Editorial

3 pages, 203 KiB

Open AccessEditorial

Special Issue: Advances in SARS-CoV-2 Infection

by Carlo Contini, John Charles Rotondo, Benedetta Perna, Matteo Guarino and Roberto De Giorgio

Microorganisms 2023, 11(4), 1048; https://doi.org/10.3390/microorganisms11041048 - 17 Apr 2023

Cited by 3 | Viewed by 983

Coronavirus Disease 2019 (COVID-19) is a life-threatening disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus which was first reported in late 2019 in China, from where it then spread worldwide [...] Full article

(This article belongs to the Special Issue Advances in SARS-CoV-2 Infection)

Research

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13 pages, 581 KiB

Open AccessArticle

Impact of the COVID-19 Pandemic on Inappropriate Use of the Emergency Department

by Abelardo Claudio Fernández Chávez, Jesús María Aranaz-Andrés, Miriam Roncal-Redin, Fernando Roldán Moll, María Jesús Estévez Rueda, Patricia Alva García, Yolanda Aranda García, Diego San Jose-Saras and on behalf Health Outcomes Research Group of the Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)

Microorganisms 2023, 11(2), 423; https://doi.org/10.3390/microorganisms11020423 - 07 Feb 2023

Cited by 1 | Viewed by 1376

Abstract

Background: Inappropriate use of the emergency department (IEDU)—consisting of the unnecessary use of the resource by patients with no clinical need—is one of the leading causes of the loss of efficiency of the health system. Specific contexts modify routine clinical practice and [...] Read more.

Background: Inappropriate use of the emergency department (IEDU)—consisting of the unnecessary use of the resource by patients with no clinical need—is one of the leading causes of the loss of efficiency of the health system. Specific contexts modify routine clinical practice and usage patterns. This study aims to analyse the influence of COVID-19 on the IEDU and its causes. Methods: A retrospective, cross-sectional study conducted in the emergency department of a high-complexity hospital. The Hospital Emergency Suitability Protocol (HESP) was used to measure the prevalence of IEDU and its causes, comparing three pairs of periods: (1) March 2019 and 2020; (2) June 2019 and 2020; and (3) September 2019 and 2020. A bivariate analysis and multivariate logistic regression models, adjusted for confounding variables, were utilized. Results: In total, 822 emergency visits were included (137 per period). A total prevalence of IEDU of 14.1% was found. There was a significant decrease in IEDU in March 2020 (OR: 0.03), with a prevalence of 0.8%. No differences were found in the other periods. A mistrust in primary care was the leading cause of IEDU (65.1%). Conclusions: The impact of COVID-19 reduced the frequency of IEDU during the period of more significant population restrictions, with IEDU returning to previous levels in subsequent months. Targeted actions in the field of population education and an improvement in primary care are positioned as strategies that could mitigate its impact. Full article

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18 pages, 678 KiB

Open AccessArticle

The Immune, Inflammatory and Hematological Response in COVID-19 Patients, According to the Severity of the Disease

by Felicia Trofin, Eduard-Vasile Nastase, Andrei Vâță, Luminița Smaranda Iancu, Cătălina Luncă, Elena Roxana Buzilă, Mădălina Alexandra Vlad and Olivia Simona Dorneanu

Microorganisms 2023, 11(2), 319; https://doi.org/10.3390/microorganisms11020319 - 27 Jan 2023

Cited by 7 | Viewed by 1721

Abstract

Introduction: The aim of this study was to evaluate the immune and inflammatory responses in COVID-19 patients by dosing specific IgM and IgG total antibodies and interleukin 6, correlating them with the hematological and biochemical blood parameters and comparing them by the form [...] Read more.

