Essential Multiorgan Pathophysiology of COVID-19

Typical manifestations of coronavirus disease-2019 (COVID-19) include mild-to-moderate "flu-like” symptoms, although more severe manifestations have been reported. The pathophysiology of COVID-19 is complex, and its clinical spectrum might not be limited to local pneumonia, but rather may represent a multisystem illness with potential for severe acute respiratory distress syndrome (ARDS) and multiorgan impairment. In this context, the aim of the present handbook is to provide an overview of possible multisystemic manifestations and therapeutic strategies, in order to guide the clinician to deal with COVID-19 critical illness and to prevent potential systemic consequences. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

COVID-19 disease and hereditary angioedema

Since December 2019, an outbreak of a novel coronavirus (SARS-CoV-2) infection causing COVID-19 disease has influenced the whole world. Angiotensin converting enzyme 2 (ACE2) receptors on type 2 pneumocytes in humans were determined as the entry for SARSCoV-2. Receptor binding and subsequently endocytosis of ACE2 diminish the cell membrane expression and also the function of ACE2. ACE2 is an enzyme involved in bradykinin metabolism. Lys-des-Arg9-BK occured with enzymatic cleaving of Lys-BK derived from low molecular weight kininogen is inactivated by ACE2 in tissues and it is a vasodilator agent having its own receptor named bradykinin B1. Non-metabolized Lys-des-Arg9-BK can be the reason for tissue vasodilation and increased vascular permeability in the patients with COVID-19. Increased bradykinin levels in patients with hereditary angioedema with C1-INH deficiency (C1-INH-HAE) do not cause increased SARS-CoV-2 infection or more severe disease. Although SARS-CoV-2 infection does not result in increased bradykinin levels, it can increase Lys-des-Arg9-BK levels.Copyright © 2020 Bilimsel Tip Yayinevi. All rights reserved.

A Scoping Review on COVID-19-Induced Cardiovascular Complications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a type of human coronavirus that resulted in the 2019 coronavirus disease (COVID-19). Although it was generally categorized as a respiratory disease, its involvement in cardiovascular complications was identified from the onset. Elevated cardiac troponin levels (a myocardial injury marker) and echocardiograms, which showed the anomalous performance of the patients' hearts, were noted in the early case reports obtained from Wuhan, China. A couple of mechanisms have been proposed to explain COVID-19-induced cardiovascular complications, with systemic inflammation being the major focus recently. Chest pain and palpitations are among the prevalent symptoms in moderate to severe COVID-19-recovering patients. Cardiac damage potentially occurs due to multifactorial factors, which include cytokine-induced inflammation, direct cardiotoxicity, and disseminated intravascular coagulation (DIC), among others. The cardiovascular manifestations include cardiac arrhythmia, cardiogenic shock, venous thromboembolism, and elevated cardiac biomarkers. Both the long- and short-term effects of these cardiovascular complications remain puzzling to researchers, as substantial evidence is yet to be gathered to reach a consensus on the severity of COVID-19 in the heart. The treatment considerations currently include antiarrhythmic management, ACEI or ARB use, anticoagulation, hemodynamic support, and immunosuppression. This review aimed to outline the pathogenesis of the various cardiac complications due to COVID-19 as well as the available treatment modalities of COVID-19 infection. Both the mechanisms and the treatments have been succinctly explained in a proper manner to ensure understanding. [ABSTRACT FROM AUTHOR] Copyright of COVID is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Potential Immunotherapy against SARS-CoV-2: Strategy and Status

