Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people

  1. Julia Hippisley-Cox1, Duncan Young2,3, Carol Coupland4, Keith M Channon5, Pui San Tan6, David A Harrison7, Kathryn Rowan8,  Paul Aveyard6, Ian D Pavord9, Peter J Watkinson5,10
  2. Correspondence to Prof Julia Hippisley-Cox, Primary Care Health Sciences, University of Oxford, Oxford OX1 

Abstract

Background 

There is uncertainty about the associations of angiotensive enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) drugs with COVID-19 disease. We studied whether patients prescribed these drugs had altered risks of contracting severe COVID-19 disease and receiving associated intensive care unit (ICU) admission.

Methods 

This was a prospective cohort study using routinely collected data from 1205 general practices in England with 8.28 million participants aged 20–99 years. We used Cox proportional hazards models to derive adjusted HRs for exposure to ACE inhibitor and ARB drugs adjusted for sociodemographic factors, concurrent medications and geographical region. The primary outcomes were: (a) COVID-19 RT-PCR diagnosed disease and (b) COVID-19 disease resulting in ICU care.

Findings 

Of 19 486 patients who had COVID-19 disease, 1286 received ICU care. ACE inhibitors were associated with a significantly reduced risk of COVID-19 disease (adjusted HR 0.71, 95% CI 0.67 to 0.74) but no increased risk of ICU care (adjusted HR 0.89, 95% CI 0.75 to 1.06) after adjusting for a wide range of confounders. Adjusted HRs for ARBs were 0.63 (95% CI 0.59 to 0.67) for COVID-19 disease and 1.02 (95% CI 0.83 to 1.25) for ICU care.

There were significant interactions between ethnicity and ACE inhibitors and ARBs for COVID-19 disease. The risk of COVID-19 disease associated with ACE inhibitors was higher in Caribbean (adjusted HR 1.05, 95% CI 0.87 to 1.28) and Black African (adjusted HR 1.31, 95% CI 1.08 to 1.59) groups than the white group (adjusted HR 0.66, 95% CI 0.63 to 0.70). A higher risk of COVID-19 with ARBs was seen for Black African (adjusted HR 1.24, 95% CI 0.99 to 1.58) than the white (adjusted HR 0.56, 95% CI 0.52 to 0.62) group.

Interpretation 

ACE inhibitors and ARBs are associated with reduced risks of COVID-19 disease after adjusting for a wide range of variables. Neither ACE inhibitors nor ARBs are associated with significantly increased risks of receiving ICU care. Variations between different ethnic groups raise the possibility of ethnic-specific effects of ACE inhibitors/ARBs on COVID-19 disease susceptibility and severity which deserves further study.

Oxygen Levels and the Digestive System

Authors: by Lung Health | Jun 9, 2016 | Oxygen LevelsResources

It might sound strange, but the respiratory system and the digestive system depend on one another for optimal function. Because oxygen is essential to the proper functioning of the body, one of the main concerns for people with chronic lung diseases is maintaining enough oxygen in their blood. The body needs energy and oxygen, so let’s take a closer look at oxygen levels and the digestive system.

What does the digestive system do?

The digestive system breaks down food so that it can become energy for the body. The digestive system is comprised of a complex system of organs, nerves, hormones, bacteria and blood work together to digest food. Digestive organs include the stomach, small intestines, large intestines, liver, pancreas and gall bladder.

What’s the connection between the respiratory system, oxygen levels and the digestive system?

The respiratory and digestive systems work together to power the body. A properly functioning respiratory system delivers adequate oxygen to the blood. Because the digestive system breaks down food and uses muscular contractions to move food through the digestive tract, it needs oxygen to function properly.

In turn, the respiratory system depends on a properly functioning digestive system to provide the fuel it needs to work effectively. Each function of the body depends on other functions, and all parts of the body need fuel and oxygen.

What are the risks of having lung disease and digestive system conditions?

