COVID-19: Current  Understanding  of  Pathophysiology

Coronavirus disease 2019 has emerged as a global pandemic, affecting millions of people across the globe. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the human cell after binding to the Angiotensin-Converting Enzyme 2 receptors, that are present in various organs. The involvement of the respiratory system is common and may progress to acute respiratory distress syndrome. Besides the involvement of respiratory system other systems like cardiovascular, renal, gastrointestinal and central nervous are not uncommon. In-depth understanding of the pathophysiological basis of organs and systems involvement and disease progression aids in the safe and effective management of the COVID-19 patients. It also helps to guide future well-designed clinical trials, which is the need of time. This review aims to explore the current understanding of pathophysiological basis of various organ system involvement in patients with COVID-19, that can have relevance for patient management and future research. We reviewed the articles in various databases to assemble the current evidences. Keywords: Coronavirus disease 2019; COVID-19; pathophysiology; severe acute respiratory syndrome coronavirus 2

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Salivary Diagnosis of COVID-19

Pakistan Armed Forces Medical Journal ◽

10.51253/pafmj.v71i6.5498 ◽

2022 ◽

Vol 71 (6) ◽

pp. 2254-55

Author(s):

Seema Shafiq ◽

Asim Riaz

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Severe Acute Respiratory Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Sore Throat ◽

Distress Syndrome ◽

Signs And Symptoms ◽

Fatality Rate ◽

Ongoing Research ◽

Global Pandemic

Dear Editor, It is indeed an honour for us to contribute towards the ongoing research regarding the latest contagion, Coronavirus disease (COVID-19) as caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leading to global pandemic with variable clinical outcomes. COVID-19 positive individuals present with a variety of signs and symptoms as sore throat, cough, fever, dyspnoea, headache, myalgia, nausea, and vomiting whereas, some develop severe acute respiratory distress syndrome with a fatality rate of about 10%.1 Possible oral findings include xerostomia, hypogeusia, and chemosensory alterations. Common routes of transmission being person-to-person via direct sneeze, cough, and droplet inhalation or by contact through mucosa of eyes, nose and saliva.

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The Pandemic Hits Us Hard, but We Don’t Lose Hope

The Hip and Knee Journal ◽

10.46355/hipknee.v2i1.72 ◽

2021 ◽

Vol 2 (1) ◽

pp. 1-4

Author(s):

Krisna Yuarno Phatama ◽

Sholahuddin Rhatomy, MD ◽

Asep Santoso ◽

Nicolaas C. Budhiparama

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Severe Acute Respiratory Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

World Health Organization ◽

Distress Syndrome ◽

World Health ◽

Global Pandemic ◽

New Variant ◽

Health Organization

At the end of 2019, we faced a new variant of the coronavirus that can cause pneumonia and acute respiratory distress syndrome-like symptoms. It started in Wuhan, Hubei Province, China, and spread quickly to the whole world.This new virus is called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and can manifest as a disease called coronavirus disease 2019 (COVID-19). On March 13th, 2020 World Health Organization (WHO) declared COVID-19 as a global pandemic, and the story of frightening pandemic begin.

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The dermatologic manifestations of COVID-19: a mini-review

Annals of Proteomics and Bioinformatics ◽

10.29328/journal.apb.1001015 ◽

2021 ◽

Vol 5 (1) ◽

pp. 042-048

Author(s):

Alharazy Sabah

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Early Diagnosis ◽

Maculopapular Rash ◽

Current Understanding ◽

Global Pandemic ◽

Dermatologic Manifestations

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in Wuhan, China, and caused coronavirus disease-19 (COVID-19), which is still a global pandemic. Dermatologic manifestations have increasingly been identified as significant extrapulmonary manifestations of COVID-19. The dermatologic manifestations associated with COVID-19 infection reported to date include maculopapular rash, vesicular lesions, urticaria-like lesions, and chilblain-like lesions. Knowledge of dermatologic manifestations of COVID-19 may be essential for early diagnosis and a better prognosis in COVID-19 patients. This review summarizes the current understanding of common COVID-19-associated dermatologic manifestations.