Introduction: The aim of this study was to evaluate the immune and inflammatory responses in COVID-19 patients by dosing specific IgM and IgG total antibodies and interleukin 6, correlating them with the hematological and biochemical blood parameters and comparing them by the form of the disease. Materials and methods: One hundred twenty-five patients with polymerase chain reaction-confirmed COVID-19, hospitalized between 15.03.2020 and 1.07.2020 in the Clinical Hospital of Infectious Diseases “Sf. Parascheva” Iaşi, were tested by chemiluminescence for the presence of anti-SARS-CoV-2 IgM and IgG and IL-6 in the serum. The results were correlated with the results of the CBC count and serum biochemical parameters detected on the admission day. The patients presented different forms of the disease (asymptomatic, mild, moderate, severe, and critical) according to World Health Organization (WHO) criteria for the clinical management of COVID-19. Results: The amplitude of the immune response was directly correlated with the form of the disease. In the asymptomatic/mild form patients, the IL-6 and CRP concentrations were significantly higher and eosinophil count was significantly lower compared with the reference interval. In the moderate form, the concentrations of IL-6, CRP, and IgG were significantly higher, compared with the reference interval, while eosinophil count and eGFR were significantly lower. In severe/critical COVID-19 patients, IL-6, CRP, NLR, PLR, glucose, AST, urea, creatinine, and eGFR were significantly higher compared with the reference interval, while eosinophil count was significantly lower. IL-6 boosted in all forms of COVID-19, with a major increase in severe and critical patients. IL-6, neutrophil count, % neutrophils, NLR, PLR, CRP, AST, and urea increased with the severity of the SARS-CoV-2 infection, and the lymphocyte count, % lymphocytes, eosinophil count, % eosinophils, and hemoglobin decreased with the increased severity of COVID-19. Conclusions: The amplitude and the moment of appearance of the immune response depended on the form of the disease. IgM generally occurred in the first 14 days of illness, and IgG appeared beginning with the second week of disease. IgG titer increased rapidly until the fourth week of disease and decreased slowly after 4 weeks. The amplitudes of all the tested inflammatory and serological markers depended on the COVID-19 form, increasing somewhat in the moderate forms and even more in the critical ones. The lymphocyte and eosinophil count are able to predict the risk of severe COVID-19. Full article

(This article belongs to the Special Issue Advances in SARS-CoV-2 Infection)

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18 pages, 5391 KiB

Open AccessArticle

Human Adenovirus and Influenza A Virus Exacerbate SARS-CoV-2 Infection in Animal Models

by Victor A. Svyatchenko, Vladimir A. Ternovoi, Roman Y. Lutkovskiy, Elena V. Protopopova, Andrei S. Gudymo, Nataliya V. Danilchenko, Ivan M. Susloparov, Nataliya P. Kolosova, Alexander B. Ryzhikov, Oleg S. Taranov, Vladimir V. Omigov, Elena V. Gavrilova, Alexander P. Agafonov, Rinat A. Maksyutov and Valery B. Loktev

Microorganisms 2023, 11(1), 180; https://doi.org/10.3390/microorganisms11010180 - 11 Jan 2023

Cited by 4 | Viewed by 2808

Abstract

In this study, we investigated the features of the infectious process by simulating co-infection with SARS-CoV-2 and human adenovirus type 5 (HAdV-5) or influenza A virus (IAV) in vitro and in vivo. The determination of infectious activity of viruses and digital PCR demonstrated [...] Read more.

In this study, we investigated the features of the infectious process by simulating co-infection with SARS-CoV-2 and human adenovirus type 5 (HAdV-5) or influenza A virus (IAV) in vitro and in vivo. The determination of infectious activity of viruses and digital PCR demonstrated that during simultaneous and sequential HAdV-5 followed by SARS-CoV-2 infection in vitro and in vivo, the HAdV-5 infection does not interfere with replication of SARS-CoV-2. The hamsters co-infected and mono-infected with SARS-CoV-2 exhibited nearly identical viral titers and viral loads of SARS-CoV-2 in the lungs. The hamsters and ferrets co-infected by SARS-CoV-2- and IAV demonstrated more pronounced clinical manifestations than mono-infected animals. Additionally, the lung histological data illustrate that HAdV-5 or IAV and SARS-CoV-2 co-infection induces more severe pathological changes in the lungs than mono-infection. The expression of several genes specific to interferon and cytokine signaling pathways in the lungs of co-infected hamsters was more upregulated compared to single infected with SARS-CoV-2 animals. Thus, co-infection with HAdV-5 or IAV and SARS-CoV-2 leads to more severe pulmonary disease in animals. Full article

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11 pages, 1468 KiB

Open AccessArticle

Association between Brain Injury Markers and Testosterone in Critically-Ill COVID-19 Male Patients

by Daria Tokic, Marijana Mikacic, Marko Kumric, Tina Ticinovic Kurir, Iva Rancic, Dinko Martinovic, Josipa Bukic, Josip Vrdoljak, Ivan Kresimir Lizatovic, Sanda Stojanovic Stipic, Daniela Supe Domic and Josko Bozic

Microorganisms 2022, 10(11), 2095; https://doi.org/10.3390/microorganisms10112095 - 22 Oct 2022

Cited by 4 | Viewed by 1341

Abstract

Accumulating data suggest that various neurologic manifestations are reported in critically-ill COVID-19 patients. Although low testosterone levels were associated with poor outcomes, the relationship between testosterone levels and indices of brain injury are still poorly understood. Therefore, we aimed to explore whether testosterone [...] Read more.

