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Viruses
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COVID-19: Prognosis and Long-Term Sequelae
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COVID-19: Prognosis and Long-Term Sequelae

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 29512

Special Issue Editors

Dr. Antonio Voza

E-Mail Website
Guest Editor
Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy
Interests: COVID-19; NIV; antibiotic treatment; pneumonia; sepsis shock
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Stefano Aliberti

E-Mail Website
Guest Editor
Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy
Interests: COVID-19; pneumonia; bronchiectasis; respiratory failure; nontuberculous mycobacteria

Special Issue Information

Dear Colleagues,

Post-COVID-19 syndrome first gained widespread recognition among social support groups and later on in scientific and medical communities. This illness is poorly understood, as it affects COVID-19 survivors at all levels of disease severity, even younger adults, children, and those not hospitalized. The precise definition of long COVID may be lacking; nevertheless, the most common symptoms reported in many studies have been fatigue and dyspnoea which last for months after acute COVID-19. To those symptoms, it could be possible to add cognitive and mental impairments, dry cough, chest and joint pains, palpitations, cardiac issues, myalgia, smell and taste dysfunctions, headaches, and gastrointestinal issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments of long COVID, which the current review aims to address. In brief, long COVID may be driven by long-term tissue damage (e.g., lung, brain, and heart) and pathological inflammation. The principle etiological hypothesis could be due to viral persistence, immune dysregulation, and autoimmunity. The associated risk factors may include the female sex, more than five early symptoms, early dyspnoea, prior psychiatric disorders, and specific biomarkers (e.g., D-dimer, CRP, and lymphocyte count); for these reasons, it could be desirable to deepen the understanding of this topic with a Special Issue.

Dr. Antonio Voza
Prof. Dr. Stefano Aliberti
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • COVID-19
  • pneumonia
  • SARS-CoV-2

Related Special Issue

Published Papers (9 papers)