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COVID-19 and Respiratory System Disorders

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.120.314515 ◽

2020 ◽

Vol 40 (11) ◽

pp. 2586-2597

Author(s):

Shari B. Brosnahan ◽

Annemijn H. Jonkman ◽

Matthias C. Kugler ◽

John S. Munger ◽

David A. Kaufman

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Severe Acute Respiratory Syndrome ◽

Respiratory System ◽

Distress Syndrome ◽

Clinical Presentation ◽

Neuromuscular Disorders ◽

Human Pathogen ◽

Common Clinical Presentation ◽

Research Questions ◽

Different Parts

The severe acute respiratory syndrome coronavirus-2 emerged as a serious human pathogen in late 2019, causing the disease coronavirus disease 2019 (COVID-19). The most common clinical presentation of severe COVID-19 is acute respiratory failure consistent with the acute respiratory distress syndrome. Airway, lung parenchymal, pulmonary vascular, and respiratory neuromuscular disorders all feature in COVID-19. This article reviews what is known about the effects of severe acute respiratory syndrome coronavirus-2 infection on different parts of the respiratory system, clues to understanding the underlying biology of respiratory disease, and highlights current and future translation and clinical research questions.

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Hyperglycemia and Angiotensin-Converting Enzyme 2 in Pulmonary Function in the Context of SARS-CoV-2 Infection

Frontiers in Medicine ◽

10.3389/fmed.2021.758414 ◽

2022 ◽

Vol 8 ◽

Author(s):

Jose R. Vargas-Rodriguez ◽

Idalia Garza-Veloz ◽

Virginia Flores-Morales ◽

Jose I. Badillo-Almaraz ◽

Maria R. Rocha-Pizaña ◽

...

Keyword(s):

Diabetes Mellitus ◽

Acute Respiratory Distress Syndrome ◽

Severe Acute Respiratory Syndrome ◽

Angiotensin Converting Enzyme ◽

Distress Syndrome ◽

Current Evidence ◽

Pathophysiological Mechanism ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Worse Prognosis

Since the appearance of the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 in China, diabetes mellitus (DM) and hyperglycemia in patients infected with SARS-CoV, represent independent predictors of mortality. Therefore, metabolic control has played a major role in the prognosis of these patients. In the current pandemic of coronavirus disease 19 (COVID-19), multiple studies have shown that DM is one of the main comorbidities associated with COVID-19 and higher risk of complications and death. The incidence and prevalence of COVID-19 complications and death related with hyperglycemia in patients with or without DM are high. There are many hypotheses related with worse prognosis and death related to COVID-19 and/or hyperglycemia. However, the information about the interplay between hyperglycemia and angiotensin-converting enzyme 2 (ACE2), the critical receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the context of SARS-CoV-2 infection, is almost null, but there is enough information to consider the possible participation of hyperglycemia in the glycation of this protein, unleashing a pool of reactions leading to acute respiratory distress syndrome and death in patients with COVID-19. In this document we investigated the current evidence related with ACE2 as a key element within the pathophysiological mechanism related with hyperglycemia extrapolating it to context of SARS-CoV-2 infection and its relationship with worse prognosis and death for COVID-19.

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Discovery of Clioquinol and Analogues as Novel Inhibitors of Severe Acute Respiratory Syndrome Coronavirus 2 Infection, ACE2 and ACE2 - Spike Protein Interaction In Vitro

10.1101/2020.08.14.250480 ◽

2020 ◽

Cited By ~ 2

Author(s):

Omonike A. Olaleye ◽

Manvir Kaur ◽

Collins Onyenaka ◽

Tolu Adebusuyi

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Cytopathic Effect ◽

Molecular Target ◽

Clinical Development ◽

Spike Protein ◽

Angiotensin Converting Enzyme 2 ◽

Global Pandemic ◽

Potential Therapeutics ◽

Micromolar Range

AbstractSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent for coronavirus disease 2019 (COVID-19), has emerged as an ongoing global pandemic. Presently, there are no clinically approved vaccines nor drugs for COVID-19. Hence, there is an urgent need to accelerate the development of effective antivirals. Here in, we discovered Clioquinol (5-chloro-7-iodo-8-quinolinol (CLQ)), a FDA approved drug and two of its analogues (7-bromo-5-chloro-8-hydroxyquinoline (CLBQ14); and 5, 7-Dichloro-8-hydroxyquinoline (CLCQ)) as potent inhibitors of SARS-CoV-2 infection induced cytopathic effect in vitro. In addition, all three compounds showed potent anti-exopeptidase activity against recombinant human angiotensin converting enzyme 2 (rhACE2) and inhibited the binding of rhACE2 with SARS-CoV-2 Spike (RBD) protein. CLQ displayed the highest potency in the low micromolar range, with its antiviral activity showing strong correlation with inhibition of rhACE2 and rhACE2-RBD interaction. Altogether, our findings provide a new mode of action and molecular target for CLQ and validates this pharmacophore as a promising lead series for clinical development of potential therapeutics for COVID-19.

