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Life
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COVID-19 and Long-COVID-19: Pathogenesis, Clinical Manifestation, and Therapeutic Options
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COVID-19 and Long-COVID-19: Pathogenesis, Clinical Manifestation, and Therapeutic Options

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Epidemiology".

Deadline for manuscript submissions: closed (15 October 2022) | Viewed by 32234

Special Issue Editors

Dr. Alessandro Santo Bortone

E-Mail Website
Guest Editor
Faculty of Medicine and Surgery, Università degli studi di Bari Aldo Moro, Bari, Italy
Interests: COVID-19
Special Issues, Collections and Topics in MDPI journals
Dr. Domenico Acanfora

E-Mail Website
Guest Editor
Unit of Internal Medicine, San Francesco Hospital, Telese Terme, Italy
Interests: inflammation; COVID-19
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A global severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic has exploded with unstoppable force from China around the world between late 2019 nowadays (COVID-19). This pandemic has similar but also different features as compared to the two prior human coronaviruses (HCoV) outbreaks, the severe acute respiratory syndrome (SARS) and the Middle-East respiratory syndrome (MERS). SARS-CoV2 has spread far more quickly and is more contagious than the other two types of HCoV. All these outbreaks have mainly respiratory symptoms ranging from sore throat, cough, and dyspnea to acute (often fatal) respiratory distress syndrome (ARDS). Patients discharged from the hospital after acute COVID-19 had an increased risk of multiorgan dysfunction, readmission, and mortality. Recent joint guidelines proposed by the National Institute for Health and Care Excellence (NICE), the Scottish Intercollegiate Guidelines Network (SIGN), and the Royal College of General Practitioners (RCGP) have divided COVID-19 infection into 3 phases—‘Acute COVID-19’ (signs and symptoms of COVID-19 infection up to 4 weeks), ‘ongoing symptomatic COVID-19’ (from 4 weeks up to 12 weeks), and ‘post-COVID-19 syndrome’ (when signs and symptoms continue beyond 12 weeks). The term ‘Long-COVID-19’ is given to the signs and symptoms that continue or develop after the ‘acute COVID-19’ phase and include both ‘ongoing symptomatic COVID- 19’ and ‘post COVID-19 syndrome’. In addition to the persistence of symptoms, it is also possible to detect abnormalities of chest radiographs and biomarkers. Pathogenesis, clinical manifestation, and therapeutic options of COVID-19 and long-COVID-19 are currently ongoing.

Dr. Alessandro Santo Bortone
Dr. Domenico Acanfora
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

  • SARS-CoV2
  • COVID-19
  • long-COVID-19
  • pathogenesis
  • clinical manifestation
  • therapeutic options

Published Papers (7 papers)

