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State-of-the-Art SARS-CoV-2 Research in Spain

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

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 21036

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Dr. Elena Moreno del Olmo

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Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain
Interests: virology; microbiota; SARS-CoV-2; HIV; molecular virology; OMICs; viral-host interactions

Special Issue Information

Dear Colleagues,

Together with other countries, Spain has been actively involved in research related to the SARS-CoV-2 pandemic virus for the last two years. Significant advances and great efforts to collaborate between health institutions, hospitals, research centers, etc. have been made to understand the mechanisms behind this new virus. Multiple experts from different fields using the best technologies available have been working to help fight against this virus. Several studies to understand the most basic molecular mechanisms, viral replication, and epidemiology together with clinical trials to test the most relevant treatments and vaccine candidates have been performed during this time.

In this Special Issue of the Viruses focused on “State-of-the-Art Virology Research in Spain” you have the opportunity to share all this work obtained from multiple collaborations and using state-of-the-art technologies to cover multiple aspects of SARS-CoV-2 infection and contribute to increasing knowledge in this important field.

Dr. Elena Moreno del Olmo
Guest Editor

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Keywords

SARS-CoV-2
technologies
epidemiology
virus-host interactions
viral pathogenesis
molecular virology
antivirals
vaccines
zoonotic viruses
immune response to viruses

Published Papers (9 papers)

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Research

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12 pages, 2122 KiB

Open AccessArticle

Wastewater-Based Epidemiology to Describe the Evolution of SARS-CoV-2 in the South-East of Spain, and Application of Phylogenetic Analysis and a Machine Learning Approach

by Jose A. Férez, Enric Cuevas-Ferrando, María Ayala-San Nicolás, Pedro J. Simón Andreu, Román López, Pilar Truchado, Gloria Sánchez and Ana Allende

Viruses 2023, 15(7), 1499; https://doi.org/10.3390/v15071499 - 03 Jul 2023

Viewed by 1306

Abstract

The COVID-19 pandemic has posed a significant global threat, leading to several initiatives for its control and management. One such initiative involves wastewater-based epidemiology, which has gained attention for its potential to provide early warning of virus outbreaks and real-time information on its spread. In this study, wastewater samples from two wastewater treatment plants (WWTPs) located in the southeast of Spain (region of Murcia), namely Murcia, and Cartagena, were analyzed using RT-qPCR and high-throughput sequencing techniques to describe the evolution of SARS-CoV-2 in the South-East of Spain. Additionally, phylogenetic analysis and machine learning approaches were applied to develop a pre-screening tool for the identification of differences among the variant composition of different wastewater samples. The results confirmed that the levels of SARS-CoV-2 in these wastewater samples changed concerning the number of SARS-CoV-2 cases detected in the population, and variant occurrences were in line with clinical reported data. The sequence analyses helped to describe how the different SARS-CoV-2 variants have been replaced over time. Additionally, the phylogenetic analysis showed that samples obtained at close sampling times exhibited a higher similarity than those obtained more distantly in time. A second analysis using a machine learning approach based on the mutations found in the SARS-CoV-2 spike protein was also conducted. Hierarchical clustering (HC) was used as an efficient unsupervised approach for data analysis. Results indicated that samples obtained in October 2022 in Murcia and Cartagena were significantly different, which corresponded well with the different virus variants circulating in the two locations. The proposed methods in this study are adequate for comparing consensus sequence types of the SARS-CoV-2 sequences as a preliminary evaluation of potential changes in the variants that are circulating in a given population at a specific time point. Full article

(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Spain)

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12 pages, 1085 KiB

Open AccessArticle

Retrospective Analysis of Vaccination Status and Predominant Viral Variants in Patients Hospitalized with COVID-19 in Reus, Spain

by Simona Iftimie, Ana F. López-Azcona, María José Lozano-Olmo, Àngels Naval-Ferrando, Vicent Domingo-Cortés, Helena Castañé, Andrea Jiménez-Franco, Anna Hernández-Aguilera, Carmen Guilarte, Francesc Riu, Jordi Camps, Jorge Joven and Antoni Castro