SARS-CoV-2, the novel coronavirus that was first reported in Wuhan, China in December 2019, has engrossed the world with immense distress. It has shattered the global healthcare system and has inflicted so much pain on humanity. COVID-19, the disease caused by a microscopic enemy, has now spread to almost all the countries in the world affecting millions of people and causing enormous casualties. World Health Organization (WHO) declared COVID-19 a pandemic on March 11, 2019. As of June 15, 2020, almost 7.70 million people have already been infected globally with 428,000 reported casualties. In the United States alone, 2.14 million people have been infected and 117,000 people have succumbed to this pandemic. A multipronged approach has been launched towards combating this pandemic with the main focus on exhaustive screening, developing efficacious therapies, and vaccines for long-term immunity. Several pharmaceutical companies in collaboration with various academic institutions and governmental organizations have started investigating new therapeutics and repurposing approved drugs so as to find fast and affordable treatments against this disease. The present communication aims at highlighting the efforts that are currently underway to treat or prevent SARS-CoV-2 infection through immunotherapy. Emphasis has been laid on discussing the approaches and platforms that are being utilized for the speedy development of therapeutic antibodies and preventive vaccines against SARS-CoV-2. The manuscript also presents a detailed discussion regarding strategy, clinical status, and timeline for the development of safe and enduring immunotherapy against SARS-CoV-2. All the details pertaining to the clinical status of each candidate have been last updated on June 15, 2020.Copyright © 2020 Bentham Science Publishers.

SARS-CoV-2 infection: a global outbreak and its implication on public health.

BACKGROUND: A novel corona virus is formally named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which results in causing coronavirus disease 2019 (COVID-19). It is the latest prevalent pandemic worldwide when compared to other infectious diseases like Avian flu, Middle East respiratory syndrome and severe acute respiratory syndrome (SARS). MAIN BODY: Coronavirus disease 2019 (COVID-19) is currently occurring pandemic over world. It was emerged in Wuhan, China, in the end of December 2019 and spreading across worldwide. As the coronavirus is spreading easily through direct contact with infected people droplets, inhalation, and also air droplets, it hit up a huge amount of population even reported with death. Still, with small amounts of asymptomatic transmission between people it spreads throughout the globe. People need special care to protect from the transmission of disease. However, there are no drugs so far that shows efficacy; there is an immediate need for the development of vaccines. In order to decrease the COVID-19 cases, organizations rapidly involve in the preparation of vaccine and many vaccines have been developed by various countries. The governments took safety measures to control the spread of virus and also to minimize morbidity and mortality rate to least possible. CONCLUSION: The purpose of this review article is to increase our understanding of COVID-19 and facilitate the people to take a move in facing challenges of the world.

POST-COVID AND ITS GASTROINTESTINAL MANIFESTATIONS

This article provides a review of the literature on such a relevant topic in the epidemiological situation, on the impact of COVID-19 on the digestive organs and post-covid manifestations from the gastrointestinal tract. A review of more than 15 international literature sources and metadata is presented, reliable factors about post-COVID manifestations are given. Depending on the course and duration of COVID-19, definitions of the diagnosis are presented. It also presents the multi-system nature of Post-COVID. The main purpose of this article is to review the literature and metadata from sources to assess the impact of COVID-19 on the gastrointestinal tract and the nature of post-COVID gastrointestinal manifestations. The COVID-19 pandemic has gripped millions of people around the world, leaving a global burden. Therefore, it is important to continue studying the theoretical and clinical foundations of the disease, both in the main period of the disease, and multiple organ manifestations of COVID-19, as systemic pathophysiological consequences. The main conclusion of this article can reasonably be said about the negative impact of SARS-CoV-2 on the gastrointestinal tract in the acute period, as well as the long-term effects of the virus on the gastrointestinal tract. The digestive organs, as well as the respiratory organs, are the entrance gates of the virus. © 2022, Science and Innovation Center Publishing House. All rights reserved.

SARS-CoV-2-mediated liver injury: pathophysiology and mechanisms of disease.