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Pathogenesis of COVID-19: ACE2, Cytokine Storm and Extrapulmonary Manifestations

Life and Science ◽

10.37185/lns.1.1.199 ◽

2021 ◽

Vol 2 (4) ◽

pp. 9

Author(s):

Muhammad Naeem ◽

Abdul Muhaymin Muhaymin ◽

Hyder Wajid Abbasi ◽

Naeem Ullah ◽

Adnan Haider ◽

...

Keyword(s):

Immune Responses ◽

Viral Entry ◽

Distress Syndrome ◽

Clinical Manifestations ◽

First Century ◽

Infected Person ◽

Alveolar Cells ◽

Angiotensin Converting Enzyme 2 ◽

Global Pandemic ◽

Taste And Smell

The coronavirus disease 19 (COVID-19) is a global pandemic of the twenty-first century and currently fourthwave is creating fear and panic worldwide. It is caused by severe acute respiratory syndrome coronavirus 2(SARS-COV-2), a highly contagious viral infection of humans. The COVID-19 can be spread mainly throughrespiratory droplet particles and in contact with a COVID-19 infected person. Clinical manifestation of COVID-19patients includes cough, fever, diarrhea, loss of taste and smell. In critical cases of COVID-19, the developmentof pneumonia and dyspnea leads to acute respiratory distress syndrome that may cause the death of thepatient. It is well established that Angiotensin-Converting Enzyme 2 (ACE2) receptors on alveolar cells act as anentry gate for the SARS-COV-2. However, ACE2 is also highly expressed in multiple extrapulmonary vital organssuch as the gastrointestinal system, cardiovascular system, kidney, etc. Therefore, the direct viral entry in theseorgans can be a likely pathway of injury. In addition, decoupling of immune responses leads to the cytokinesstorm, which might contribute to the injury of extrapulmonary organs. In this review, we report the multipleorgan pathogenesis and clinical manifestations of COVID-19 patients, which could aid clinicians and researchersin prioritizing therapeutics remedies and developing research for all vital body systems involved.

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Metabolic Syndrome “Interacts” With COVID-19

BIO Integration ◽

10.15212/bioi-2020-0035 ◽

2020 ◽

Author(s):

Zeling Guo ◽

Shanping Jiang ◽

Zilun Li ◽

Sifan Chen

Keyword(s):

Metabolic Disorders ◽

Distress Syndrome ◽

Metabolic Diseases ◽

Clinical Manifestations ◽

Severe Pneumonia ◽

Symptomatic Treatment ◽

Angiotensin Converting Enzyme 2 ◽

Treatment And Prevention ◽

Global Pandemic ◽

Metabolic Comorbidities

COVID-19, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emerged as a global pandemic and poses a great threat to public health and society in general. SARS-CoV-2 invades cells via its spike protein, which initiates endocytosis via its binding to host receptor angiotensin-converting enzyme 2 (ACE2) and membrane fusion after being cleaved by the serine protease, TMPRSS2. The most common clinical manifestations are fever, dry cough, fatigue and abnormalities on chest computed tomography (CT). However, some patients rapidly progress to severe pneumonia and develop acute respiratory distress syndrome (ARDS). Furthermore, SARS-CoV-2 triggers a severe cytokine storm, which may explain the deterioration of pre-existing metabolic disorders. Interestingly, conversely, underlying metabolic-related diseases, including hypertension, diabetes, cardiovascular disease, etc., are associated with progression and poor prognosis of COVID-19. The putative mechanisms are dysregulation of ACE2, impaired immunity especially uncontrolled hyperinflammation, hypercoagulability, etc. In this review, we summarize the crosstalk between COVID-19 and metabolic diseases and propose that in addition to controlling COVID-19, more intensive attention should be paid to the symptomatic treatment and prevention of pre-existing and foreseeable metabolic comorbidities.