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Research

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13 pages, 1102 KiB  
Article
Self-Reported Long COVID in the General Population: Sociodemographic and Health Correlates in a Cross-National Sample
by Tore Bonsaksen, Janni Leung, Daicia Price, Mary Ruffolo, Gary Lamph, Isaac Kabelenga, Hilde Thygesen and Amy Østertun Geirdal
Life 2022, 12(6), 901; https://doi.org/10.3390/life12060901 - 15 Jun 2022
Cited by 8 | Viewed by 2936
Abstract
We aimed to gain knowledge of possible sociodemographic predictors of long COVID and whether long COVID was associated with health outcomes almost two years after the pandemic outbreak. There were 1649 adults who participated in the study by completing a cross-sectional online survey [...] Read more.
We aimed to gain knowledge of possible sociodemographic predictors of long COVID and whether long COVID was associated with health outcomes almost two years after the pandemic outbreak. There were 1649 adults who participated in the study by completing a cross-sectional online survey disseminated openly in Norway, the UK, the USA, and Australia between November 2021 and January 2022. Participants were defined as having long COVID based on self-reports that they had been infected by COVID-19 and were experiencing long-lasting COVID symptoms. Logistic regression analyses were used to examine possible sociodemographic predictors, and multivariate analysis of variance was used to examine whether long COVID status was associated with health outcomes. None of the sociodemographic variables was significantly associated with reporting long COVID. Having long COVID was associated with higher levels of psychological distress, fatigue, and perceived stress. The effect of long COVID on health outcomes was greater among men than among women. In conclusion, long COVID appeared across sociodemographic groups. People with long COVID reported worsened health outcomes compared to those who had had COVID-19 but without long-term symptoms. Men experiencing long COVID appear to be particularly vulnerable to experiencing poorer health outcomes; health services may pay extra attention to potentially unnoticed needs for support among men experiencing long COVID. Full article
(This article belongs to the Special Issue COVID-19 and Long-COVID-19: Pathogenesis, Clinical Manifestation, and Therapeutic Options)
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10 pages, 1689 KiB  
Article
COVID-19 on Chest CT: Translating Known Microscopic Findings to Imaging Observations
by Belinda Dsouza, Kathleen M. Capaccione, Aron Soleiman, Jay Leb and Mary Salvatore
Life 2022, 12(6), 855; https://doi.org/10.3390/life12060855 - 08 Jun 2022
Cited by 2 | Viewed by 2105
Abstract
Purpose: To describe the imaging findings of COVID-19 and correlate them with their known pathology observations. Methods: This is an IRB-approved retrospective study performed at Columbia University Irving Medical Center (IRB # AAAS9652) that included symptomatic adult patients (21 years or [...] Read more.
Purpose: To describe the imaging findings of COVID-19 and correlate them with their known pathology observations. Methods: This is an IRB-approved retrospective study performed at Columbia University Irving Medical Center (IRB # AAAS9652) that included symptomatic adult patients (21 years or older) who presented to our emergency room and tested positive for COVID-19 and were either admitted or discharged with at least one chest CT from 11 March 2020 through 1 July 2020. CT scans were ordered by the physicians caring for the patients; our COVID-19 care protocols did not specify the timing for chest CT scans. A scoring system was used to document the extent of pulmonary involvement. The total CT grade was the sum of the individual lobar grades and ranged from 0 (no involvement) to 16 (maximum involvement). The distribution of lung abnormalities was described as peripheral (involving the outer one-third of the lung), central (inner two-thirds of the lung), or both. Additional CT findings, including the presence of pleural fluid, atelectasis, fibrosis, cysts, and pneumothorax, were recorded. Contrast-enhanced CT scans were evaluated for the presence of a pulmonary embolism, while non-contrast chest CT scans were evaluated for hyperdense vessels. Results: 209 patients with 232 CT scans met the inclusion criteria. The average age was 61 years (range 23–97 years), and 56% of the patients were male. The average score reflecting the extent of the disease on the CT was 10.2 (out of a potential grade of 16). Further, 73% of the patients received contrast, which allowed the identification of a pulmonary embolism in 21%. Of those without contrast, 33% had hyperdense vessels, which might suggest a chronic pulmonary embolism. Further, 47% had peripheral opacities and 9% had a Hampton’s hump, and 78% of the patients had central consolidation, while 28% had round consolidations. Atelectasis was, overall, infrequent at 5%. Fibrosis was observed in 11% of those studied, with 6% having cysts and 3% pneumothorax. Conclusions: The CT manifestations of COVID-19 can be divided into findings related to endothelial and epithelial injury, as were seen on prior post-mortem reports. Endothelial injury may benefit from treatments to stabilize the endothelium. Epithelial injury is more prone to developing pulmonary fibrotic changes. Full article
(This article belongs to the Special Issue COVID-19 and Long-COVID-19: Pathogenesis, Clinical Manifestation, and Therapeutic Options)
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9 pages, 567 KiB  
Article
Changes in the Mean of Medical Visits Due to Psychiatric Disease in Korean Children and Adolescents before and during the COVID-19 Pandemic
by So Young Kim, Na-Eun Lee, Dae Myoung Yoo, Ji Hee Kim, Mi Jung Kwon, Joo-Hee Kim, Woo Jin Bang and Hyo Geun Choi
Life 2022, 12(4), 600; https://doi.org/10.3390/life12040600 - 18 Apr 2022
Cited by 6 | Viewed by 1794
Abstract
The COVID-19 pandemic has been suggested to have adverse impacts on psychiatric disorders. This study aimed to investigate the changes in medical visits due to a wide range of psychiatric disorders in children during the COVID-19 pandemic. The medical visits of all Korean [...] Read more.
The COVID-19 pandemic has been suggested to have adverse impacts on psychiatric disorders. This study aimed to investigate the changes in medical visits due to a wide range of psychiatric disorders in children during the COVID-19 pandemic. The medical visits of all Korean children and adolescents (0–19 years old) due to the 12 following psychiatric disorders were investigated: autism; attention-deficit/hyperactivity disorder (ADHD); depressive disorder; bipolar disorder; primary insomnia; schizophrenia; panic disorder; hypochondriasis; posttraumatic stress disorder (PTSD); anxiety disorder; anorexia nervosa; and adephagia. The mean medical visits before and during the COVID-19 pandemic were compared. The mean number of clinical visits due to autism, ADHD, depressive disorder, bipolar disorder, panic disorder, hypochondriasis, PTSD, anxiety disorder, and anorexia nervosa was higher during the COVID-19 pandemic than before the COVID-19 pandemic (all p < 0.05). The higher mean number of medical visits due to psychiatric disorders was maintained in age and sex subgroups. The female and adolescent groups demonstrated a higher mean number of medical visits due to psychiatric disorders during the COVID-19 pandemic. The medical visits due to many psychiatric disorders were higher during the COVID-19 pandemic than before COVID-19 in children and adolescents in Korea. Women and adolescents were more susceptible to psychiatric disorders during the COVID-19 pandemic. Full article
(This article belongs to the Special Issue COVID-19 and Long-COVID-19: Pathogenesis, Clinical Manifestation, and Therapeutic Options)
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Review