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Research

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11 pages, 738 KiB  
Article
SARS-CoV-2 RNAemia and Disease Severity in COVID-19 Patients
by Merlin Jayalal Lawrence Panchali, Choon-Mee Kim, Jun-Won Seo, Da-Young Kim, Na-Ra Yun and Dong-Min Kim
Viruses 2023, 15(7), 1560; https://doi.org/10.3390/v15071560 - 16 Jul 2023
Cited by 1 | Viewed by 1093
Abstract
Objective: The clinical implications of SARS-CoV-2 RNA viremia in blood (RNAemia) remain uncertain despite gaining more prognostic implications for coronavirus disease 2019 (COVID-19). However, the clinical relevance of SARS-CoV-2 RNAemia has not been well documented. Methods: We conducted a cohort study on 95 [...] Read more.
Objective: The clinical implications of SARS-CoV-2 RNA viremia in blood (RNAemia) remain uncertain despite gaining more prognostic implications for coronavirus disease 2019 (COVID-19). However, the clinical relevance of SARS-CoV-2 RNAemia has not been well documented. Methods: We conducted a cohort study on 95 confirmed COVID-19 patients and explored the prospects with evidence of SARS-CoV-2 RNAemia in association with various clinical characteristics. We performed reverse transcription-polymerase chain reaction and studied the risk factors of SARS-CoV-2 RNAemia using logistic regression analysis. Results: The presence of SARS-CoV-2 RNAemia in critical or fatal cases was the highest (66.7%), followed by severe (12.5%) and mild to moderate (1.7%) in admission samples. SARS-CoV-2 viral RNAemia was detected on admission and 1st week samples; however, RNAemia was not detected on the samples collected on the second week post-symptom onset. Multiple regression analysis showed that the severity of the disease was an independent predictor of RNAemia (p < 0.021), and the Kaplan–Meier survival curve estimated an increased mortality rate in SARS-CoV-2 RNAemia cases (p < 0.001). Conclusions: Our study demonstrated that SARS-CoV-2 RNAemia is a predictive risk factor for clinical severity in COVID-19 patients. Hence, we showed that blood RNAemia might be a critical marker for disease severity and mortality. Full article
(This article belongs to the Special Issue COVID-19: Prognosis and Long-Term Sequelae)
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15 pages, 3686 KiB  
Article
Immunoglobulin A as a Key Immunological Molecular Signature of Post-COVID-19 Conditions
by Graziele F. Sousa, Raphael M. Carpes, Carina A. O. Silva, Marcela E. P. Pereira, Amanda C. V. F. Silva, Viktoria A. G. S. Coelho, Evenilton P. Costa, Flávia B. Mury, Raquel S. Gestinari, Jackson Souza-Menezes, Manuela Leal-da-Silva, José L. Nepomuceno-Silva, Amilcar Tanuri, Orlando C. Ferreira-Júnior and Cintia Monteiro-de-Barros
Viruses 2023, 15(7), 1545; https://doi.org/10.3390/v15071545 - 13 Jul 2023
Viewed by 1599
Abstract
COVID-19 has infected humans worldwide, causing millions of deaths or prolonged symptoms in survivors. The transient or persistent symptoms after SARS-CoV-2 infection have been defined as post-COVID-19 conditions (PCC). We conducted a study of 151 Brazilian PCC patients to analyze symptoms and immunoglobulin [...] Read more.
COVID-19 has infected humans worldwide, causing millions of deaths or prolonged symptoms in survivors. The transient or persistent symptoms after SARS-CoV-2 infection have been defined as post-COVID-19 conditions (PCC). We conducted a study of 151 Brazilian PCC patients to analyze symptoms and immunoglobulin profiles, taking into account sex, vaccination, hospitalization, and age. Fatigue and myalgia were the most common symptoms, and lack of vaccination, hospitalization, and neuropsychiatric and metabolic comorbidities were relevant to the development of PCC. Analysis of serological immunoglobulins showed that IgA was higher in PCC patients, especially in the adult and elderly groups. Also, non-hospitalized and hospitalized PCC patients produced high and similar levels of IgA. Our results indicated that the detection of IgA antibodies against SARS-CoV-2 during the course of the disease could be associated with the development of PCC and may be an immunological signature to predict prolonged symptoms in COVID-19 patients. Full article
(This article belongs to the Special Issue COVID-19: Prognosis and Long-Term Sequelae)
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12 pages, 670 KiB  
Article
Do COVID-19 Vaccinations Affect the Most Common Post-COVID Symptoms? Initial Data from the STOP-COVID Register–12-Month Follow-Up
by Mateusz Babicki, Joanna Kapusta, Karolina Pieniawska-Śmiech, Żaneta Kałuzińska-Kołat, Damian Kołat, Agnieszka Mastalerz-Migas, Piotr Jankowski and Michał Chudzik
Viruses 2023, 15(6), 1370; https://doi.org/10.3390/v15061370 - 13 Jun 2023
Cited by 1 | Viewed by 1603
Abstract
Around the world, various vaccines have been developed to prevent the SARS-CoV-2 virus infection and consequently the COVID-19 disease. However, many patients continue to report persistent symptoms after the acute phase. Since gathering scientific information on long COVID and post-COVID syndrome has become [...] Read more.
