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SARS-CoV-2 Infection: Focus on Pathophysiological Characteristics, Complications and Effects of Vaccinations

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Microbiology in Human Health and Disease".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 25103

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Dr. Barbara Brogna

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Unit Interventional and Emergency Radiology, AORN, San Giuseppe Moscati Hospital, Contrada Amoretta, 83100 Avellino, Italy
Interests: chest imaging; COVID-19; gastrointestinal imaging; emergency
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Prof. Dr. Marina Piscopo

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Department of Biology, University of Naples Federico II, 80138 Napoli, NA, Italy
Interests: histones; sperm proteins; environmental pollution; heavy metals; reproductive health; sperm chromatin; epigenetic modifications; marine organisms; human spermatogenesis
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Dr. Carlo Brogna

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Department of Research, Craniomed Group Facility Srl., 20091 Bresso, Italy
Interests: acetylcholine; bacteriophage; toxin; viruses; coronavirus; bacteria

Special Issue Information

Dear Colleagues,

This Special Issue aims to include high-quality works on both the pathophysiological characteristics and complications of SARS-CoV-2 infections during the different phases of the pandemic, with particular emphasis on pandemic risk assessment, the role of predictive and prognostic biomarkers, if there is a link between autoimmunity and long COVID, the role of the gut and lung microbiome, and the role of imaging and artificial intelligence.

Dr. Barbara Brogna
Prof. Dr. Marina Piscopo
Dr. Carlo Brogna
Guest Editors

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Keywords

SARS-CoV-2 complications
SARS-CoV2 prognostic and predictive biomarkers
long COVID-19 and autoimmune disease
COVID-19 and microbiome
artificial intelligence

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Published Papers (7 papers)

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12 pages, 1083 KB

Open AccessArticle

Obesity and COVID-19: Pathophysiological Insights and Pulmonary Complications in a Retrospective Cohort Study

by Cristina Stefania Dumitru, Raul Patrascu, Alexia Manole, Ionut Dragos Capraru, Fira-Mladinescu Corneluta, Felicia Manole, Dorin Novacescu and Flavia Zara

Biomedicines 2025, 13(8), 2009; https://doi.org/10.3390/biomedicines13082009 - 18 Aug 2025

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Abstract

Background/Objectives: Obesity is a major modifier of COVID-19 outcomes, contributing to increased disease severity and complications. This study aimed to assess the impact of obesity on clinical severity, pulmonary involvement, and in-hospital mortality among COVID-19 patients and to identify independent predictors of severe disease. Methods: We conducted a retrospective cohort study of 3005 hospitalized adults with RT-PCR-confirmed COVID-19 between 1 January 2020 and 1 March 2023. Patients were stratified by obesity status (body mass index (BMI) ≥ 30 kg/m²). Clinical, comorbidity, imaging, and laboratory data, as well as vaccination status (vaccinated or unvaccinated), were collected. Multivariate regression and gradient boosting models were used to identify predictors of severe outcomes. Effect estimates are expressed as relative risks (RRs) with 95% confidence intervals (CIs). Results: Obese patients (n = 894) showed significantly higher rates of severe COVID-19 (31.7% vs. 22.4%, p < 0.001) and more extensive lung damage (>50% involvement: 27.9% vs. 22.0%, p < 0.001), with lower admission SpO₂ (92.1 ± 4.0% vs. 94.2 ± 3.2%, p < 0.001). Hypoxemia (SpO₂ < 90%) was more frequent in obese individuals. The relative risk (RR) for severe disease was 1.41 (95% CI 1.25–1.60), and for >50% lung involvement, it was 1.27 (95% CI 1.11–1.45). Age > 65 years was the strongest predictor of mortality, particularly in non-obese patients. Gradient boosting models outperformed logistic regression (AUC = 0.92 vs. 0.87). Conclusions: Obesity independently predicts severe COVID-19 and pulmonary impairment. These findings support obesity-based risk stratification for clinical management and public health interventions. Full article