BACKGROUND: SARS-CoV-2-induced severe inflammatory response can be associated with severe medical consequences leading to multi-organ failure, including the liver. The main mechanism behind this assault is the aggressive cytokine storm that induces cytotoxicity in various organs. Of interest, hepatic stellate cells (HSC) respond acutely to liver injury through several molecular mechanisms, hence furthering the perpetuation of the cytokine storm and its resultant tissue damage. In addition, hepatocytes undergo apoptosis or necrosis resulting in the release of pro-inflammatory and pro-fibrogenic mediators that lead to chronic liver inflammation. AIMS: The aim of this review is to summarize available data on SARS-CoV-2-induced liver inflammation in addition to evaluate the potential effect of anti-inflammatory drugs in attenuating SARS-CoV-2-induced liver inflammation. METHODS: Thorough PubMed search was done to gather and summarize published data on SARS-CoV-2-induced liver inflammation. Additionally, various anti-inflammatory potential treatments were also documented. RESULTS: Published data documented SARS-CoV-2 infection of liver tissues and is prominent in most liver cells. Also, histological analysis showed various features of tissues damage, e.g., hepatocellular necrosis, mitosis, cellular infiltration, and fatty degeneration in addition to microvesicular steatosis and inflammation. Finally, the efficacy of the different drugs used to treat SARS-CoV-2-induced liver injury, in particular the anti-inflammatory remedies, are likely to have some beneficial effect to treat liver injury in COVID-19. CONCLUSION: SARS-CoV-2-induced liver inflammation is a serious condition, and drugs with potent anti-inflammatory effect can play a major role in preventing irreversible liver damage in COVID-19.

Molecular Docking of Moringa Oleifera Compounds with Human Ace2 Receptor: For Covid-19 Drug Candidate

COVID-19 is an infectious disease caused by a new coronavirus called Sars Corona Virus-2 (SARS-CoV-2). SARS-CoV-2 which can infect humans due to an interaction between the Spike glycoprotein (protein S) virus and these Angiotensin-converting enzyme 2 (ACE2) receptor. Moringa oleifera is a plant known as phytomedicines and has excellent benefits. This study aims to identify the physicochemical characteristics of compounds in M. oleifera and their potential for blocking interactions between S glycoprotein and ACE2 receptors. ADMET analysis was conducted by using the TCMSP web-based application and evaluated by using the Lipinski and TCMSP criteria. The docking process used the Chimera UCSF program so that the grid box region and its affinity energy values are known. The results showed that phytol compounds have the most physicochemical characteristics following Lipinski and TCSM criteria and have the lowest affinity energy when interacting with ACE2 receptors. This study concluded that phytol is a compound in Moringa oleifera which has the smallest pharmacological effect and has the most potential for preventing interactions between SARS-CoV-2 S protein and ACE2 receptors. Copyright © 2022, Veterinary Practitioner. All rights reserved.

COVID-19: a new emerging respiratory disease from the neurological perspective.

Coronavirus disease 2019 (COVID-19) has become a challenging public health catastrophe worldwide. The newly emerged disease spread in almost all countries and infected 100 million persons worldwide. The infection is not limited to the respiratory system but involves various body systems and may lead to multiple organ failure. Tissue degenerative changes result from direct viral invasion, indirect consequences, or through an uncontrolled immune response. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads to the brain via hematogenous and neural routes accompanied with dysfunction of the blood-brain barrier. The involvement of the central nervous system is now suspected to be among the main causes of death. The present review discusses the historical background of coronaviruses, their role in previous and ongoing pandemics, the way they escape the immune system, why they are able to spread despite all undertaken measures, in addition to the neurological manifestations, long-term consequences of the disease, and various routes of viral introduction to the CNS.

Withania somnifera (L.) Dunal (Ashwagandha) for the possible therapeutics and clinical management of SARS-CoV-2 infection: Plant-based drug discovery and targeted therapy.

Coronavirus disease 2019 (COVID-19) pandemic has killed huge populations throughout the world and acts as a high-risk factor for elderly and young immune-suppressed patients. There is a critical need to build up secure, reliable, and efficient drugs against to the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Bioactive compounds of Ashwagandha [Withania somnifera (L.) Dunal] may implicate as herbal medicine for the management and treatment of patients infected by SARS-CoV-2 infection. The aim of the current work is to update the knowledge of SARS-CoV-2 infection and information about the implication of various compounds of medicinal plant Withania somnifera with minimum side effects on the patients' organs. The herbal medicine Withania somnifera has an excellent antiviral activity that could be implicated in the management and treatment of flu and flu-like diseases connected with SARS-CoV-2. The analysis was performed by systematically re-evaluating the published articles related to the infection of SARS-CoV-2 and the herbal medicine Withania somnifera. In the current review, we have provided the important information and data of various bioactive compounds of Withania somnifera such as Withanoside V, Withanone, Somniferine, and some other compounds, which can possibly help in the management and treatment of SARS-CoV-2 infection. Withania somnifera has proved its potential for maintaining immune homeostasis of the body, inflammation regulation, pro-inflammatory cytokines suppression, protection of multiple organs, anti-viral, anti-stress, and anti-hypertensive properties. Withanoside V has the potential to inhibit the main proteases (Mpro) of SARS-CoV-2. At present, synthetic adjuvant vaccines are used against COVID-19. Available information showed the antiviral activity in Withanoside V of Withania somnifera, which may explore as herbal medicine against to SARS-CoV-2 infection after standardization of parameters of drug development and formulation in near future.