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ECMO combined with prone positioning strategies in COVID-19 respiratory distress syndrome

Perfusion ◽

10.1177/0267659121995999 ◽

2021 ◽

pp. 026765912199599

Author(s):

Yue Xu ◽

Yueh-ting Chou ◽

Xin-guang Wei ◽

Shan-feng Zhang ◽

Feng Jiang ◽

...

Keyword(s):

Public Health ◽

Severe Acute Respiratory Syndrome ◽

Conventional Treatment ◽

Distress Syndrome ◽

Case Reports ◽

Public Health Emergency ◽

Prone Positioning ◽

Previous Evidence ◽

Global Pandemic ◽

Similar Patient

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has already become a global pandemic as a public health emergency of international concern. Previous evidence from similar patient populations proved that carefully selected patients with severe ARDS who did not benefit from conventional treatment might be successfully supported with Veno-Venous extracorporeal membrane oxygenation (V-V ECMO). We now share the case reports of COVID-19 patients with ECMO combined prone position strategies.

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Multi-Organ System Dysfunction in Covid-19 – A Review

Journal of Evolution of Medical and Dental Sciences ◽

10.14260/jemds/2021/135 ◽

2021 ◽

Vol 10 (9) ◽

pp. 632-637

Author(s):

Pooja Bhadoria ◽

Harsha Rathore

Keyword(s):

Nervous System ◽

Gastrointestinal Tract ◽

Severe Acute Respiratory Syndrome ◽

Angiotensin Converting Enzyme ◽

Wide Distribution ◽

Multiple Organ ◽

Organ System ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Organ Systems

With a continuous increase in Covid-19 cases, patients infected with SARS-CoV-2 have shown a wide variety of symptoms including fever, shortness of breath, cough, myalgia, dizziness, headache, impaired consciousness, abdominal pain and diarrhoea. Lab studies have shown higher leukocyte counts and neutrophil-lymphocyte ratio (NLR), decreased lymphocytes, increased prothrombin time and a partial thromboplastin time, increased serum lactate dehydrogenase, ferritin and various other markers, indicating multiple organ system dysfunction including respiratory system, immune system, nervous system and gastrointestinal tract. Apart from these, heart and kidneys are also found to be affected in some patients. Patients presenting with previous history of diseases such as cardiovascular diseases, kidney diseases, pregnant females, neonates, immunosuppressed patients, and aged people have shown poor prognosis of disease. Various studies suggest possible reasons of multiple organ dysfunctions including wide distribution of angiotensin-converting enzyme 2 (ACE-2) receptors, cytokine storm and hypercoagulability of blood. We have listed the various organ systems affected by the virus and possible explanations as to why and how these organ systems are affected. SARS-CoV-2 outbreak has caused a global pandemic, with more than 33,400,000 confirmed cases of Covid-19, including more than 1,000,000 deaths, reported to World Health Organization (WHO) globally till 30 September 2020. 1 with a basic reproductive number estimated to be 2.2 (1.4 - 3.9) the virus spread is very fast affecting many individuals across the globe. 2 One of the major causes of efficient spread of SARS-CoV-2 in humans is the angiotensin-converting enzyme 2 receptors, used by the virus to enter the cells. 3 Hence, wide distribution of angiotensin-converting enzyme 2 receptors in body including lungs, kidney, bladder, gastrointestinal tract, heart, central nervous system and peripheral nervous system4 and even placenta5 is one of the reasons the virus is found to affect these organs. Two closely related viruses causing Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) were also found to affect multiple organ systems. SARS‐CoV-1 was found in the respiratory pathway (trachea, bronchus, lung), gastrointestinal tract (stomach, small intestines), glands (sweat gland, liver, pancreas, parathyroid, pituitary, adrenal gland), renal system (convoluted renal tubules) and brain tissue (cerebrum) in the autopsy samples of patients who died because of severe acute respiratory syndrome. 6 Respiratory, circulatory, gastrointestinal, haematological, renal and hepatological symptoms were also found to be affected in patients with Middle East respiratory syndrome infection. 7 Though the virus is found to affect multiple organ systems, the underlying mechanisms are not clearly understood.

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