various animal CoVs. Information on animal CoVs might enhance our understanding of SARS-CoV-2, and accordingly, benefit the development of effective control and prevention strategies against COVID-19. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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33 pages, 4217 KiB  
Review
Coronavirus (SARS-CoV-2) Pandemic: Future Challenges for Dental Practitioners
by Ioana Roxana Bordea, Edit Xhajanka, Sebastian Candrea, Simion Bran, Florin Onișor, Alessio Danilo Inchingolo, Giuseppina Malcangi, Van H Pham, Angelo Michele Inchingolo, Antonio Scarano, Felice Lorusso, Ciro Gargiulo Isacco, Sergey K Aityan, Andrea Ballini, Gianna Dipalma and Francesco Inchingolo
Microorganisms 2020, 8(11), 1704; https://doi.org/10.3390/microorganisms8111704 - 31 Oct 2020
Cited by 73 | Viewed by 5130
Abstract
In the context of the SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) pandemic, the medical system has been subjected to many changes. Face-to-face treatments have been suspended for a period of time. After the lockdown, dentists have to be aware of the modalities [...] Read more.
In the context of the SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) pandemic, the medical system has been subjected to many changes. Face-to-face treatments have been suspended for a period of time. After the lockdown, dentists have to be aware of the modalities to protect themselves and their patients in order not to get infected. Dental practitioners are potentially exposed to a high degree of contamination with SARS-CoV-2 while performing dental procedures that produce aerosols. It should also be noted that the airways, namely the oral cavity and nostrils, are the access pathways for SARS-CoV-2. In order to protect themselves and their patients, they have to use full personal protective equipment. Relevant data regarding this pandemic are under evaluation and are still under test. In this article, we made a synthesis about the way in which SARS-CoV-2 spreads, how to diagnose a novel corona virus infection, what the possible treatments are, and which protective personal equipment we can use to stop its spreading. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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18 pages, 485 KiB  
Review
More than Pneumonia: Distinctive Features of SARS-Cov-2 Infection. From Autopsy Findings to Clinical Implications: A Systematic Review
by Stefano D’Errico, Martina Zanon, Martina Montanaro, Davide Radaelli, Francesco Sessa, Giulio Di Mizio, Angelo Montana, Salvatore Corrao, Monica Salerno and Cristoforo Pomara
Microorganisms 2020, 8(11), 1642; https://doi.org/10.3390/microorganisms8111642 - 23 Oct 2020
Cited by 33 | Viewed by 3695
Abstract
Despite safety recommendations for the management of corpses with COVID-19 infection and the high number of deaths worldwide, the post-mortem investigation rate is extremely low as well as the scientific contributions describing the pathological features. The first results of post-mortem investigations provided interesting [...] Read more.
Despite safety recommendations for the management of corpses with COVID-19 infection and the high number of deaths worldwide, the post-mortem investigation rate is extremely low as well as the scientific contributions describing the pathological features. The first results of post-mortem investigations provided interesting findings and contributed to promoting unexplored therapeutic approaches and new frontiers of research. A systematic review is provided with the aim of summarizing all autopsy studies up to February 2020 in which a complete post-mortem investigation in patients with COVID-19 disease was performed, focusing on histopathological features. We included case reports, case series, retrospective and prospective studies, letters to the editor, and reviews. A total of 28 studies fulfilled the inclusion criteria, producing a pooled dataset of 407 full autopsies. Analyzing the medical history data, only 12 subjects had died without any comorbidities (for 15 cases the data were not available). The post-mortem investigation highlighted that acute respiratory distress syndrome (ARDS) and multiple organ failure represent the main clinical features of COVID-19 disease, often leading to pulmonary thromboembolism and superimposed bronchopneumonia. The discussed data showed a strict relationship among the inflammatory processes, diffuse alveolar, and endothelial damage. In light of these results, the full autopsy can be considered as the gold standard to investigate unknown infections or pathogens resulting in death. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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22 pages, 1476 KiB  
Review
Renin Angiotensin System, COVID-19 and Male Fertility: Any Risk for Conceiving?
by Lorella Pascolo, Gabriella Zito, Luisa Zupin, Stefania Luppi, Elena Giolo, Monica Martinelli, Daniela De Rocco, Sergio Crovella and Giuseppe Ricci
Microorganisms 2020, 8(10), 1492; https://doi.org/10.3390/microorganisms8101492 - 28 Sep 2020
Cited by 19 | Viewed by 4571
Abstract
The current knowledge concerning the connection between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the renin–angiotensin system (RAS) system in the male reproductive apparatus is still limited, so dedicated studies are urgently required. Concerns about the male fertility consequences of SARS-CoV-2 infection [...] Read more.