Around the world, various vaccines have been developed to prevent the SARS-CoV-2 virus infection and consequently the COVID-19 disease. However, many patients continue to report persistent symptoms after the acute phase. Since gathering scientific information on long COVID and post-COVID syndrome has become an urgent issue, we decided to investigate them in relation to the vaccination status of patients from the STOP-COVID registry. In this retrospective study, we analyzed data from the medical visit after contraction of COVID-19 and follow-up visits in the 3rd and 12th month after the disease. In total, 801 patients were included in the analysis. The most frequent complaints after 12 months included deterioration of exercise tolerance (37.5%), fatigue (36.3%), and memory/concentration difficulties (36.3%). In total, 119 patients declared that they had been diagnosed with at least one new chronic disease since the end of isolation, and 10.6% required hospitalization. The analysis of individual symptoms revealed that headache (p = 0.001), arthralgia (p = 0.032), and dysregulation of hypertension (p = 0.030) were more common in unvaccinated patients. Considering headache and muscle pain, people vaccinated after the disease manifested these symptoms less frequently. Subsequent research is needed to consider vaccines as a preventive factor for post-COVID syndrome. Full article
(This article belongs to the Special Issue COVID-19: Prognosis and Long-Term Sequelae)
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11 pages, 635 KiB  
Article
Post-COVID-19 Syndrome in Non-Hospitalized Individuals: Healthcare Situation 2 Years after SARS-CoV-2 Infection
by Inge Kirchberger, Christine Meisinger, Tobias D. Warm, Alexander Hyhlik-Dürr, Jakob Linseisen and Yvonne Goßlau
Viruses 2023, 15(6), 1326; https://doi.org/10.3390/v15061326 - 05 Jun 2023
Cited by 4 | Viewed by 8387
Abstract
Although “post-COVID-19 syndrome” (PCS) is reported to be common even in non-hospitalized individuals, long-term information on symptom burden, healthcare needs, utilization, and satisfaction with healthcare is scarce. The objectives of this study were to describe symptom burden, healthcare utilization and experiences with the [...] Read more.
Although “post-COVID-19 syndrome” (PCS) is reported to be common even in non-hospitalized individuals, long-term information on symptom burden, healthcare needs, utilization, and satisfaction with healthcare is scarce. The objectives of this study were to describe symptom burden, healthcare utilization and experiences with the healthcare offered for PCS in a German sample of non-hospitalized persons 2 years after SARS-CoV-2 infection. Individuals with past COVID-19 confirmed by positive polymerase chain reaction testing were examined at the University Hospital of Augsburg from 4 November 2020 to 26 May 2021 and completed a postal questionnaire between 14 June 2022 and 1 November 2022. Participants who self-reported the presence of fatigue, dyspnea on exertion, memory problems or concentration problems were classified as having PCS. Of the 304 non-hospitalized participants (58.2% female, median age 53.5), 210 (69.1%) had a PCS. Among these, 18.8% had slight to moderate functional limitations. Participants with PCS showed a significantly higher utilization of healthcare and a large proportion complained about lacking information on persistent COVID-19 symptoms and problems finding competent healthcare providers. The results indicate the need to optimize patient information on PCS, facilitate access to specialized healthcare providers, provide treatment options in the primary care setting and improve the education of healthcare providers. Full article
(This article belongs to the Special Issue COVID-19: Prognosis and Long-Term Sequelae)
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14 pages, 244 KiB  
Article
How do German General Practitioners Manage Long-/Post-COVID? A Qualitative Study in Primary Care
by Beatrice E. Bachmeier, Salome Hölzle, Mohamed Gasser and Marjan van den Akker
Viruses 2023, 15(4), 1016; https://doi.org/10.3390/v15041016 - 20 Apr 2023
Cited by 3 | Viewed by 1655
Abstract
Background: Many patients with ongoing complaints after a SARS-CoV-2 infection are treated in primary care. Existing medical guidelines on how to diagnose and treat Long-/Post-COVID are far from being comprehensive. This study aims to describe how German general practitioners (GPs) deal with this [...] Read more.
Background: Many patients with ongoing complaints after a SARS-CoV-2 infection are treated in primary care. Existing medical guidelines on how to diagnose and treat Long-/Post-COVID are far from being comprehensive. This study aims to describe how German general practitioners (GPs) deal with this situation, what problems they experience when managing such patients, and how they solve problems associated with the diagnosis and treatment of Long-/Post-COVID. Methods and Findings: We conducted a qualitative study and interviewed 11 GPs. The most commonly described symptoms were ongoing fatigue, dyspnea, chest tightness and a decrease in physical capacity. The most common way to identify Long-/Post-COVID was by exclusion. Patients suffering from Long-/Post-COVID were generally treated by their GPs and rarely referred. A very common non-pharmacological intervention was to take a wait-and-see approach and grant sick leave. Other non-pharmacological interventions included lifestyle advices, physical exercise, acupuncture and exercises with intense aromas. Pharmacological treatments focused on symptoms, like respiratory symptoms or headaches. Our study’s main limitations are the small sample size and therefore limited generalizability of results. Conclusions: Further research is required to develop and test pharmaceutical and non-pharmaceutical interventions for patients with Long-/Post-COVID. In addition, strategies to prevent the occurrence of Long-/Post-COVID after an acute infection with SARS-CoV-2 have to be developed. The routine collection of data on the diagnosis and management of Long-/Post-COVID may help in the formulation of best practices. It is up to policymakers to facilitate the necessary implementation of effective interventions in order to limit the huge societal consequences of large groups of patients suffering from Long-/Post-COVID. Full article
(This article belongs to the Special Issue COVID-19: Prognosis and Long-Term Sequelae)