Accumulating data suggest that various neurologic manifestations are reported in critically-ill COVID-19 patients. Although low testosterone levels were associated with poor outcomes, the relationship between testosterone levels and indices of brain injury are still poorly understood. Therefore, we aimed to explore whether testosterone levels are associated with glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), biomarkers of brain injury, in patients with a severe form of COVID-19. The present study was conducted on 65 male patients aged 18–65 with severe COVID-19. Blood samples were collected at three time points: upon admission to ICU, 7 days after, and 14 days after. In patients with neurological sequels (n = 20), UCH-L1 serum concentrations at admission were markedly higher than in patients without them (240.0 (155.4–366.4) vs. 146.4 (92.5–243.9) pg/mL, p = 0.022). GFAP concentrations on admission did not differ between the groups (32.2 (24.2–40.1) vs. 29.8 (21.8–39.4) pg/mL, p = 0.372). Unlike GFAP, UCH-L1 serum concentrations exhibited a negative correlation with serum testosterone in all three time points (r = −0.452, p < 0.001; r = −0.430, p < 0.001 and r = −0.476, p = 0.001, respectively). The present study suggests that the traumatic brain injury biomarker UCH-L1 may be associated with neurological impairments seen in severe COVID-19. Moreover, a negative correlation between UCH-L1 and serum testosterone concentrations implies that testosterone may have a role in the development of neurological sequels in critically-ill COVID-19 patients. Full article

(This article belongs to the Special Issue Advances in SARS-CoV-2 Infection)

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19 pages, 3643 KiB

Open AccessArticle

Epidemiological and Serological Analysis of a SARS-CoV-2 Outbreak in a Nursing Home: Impact of SARS-CoV-2 Vaccination and Enhanced Neutralizing Immunity Following Breakthrough Infection

by Barbara I. Streibl, Heidi Lahne, Andreas Grahl, Philipp Agsten, Magdalena Bichler, Christa Büchl, Marco Damzog, Ute Eberle, Stefan Gärtner, Bernhard Hobmaier, Gabriele Margos, Martin Hoch, Sabrina Jungnick, Walter Jonas, Katharina Katz, Liane Laubert, Barbara Schutt, Cornelia Seidl, Bianca Treis, Daniel Weindl, Karen Zilch, Manfred Wildner, Bernhard Liebl, Nikolaus Ackermann, Andreas Sing and Volker Fingerle Show full author list Hide full author list

Microorganisms 2022, 10(9), 1809; https://doi.org/10.3390/microorganisms10091809 - 09 Sep 2022

Cited by 3 | Viewed by 1485

Abstract

Background: Despite a vaccination rate of 82.0% (n = 123/150), a SARS-CoV-2 (Alpha) outbreak with 64.7% (n = 97/150) confirmed infections occurred in a nursing home in Bavaria, Germany. Objective: the aim of this retrospective cohort study was to [...] Read more.

Background: Despite a vaccination rate of 82.0% (n = 123/150), a SARS-CoV-2 (Alpha) outbreak with 64.7% (n = 97/150) confirmed infections occurred in a nursing home in Bavaria, Germany. Objective: the aim of this retrospective cohort study was to examine the effects of the Corminaty vaccine in a real-life outbreak situation and to obtain insights into the antibody response to both vaccination and breakthrough infection. Methods: the antibody status of 106 fully vaccinated individuals (54/106 breakthrough infections) and epidemiological data on all 150 residents and facility staff were evaluated. Results: SARS-CoV-2 infections (positive RT-qPCR) were detected in 56.9% (n = 70/123) of fully vaccinated, compared to 100% (n = 27/27) of incompletely or non-vaccinated individuals. The proportion of hospitalized and deceased was 4.1% (n = 5/123) among fully vaccinated and therewith lower compared to 18.5% (n = 5/27) hospitalized and 11.1% (n = 3/27) deceased among incompletely or non-vaccinated. Ct values were significantly lower in incompletely or non-vaccinated (p = 0.02). Neutralizing antibodies were detected in 99.1% (n = 105/106) of serum samples with significantly higher values (p < 0.001) being measured post-breakthrough infection.