Molecular dynamics simulations highlight the altered binding landscape at the spike-ACE2 interface between the Delta and Omicron variants compared to the SARS-CoV-2 original strain.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 variant (Omicron), represents a significant deviation in genetic makeup and function compared to previous variants. Following the BA.1 sublineage, the BA.2 and BA.3 Omicron subvariants became dominant, and currently the BA.4 and BA.5, which are quite distinct variants, have emerged. Using molecular dynamics simulations, we investigated the binding characteristics of the Delta and Omicron (BA.1) variants in comparison to wild-type (WT) at the interface of the spike protein receptor binding domain (RBD) and human angiotensin converting enzyme-2 (ACE2) ectodomain. The primary aim was to compare our molecular modelling systems with previously published observations, to determine the robustness of our approach for rapid prediction of emerging future variants. Delta and Omicron were found to bind to ACE2 with similar affinities (-39.4 and -43.3 kcal/mol, respectively) and stronger than WT (-33.5 kcal/mol). In line with previously published observations, the energy contributions of the non-mutated residues at the interface were largely retained between WT and the variants, with F456, F486, and Y489 having the strongest energy contributions to ACE2 binding. Further, residues N440K, Q498R, and N501Y were predicted to be energetically favourable in Omicron. In contrast to Omicron, which had the E484A and K417N mutations, intermolecular bonds were detected for the residue pairs E484:K31 and K417:D30 in WT and Delta, in accordance with previously published findings. Overall, our simplified molecular modelling approach represents a step towards predictive model systems for rapidly analysing arising variants of concern.

Characterization of Entry Pathways, Species-Specific Angiotensin-Converting Enzyme 2 Residues Determining Entry, and Antibody Neutralization Evasion of Omicron BA.1, BA.1.1, BA.2, and BA.3 Variants.

The SARS-CoV-2 Omicron variants were first detected in November 2021, and several Omicron lineages (BA.1, BA.2, BA.3, BA.4, and BA.5) have since rapidly emerged. Studies characterizing the mechanisms of Omicron variant infection and sensitivity to neutralizing antibodies induced upon vaccination are ongoing by several groups. In the present study, we used pseudoviruses to show that the transmembrane serine protease 2 (TMPRSS2) enhances infection of BA.1, BA.1.1, BA.2, and BA.3 Omicron variants to a lesser extent than ancestral D614G. We further show that Omicron variants have higher sensitivity to inhibition by soluble angiotensin-converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G. The Omicron variants also more efficiently used ACE2 receptors from 9 out of 10 animal species tested, and unlike the D614G variant, used mouse ACE2 due to the Q493R and Q498R spike substitutions. Finally, neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7- to 8-fold less potent than the D614G. These results provide insights into the transmissibility and immune evasion capacity of the emerging Omicron variants to curb their ongoing spread. IMPORTANCE The ongoing emergence of SARS-CoV-2 Omicron variants with an extensive number of spike mutations poses a significant public health and zoonotic concern due to enhanced transmission fitness and escape from neutralizing antibodies. We studied three Omicron lineage variants (BA.1, BA.2, and BA.3) and found that transmembrane serine protease 2 has less influence on Omicron entry into cells than on D614G, and Omicron exhibits greater sensitivity to endosomal entry inhibition compared to D614G. In addition, Omicron displays more efficient usage of diverse animal species ACE2 receptors than D614G. Furthermore, due to Q493R/Q498R substitutions in spike, Omicron, but not D614G, can use the mouse ACE2 receptor. Finally, three doses of Pfizer/BNT162b2 mRNA vaccination elicit high neutralization titers against Omicron variants, although the neutralization titers are still 7- to 8-fold lower those that against D614G. These results may give insights into the transmissibility and immune evasion capacity of the emerging Omicron variants to curb their ongoing spread.