Review

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15 pages, 831 KiB  
Review
How Does Long-COVID Impact Prognosis and the Long-Term Sequelae?
by Carolina Baroni, Jorge Potito, María Eugenia Perticone, Paola Orausclio and Carlos Marcelo Luna
Viruses 2023, 15(5), 1173; https://doi.org/10.3390/v15051173 - 15 May 2023
Cited by 4 | Viewed by 2039
Abstract
Context: We reviewed what has been studied and published during the last 3 years about the consequences, mainly respiratory, cardiac, digestive, and neurological/psychiatric (organic and functional), in patients with COVID-19 of prolonged course. Objective: To conduct a narrative review synthesizing current clinical evidence [...] Read more.
Context: We reviewed what has been studied and published during the last 3 years about the consequences, mainly respiratory, cardiac, digestive, and neurological/psychiatric (organic and functional), in patients with COVID-19 of prolonged course. Objective: To conduct a narrative review synthesizing current clinical evidence of abnormalities of signs, symptoms, and complementary studies in COVID-19 patients who presented a prolonged and complicated course. Methods: A review of the literature focused on the involvement of the main organic functions mentioned, based almost exclusively on the systematic search of publications written in English available on PubMed/MEDLINE. Results: Long-term respiratory, cardiac, digestive, and neurological/psychiatric dysfunction are present in a significant number of patients. Lung involvement is the most common; cardiovascular involvement may happen with or without symptoms or clinical abnormalities; gastrointestinal compromise includes the loss of appetite, nausea, gastroesophageal reflux, diarrhea, etc.; and neurological/psychiatric compromise can produce a wide variety of signs and symptoms, either organic or functional. Vaccination is not associated with the emergence of long-COVID, but it may happen in vaccinated people. Conclusions: The severity of illness increases the risk of long-COVID. Pulmonary sequelae, cardiomyopathy, the detection of ribonucleic acid in the gastrointestinal tract, and headaches and cognitive impairment may become refractory in severely ill COVID-19 patients. Full article
(This article belongs to the Special Issue COVID-19: Prognosis and Long-Term Sequelae)
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19 pages, 1933 KiB  
Review
Efficacy of Therapeutic Exercise in Reversing Decreased Strength, Impaired Respiratory Function, Decreased Physical Fitness, and Decreased Quality of Life Caused by the Post-COVID-19 Syndrome
by Diego Fernández-Lázaro, Gema Santamaría, Nerea Sánchez-Serrano, Eva Lantarón Caeiro and Jesús Seco-Calvo
Viruses 2022, 14(12), 2797; https://doi.org/10.3390/v14122797 - 15 Dec 2022
Cited by 18 | Viewed by 4018
Abstract
In the current global scenario, many COVID-19 survivors present a severe deterioration in physical strength, respiratory function, and quality of life due to persistent symptoms and post-acute consequences of SARS-CoV-2 infection. These alterations are known as post-COVID-19 syndrome for which there is no [...] Read more.
In the current global scenario, many COVID-19 survivors present a severe deterioration in physical strength, respiratory function, and quality of life due to persistent symptoms and post-acute consequences of SARS-CoV-2 infection. These alterations are known as post-COVID-19 syndrome for which there is no specific and effective treatment for their management. Currently, therapeutic exercise strategies (ThEx) are effective in many diseases by reducing the appearance of complications and side effects linked to treatment, and are consequently of great relevance. In this study, we review the effect of ThEX in reversing decreased strength, impaired respiratory function, decreased physical fitness, and decreased quality of life (QoL) caused by post-COVID-19 syndrome. A literature search was conducted through the electronic databases, Medline (PubMed), SciELO and Cochrane Library Plus for this structured narrative review for studies published from database retrieval up till 12 December 2022. A total of 433 patients with post-COVID-19 syndrome condition (60% women) were included in the nine studies which met the inclusion/exclusion criteria. Overall, post-COVID-19 syndrome patients who followed a ThEx intervention showed improvements in strength, respiratory function, physical fitness and QoL, with no exercise-derived side effects. Thus, ThEx based on strength, aerobic and respiratory training could be an adjuvant non-pharmacological tool in the modulation of post-COVID-19 syndrome. Full article
(This article belongs to the Special Issue COVID-19: Prognosis and Long-Term Sequelae)
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9 pages, 440 KiB  
Review
Interventions for Improving Long COVID-19 Symptomatology: A Systematic Review
by Nicola Veronese, Roberta Bonica, Sergio Cotugno, Ottavia Tulone, Michele Camporeale, Lee Smith, Mike Trott, Olivier Bruyere, Luigi Mirarchi, Giuseppina Rizzo, Davide Fiore Bavaro, Mario Barbagallo, Ligia J. Dominguez, Claudia Marotta, Andrea Silenzi, Emanuele Nicastri, Annalisa Saracino and Francesco Di Gennaro
Viruses 2022, 14(9), 1863; https://doi.org/10.3390/v14091863 - 24 Aug 2022
Cited by 21 | Viewed by 4841
Abstract
Introduction: Although the understanding of several aspects of long COVID-19 syndrome is increasing, there is limited literature regarding the treatment of these signs and symptoms. The aim of our systematic review was to understand which therapies have proved effective against the symptoms of [...] Read more.
Introduction: Although the understanding of several aspects of long COVID-19 syndrome is increasing, there is limited literature regarding the treatment of these signs and symptoms. The aim of our systematic review was to understand which therapies have proved effective against the symptoms of long COVID-19. Methods: A systematic search for randomized controlled or clinical trials in several databases was conducted through 15 May 2022. Specific inclusion criteria included: (1) intervention studies, either randomized controlled (RCTs) or clinical trials; (2) diagnosis of long COVID-19, according to the World Health Organization criteria; (3) presence of long COVID-19 for at least 12 weeks after SARS-CoV-2 infection. Results: We initially found 1638 articles to screen. After removing 1602 works based on their title/abstract, we considered 35 full texts, and among them, two intervention studies were finally included. The first RCT focused on the greater improvement of treatment combining olfactory rehabilitation with oral supplementation with Palmitoylethanolamide and Luteolin in patients with olfactory dysfunction after COVID-19. The second study evaluated the positive impact of aromatherapy vs. standard care in adult females affected by fatigue. Conclusion: Our systematic review found only two intervention studies focused on patients affected by long COVID-19. More intervention studies are needed to investigate potentially positive interventions for long COVID-19 symptoms. Full article
(This article belongs to the Special Issue COVID-19: Prognosis and Long-Term Sequelae)
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Other

