COVID-19 Associated Thyroid Dysfunction and Other Comorbidities and Its Management Using Phytochemical-Based Therapeutics- A Natural Way.

The present severe acute respiratory syndrome-2 (SARS-CoV-2) mediated Coronavirus pandemic (COVID-19) and post-COVID-19 complications affect human life drastically. Patients who have been cured of COVID-19 infection are now experiencing post-COVID-19 associated comorbidities, which have increased mortality rates.  The SARS-CoV-2 infection distresses the lungs, kidneys, gastrointestinal tract, and various endocrine glands, including the thyroid. The emergence of variants which includes Omicron (B.1.1.529) and its lineages threaten the world severely. Among different therapeutic approaches, phytochemical-based therapeutics are not only cost-effective but also have lesser side effects. Recently a plethora of studies have shown the therapeutic efficacy of various phytochemicals for the treatment of COVID-19. Besides this, various phytochemicals have been found efficacious in treating several inflammatory diseases, including thyroid-related anomalies. The method of the phytochemical formulation is quick and facile and the raw materials for such herbal preparations are approved worldwide for human use against certain disease conditions. Owing to the advantages of phytochemicals, this review primarily discusses the COVID-19-related thyroid dysfunction and the role of key phytochemicals to deal with thyroid anomaly and post-COVID-19 complications. Further, this review shed light on the mechanism via which COVID-19 and its related complication affect organ function of the body, along with the mechanistic insight into the way by which phytochemicals could help to cure post-COVID-19 complications in thyroid patients. Considering the advantages offered by phytochemicals as a safer and cost-effective medication they can be potentially used to combat COVID-19-associated comorbidities.

Pulmonary complications following COVID-19 infection.

In the relatively short period of time since December 2019, hundreds of millions of people globally have been infected with SARS-CoV-2, irrespective of their age, gender or ethnicity. Over that time, numerous mutations of various degrees of virulence and patho-genicity have occurred. The course of COVID-19 infection, an acute disease caused by the virus, is rather varied, ranging from asym-ptomatic or symptoms of common viral respiratory diseases to critical, with multiorgan failure and high mortality in high-risk patients. The overall mortality of the disease is 1-2 %. Unlike other viral respiratory diseases, this infection is often associated with frequent and rather diverse clinical manifestations developing after the acute phase of the infection, that is, more than 28 days after its onset. These complications are observed in both individuals with mild illness treated at home and inpatients with severe to critical illness. They develop both early after acute infection and some time after recovering from the disease. This rather heterogeneous group of pathologies may affect various organs and organ systems, with respiratory tract involvement being the most common and one of the most serious complications. Severe respiratory post-COVID-19 complications often include respiratory tract infections, in particular pneumonia.Copyright © 2022, Trios spol. s.r.o.. All rights reserved.

Mucormycosis, past and present: a comprehensive review.

Mucormycosis is an emerging opportunistic angioinvasive fungal infection. Predisposing factors such as diabetes, neutropenia, long-term corticosteroid therapy, solid organ transplantation and immunosuppression contribute to its occurrence. This disease was not of significant concern prior to the COVID-19 pandemic, but gained prominence due to infections in COVID-19 patients. Mucormycosis needs special attention and coordinated efforts of the scientific community and medical professionals to reduce morbidity and mortality. Here we present an overview of the epidemiology and prevalence of mucormycosis in the pre- and post-COVID-19 eras, the factors that contributed to the abrupt increase in COVID-19-associated mucormycosis (CAM), the actions taken by the regulatory agencies (including Code Mucor and CAM registry), the existing diagnostic tools and CAM management strategies.