The current knowledge concerning the connection between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the renin–angiotensin system (RAS) system in the male reproductive apparatus is still limited, so dedicated studies are urgently required. Concerns about the male fertility consequences of SARS-CoV-2 infection have started to emerge, since epidemiologic studies observed that this coronavirus affects male patients more frequently and with increased severity, possibly because of the hormone-regulated expression of angiotensin-converting enzyme 2 (ACE2) receptor. A disturbance in fertility is also expected based on studies of the previous SARS-CoV infection, which targets the same ACE2 receptor when entering the host cells. In addition, bioinformatics analyses reveal the abundant expression of ACE2 receptor in the male reproductive tissues, particularly in the testis. It has been proposed that pharmacological intervention favoring the angiotensin-(1–7)/ACE2/Mas receptor pathway and increasing ACE2 expression and activity could greatly prevent inflammatory lesions in this area. Finally, in laboratories performing assisted reproductive technologies it is recommended that more attention should be paid not only to sperm quality but also to safety aspects. Data about the potential infectivity of seminal fluid are in fact conflicting and do not exclude risks for both personnel and patients. The potential infectivity of SARS-CoV-2 in reproductive male tissues should be strongly considered and further investigated for the proper management of in vitro fertilization procedures. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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21 pages, 1485 KiB  
Review
COVID-19 Is a Multifaceted Challenging Pandemic Which Needs Urgent Public Health Interventions
by Carlo Contini, Elisabetta Caselli, Fernanda Martini, Martina Maritati, Elena Torreggiani, Silva Seraceni, Fortunato Vesce, Paolo Perri, Leonzio Rizzo and Mauro Tognon
Microorganisms 2020, 8(8), 1228; https://doi.org/10.3390/microorganisms8081228 - 12 Aug 2020
Cited by 31 | Viewed by 17611
Abstract
Until less than two decades ago, all known human coronaviruses (CoV) caused diseases so mild that they did not stimulate further advanced CoV research. In 2002 and following years, the scenario changed dramatically with the advent of the new more pathogenic CoVs, including [...] Read more.
Until less than two decades ago, all known human coronaviruses (CoV) caused diseases so mild that they did not stimulate further advanced CoV research. In 2002 and following years, the scenario changed dramatically with the advent of the new more pathogenic CoVs, including Severe Acute Respiratory Syndome (SARS-CoV-1), Middle Eastern respiratory syndrome (MERS)-CoV, and the new zoonotic SARS-CoV-2, likely originated from bat species and responsible for the present coronavirus disease (COVID-19), which to date has caused 15,581,007 confirmed cases and 635,173 deaths in 208 countries, including Italy. SARS-CoV-2 transmission is mainly airborne via droplets generated by symptomatic patients, and possibly asymptomatic individuals during incubation of the disease, although for the latter, there are no certain data yet. However, research on asymptomatic viral infection is currently ongoing worldwide to elucidate the real prevalence and mortality of the disease. From a clinical point of view, COVID-19 would be defined as “COVID Planet “ because it presents as a multifaceted disease, due to the large number of organs and tissues infected by the virus. Overall, based on the available published data, 80.9% of patients infected by SARS-CoV-2 develop a mild disease/infection, 13.8% severe pneumonia, 4.7% respiratory failure, septic shock, or multi-organ failure, and 3% of these cases are fatal, but mortality parameter is highly variable in different