Viruses 2023, 15(4), 886; https://doi.org/10.3390/v15040886 - 30 Mar 2023

Viewed by 1209

Abstract

SARS-CoV-2 infection in already-vaccinated individuals is still possible and may require hospitalization. The aim of the present study was to evaluate the clinical evolution of patients with COVID-19 admitted to a public hospital. The outcomes were assessed in relation to the predominant viral variant and the vaccination status. This retrospective study was performed on 1295 COVID-19-positive patients who attended a 352-bed university hospital between 2021 and 2022. Clinical variables and vaccination status were recorded. Of the patients, 799 had not been vaccinated (NV, 61.7%), 449 were partially vaccinated (PV, 34.7%), and 47 were completely vaccinated (CV, 3.6%). The mean age of the CV patients was significantly higher than that of PV and NV. Additionally, they had higher percentages of chronic diseases. The outcomes depended on age but not on vaccination status. There were 209 patients admitted during the Omicron-infection period, of whom 70 (33.5%) were NV, 135 (64.6%) were PV, and 4 (1.9%) were CV. In conclusion, correct vaccination greatly reduces the risk of acquiring severe COVID-19. Partial vaccination does not guarantee protection of the population. This highlights the need for continuous vaccination promotion with all recommended doses, while also investigating alternative treatments for those patients who do not respond to the vaccines. Full article

(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Spain)

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9 pages, 653 KiB

Open AccessCommunication

Temporal Series Analysis of Population Cycle Threshold Counts as a Predictor of Surge in Cases and Hospitalizations during the SARS-CoV-2 Pandemic

by Fernando Cava, Jesús San Román, Pablo Barreiro, Francisco Javier Candel, Francisco Javier Álvarez-Timón, David Melero, Nerea Coya, Raquel Guillén, David Cantarero-Prieto, Javier Lera-Torres, Noelia Cobo-Ortiz, Jesús Canora, Francisco Javier Martínez-Peromingo, Raquel Barba, María del Mar Carretero, Juan Emilio Losa and Antonio Zapatero

Viruses 2023, 15(2), 421; https://doi.org/10.3390/v15020421 - 02 Feb 2023

Cited by 2 | Viewed by 1515

Abstract

Tools to predict surges in cases and hospitalizations during the COVID-19 pandemic may help guide public health decisions. Low cycle threshold (CT) counts may indicate greater SARS-CoV-2 concentrations in the respiratory tract, and thereby may be used as a surrogate marker of enhanced viral transmission. Several population studies have found an association between the oscillations in the mean CT over time and the evolution of the pandemic. For the first time, we applied temporal series analysis (Granger-type causality) to validate the CT counts as an epidemiological marker of forthcoming pandemic waves using samples and analyzing cases and hospital admissions during the third pandemic wave (October 2020 to May 2021) in Madrid. A total of 22,906 SARS-CoV-2 RT-PCR-positive nasopharyngeal swabs were evaluated; the mean CT value was 27.4 (SD: 2.1) (22.2% below 20 cycles). During this period, 422,110 cases and 36,727 hospital admissions were also recorded. A temporal association was found between the CT counts and the cases of COVID-19 with a lag of 9–10 days (p ≤ 0.01) and hospital admissions by COVID-19 (p < 0.04) with a lag of 2–6 days. According to a validated method to prove associations between variables that change over time, the short-term evolution of average CT counts in the population may forecast the evolution of the COVID-19 pandemic. Full article

(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Spain)

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12 pages, 1013 KiB

Open AccessArticle

Comparative Study of Vaccinated and Unvaccinated Hospitalised Patients: A Retrospective Population Study of 500 Hospitalised Patients with SARS-CoV-2 Infection in a Spanish Population of 220,000 Inhabitants

by José M. Ruiz-Giardin, Marta Rivilla, Nieves Mesa, Alejandro Morales, Luis Rivas, Aída Izquierdo, Almudena Escribá, Juan V. San Martín, David Bernal-Bello, Elena Madroñal, Ana I. Farfán, Marta Guerrero, Ruth Calderón, Miguel A. Duarte, Sara I. Piedrabuena, María Toledano-Macías, José Á. Satué, Jorge Marrero, Cristina L. de Ancos, Begoña Frutos, Rafael Cristóbal, Guillermo Soria, Ibone Ayala-Larrañaga, Lorena Carpintero, Miguel de Hita, Celia Lara, Álvaro R. Llerena, Virginia García, Raquel Jiménez, Vanesa García, Elena M. Saiz-Lou, Santiago Prieto, Natalia González-Pereira, Luis Antonio Lechuga, Jorge Tarancón and Sonia Gonzalo Show full author list Hide full author list