Virtual Screening Attributes Male Biased COVID-19 Mortality to Predicted Antiviral Activity of Female Sex Hormones

Background: Coronavirus disease-19 (COVID-19) is a newly emerged pandemic leading to a state of international alert and leaving millions of infections and thousands of deaths all over the world. Analysis of statistics and epidemiological data for the pandemic outcome pinpointed a puzzling influence of human sex on the heterogeneous outcome of COVID-19, where hospital admissions and mortality were higher among males than females. Two theories explained the observed male-biased COVID-19 mortality based on either dosage of immunoregulatory genes coded in X- chromosomes, or on the abundance of the angiotensin-converting enzyme two (ACE2) receptors in males than females.Objective: In our study, we propose a third scenario through virtual screening of direct antiviral effects of sex hormones.Materials and Methods: Updated screening statistics from 47 countries displaying sex-disaggregated data on COVID-19 were employed and visualized in the form of heatmaps depicting sex difference effects on statistics of cases and deaths. Molecular docking and binding simulations of investigated sex steroids against COVID-19 specific proteins were investigated.Results: Analysis of COVID-19 sex-disaggregated data confirmed that male-biased mortality and computer-aided docking found unexpected female sex hormones biased binding against key targets implicated in the life cycle of COVID-19 compared to the male sex hormone testosterone. Other investigated steroids showed promising docking scores, while the male sex hormone exhibited the lowest affinity.Conclusion: Female sex hormones virtually exhibit direct anti-COVID-19 effect, the proposed antiviral effect of sex hormones should be considered to explain the outcomes of mortality. Moreover, the fluctuation of sex hormones influences sex and personal derived-differential response to COVID-19 infection. © 2021, Bentham Science Publishers. All rights reserved.

[COVID-19 related stroke]. / Insul't, assotsiirovannyi s COVID-19.

The COVID-19 pandemic had a significant impact on both the incidence of acute cerebral circulatory disorders and the structure of mortality. SARS-CoV-2 increases the risk of both ischemic and hemorrhagic stroke. The key pathogenetic links underlying the development of cerebral stroke in COVID-19 are impaired functioning of angiotensin 2 receptors, accompanied by the accumulation of excess angiotensin 2, endothelial dysfunction, hypercoagulation, hyperproduction of proinflammatory cytokines and oxidative storm. In patients with stroke and COVID-19, the severity of the lesion is associated with a dual mechanism of ischemia - systemic and cerebral. The possibilities of medical correction of systemic disorders associated with coronavirus infection, as well as local ones caused by ischemic or hemorrhagic brain damage, are limited. Substances with antioxidant activity could potentially be effective in patients with stroke and COVID-1.

Angiotensin-converting enzyme 2 as a potential therapeutic target for COVID-19: A review.

As of August 16, 2021, there have been 207,173,086 confirmed cases and 4,361,996 deaths due to the coronavirus disease (COVID-19), and the pandemic remains a global challenge. To date, no effective and approved drugs are available for the treatment of COVID-19. Angiotensin-converting enzyme 2 (ACE2) plays a crucial role in the invasion into host cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19. Notably, ACE2 density is influenced by medical conditions, such as hypertension, or by drugs, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), which can change the fate of SARS-CoV-2 infectivity. ACE2 is a target for these drugs and can be manipulated to limit the viral entry and replication within the cells. Different strategies aimed at blocking ACE2 with small molecules, peptides, and antibodies, or by neutralizing the virus through its competitive binding with human recombinant soluble ACE2 (hrsACE2) are currently under investigation. In this article, we review the current state of knowledge that emphasizes the need to find effective therapeutic agents against COVID-19 by exploiting ACE2 as a potential target. The increased soluble ACE2 levels and the application of hrsACE2 in patients with COVID-19 can be implemented to control the disease. It has not yet been established whether hypertension and other comorbidities, independent of age, have a direct role in COVID-19. Therefore, the use of renin-angiotensin system inhibitors, ACEIs and ARBs, should not be discontinued during COVID-19 treatment.