(This article belongs to the Special Issue SARS-CoV-2 Infection: Focus on Pathophysiological Characteristics, Complications and Effects of Vaccinations)

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16 pages, 1429 KB

Open AccessArticle

Prognostic Impact of Vaccination, Comorbidity, and Inflammatory Biomarkers on Clinical Outcome in Hospitalized Patients with COVID-19

by Sandra Bižić-Radulović, Tijana Subotički, Olivera Mitrović Ajtić, Teodora Dragojević, Emilija Živković, Sanja Miljatović, Dalibor Petrović, Dejana Stanisavljević, Snežana Jovanović, Milanko Šekler, Dejan Vidanović, Bojana Beleslin Čokić and Vladan P. Čokić

Biomedicines 2025, 13(8), 1995; https://doi.org/10.3390/biomedicines13081995 - 16 Aug 2025

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Background/Objectives: The coronavirus disease 2019 (COVID-19) has more severe symptoms and increased mortality among men than women. To address the prognostic impact of vaccination, comorbidities, and inflammatory biomarkers on classified clinical outcomes in hospitalized COVID-19 patients, we compared common and sex differences. Methods: Besides laboratory and clinical parameters at hospital admission, we performed a common and sex-based comparative analysis for the clinical outcomes, RT-qPCR analyses, and measured severe acute respiratory syndrome coronavirus (SARS-CoV-2)-specific IgM and IgG antibody levels of 702 COVID-19 patients in a single centre from June 2020 to April 2022. Results: Pro-inflammatory biomarkers (C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, lactate dehydrogenase (LDH), D-dimer, ferritin), and liver enzymes (AST, ALT, GGT) were significantly more increased in COVID-19 male patients and generally elevated with the severity of clinical outcome, regardless of the SARS-CoV-2 variant. Cycle threshold (Ct) values of RT-qPCR testing were in negative correlation with IL-6 in COVID-19 male patients, indicating that higher viral load largely increased IL-6 levels in parallel with the severity of clinical outcome and regardless of vaccination. IgG levels were higher in early post-COVID-19 male patients. Comorbidities were more frequent in COVID-19 female patients and generally more common in the severe clinical outcomes. Vaccination was negatively correlated with the severity of clinical outcome, liver enzymes, LDH, and inflammatory parameters in hospitalized COVID-19 patients, while the risk of pneumonia was reduced. Vaccination reduced the need for corticosteroid and anti-inflammatory therapies, but increased the need for antiviral drug treatment. Conclusions: In addition to confirming inflammatory biomarkers and the importance of anti-inflammatory therapy in vaccinated patients, this study showed that vaccination reduces, but does not prevent, mortality in patients with COVID-19. Full article

(This article belongs to the Special Issue SARS-CoV-2 Infection: Focus on Pathophysiological Characteristics, Complications and Effects of Vaccinations)

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18 pages, 1416 KB

Open AccessArticle

Herpes Zoster Reactivation Following COVID-19 and the Risk of Renal, Infectious, and Autoimmune Complications: A Global Propensity-Matched Cohort Study

by Ming-Hung Chien, Joshua Wang, Kuo-Cheng Lu and Chien-Lin Lu

Biomedicines 2025, 13(7), 1628; https://doi.org/10.3390/biomedicines13071628 - 2 Jul 2025