Viruses 2022, 14(10), 2284; https://doi.org/10.3390/v14102284 - 17 Oct 2022

Cited by 5 | Viewed by 2366

Abstract

Objectives. This study aimed to compare the characteristics of fully and partially vaccinated or unvaccinated coronavirus disease 2019 (COVID-19) patients who were hospitalised in a population of 220,000 habitants. Methods: Retrospective, observational, and population studies were conducted on patients who were hospitalised due to COVID-19 from March to October 2021. We assessed the impact of vaccination and other risk factors through Cox multivariate analysis. Results: A total of 500 patients were hospitalised, among whom 77 (15.4%) were fully vaccinated, 86 (17.2%) were partially vaccinated, and 337 (67.4%) were unvaccinated. Fully vaccinated (FV) patients were older and had a higher Charlson index than those of partially vaccinated and unvaccinated patients (NFV). Bilateral pneumonia was more frequent among NFV (259/376 (68.9%)) than among FV patients (32/75 (42.7%)). The former had more intensive care unit admissions (63/423) than the latter (4/77); OR: 2.80; CI (1.07–9.47). Increasing age HZ: 1.1 (1.06–1.14)) and haematological disease at admission HZ: 2.99 (1.26–7.11)) were independent risk factors for higher mortality during the first 30 days of hospitalisation. The probability of an earlier discharge in the subgroup of 440 patients who did not die during the first 30 days of hospitalisation was related to age (older to younger: HZ: 0.98 (0.97–0.99)) and vaccination status. Conclusions: Among the patients hospitalised because of COVID-19, complete vaccination was associated with less severe forms of COVID-19, with an earlier discharge date. Age and haematological disease were related to a higher mortality rate during the first 30 days of hospitalisation. Full article

(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Spain)

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16 pages, 2911 KiB

Open AccessArticle

SARS-CoV-2 Seroprevalence Study in Pediatric Patients and Health Care Workers Using Multiplex Antibody Immunoassays

by Esther Prados de la Torre, Ignacio Obando, Marta Vidal, Beatriz de Felipe, Ruth Aguilar, Luis Izquierdo, Carlo Carolis, Peter Olbrich, Ana Capilla-Miranda, Pau Serra, Pere Santamaria, Pilar Blanco-Lobo, Gemma Moncunill, Manuel J. Rodríguez-Ortega and Carlota Dobaño

Viruses 2022, 14(9), 2039; https://doi.org/10.3390/v14092039 - 14 Sep 2022

Cited by 2 | Viewed by 1636

Abstract

SARS-CoV-2 infection has become a global health problem specially exacerbated with the continuous appearance of new variants. Healthcare workers (HCW) have been one of the most affected sectors. Children have also been affected, and although infection generally presents as a mild disease, some have developed the Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We recruited 190 adults (HCW and cohabitants, April to June 2020) and 57 children (April 2020 to September 2021), of whom 12 developed PIMS-TS, in a hospital-based study in Spain. Using an in-house Luminex assay previously validated, antibody levels were measured against different spike and nucleocapsid SARS-CoV-2 proteins, including the receptor-binding domain (RBD) of the Alpha, Beta, Gamma, and Delta variants of concern (VoC). Seropositivity rates obtained from children and adults, respectively, were: 49.1% and 11% for IgG, 45.6% and 5.8% for IgA, and 35.1% and 7.3% for IgM. Higher antibody levels were detected in children who developed PIMS-TS compared to those who did not. Using the COVID-19 IgM/IgA ELISA (Vircell, S.L.) kit, widely implemented in Spanish hospitals, a high number of false positives and lower seroprevalences compared with the Luminex estimates were found, indicating a significantly lower specificity and sensitivity. Comparison of antibody levels against RBD-Wuhan versus RBD-VoCs indicated that the strongest positive correlations for all three isotypes were with RBD-Alpha, while the lowest correlations were with RBD-Delta for IgG, RBD-Gamma for IgM, and RBD-Beta for IgA. This study highlights the differences in antibody levels between groups with different demographic and clinical characteristics, as well as reporting the IgG, IgM, and IgA response to RBD VoC circulating at the study period. Full article