Ocular COVID-19: Eyes as a Reservoir to Conceal and Spread SARSCoV- 2.

Ocular tissues can serve as a reservoir for the SARS-CoV-2 virus which can not only cause conjunctivitis but also serve as a source of infection transmission to others. Additionally, the eye and its tear drainage apparatus can track the SARS-CoV-2 from the eye into the respiratory tract of the patient. The potential ocular presence of the SARS-CoV-2 in the eye of a patient can target ACE2 receptors in the endothelium of the conjunctival vessels and use the lacrimal sac a potential space to evade immune detection and clinical isolation. The recently reported case of COVID-19 after the acquisition of SARS-CoV-2 from a COVID-19 patient should alert the healthcare professionals dealing with COVID-19 patients that wearing masks alone cannot guarantee protection against infection transmission. Further studies, like isolation of SARS-CoV-2 from the eyes of patients with COVID-19, are needed to identify the eyes as a potential source of SARS-CoV-2 infection transmission.

Diverse Manifestations of COVID-19: Some Suggested Mechanisms.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the novel respiratory disease COVID-19, has reached pandemic status and presents a wide range of manifestations of diverse magnitude, including fever, cough, shortness of breath, and damage to vital organs, such as the heart, lung, kidney, and brain. Normally, older individuals and those with underlying health issues are more at risk. However, about 40% of COVID-19 positive individuals are asymptomatic. This review aims to identify suggested mechanisms of diverse manifestations of COVID-19. Studies suggest that T cell-mediated immunity and specific and/or nonspecific immunity from other vaccines could protect against SARS-CoV-2. The potential role of cross-reacting antibodies to coronaviruses that cause the common cold, mumps virus, polio virus, and pneumococcal bacteria are also suggested to help protect against COVID-19. Decreased production of Type I interferons (IFN-α and IFN-ß) could also be linked to COVID-19 manifestations. Several studies suggest that ACE2 cell membrane receptors are involved in SARS-CoV-2 infection. However, the relationship between an abundance of ACE2 receptors and the infectivity of the virus is unknown. Unlocking these manifestation mysteries could be crucial as this could help researchers better understand the virulence, pathology, and immune responses associated with SARS-CoV-2, leading to the development of effective therapies and treatment plans.

Comparative Analysis of Susceptibility and Severity of COVID-19 in Countries from the Eastern and the Western World Till March '21.

Majority of the world's human population today is affected by Covid-19. The disease has not only exhibited differences in susceptibility among people of different countries, but also the mortality rate. In general, Western world has been reporting a greater number of infected cases than eastern countries. Even the mortality rates are quite high there. The aim of this study was to analyse the data available on the infectivity and mortality rates of Covid-19 in different countries till March'21 and then reviewed the literature to find reasons for the differences in susceptibility and severity in eastern and western countries. The reasons for the observed differences may be: (i) Eastern countries followed stricter modalities and got grace period to create better healthcare facilities to tackle COVID-19. This probably also slowed the transmission of virus and its evolution, (ii) Vaccination policies in the east may have provided some immunity due to cross reactivity, (iii) Frequent exposure to infections at young age in eastern countries might be helping in better immunity, (iv) Mutations in viral genome may be geography based and (v) Genetic differences in the immune system of the hosts with respect to ACE receptors and MHC may be playing an important role. In this article, an attempt has been made to put forth and discuss these plausible reasons along with suitable evidences. These findings may help in future research on the diagnosis, treatment and prevention of Covid-19.

Hypertension as a manifestation of COVID-19 pneumonia.

Several factors such as hypertension, bile duct disease, and age can affect the duration of COVID, which can lead to long COVID. Any course of coronavirus infection could have a diverse nature of clinical forms and should have a personalized approach.