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Background: Herpes zoster (HZ), resulting from the reactivation of latent varicella-zoster virus, has been increasingly observed in individuals following COVID-19. Given the shared immunological disturbances between the two conditions, this study aimed to investigate whether HZ following COVID-19 is associated with an elevated risk of renal, infectious, and autoimmune complications. Methods: This retrospective cohort study utilized data from the TriNetX global federated health network, encompassing over 9 million adults diagnosed with COVID-19 between January 2020 and January 2022. Patients who developed HZ within one year following COVID-19 diagnosis were compared to 1:1 propensity score-matched controls without HZ. Time-to-event analyses over a three-year follow-up period were conducted to estimate the risks of major adverse kidney events (MAKE; defined as acute kidney injury, dialysis dependence, or severely reduced kidney function with eGFR <30 mL/min/1.73 m²), sepsis, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), using Kaplan–Meier survival curves and Cox proportional hazards models. Results: HZ following COVID-19 was significantly associated with increased risks of all four outcomes: MAKE (HR 1.940, 95% CI: 1.866–2.017), sepsis (HR 2.362, 95% CI: 2.250–2.479), SLE (HR 2.667, 95% CI: 2.254–3.156), and RA (HR 2.484, 95% CI: 2.267–2.730). Subgroup analyses identified older age, diabetes, impaired renal function, and elevated inflammatory markers as key risk-enhancing factors. Conclusions: HZ following COVID-19 may serve as a clinical indicator of systemic immune dysregulation and is independently associated with increased long-term risks of renal, infectious, and autoimmune sequelae. Enhanced monitoring of this high-risk population is warranted. Full article

(This article belongs to the Special Issue SARS-CoV-2 Infection: Focus on Pathophysiological Characteristics, Complications and Effects of Vaccinations)

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10 pages, 253 KB

Open AccessArticle

The Clinical Impact of the Omicron Variant on Octogenarian Hospitalized COVID-19 Patients: The Results from CoviCamp Cohort

by Pierantonio Grimaldi, Mariantonietta Pisaturo, Antonio Russo, Salvatore Martini, Francesca Ambrisi, Filomena Milite, Giovanni Di Caprio, Fabio Giuliano Numis, Ivan Gentile, Vincenzo Sangiovanni, Vincenzo Esposito, Rossella Pacilio, Giosuele Calabria, Raffaella Pisapia, Canio Carriero, Alfonso Masullo, Elio Manzillo, Grazia Russo, Roberto Parrella, Sebastiano Leone, Michele Gambardella, Antonio Ponticiello and Nicola Coppola Show full author list Hide full author list

Biomedicines 2025, 13(7), 1563; https://doi.org/10.3390/biomedicines13071563 - 26 Jun 2025

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Introduction: This study aims to investigate the clinical impact of Omicron Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection on the clinical presentation of Coronavirus Disease 2019 (COVID-19) in the very old (≥80 years old) population. Methods: All patients aged 80 years or older, hospitalized from March 2020 to June 2023 with a SARS-CoV-2 infection in one of the 17 COVID-19 units in eight cities of Campania, southern Italy, were enrolled in a multicenter, observational, retrospective study. Results: 341 patients ≥ 80 years of age were included: 80 of them in the Omicron and 261 in the non-Omicron period. Patients admitted during the Omicron period were older (p = 0.0001) and more comorbid, showing more frequently arterial hypertension (p = 0.018), cardiovascular disease (p = 0.0001), chronic kidney disease (CKD) (p = 0.002), chronic obstructive pulmonary disease (COPD) (p = 0.001), and active cancer (p = 0.0001). Severe and critical outcomes were observed more often in the non-Omicron variant (p = 0.0001). Patients in the Omicron group did not show a significantly prolonged hospitalization time (p = 0.063) or a higher likelihood of death during hospitalization (p = 0.097). Discussion: In our study, despite the greater frailty of patients hospitalized during the Omicron period, the disease appeared less severe compared to previous waves, suggesting that the lower severity of the disease could be attributed to virological rather than population characteristics. These findings underscore the importance of prevention strategies for older people, as the administration of vaccination and early antiviral therapies in at-risk subjects. Full article

(This article belongs to the Special Issue SARS-CoV-2 Infection: Focus on Pathophysiological Characteristics, Complications and Effects of Vaccinations)