countries. Clinically, SARS-CoV-2 causes severe primary interstitial viral pneumonia and a “cytokine storm syndrome”, characterized by a severe and fatal uncontrolled systemic inflammatory response triggered by the activation of interleukin 6 (IL-6) with development of endothelitis and generalized thrombosis that can lead to organ failure and death. Risk factors include advanced age and comorbidities including hypertension, diabetes, and cardiovascular disease. Virus entry occurs via binding the angiotensin-converting enzyme 2 (ACE2) receptor present in almost all tissues and organs through the Spike (S) protein. Currently, SARS-CoV-2 infection is prevented by the use of masks, social distancing, and improved hand hygiene measures. This review summarizes the current knowledge on the main biological and clinical features of the SARS-CoV-2 pandemic, also focusing on the principal measures taken in some Italian regions to face the emergency and on the most important treatments used to manage the COVID-19 pandemic. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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15 pages, 547 KiB  
Review
From Wuhan to COVID-19 Pandemic: An Up-to-Date Review of Its Pathogenesis, Potential Therapeutics, and Recent Advances
by Ikrame Zeouk, Khadija Bekhti and Jacob Lorenzo-Morales
Microorganisms 2020, 8(6), 850; https://doi.org/10.3390/microorganisms8060850 - 04 Jun 2020
Cited by 5 | Viewed by 6075
Abstract
The emergence of a novel human coronavirus (SARS-CoV-2) causing severe contagious respiratory tract infections presents a serious threat to public health worldwide. To date, there are no specific antiviral agents available for this disease, currently known as COVID-19. Therefore, genomic sequencing and therapeutic [...] Read more.
The emergence of a novel human coronavirus (SARS-CoV-2) causing severe contagious respiratory tract infections presents a serious threat to public health worldwide. To date, there are no specific antiviral agents available for this disease, currently known as COVID-19. Therefore, genomic sequencing and therapeutic clinical trials are being conducted to develop effective antiviral agents. Several reports have investigated FDA-approved drugs as well as in silico virtual screening approaches such as molecular docking and modeling to find novel antiviral agents. Until now, antiparasitic drugs such as chloroquine have shown the most relevant results. Furthermore, there is an urgent need to understand the pathogenesis of this novel coronavirus, its transmission routes, surface survival and evolution in the environment. So far, the scientific community has indicated a possible transmission of COVID-19 via blood transfusion which is challenging in the case of asymptomatic individuals. Protocols for pathogen inactivation are also needed. In this paper, we reviewed recent findings about this life-threatening pandemic. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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6 pages, 512 KiB  
Case Report
First Case of a COVID-19 Patient Infected by Delta AY.4 with a Rare Deletion Leading to a N Gene Target Failure by a Specific Real Time PCR Assay: Novel Omicron VOC Might Be Doing Similar Scenario?
by Mohammad Alkhatib, Maria Concetta Bellocchi, Greta Marchegiani, Sandro Grelli, Valeria Micheli, Daniele Stella, Bartolomeo Zerillo, Luca Carioti, Valentina Svicher, Paola Rogliani and Francesca Ceccherini-Silberstein
Microorganisms 2022, 10(2), 268; https://doi.org/10.3390/microorganisms10020268 - 25 Jan 2022
Cited by 12 | Viewed by 2635
Abstract
Herein, we report a case of an Italian male infected by Delta sublineage AY.4 harboring an atypical deletion, leading to a N gene target failure (NGTF) by a commercial molecular assay for SARS-CoV-2 diagnosis (AllplexTM SARS-CoV-2 Assay, Seegene). A 59-year-old unvaccinated patient [...] Read more.