α

-N-antibodies were detected in 37.7% of PCR positive but not in PCR negative individuals. Conclusion: Altogether, our data indicate that SARS-CoV-2 vaccination does provide protection against infection, severe disease progression and death with regards to the Alpha variant. Nonetheless, it also shows that infection and transmission are possible despite full vaccination. It further indicates that breakthrough infections can significantly enhance

α

-S- and neutralizing antibody responses, indicating a possible benefit from booster vaccinations. Full article

(This article belongs to the Special Issue Advances in SARS-CoV-2 Infection)

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10 pages, 258 KiB

Open AccessEditor’s ChoiceArticle

Role of Intracellular Pulmonary Pathogens during SARS-CoV-2 Infection in the First Pandemic Wave of COVID-19: Clinical and Prognostic Significance in a Case Series of 1200 Patients

by Matteo Guarino, Benedetta Perna, Francesca Cuoghi, Michele Domenico Spampinato, Alice Eleonora Cesaro, Francesca Manza, Adriana Pretula, Anastasio Grilli, Martina Maritati, Giacomo Caio, Aldo Carnevale, Maria Elena Flacco, Roberto De Giorgio and Carlo Contini

Microorganisms 2022, 10(8), 1636; https://doi.org/10.3390/microorganisms10081636 - 12 Aug 2022

Cited by 4 | Viewed by 1818

Abstract

Background: Since 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) has caused millions of deaths worldwide and is the second most serious pandemic after the Spanish flu. Despite SARS-CoV-2 infection having a dominant effect on morbidity and life-threatening outcomes, [...] Read more.

Background: Since 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) has caused millions of deaths worldwide and is the second most serious pandemic after the Spanish flu. Despite SARS-CoV-2 infection having a dominant effect on morbidity and life-threatening outcomes, the role of bacterial co-infection in patients with COVID-19 is poorly understood. The present study aimed to verify the existence of bacterial co-infections and their possible role as cofactors worsening COVID-19-related clinical manifestations. Methods: All patients with suspected SARS-CoV-infection, hospitalised in COVID-19 wards at the Sant’Anna University Hospital of Ferrara, were retrospectively included in this single-centre study and their specific bacterial serologies were assessed. Univariate and logistic regression analyses were performed. Results: A total of 1204 individual records were retrieved. Among them, 959 were excluded because of a negative nasopharyngeal swab or missing data; of the eligible 245 patients, 51 were co-infected. Compared to patients with SARS-CoV-2 infection alone, those with Chlamydia pneumoniae or Mycoplasma pneumoniae co-infections had worse respiratory/radiological features and more intensive care unit admissions. However, the co-infection did not result in a higher mortality rate. Conclusions: The present study, comparing clinical, laboratory and radiological findings between patients with COVID-19 vs. those with co-infections (C. pneumoniae or M. pneumoniae) showed that, on admission, these features were worse in co-infected patients, although the mortality rate did not differ between the two groups. Full article

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10 pages, 425 KiB

Open AccessArticle

SARS-CoV-2 Mutations and Variants May Muddle the Sensitivity of COVID-19 Diagnostic Assays

by Mohammad Alkhatib, Luca Carioti, Stefano D’Anna, Francesca Ceccherini-Silberstein, Valentina Svicher and Romina Salpini

Microorganisms 2022, 10(8), 1559; https://doi.org/10.3390/microorganisms10081559 - 02 Aug 2022

Cited by 5 | Viewed by 1852

Abstract

The performance of diagnostic polymerase chain reaction (PCR) assays can be impacted by SARS-CoV-2 variability as this is dependent on the full complementarity between PCR primers/probes and viral target templates. Here, we investigate the genetic variability of SARS-CoV-2 regions recognized by primers/probes utilized [...] Read more.