The devastating effects of the COVID-19 pandemic have been further enhanced by various secondary illnesses, particularly opportunistic fungal infections such as mucormycosis. Mucormycosis or 'black fungus' primarily affects people with weakened immunity, those with medical conditions such as diabetes or cancer and those who use medications that reduce the body's capacity to resist infections and disease. The infection starts in the sinuses or the lungs after breathing in spores of the black fungus from the air. In just 2 months between 5 May and 12 July 2021, this uncommon but fatal fungal illness was responsible for 41,512 cases and 3554 fatalities in India alone. The government of India declared a mucormycosis epidemic in May 2021. The majority of such cases occurred during active SARS-CoV-2 outbreaks in India in 2021. Black fungus took over while the host defenses were compromised and the globe was preoccupied tackling the COVID-19 pandemic. Steroids prescribed in amounts and time spans that far exceeded WHO recommendations to manage severe COVID-19 cases, potentially weakened patients' immune systems, and raised blood sugar levels making them vulnerable to fungal invasion. Early diagnosis and treatment are the keys to a patient's survival. Simple means such as maintaining hygienic conditions, avoiding contact with an infected person, judiciously using steroid medications and antibiotics and properly managing high blood sugar can help protect an individual from black-fungus infection.

Plitidepsin in adult patients with COVID-19 requiring hospital admission: A long-term follow-up analysis.

Introduction: The APLICOV-PC study assessed the safety and preliminary efficacy of plitidepsin in hospitalized adult patients with COVID-19. In this follow-up study (E-APLICOV), the incidence of post-COVID-19 morbidity was evaluated and any long-term complications were characterized. Methods: Between January 18 and March 16, 2022, 34 of the 45 adult patients who received therapy with plitidepsin in the APLICOV-PC study were enrolled in E-APLICOV (median time from plitidepsin first dose to E-APLICOV enrollment, 16.8 months [range, 15.2-19.5 months]). All patients were functionally autonomous with regard to daily living (Barthel index: 100) and had normal physical examinations. Results: From the APLICOV-PC date of discharge to the date of the extension visit, neither Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5) grade 3-4 complications nor QT prolongation or significant electrocardiogram (EKG) abnormalities were reported. Five (14.7%) patients had another COVID-19 episode after initial discharge from APLICOV-PC, and in 2 patients (5.9%), previously unreported chest X-ray findings were documented. Spirometry and lung-diffusion tests were normal in 29 (85.3%) and 27 (79.4%) patients, respectively, and 3 patients needed additional oxygen supplementation after initial hospital discharge. None of these patients required subsequent hospital readmission for disease-related complications. Discussion: In conclusion, plitidepsin has demonstrated a favorable long-term safety profile in adult patients hospitalized for COVID-19. With the constraints of a low sample size and a lack of control, the rate of post-COVID-19 complications after treatment with plitidepsin is in the low range of published reports. (ClinicalTrials.gov Identifier: NCT05121740; https://clinicaltrials.gov/ct2/show/NCT05121740).

Thyroid dysfunction as a long-term post-COVID-19 complication in mild-to-moderate COVID-19

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), may lead to thyroid disorders, including both thyrotoxicosis and suppression of thyroid function. The aim of the present study was to assess the post-COVID-19 effects on thyroid function in patients without history of thyroid disease after complete recovery from mild-to-moderate COVID-19. Thyroid function tests [thyroid-stimulating hormone (TSH), free thyroxine (fT4), antithyroid antibodies] were performed on 113 patients (median age of 43.0 years;31.0% male) two months after initial SARS-CoV-2 infection. TSH and fT4 were determined again one month later in this observational, prospective study. Thyroid dysfunction was registered in 61.1% of the patients (78.3% subclinical hypothyroidism, 13% subclinical hyperthyroidism and 8.7% overt hypothyroidism) two months after COVID-19. Moderate rather than mild manifestation of COVID-19 was significantly associated with a higher risk of thyroid dysfunction (OR 5.33;95% CI: 1.70–16.69, p = 0.002), presence of thyroglobulin antibodies and need for levothyroxine therapy. At the follow-up, the subclinical hypothyroidism persisted in 28.3% of the subjects. Moreover, the TSH level was significantly reduced in comparison to the second month after the initial COVID-19 infection in all the patients (p < 0.001), but not in those with subclinical hypothyroidism and without hormone replacement therapy. Our findings indicate that COVID-19 could have long-term, negative effects on thyroid function. Therefore, thyroid function testing should be included in the follow-up algorithm of COVID-19 survivors. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Post-COVID-19 Syndrome: A Novel Diagnosis.

Patients with post-COVID-19 syndrome have reported a wide array of symptoms that include autonomic dysfunction. It is hypothesized that this may be secondary to interruption of baroreflex pathways in the carotid arteries or nucleus tractus solitarius, however, confirming studies have yet to be performed. A limited number of studies have highlighted the presence of an exaggerated baroreflex response in patients with a post-COVID-19 syndrome that mirror other chronic autonomic dysfunction-related conditions.