Herein, we report a case of an Italian male infected by Delta sublineage AY.4 harboring an atypical deletion, leading to a N gene target failure (NGTF) by a commercial molecular assay for SARS-CoV-2 diagnosis (AllplexTM SARS-CoV-2 Assay, Seegene). A 59-year-old unvaccinated patient was hospitalized for pulmonary embolism, with first negative results obtained by both molecular and antigen tests. After several days of viral negativity, he presented positive results for E and RdRP/S genes, but negative in N gene. Negativity in N gene was repeatedly confirmed in the following days. Suspecting an infection by the Omicron variant, SARS-CoV-2 genome sequencing was rapidly performed from nasopharyngeal swab by MiSeq and revealed the presence of the Delta sublineage AY.4 variant with an atypical deletion of six nucleotides, leading to G214-G215 deletion in the Nucleocapsid, thus responsible for NGTF. The analysis of GISAID sequences (N = 2,618,373 12 January 2022) showed that G214-G215 deletion is rarely occurring in most circulating Delta lineages and sublineages in the globe and Europe, with an overall prevalence never exceeding 0.2%. Hence, this study highlights the importance to perform SARS-CoV-2 sequencing and to characterize novel mutations/deletions that could jeopardize the proper interpretation of molecular diagnostic tests. Based on these assumptions, the role of deletions in the recently identified Omicron variant deserves further investigation. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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2 pages, 192 KiB  
Reply
Reply to Schulte-Pelkum, J. Comment on “Favresse et al. Persistence of Anti-SARS-CoV-2 Antibodies Depends on the Analytical Kit: A Report for Up to 10 Months after Infection. Microorganisms 2021, 9, 556”
by Julien Favresse, Constant Gillot and Jonathan Douxfils
Microorganisms 2021, 9(9), 1849; https://doi.org/10.3390/microorganisms9091849 - 31 Aug 2021
Cited by 3 | Viewed by 1394
Abstract
We thank the authors of this Response Letter for their comment on our previous article [...] Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
2 pages, 174 KiB  
Comment
Comment on Favresse et al. Persistence of Anti-SARS-CoV-2 Antibodies Depends on the Analytical Kit: A Report for Up to 10 Months after Infection. Microorganisms 2021, 9, 556
by Johannes Schulte-Pelkum
Microorganisms 2021, 9(8), 1786; https://doi.org/10.3390/microorganisms9081786 - 23 Aug 2021
Cited by 3 | Viewed by 1509
Abstract
We thank the authors of the article [...] Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
6 pages, 992 KiB  
Case Report
Multisystem Inflammatory Syndrome in an Adult (MIS-A) Successfully Treated with Anakinra and Glucocorticoids
by Paolo Cattaneo, Alessandro Volpe, Chiara Simona Cardellino, Niccolò Riccardi, Giulia Bertoli, Tamara Ursini, Arjola Ustalli, Giovanni Lodi, Ivan Daroui and Andrea Angheben
Microorganisms 2021, 9(7), 1393; https://doi.org/10.3390/microorganisms9071393 - 28 Jun 2021
Cited by 19 | Viewed by 3126
Abstract
During the current SARS-CoV-2 pandemic, a novel syndrome termed “multisystem inflammatory syndrome in children” (MIS-C) has emerged. MIS-C was linked to COVID-19 and shared some features with Kawasaki disease and Toxic Shock Syndrome, with a common pathogenetic substrate of hyperinflammation and cytokine storm. [...] Read more.
During the current SARS-CoV-2 pandemic, a novel syndrome termed “multisystem inflammatory syndrome in children” (MIS-C) has emerged. MIS-C was linked to COVID-19 and shared some features with Kawasaki disease and Toxic Shock Syndrome, with a common pathogenetic substrate of hyperinflammation and cytokine storm. Lately, MIS was also described in adults (≥21 years of age) and named “MIS-A”. There is no consensus about the treatment of MIS-A; successful use of glucocorticoids and immunoglobulins has been reported in case series, but more solid evidence is lacking. Furthermore, the role of biologic agents with proven benefits against COVID-19, MIS-C, or Kawasaki disease is still unexplored. In this report, we detail the clinical picture and the diagnostic process that led to the diagnosis of MIS-A in a 27-year-old man, focusing on its treatment with anakinra and glucocorticoids, which resulted in full recovery. To our knowledge, this is the first report of the successful use of anakinra for MIS-A, a drug that has already proven useful in the treatment of refractive cases of MIS-C. Anakinra may also play a pivotal role for the treatment of MIS-A. Full article
(This article belongs to the Special Issue COVID-19: Focusing on Epidemiologic, Virologic, and Clinical Studies)
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