The performance of diagnostic polymerase chain reaction (PCR) assays can be impacted by SARS-CoV-2 variability as this is dependent on the full complementarity between PCR primers/probes and viral target templates. Here, we investigate the genetic variability of SARS-CoV-2 regions recognized by primers/probes utilized by PCR diagnostic assays based on nucleotide mismatching analysis. We evaluated the genetic variation in the binding regions of 73 primers/probes targeting the Nucleocapsid (N, N = 36), Spike (S, N = 22), and RNA-dependent RNA-polymerase/Helicase (RdRp/Hel, N = 15) of the publicly available PCR-based assays. Over 4.9 million high-quality SARS-CoV-2 genome sequences were retrieved from GISAID and were divided into group-A (all except Omicron, >4.2 million) and group-B (only Omicron, >558 thousand). In group-A sequences, a large range of variability in primers/probes binding regions in most PCR assays was observed. Particularly, 87.7% (64/73) of primers/probes displayed ≥1 mismatch with their viral targets, while 8.2% (6/73) contained ≥2 mismatches and 2.7% (2/73) contained ≥3 mismatches. In group-B sequences, 32.9% (24/73) of primers/probes were characterized by ≥1 mismatch, 13.7% (10/73) by ≥2 mismatches, and 5.5% (4/73) by ≥3 mismatches. The high rate of single and multiple mismatches- found in the target regions of molecular assays used worldwide for SARS-CoV-2 diagnosis reinforces the need to optimize and constantly update these assays according to SARS-CoV-2 genetic evolution and the future emergence of novel variants. Full article

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11 pages, 1741 KiB

Open AccessArticle

Effects of Antibody Responses to Pre-Existing Coronaviruses on Disease Severity and Complement Activation in COVID-19 Patients

by Massimo Cugno, Pier Luigi Meroni, Dario Consonni, Samantha Griffini, Elena Grovetti, Cristina Novembrino, Adriana Torri, Gloria Griffante, Marisa Gariglio, Luca Varani and Flora Peyvandi

Microorganisms 2022, 10(6), 1191; https://doi.org/10.3390/microorganisms10061191 - 10 Jun 2022

Cited by 5 | Viewed by 1726

Abstract

The severity of coronavirus disease 2019 (COVID-19) may be influenced by pre-existing immune responses against endemic coronaviruses, but conflicting data have been reported. We studied 148 patients who were hospitalised because of a confirmed diagnosis of COVID-19, classified mild in 58, moderate in [...] Read more.

The severity of coronavirus disease 2019 (COVID-19) may be influenced by pre-existing immune responses against endemic coronaviruses, but conflicting data have been reported. We studied 148 patients who were hospitalised because of a confirmed diagnosis of COVID-19, classified mild in 58, moderate in 44, and severe in 46. The controls were 27 healthy subjects. At admission, blood samples were collected for the measurement of biomarkers of disease severity and levels of the IgG against the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and pre-existing coronaviruses OC43, HKU1, NL63 and 229E. Higher levels of IgG antibodies against the RBD of pre-existing coronavirus (with the highest significance for anti-HKU1 IgG, p = 0.01) were found in patients with mild disease, compared with those with moderate or severe disease. Multivariable logistic regression confirmed the association of high levels of antibodies to pre-existing coronavirus with mild disease and showed their associations with low levels of the complement activation marker SC5b-9 (p range = 0.007–0.05). High levels of anti-NL63 antibodies were associated with low levels of the coagulation activation marker D-dimer (p = 0.04), while high levels of IgG against 229E were associated with low levels of the endothelial activation marker von Willebrand factor (p = 0.05). Anti-SARS-CoV-2-neutralising activity of plasma positively correlated with anti-SARS-CoV-2 IgG (r = 0.53, p = 0.04) and with anti-HKU1 IgG (r = 0.51, p = 0.05). In hospitalised patients with COVID-19, high levels of antibodies to pre-existing coronaviruses are associated with mild disease, suggesting that their measurement could be useful in predicting the severity of the disease. Full article

(This article belongs to the Special Issue Advances in SARS-CoV-2 Infection)

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15 pages, 585 KiB

Open AccessArticle

SARS-CoV-2 Vaccine Alpha and Delta Variant Breakthrough Infections Are Rare and Mild but Can Happen Relatively Early after Vaccination

by Jelissa Katharina Peter, Fanny Wegner, Severin Gsponer, Fabrice Helfenstein, Tim Roloff, Rahel Tarnutzer, Kerstin Grosheintz, Moritz Back, Carla Schaubhut, Sabina Wagner, Helena M. B. Seth-Smith, Patrick Scotton, Maurice Redondo, Christiane Beckmann, Tanja Stadler, Andrea Salzmann, Henriette Kurth, Karoline Leuzinger, Stefano Bassetti, Roland Bingisser, Martin Siegemund, Maja Weisser, Manuel Battegay, Sarah Tschudin Sutter, Aitana Lebrand, Hans H. Hirsch, Simon Fuchs and Adrian Egli Show full author list Hide full author list

Microorganisms 2022, 10(5), 857; https://doi.org/10.3390/microorganisms10050857 - 21 Apr 2022

Cited by 7 | Viewed by 2459

Abstract

(1) Background: Some COVID-19 vaccine recipients show breakthrough infection. It remains unknown, which factors contribute to risks and severe outcomes. Our aim was to identify risk factors for SCoV2 breakthrough infections in fully vaccinated individuals. (2) Methods: We conducted a retrospective case-control study [...] Read more.