(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Spain)

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13 pages, 1572 KiB

Open AccessArticle

Assessing the Impact of SARS-CoV-2 Lineages and Mutations on Patient Survival

by Carlos Loucera, Javier Perez-Florido, Carlos S. Casimiro-Soriguer, Francisco M. Ortuño, Rosario Carmona, Gerrit Bostelmann, L. Javier Martínez-González, Dolores Muñoyerro-Muñiz, Román Villegas, Jesus Rodriguez-Baño, Manuel Romero-Gomez, Nicola Lorusso, Javier Garcia-León, Jose M. Navarro-Marí, Pedro Camacho-Martinez, Laura Merino-Diaz, Adolfo de Salazar, Laura Viñuela, The Andalusian COVID-19 Sequencing Initiative, Jose A. Lepe, Federico Garcia and Joaquin Dopazo Show full author list Hide full author list

Viruses 2022, 14(9), 1893; https://doi.org/10.3390/v14091893 - 27 Aug 2022

Cited by 4 | Viewed by 2621

Abstract

Objectives: More than two years into the COVID-19 pandemic, SARS-CoV-2 still remains a global public health problem. Successive waves of infection have produced new SARS-CoV-2 variants with new mutations for which the impact on COVID-19 severity and patient survival is uncertain. Methods: A total of 764 SARS-CoV-2 genomes, sequenced from COVID-19 patients, hospitalized from 19th February 2020 to 30 April 2021, along with their clinical data, were used for survival analysis. Results: A significant association of B.1.1.7, the alpha lineage, with patient mortality (log hazard ratio (LHR) = 0.51, C.I. = [0.14,0.88]) was found upon adjustment by all the covariates known to affect COVID-19 prognosis. Moreover, survival analysis of mutations in the SARS-CoV-2 genome revealed 27 of them were significantly associated with higher mortality of patients. Most of these mutations were located in the genes coding for the S, ORF8, and N proteins. Conclusions: This study illustrates how a combination of genomic and clinical data can provide solid evidence for the impact of viral lineage on patient survival. Full article

(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Spain)

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10 pages, 452 KiB

Open AccessArticle

Systemic Autoimmune Diseases in Patients Hospitalized with COVID-19 in Spain: A Nation-Wide Registry Study

by Víctor Moreno-Torres, Carmen de Mendoza, Susana Mellor-Pita, María Martínez-Urbistondo, Pedro Durán-del Campo, Pablo Tutor-Ureta, José-Manuel Vázquez-Comendador, Jorge Calderón-Parra, Elena Múñez-Rubio, Antonio Ramos-Martínez, Ana Fernández-Cruz, Raquel Castejón and Juan-Antonio Vargas-Nuñez

Viruses 2022, 14(8), 1631; https://doi.org/10.3390/v14081631 - 26 Jul 2022

Cited by 10 | Viewed by 1902

Abstract

We aimed to evaluate the clinical outcome of Systemic Autoimmune Diseases (SADs) patients hospitalized with COVID-19 in Spain, before the introduction of SARS-CoV-2 vaccines. A nationwide, retrospective and observational analysis of the patients admitted during 2020, based on the ICD10 codes in the National Registry of Hospital Discharges, was performed. Among 117,694 patients, only 892 (0.8%) presented any type of SAD before COVID-19-related admission: Sjogren’s Syndrome constituted 25%, Systemic Vasculitides 21%, Systemic Lupus Erythematosus 19%, Sarcoidosis 17%, Systemic Sclerosis 11%, Mixed and Undifferentiated Connective Tissue Disease 4%, Behçet’s Disease 4% and Inflammatory Myopathies 2%. The in-hospital mortality rate was higher in SAD individuals (20% vs. 16%, p < 0.001). After adjustment by baseline conditions, SADs were not associated with a higher mortality risk (OR = 0.93, 95% CI 0.78–1.11). Mortality in the SADs patients was determined by age (OR = 1.05, 95% CI 1.04–1.07), heart failure (OR = 1.67, 95% CI 1.10–2.49), chronic kidney disease (OR = 1.29, 95% CI 1.05–1.59) and liver disease (OR = 1.97, 95% CI 1.13–3.44). In conclusion, the higher COVID-19 mortality rate seen in SADs patients hospitalized in Spain in 2020 was related to the higher burden of comorbidities, secondary to direct organ damage and sequelae of their condition. Whilst further studies should evaluate the impact of baseline immunosuppression on COVID-19 outcomes in this population, efforts should be focused on the optimal management of SAD to minimize the impact of the organ damage that has been shown to determine COVID-19 prognosis. Full article