Effects of vaccination, new SARS-CoV-2 variants and reinfections on post-COVID-19 complications.

Post-COVID-19 complications involve a variety of long-lasting health complications emerging in various body systems. Since the prevalence of post-COVID-19 complications ranges from 8-47% in COVID-19 survivors, it represents a formidable challenge to COVID-19 survivors and the health care system. Post-COVID-19 complications have already been studied in the connection to risk factors linked to their higher probability of occurrence and higher severity, potential mechanisms underlying the pathogenesis of post-COVID-19 complications, and their functional and structural correlates. Vaccination status has been recently revealed to represent efficient prevention from long-term and severe post-COVID-19 complications. However, the exact mechanisms responsible for vaccine-induced protection against severe and long-lasting post-COVID-19 complications remain elusive. Also, to the best of our knowledge, the effects of new SARS-CoV-2 variants and SARS-CoV-2 reinfections on post-COVID-19 complications and their underlying pathogenesis remain to be investigated. This hypothesis article will be dedicated to the potential effects of vaccination status, SARS-CoV-2 reinfections, and new SARS-CoV-2 variants on post-COVID-19 complications and their underlying mechanisms Also, potential prevention strategies against post-COVID complications will be discussed.

Tangled quest of post-COVID-19 infection-caused neuropathology and what 3P nano-bio-medicine can solve?

COVID-19-caused neurological problems are the important post-CoV-2 infection complications, which are recorded in ~ 40% of critically ill COVID-19 patients. Neurodegeneration (ND) is one of the most serious complications. It is necessary to understand its molecular mechanism(s), define research gaps to direct research to, hopefully, design new treatment modalities, for predictive diagnosis, patient stratification, targeted prevention, prognostic assessment, and personalized medical services for this type of complication. Individualized nano-bio-medicine combines nano-medicine (NM) with clinical and molecular biomarkers based on omics data to improve during- and post-illness management or post-infection prognosis, in addition to personalized dosage profiling and drug selection for maximum treatment efficacy, safety with least side-effects. This review will enumerate proteins, receptors, and enzymes involved in CoV-2 entrance into the central nervous system (CNS) via the blood-brain barrier (BBB), and list the repercussions after that entry, ranging from neuroinflammation to neurological symptoms disruption mechanism. Moreover, molecular mechanisms that mediate the host effect or viral detrimental effect on the host are discussed here, including autophagy, non-coding RNAs, inflammasome, and other molecular mechanisms of CoV-2 infection neuro-affection that are defined here as hallmarks of neuropathology related to COVID-19 infection. Thus, a couple of questions are raised; for example, "What are the hallmarks of neurodegeneration during COVID-19 infection?" and "Are epigenetics promising solution against post-COVID-19 neurodegeneration?" In addition, nano-formulas might be a better novel treatment for COVID-19 neurological complications, which raises one more question, "What are the challenges of nano-bio-based nanocarriers pre- or post-COVID-19 infection?" especially in the light of omics-based changes/challenges, research, and clinical practice in the framework of predictive preventive personalized medicine (PPPM / 3P medicine).

Post COVID-19 complications, adjunct therapy explored, and steroidal after effects