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24 pages, 1625 KiB  
Review
Endothelial Dysfunction in COVID-19: Potential Mechanisms and Possible Therapeutic Options
by Maria Chiara Pelle, Isabella Zaffina, Stefania Lucà, Valentina Forte, Vincenzo Trapanese, Melania Melina, Federica Giofrè and Franco Arturi
Life 2022, 12(10), 1605; https://doi.org/10.3390/life12101605 - 14 Oct 2022
Cited by 13 | Viewed by 3673
Abstract
SARS-CoV-2, a novel coronavirus found in Wuhan (China) at the end of 2019, is the etiological agent of the current pandemic that is a heterogeneous disease, named coronavirus disease 2019 (COVID-19). SARS-CoV-2 affects primarily the lungs, but it can induce multi-organ involvement such [...] Read more.
SARS-CoV-2, a novel coronavirus found in Wuhan (China) at the end of 2019, is the etiological agent of the current pandemic that is a heterogeneous disease, named coronavirus disease 2019 (COVID-19). SARS-CoV-2 affects primarily the lungs, but it can induce multi-organ involvement such as acute myocardial injury, myocarditis, thromboembolic eventsandrenal failure. Hypertension, chronic kidney disease, diabetes mellitus and obesity increase the risk of severe complications of COVID-19. There is no certain explanation for this systemic COVID-19 involvement, but it could be related to endothelial dysfunction, due to direct (endothelial cells are infected by the virus) and indirect damage (systemic inflammation) factors. Angiotensin-converting enzyme 2 (ACE2), expressed in human endothelium, has a fundamental role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In fact, ACE2 is used as a receptor by SARS-CoV-2, leading to the downregulation of these receptors on endothelial cells; once inside, this virus reduces the integrity of endothelial tissue, with exposure of prothrombotic molecules, platelet adhesion, activation of coagulation cascades and, consequently, vascular damage. Systemic microangiopathy and thromboembolism can lead to multi-organ failure with an elevated risk of death. Considering the crucial role of the immunological response and endothelial damage in developing the severe form of COVID-19, in this review, we will attempt to clarify the underlying pathophysiological mechanisms. Full article
(This article belongs to the Special Issue COVID-19 and Long-COVID-19: Pathogenesis, Clinical Manifestation, and Therapeutic Options)
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13 pages, 267 KiB  
Review
COVID-19 Vaccine and Long COVID: A Scoping Review
by Aqsa Mumtaz, Abdul Ahad Ehsan Sheikh, Amin Moazzam Khan, Subaina Naeem Khalid, Jehanzaeb Khan, Adeel Nasrullah, Shazib Sagheer and Abu Baker Sheikh
Life 2022, 12(7), 1066; https://doi.org/10.3390/life12071066 - 16 Jul 2022
Cited by 26 | Viewed by 4796
Abstract
As the COVID-19 pandemic progresses, changing definitions and therapeutics regarding the post-acute sequela of COVID-19, particularly long COVID, have become a subject of great interest and study. The study aims to describe the pathophysiology and discuss different therapeutic agents currently available for long [...] Read more.
As the COVID-19 pandemic progresses, changing definitions and therapeutics regarding the post-acute sequela of COVID-19, particularly long COVID, have become a subject of great interest and study. The study aims to describe the pathophysiology and discuss different therapeutic agents currently available for long COVID. Another objective is to assess comparative efficacy between different types of vaccines on symptoms of long COVID. A preliminary search was conducted using Ovid Medline, Embase, medRxiv, and NIH COVID-19 portfolios. A total of 16 studies were included in our review. Despite some of the data showing variable results, most of the vaccinated patients reported improvement in long COVID symptoms with no significant difference between various types of vaccines. Further trials are needed to better identify the comparative efficacy of vaccines for long COVID and ascertain other therapeutic modalities. Full article
(This article belongs to the Special Issue COVID-19 and Long-COVID-19: Pathogenesis, Clinical Manifestation, and Therapeutic Options)
13 pages, 1116 KiB  
Review
Long COVID in Children and Adolescents
by Valentina Fainardi, Aniello Meoli, Giulia Chiopris, Matteo Motta, Kaltra Skenderaj, Roberto Grandinetti, Andrea Bergomi, Francesco Antodaro, Stefano Zona and Susanna Esposito
Life 2022, 12(2), 285; https://doi.org/10.3390/life12020285 - 14 Feb 2022
Cited by 69 | Viewed by 13551
Abstract
Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has caused significant mortality and morbidity worldwide. In children, the acute SARS-CoV-2 infection is often asymptomatic or paucisymptomatic, and life-threatening complications are rare. Nevertheless, there are two long-term consequences of SARS-CoV-2 infection in children that raise [...] Read more.
Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has caused significant mortality and morbidity worldwide. In children, the acute SARS-CoV-2 infection is often asymptomatic or paucisymptomatic, and life-threatening complications are rare. Nevertheless, there are two long-term consequences of SARS-CoV-2 infection in children that raise concern: multisystem inflammatory syndrome in children (MIS-C) and long COVID. While the understanding and the experience regarding the acute phase of SARS-CoV-2 infection have remarkably increased over time, scientific and clinical research is still exploring the long-term effects of COVID-19. In children, data on long COVID are scant. Reports are conflicting regarding its prevalence, duration and impact on daily life. This narrative review explored the latest literature regarding long COVID-19 in the pediatric population. We showed that long COVID in children might be a relevant clinical problem. In most cases, the prognosis is good, but some children may develop long-term symptoms with a significant impact on their daily life. The paucity of studies on long COVID, including a control group of children not infected by SARS-CoV-2, prevents us from drawing firm conclusions. Whether the neuropsychiatric symptoms widely observed in children and adolescents with long COVID are the consequence of SARS-CoV-2 infection or are due to the tremendous stress resulting from the restrictions and the pandemics is still not clear. In both cases, psychological support can play a fundamental role in managing COVID pandemics in children. More knowledge is needed to share a standardized definition of the syndrome and improve its management and treatment. Full article
(This article belongs to the Special Issue COVID-19 and Long-COVID-19: Pathogenesis, Clinical Manifestation, and Therapeutic Options)
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Other