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10 pages, 2838 KiB  
Systematic Review
The Clinical Efficacy and Safety of Anti-Viral Agents for Non-Hospitalized Patients with COVID-19: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
by Chih-Cheng Lai, Ya-Hui Wang, Kuang-Hung Chen, Chao-Hsien Chen and Cheng-Yi Wang
Viruses 2022, 14(8), 1706; https://doi.org/10.3390/v14081706 - 02 Aug 2022
Cited by 44 | Viewed by 3351
Abstract
This network meta-analysis compared the clinical efficacy and safety of anti-viral agents for the prevention of disease progression among non-hospitalized patients with COVID-19. PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched from their [...] Read more.
This network meta-analysis compared the clinical efficacy and safety of anti-viral agents for the prevention of disease progression among non-hospitalized patients with COVID-19. PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched from their inception to 28 May 2022. Only randomized controlled trials (RCTs) that investigated the clinical efficacy of anti-viral agents for non-hospitalized patients with COVID-19 were included. Three RCTs involving 4241 patients were included. Overall, anti-viral agents were associated with a significantly lower risk of COVID-19 related hospitalization or death compared with the placebo (OR, 0.23; 95% CI: 0.06–0.96; p = 0.04). Compared with the placebo, patients receiving nirmatrelvir plus ritonavir had the lowest risk of hospitalization or death (OR, 0.12; 95% CI: 0.06–0.24), followed by remdesivir (OR, 0.13; 95% CI: 0.03–0.57) and then molnupiravir (OR, 0.67; 95% CI: 0.46–0.99). The rank probability for each treatment calculated using the P-score revealed that nirmatrelvir plus ritonavir was the best anti-viral treatment, followed by remdesivir and then molnupiravir. Finally, anti-viral agents were not associated with an increased risk of adverse events compared with the placebo. For non-hospitalized patients with COVID-19 who are at risk of disease progression, the currently recommended three anti-viral agents, nirmatrelvir plus ritonavir, molnupiravir and remdesivir, should continue to be recommended for the prevention of disease progression. Among them, oral nirmatrelvir plus ritonavir and intravenous remdesivir seem to be the better choice, followed by molnupiravir, as determined by this network meta-analysis. Additionally, these three anti-viral agents were shown to be as tolerable as the placebo in this clinical setting. Full article
(This article belongs to the Special Issue COVID-19: Prognosis and Long-Term Sequelae)
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