(1) Background: Some COVID-19 vaccine recipients show breakthrough infection. It remains unknown, which factors contribute to risks and severe outcomes. Our aim was to identify risk factors for SCoV2 breakthrough infections in fully vaccinated individuals. (2) Methods: We conducted a retrospective case-control study from 28 December 2020 to 25 October 2021. Data of all patients with breakthrough infection was compared to data of all vaccine recipients in the Canton of Basel-City, Switzerland. Further, breakthrough infections by Alpha- and Delta-variants were compared. (3) Results: Only 0.39% (488/126,586) of all vaccine recipients suffered from a breakthrough infection during the observational period, whereof most cases were asymptomatic or mild (97.2%). Breakthrough infections after full vaccination occurred in the median after 78 days (IQR 47-123.5). Factors with lower odds for breakthrough infection were age (OR 0.987) and previous COVID-19 infection prior to vaccination (OR 0.296). Factors with higher odds for breakthrough infection included vaccination with Pfizer/BioNTech instead of Moderna (OR 1.459), chronic disease (OR 2.109), and healthcare workers (OR 1.404). (4) Conclusions: Breakthrough infections are rare and mild but can occur early after vaccination. This implies that booster vaccination might be initiated earlier, especially for risk groups. Due to new variants emerging repeatedly, continuous monitoring of breakthrough infections is crucial. Full article

(This article belongs to the Special Issue Advances in SARS-CoV-2 Infection)

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11 pages, 961 KiB

Open AccessArticle

A New Early Predictor of Fatal Outcome for COVID-19 in an Italian Emergency Department: The Modified Quick-SOFA

by Matteo Guarino, Benedetta Perna, Francesca Remelli, Francesca Cuoghi, Alice Eleonora Cesaro, Michele Domenico Spampinato, Martina Maritati, Carlo Contini and Roberto De Giorgio

Microorganisms 2022, 10(4), 806; https://doi.org/10.3390/microorganisms10040806 - 12 Apr 2022

Cited by 6 | Viewed by 1877

Abstract

Background: Since 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a rapidly spreading pandemic. The present study aims to compare a modified quick SOFA (MqSOFA) score with the NEWS-2 score to predict in-hospital mortality (IHM), 30-days mortality and recovery [...] Read more.

Background: Since 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a rapidly spreading pandemic. The present study aims to compare a modified quick SOFA (MqSOFA) score with the NEWS-2 score to predict in-hospital mortality (IHM), 30-days mortality and recovery setting. Methods: All patients admitted from March to October 2020 to the Emergency Department of St. Anna Hospital, Ferrara, Italy with clinically suspected SARS-CoV-2 infection were retrospectively included in this single-centre study and evaluated with the MqSOFA and NEWS-2 scores. Statistical and logistic regression analyses were applied to our database. Results: A total of 3359 individual records were retrieved. Among them, 2716 patients were excluded because of a negative nasopharyngeal swab and 206 for lacking data; thus, 437 patients were eligible. The data showed that the MqSOFA and NEWS-2 scores equally predicted IHM (p < 0.001) and 30-days mortality (p < 0.001). Higher incidences of coronary artery disease, congestive heart failure, cerebrovascular accidents, dementia, chronic kidney disease and cancer were found in the deceased vs. survived group. Conclusions: In this study we confirmed that the MqSOFA score was non-inferior to the NEWS-2 score in predicting IHM and 30-days mortality. Furthermore, the MqSOFA score was easier to use than NEWS-2 and is more suitable for emergency settings. Neither the NEWS-2 nor the MqSOFA scores were able to predict the recovery setting. Full article

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Review

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15 pages, 1218 KiB

Open AccessReview

Idiopathic Pulmonary Fibrosis and Post-COVID-19 Lung Fibrosis: Links and Risks

by Filippo Patrucco, Paolo Solidoro, Francesco Gavelli, Daria Apostolo and Mattia Bellan

Microorganisms 2023, 11(4), 895; https://doi.org/10.3390/microorganisms11040895 - 30 Mar 2023

Cited by 13 | Viewed by 4788

Abstract

Idiopathic pulmonary fibrosis (IPF) is considered the paradigmatic example of chronic progressive fibrosing disease; IPF does not result from a primary immunopathogenic mechanism, but immune cells play a complex role in orchestrating the fibrosing response. These cells are activated by pathogen-associated or danger-associated [...] Read more.