For COVID-19 survivors, defeating the virus is just the beginning of a long road to recovery. The inducibility and catastrophic effects of the virus are distributed across multiple organs. The induction of cytokine storms in COVID-19 patients is due to the interaction of the SARS-CoV-2 virus and the host receptor, leading to various immunopathological consequences that may eventually lead to death. So far, COVID-19 has affected tons of people across the world, but there is still no effective treatment. Patients facing complications of COVID-19 after recovery have shown extensive clinical symptoms similar to that of patients recovering from previously circulating coronaviruses. Previous knowledge and literature have opened up ways to treat this disease and manage post-COVID-19 complications, which pose a severe challenge to the health system globally and may exacerbate the fragmentation of diseases. The use of steroids as a treatment has resulted in various health problems and side-effects in COVID-19 patients. This review discusses various post-COVID-19 complications observed and adjunctive therapies used along with common COVID-19 treatment and spotlights their side effects and consequences. This review provides the latest literature on COVID-19, which emphasizes the subsequent complications in various organs, side effects of drugs, and alternative regimens used to treat COVID-19.Alternate :Pour les survivants de la COVID-19, vaincre le virus n’est que le début d’un long chemin vers la guérison. L’inductibilité virale et les effets catastrophiques qui en découlent sont disséminés dans plusieurs organes. L’induction de tempêtes de cytokines chez les patients atteints de COVID-19 est due à l’interaction entre le virus SRAS-CoV-2 et le récepteur de l’hôte, entraînant diverses conséquences immunopathologiques, susceptibles de mener ultimement à la mort. Jusqu’à présent, le virus a frappé des millions de personnes partout dans le monde, mais il n’existe toujours pas de traitement efficace. Les patients qui présentent des complications de la COVID-19 après leur convalescence ont manifesté de nombreux symptômes cliniques semblables à ceux provoqués par d’autres coronavirus ayant circulé auparavant. Les connaissances antérieures et la littérature ont ouvert une fenêtre sur des moyens de traiter la COVID-19 et de prendre en charge les complications qui surviennent après l’infection, lesquelles posent un grave problème pour le système de santé mondial et ont le potentiel de multiplier les déclinaisons de la maladie. L’utilisation de stéroïdes comme traitement a révélé divers problèmes de santé et effets secondaires chez les patients atteints de la COVID-19. Cette revue de littérature dresse un portrait détaillé des diverses complications post-COVID-19 observées et des traitements adjuvants utilisés en association avec les médicaments couramment employés pour traiter la COVID-19, et met en évidence leurs effets secondaires et leurs conséquences. L’article offre une synthèse de la plus récente littérature sur la COVID-19, qui se concentre sur les complications subséquentes touchant divers organes, les effets secondaires des médicaments et les autres traitements qui ont été utilisés contre cette maladie. [Traduit par la Rédaction]

Virtual screening of functional foods and dissecting their roles in modulating gene functions to support post COVID-19 complications.

COVID-19 has become the focal point since 2019 after the outbreak of coronavirus disease. Many drugs are being tested and used to treat coronavirus infections; different kinds of vaccines are also introduced as preventive measure. Alternative therapeutics are as well incorporated into the health guidelines of some countries. This research aimed to look into the underlying mechanisms of functional foods and how they may improve the long-term post COVID-19 cardiovascular, diabetic, and respiratory complications through their bioactive compounds. The potentiality of nine functional foods for post COVID-19 complications was investigated through computational approaches. A total of 266 bioactive compounds of these foods were searched via extensive literature reviewing. Three highly associated targets namely troponin I interacting kinase (TNNI3K), dipeptidyl peptidase 4 (DPP-4), and transforming growth factor beta 1 (TGF-ß1) were selected for cardiovascular, diabetes, and respiratory disorders, respectively, after COVID-19 infections. Best docked compounds were further analyzed by network pharmacological tools to explore their interactions with complication-related genes (MAPK1 and HSP90AA1 for cardiovascular, PPARG and TNF-alpha for diabetes, and AKT-1 for respiratory disorders). Seventy-one suggested compounds out of one-hundred and thirty-nine (139) docked compounds in network pharmacology recommended 169 Gene Ontology (GO) items and 99 Kyoto Encyclopedia of Genes and Genomes signaling pathways preferably AKT signaling pathway, MAPK signaling pathway, ACE2 receptor signaling pathway, insulin signaling pathway, and PPAR signaling pathway. Among the chosen functional foods, black cumin, fenugreek, garlic, ginger, turmeric, bitter melon, and Indian pennywort were found to modulate the actions. Results demonstrate that aforesaid functional foods have attenuating roles to manage post COVID-19 complications. PRACTICAL APPLICATIONS: Functional foods have been approaching a greater interest due to their medicinal uses other than gastronomic pleasure. Nine functional food resources have been used in this research for their traditional and ethnopharmacological uses, but their directive-role in modulating the genes involved in the management of post COVID-19 complications is inadequately studied and reported. Therefore, the foods types used in this research may be prioritized to be used as functional foods for ameliorating the major post COVID-19 complications through appropriate science.