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13 pages, 943 KB

Open AccessArticle

Prevalence, Evolution and Prognostic Factors of PASC in a Cohort of Patients Discharged from a COVID Unit

by Mariantonietta Pisaturo, Antonio Russo, Pierantonio Grimaldi, Caterina Monari, Simona Imbriani, Klodian Gjeloshi, Carmen Ricozzi, Roberta Astorri, Caterina Curatolo, Roberta Palladino, Francesco Caruso, Francesca Ambrisi, Lorenzo Onorato and Nicola Coppola

Biomedicines 2025, 13(6), 1414; https://doi.org/10.3390/biomedicines13061414 - 9 Jun 2025

Cited by 1 | Viewed by 671

Abstract

Background and Aim: PASC is a potentially debilitating clinical condition consisting of different general symptoms experienced by about 10% of patients with previous SARS-CoV-2 infection. Our study analyses a cohort of patients with a history of hospitalization for COVID-19 and aims to evaluate prognostic factors for experiencing PASC and to investigate the characteristics of patients experiencing PASC symptoms. Methods: This is an observational, monocentric retrospective study including all adult patients admitted to our COVID unit from 28 February 2020 to 30 April 2022, discharged alive, and having performed at least one follow-up visit at our post-COVID outpatient clinic after a minimum of three months from discharge. Patients who experienced persistent clinical manifestations or the development of new symptoms three months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least two months with no other explanation, were defined as having PASC. Results: A total of 429 patients were discharged alive from our COVID Unit and 244 patients performed at least one follow-up visit in our outpatient clinic. Of these, 134 patients did not experience PASC, while 110 patients experienced PASC. Long-COVID patients were more frequently female (43.6% vs. 31.3%, p = 0.048), more frequently presented throat pain and headache at hospital admission (respectively 8.9% vs. 2.5%, p = 0.041 and 15.8% vs. 5%, p = 0.007), and were more likely to have a history of type 2 diabetes mellitus (25.5% vs. 13%, p =0.013). At the multivariable analysis, female gender, type 2 diabetes, and headache at admission were factors associated with PASC. All 46 patients who performed at least two different admissions in our outpatient clinic were divided in two groups: the first including the 16 patients who experienced a reduction or a resolution of symptoms related to COVID-19, the second comprising the 30 patients who experienced clinical worsening or persisting symptoms. Smoking habit was more represented among patients with stable or worsening symptoms (42.3% vs. 7.7%, p = 0.042); myalgias at admission were more frequent in the clinical worsening group (27.6% vs. 0%, p= 0.039); and a larger amount of patients who reported neuropsychiatric symptoms and respiratory symptoms were in the stable or worsening PASC symptoms group. Discussion: In conclusion, this study underscores the complexity of PASC, identifying female sex, Type 2 diabetes, and certain acute COVID-19 symptoms as potential predisposing factors for its development. PASC still represents a substantial public health challenge, and ongoing efforts are essential to better understand its underlying mechanisms and improve patient outcomes. Full article

(This article belongs to the Special Issue SARS-CoV-2 Infection: Focus on Pathophysiological Characteristics, Complications and Effects of Vaccinations)

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19 pages, 852 KB

Open AccessEditor’s ChoiceArticle

Autoantibodies Targeting G-Protein-Coupled Receptors and RAS-Related Molecules in Post-Acute COVID Vaccination Syndrome: A Retrospective Case Series Study

by Mauro Mantovani, Paolo Bellavite, Serafino Fazio, Giuseppe Di Fede, Marco Tomasi, Daniele Belli and Elisabetta Zanolin

Biomedicines 2024, 12(12), 2852; https://doi.org/10.3390/biomedicines12122852 - 15 Dec 2024