Idiopathic pulmonary fibrosis (IPF) is considered the paradigmatic example of chronic progressive fibrosing disease; IPF does not result from a primary immunopathogenic mechanism, but immune cells play a complex role in orchestrating the fibrosing response. These cells are activated by pathogen-associated or danger-associated molecular patterns generating pro-fibrotic pathways or downregulating anti-fibrotic agents. Post-COVID pulmonary fibrosis (PCPF) is an emerging clinical entity, following SARS-CoV-2 infection; it shares many clinical, pathological, and immune features with IPF. Similarities between IPF and PCPF can be found in intra- and extracellular physiopathological pro-fibrotic processes, genetic signatures, as well as in the response to antifibrotic treatments. Moreover, SARS-CoV-2 infection can be a cause of acute exacerbation of IPF (AE-IPF), which can negatively impact on IPF patients’ prognosis. In this narrative review, we explore the pathophysiological aspects of IPF, with particular attention given to the intracellular signaling involved in the generation of fibrosis in IPF and during the SARS-CoV-2 infection, and the similarities between IPF and PCPF. Finally, we focus on COVID-19 and IPF in clinical practice. Full article

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17 pages, 1801 KiB

Open AccessReview

Epigenetic Targets and Pathways Linked to SARS-CoV-2 Infection and Pathology

by Ali A. Rabaan, Mohammed Aljeldah, Basim R. Al Shammari, Roua A. Alsubki, Jawaher Alotaibi, Yousef N. Alhashem, Neda A. Alali, Tarek Sulaiman, Zainab Alsalem, Huda A. Bajunaid, Mohammed Garout, Heba A. Alsaffar, Souad A. Almuthree, Doha Hudhaiah, Azhar M. Alzaher, Fatimah A. Alshaikh, Amer Alshengeti, Mustafa A. Najim, Ramadan Abdelmoez Farahat and Ranjan K. Mohapatra

Microorganisms 2023, 11(2), 341; https://doi.org/10.3390/microorganisms11020341 - 30 Jan 2023

Cited by 2 | Viewed by 2056

Abstract

The scale at which the SARS-CoV-2/COVID-19 pandemic has spread remains enormous. Provided the genetic makeup of the virus and humans is readily available, the quest for knowing the mechanism and epidemiology continues to prevail across the entire scientific community. Several aspects, including immunology, [...] Read more.

The scale at which the SARS-CoV-2/COVID-19 pandemic has spread remains enormous. Provided the genetic makeup of the virus and humans is readily available, the quest for knowing the mechanism and epidemiology continues to prevail across the entire scientific community. Several aspects, including immunology, molecular biology, and host-pathogen interaction, are continuously being dug into for preparing the human race for future pandemics. The exact reasons for vast differences in symptoms, pathophysiological implications of COVID-infections, and mortality differences remain elusive. Hence, researchers are also looking beyond traditional genomics, proteomics, and transcriptomics approach, especially entrusting the environmental regulation of the genetic landscape of COVID–human interactions. In line with these questions lies a critical process called epigenetics. The epigenetic perturbations in both host and parasites are a matter of great interest to unravel the disparities in COVID-19 mortalities and pathology. This review provides a deeper insight into current research on the epigenetic landscape of SARS-CoV-2 infection in humans and potential targets for augmenting the ongoing investigation. It also explores the potential targets, pathways, and networks associated with the epigenetic regulation of processes involved in SARS-CoV-2 pathology. Full article

(This article belongs to the Special Issue Advances in SARS-CoV-2 Infection)

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22 pages, 686 KiB

Open AccessReview

Advanced Molecular and Immunological Diagnostic Methods to Detect SARS-CoV-2 Infection

by John Charles Rotondo, Fernanda Martini, Martina Maritati, Elisabetta Caselli, Carla Enrica Gallenga, Matteo Guarino, Roberto De Giorgio, Chiara Mazziotta, Maria Letizia Tramarin, Giada Badiale, Mauro Tognon and Carlo Contini

Microorganisms 2022, 10(6), 1193; https://doi.org/10.3390/microorganisms10061193 - 10 Jun 2022

Cited by 39 | Viewed by 4471

Abstract

COVID-19 emerged in late 2019 in China and quickly spread across the globe, causing over 521 million cases of infection and 6.26 million deaths to date. After 2 years, numerous advances have been made. First of all, the preventive vaccine, which has been [...] Read more.