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31 pages, 4597 KiB  
Systematic Review
Identification of Suitable Drug Combinations for Treating COVID-19 Using a Novel Machine Learning Approach: The RAIN Method
by Aliakbar Kiaei, Nader Salari, Mahnaz Boush, Kamran Mansouri, Amin Hosseinian-Far, Hooman Ghasemi and Masoud Mohammadi
Life 2022, 12(9), 1456; https://doi.org/10.3390/life12091456 - 19 Sep 2022
Cited by 2 | Viewed by 2225
Abstract
COVID-19 affects several human genes, each with its own p-value. The combination of drugs associated with these genes with small p-values may lead to an estimation of the combined p-value between COVID-19 and some drug combinations, thereby increasing the effectiveness [...] Read more.
COVID-19 affects several human genes, each with its own p-value. The combination of drugs associated with these genes with small p-values may lead to an estimation of the combined p-value between COVID-19 and some drug combinations, thereby increasing the effectiveness of these combinations in defeating the disease. Based on human genes, we introduced a new machine learning method that offers an effective drug combination with low combined p-values between them and COVID-19. This study follows an improved approach to systematic reviews, called the Systematic Review and Artificial Intelligence Network Meta-Analysis (RAIN), registered within PROSPERO (CRD42021256797), in which, the PRISMA criterion is still considered. Drugs used in the treatment of COVID-19 were searched in the databases of ScienceDirect, Web of Science (WoS), ProQuest, Embase, Medline (PubMed), and Scopus. In addition, using artificial intelligence and the measurement of the p-value between human genes affected by COVID-19 and drugs that have been suggested by clinical experts, and reported within the identified research papers, suitable drug combinations are proposed for the treatment of COVID-19. During the systematic review process, 39 studies were selected. Our analysis shows that most of the reported drugs, such as azithromycin and hydroxyl-chloroquine on their own, do not have much of an effect on the recovery of COVID-19 patients. Based on the result of the new artificial intelligence, on the other hand, at a significance level of less than 0.05, the combination of the two drugs therapeutic corticosteroid + camostat with a significance level of 0.02, remdesivir + azithromycin with a significance level of 0.03, and interleukin 1 receptor antagonist protein + camostat with a significance level 0.02 are considered far more effective for the treatment of COVID-19 and are therefore recommended. Additionally, at a significance level of less than 0.01, the combination of interleukin 1 receptor antagonist protein + camostat + azithromycin + tocilizumab + oseltamivir with a significance level of 0.006, and the combination of interleukin 1 receptor antagonist protein + camostat + chloroquine + favipiravir + tocilizumab7 with corticosteroid + camostat + oseltamivir + remdesivir + tocilizumab at a significant level of 0.009 are effective in the treatment of patients with COVID-19 and are also recommended. The results of this study provide sets of effective drug combinations for the treatment of patients with COVID-19. In addition, the new artificial intelligence used in the RAIN method could provide a forward-looking approach to clinical trial studies, which could also be used effectively in the treatment of diseases such as cancer. Full article
(This article belongs to the Special Issue COVID-19 and Long-COVID-19: Pathogenesis, Clinical Manifestation, and Therapeutic Options)
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