(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Spain)

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Review

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17 pages, 326 KiB

Open AccessReview

SARS-CoV-2 Infection and Preeclampsia—How an Infection Can Help Us to Know More about an Obstetric Condition

by Otilia González-Vanegas and Oscar Martinez-Perez

Viruses 2023, 15(7), 1564; https://doi.org/10.3390/v15071564 - 17 Jul 2023

Cited by 4 | Viewed by 1159

Abstract

Pregnant women with SARS-CoV-2 infection have a significantly higher risk of maternal death, ICU admission, preterm delivery, and stillbirth compared to those without infection. Additionally, the risk of preeclampsia (PE) increases in pregnant women infected with SARS-CoV-2, particularly in severe cases. The association between COVID-19 and PE is likely attributed to various mechanisms, including direct effects of the virus on trophoblast function and the arterial wall, exaggerated inflammatory response in pregnant women, local inflammation leading to placental ischemia, SARS-CoV-2-related myocardial injury, cytokine storm, and thrombotic microangiopathy. This paper aims to explore the similarities between PE and SARS-CoV-2 infection, considering COVID-19 as a valuable study model. By examining these parallels, we can enhance our knowledge and comprehension of PE. We wish to emphasize the potential for COVID-19-induced myocardial injury in pregnant women and its connection to the increased maternal mortality rate. Full article

(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Spain)

Other

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14 pages, 481 KiB

Open AccessSystematic Review

Long-COVID Symptoms in Individuals Infected with Different SARS-CoV-2 Variants of Concern: A Systematic Review of the Literature

by César Fernández-de-las-Peñas, Kin Israel Notarte, Princess Juneire Peligro, Jacqueline Veronica Velasco, Miguel Joaquín Ocampo, Brandon Michael Henry, Lars Arendt-Nielsen, Juan Torres-Macho and Gustavo Plaza-Manzano

Viruses 2022, 14(12), 2629; https://doi.org/10.3390/v14122629 - 25 Nov 2022

Cited by 73 | Viewed by 6118

Abstract

The association of SARS-CoV-2 variants with long-COVID symptoms is still scarce, but new data are appearing at a fast pace. This systematic review compares the prevalence of long-COVID symptoms according to relevant SARS-CoV-2 variants in COVID-19 survivors. The MEDLINE, CINAHL, PubMed, EMBASE and Web of Science databases, as well as the medRxiv and bioRxiv preprint servers, were searched up to 25 October 2022. Case-control and cohort studies analyzing the presence of post-COVID symptoms appearing after an acute SARS-CoV-2 infection by the Alpha (B.1.1.7), Delta (B.1.617.2) or Omicron (B.1.1.529/BA.1) variants were included. Methodological quality was assessed using the Newcastle–Ottawa Scale. From 430 studies identified, 5 peer-reviewed studies and 1 preprint met the inclusion criteria. The sample included 355 patients infected with the historical variant, 512 infected with the Alpha variant, 41,563 infected with the Delta variant, and 57,616 infected with the Omicron variant. The methodological quality of all studies was high. The prevalence of long-COVID was higher in individuals infected with the historical variant (50%) compared to those infected with the Alpha, Delta or Omicron variants. It seems that the prevalence of long-COVID in individuals infected with the Omicron variant is the smallest, but current data are heterogeneous, and long-term data have, at this stage, an obviously shorter follow-up compared with the earlier variants. Fatigue is the most prevalent long-COVID symptom in all SARS-CoV-2 variants, but pain is likewise prevalent. The available data suggest that the infection with the Omicron variant results in fewer long-COVID symptoms compared to previous variants; however, the small number of studies and the lack of the control of cofounders, e.g., reinfections or vaccine status, in some studies limit the generality of the results. It appears that individuals infected with the historical variant are more likely to develop long-COVID symptomatology. Full article

(This article belongs to the Special Issue State-of-the-Art SARS-CoV-2 Research in Spain)

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