COVID-19 emerged in late 2019 in China and quickly spread across the globe, causing over 521 million cases of infection and 6.26 million deaths to date. After 2 years, numerous advances have been made. First of all, the preventive vaccine, which has been implemented in record time, is effective in more than 95% of cases. Additionally, in the diagnostic field, there are numerous molecular and antigenic diagnostic kits that are equipped with high sensitivity and specificity. Real Time-PCR-based assays for the detection of viral RNA are currently considered the gold-standard method for SARS-CoV-2 diagnosis and can be used efficiently on pooled nasopharyngeal, or oropharyngeal samples for widespread screening. Moreover, additional, and more advanced molecular methods such as droplet-digital PCR (ddPCR), clustered regularly interspaced short palindromic repeats (CRISPR) and next-generation sequencing (NGS), are currently under development to detect the SARS-CoV-2 RNA. However, as the number of subjects infected with SARS-CoV-2 continuously increases globally, health care systems are being placed under increased stress. Thus, the clinical laboratory plays an important role, helping to select especially asymptomatic individuals who are actively carrying the live replicating virus, with fast and non-invasive molecular technologies. Recent diagnostic strategies, other than molecular methods, have been adopted to either detect viral antigens, i.e., antigen-based immunoassays, or human anti-SARS-CoV-2 antibodies, i.e., antibody-based immunoassays, in nasal or oropharyngeal swabs, as well as in blood or saliva samples. However, the role of mucosal sIgAs, which are essential in the control of viruses entering the body through mucosal surfaces, remains to be elucidated, and in particular the role of the immune response in counteracting SARS-CoV-2 infection, primarily at the site(s) of virus entry that appears to be promising. Full article

(This article belongs to the Special Issue Advances in SARS-CoV-2 Infection)

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Open AccessBrief Report

Performance of Dried Blood Spot Samples in SARS-CoV-2 Serolomics

by Rima Jeske, Uta Merle, Barbara Müller, Tim Waterboer and Julia Butt

Microorganisms 2022, 10(7), 1311; https://doi.org/10.3390/microorganisms10071311 - 29 Jun 2022

Cited by 1 | Viewed by 1308

Abstract

Numerous sero-epidemiological studies have been initiated to investigate the spread and dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To address the concomitant need for serological high-throughput assays, a bead-based multiplex serology assay, specific for SARS-CoV-2, had been developed. SARS-CoV-2 serolomics allows [...] Read more.

Numerous sero-epidemiological studies have been initiated to investigate the spread and dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To address the concomitant need for serological high-throughput assays, a bead-based multiplex serology assay, specific for SARS-CoV-2, had been developed. SARS-CoV-2 serolomics allows for measuring antibody responses to almost the entire SARS-CoV-2 proteome in up to 2000 serum samples per day. To enlarge the pool of eligible sample collection methods, we here test the compatibility of serolomics with dried blood spot (DBS)-derived eluates. Antibody levels of nine SARS-CoV-2 antigens, including the nucleocapsid (N) and receptor-binding domain of the spike protein (S1-RBD), were measured in 142 paired DBS and serum samples. The numeric correlation between the two sample types was high, with a Pearson’s r of 0.88 for both S1-RBD and N and intraclass correlation coefficients of 0.93 and 0.92, respectively. Systematically reduced antibody levels in DBS eluates were compensated by lowering the cutoffs for seropositivity accordingly. This enabled the concordant classification of SARS-CoV-2 seropositivity, without loss in sensitivity. Antibody levels against accessory SARS-CoV-2 antigens also showed a high concordance, demonstrating that DBS-derived eluates are eligible for SARS-CoV-2 serolomics. DBS cards facilitate the collection of blood samples, as they obviate the need for medically trained personnel and can be shipped at room temperature. In combination with SARS-CoV-2 serolomics, DBS cards enable powerful sero-epidemiological studies, thus allowing for the monitoring of patients and epidemiological analyses in resource-poor settings. Full article

(This article belongs to the Special Issue Advances in SARS-CoV-2 Infection)

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