Cited by 1 | Viewed by 19686

Abstract

Background/Objectives: While post-acute COVID-19 syndrome is well known and extensively studied, the post-acute COVID vaccination syndrome (PACVS) is a more recent nosological entity that is poorly defined at the immunopathological level, although it shares many symptoms with the sequelae of viral infections. Methods: This single-center retrospective study reports a case series of 17 subjects vaccinated with mRNA or adenoviral vector vaccines who were healthy before vaccination and had never been infected with SARS-CoV-2 but who presented with symptoms similar to PACVS for a median time of 20 months (min 4, max 32). The medical records of all patients referred to our outpatient clinic over a one-year period were retrospectively analyzed. Results: In this group, serological tests showed that, in addition to positivity for anti-spike protein antibodies, a high percentage of subjects were positive for antibodies against G protein-coupled receptors and molecules involved in the response to SARS-CoV-2. In a panel of 16 autoantibodies tested, a few were positively associated with some of the symptoms reported by patients: anti-ATR1 with lymphadenopathy and/or tonsillitis; anti-ACE2 with skin symptoms such as ecchymosis, skin oedema, and rash; anti-MAS1 with widespread burning sensation; and anti-STAB1 with skin oedema and rash. Anti-ADRA2A were negatively associated with memory loss and/or mental fog. ACE2 correlated with the serum levels of anti-S antibodies, supporting the hypothesis of an anti-idiotype mechanism in the immunopathogenesis of PACVS. Conclusions: This exploratory analysis suggests that the levels of autoantibodies directed against ACE2, and probably also MAS1 and STAB1, may serve as biomarkers for PACVS. Full article

(This article belongs to the Special Issue SARS-CoV-2 Infection: Focus on Pathophysiological Characteristics, Complications and Effects of Vaccinations)

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18 pages, 7265 KB

Open AccessCase Report

New Neonatal and Prenatal Approach to Home Therapy with Amoxicillin, Rifaximin, and Anti-Inflammatory Drugs for Pregnant Women with COVID-19 Infections—Monitoring of Fetal Growth as a Prognostic Factor: A Triple Case Series (N.A.T.H.A.N.)

by Carlo Brogna, Grazia Castellucci, Elrashdy M. Redwan, Alberto Rubio-Casillas, Luigi Montano, Gianluca Ciammetti, Marino Giuliano, Valentina Viduto, Mark Fabrowski, Gennaro Lettieri, Carmela Marinaro and Marina Piscopo

Biomedicines 2025, 13(8), 1858; https://doi.org/10.3390/biomedicines13081858 - 30 Jul 2025

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Abstract

Background: Since the COVID-19 pandemic, managing acute infections in symptomatic individuals, regardless of vaccination status, has been widely debated and extensively studied. Even more concerning, however, is the impact of COVID-19 on pregnant women—especially its effects on fetuses and newborns. Several studies have documented complications in both expectant mothers and their infants following infection. Methods: In our previous works, we provided scientific evidence of the bacteriophage behavior of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). This demonstrated that a well-defined combination of two antibiotics, amoxicillin and rifaximin, is associated with the same statistics for subjects affected by severe cases of SARS-CoV-2, regardless of vaccination status. We considered the few cases in the literature regarding the management of pregnancies infected with SARS-CoV-2, as well as previous data published in our works. In this brief case series, we present two pregnancies from the same unvaccinated mother—one prior to the COVID-19 pandemic and the other during the spread of the Omicron variant—as well as one pregnancy from a mother vaccinated against COVID-19. We describe the management of acute maternal infection using a previously published protocol that addresses the bacteriophage and toxicological mechanisms associated with SARS-CoV-2. Results: The three pregnancies are compared based on fetal growth and ultrasound findings. This report highlights that, even in unvaccinated mothers, timely and well-guided management of symptomatic COVID-19 can result in positive outcomes. In all cases, intrauterine growth remained within excellent percentiles, and the births resulted in optimal APGAR scores. Conclusions: This demonstrates that a careful and strategic approach, guided by ultrasound controls, can support healthy pregnancies during SARS-CoV-2 infection, regardless of vaccination status. Full article

(This article belongs to the Special Issue SARS-CoV-2 Infection: Focus on Pathophysiological Characteristics, Complications and Effects of Vaccinations)

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