In many cases, oxygen levels and the digestive system go hand-in-hand. COPD and other chronic lung diseases carry a risk for certain digestive disorders. Because some foods and drinks can cause symptom flare-ups, it’s important to know what to eat and what to avoid. Foods such as dairy and cruciferous vegetables are linked to increased mucus production and gas. Certain foods can also make GERD symptoms worse.

GERD or gastroesophageal reflux disease is common among people with COPD. GERD is a digestive disorder in which the stomach valve that keeps stomach acid down weakens or malfunctions, allowing stomach acid into the esophagus. If stomach acid reaches the lungs, it can result in irritation, increased coughing and shortness of breath.

GERD Symptoms include:

  • Dry cough
  • Chest pain
  • Difficulty swallowing
  • Hoarseness or sore throat
  • Burning in the chest or throat
  • Sensation of a lump in the throat
  • Regurgitation of stomach contents

What can I do to improve my blood oxygen levels?

Talk with your doctor about any new or worsening symptoms. See your doctor regularly, even if you’re feeling well. Now that you have information about oxygen levels and the digestive system, discuss your oxygen, food and exercise needs with your doctor. You and your physician can decide, together, on the best treatment plan for you.

Cellular therapy also helps many people with chronic lung diseases breathe easier by promoting the healing of lung tissue from within the body. The Lung Health Institute extracts cells from a patient’s blood separates them and then returns them intravenously. The cells may travel with the blood through the heart and into the lungs to become oxygenated. Once in the lungs, the majority of the cells become trapped in the pulmonary trap, and the now oxygen-rich blood travels to the rest of the body. In fact, many patients report improved lung function and are able to come off their supplemental oxygen after treatment. 

How does coronavirus kill? Clinicians trace a ferocious rampage through the body, from brain to toes

Authors: By Meredith WadmanJennifer Couzin-FrankelJocelyn KaiserCatherine MatacicApr. 17, 2020 , 6:45 PM

On rounds in a 20-bed intensive care unit one recent day, physician Joshua Denson assessed two patients with seizures, many with respiratory failure and others whose kidneys were on a dangerous downhill slide. Days earlier, his rounds had been interrupted as his team tried, and failed, to resuscitate a young woman whose heart had stopped. All shared one thing, says Denson, a pulmonary and critical care physician at the Tulane University School of Medicine. “They are all COVID positive.”

As the number of confirmed cases of COVID-19 surges past 2.2 million globally and deaths surpass 150,000, clinicians and pathologists are struggling to understand the damage wrought by the coronavirus as it tears through the body. They are realizing that although the lungs are ground zero, its reach can extend to many organs including the heart and blood vessels, kidneys, gut, and brain.

“[The disease] can attack almost anything in the body with devastating consequences,” says cardiologist Harlan Krumholz of Yale University and Yale-New Haven Hospital, who is leading multiple efforts to gather clinical data on COVID-19. “Its ferocity is breathtaking and humbling.”

Understanding the rampage could help the doctors on the front lines treat the fraction of infected people who become desperately and sometimes mysteriously ill. Does a dangerous, newly observed tendency to blood clotting transform some mild cases into life-threatening emergencies? Is an overzealous immune response behind the worst cases, suggesting treatment with immune-suppressing drugs could help? What explains the startlingly low blood oxygen that some physicians are reporting in patients who nonetheless are not gasping for breath? “Taking a systems approach may be beneficial as we start thinking about therapies,” says Nilam Mangalmurti, a pulmonary intensivist at the Hospital of the University of Pennsylvania (HUP).

What follows is a snapshot of the fast-evolving understanding of how the virus attacks cells around the body, especially in the roughly 5% of patients who become critically ill. Despite the more than 1000 papers now spilling into journals and onto preprint servers every week, a clear picture is elusive, as the virus acts like no pathogen humanity has ever seen. Without larger, prospective controlled studies that are only now being launched, scientists must pull information from small studies and case reports, often published at warp speed and not yet peer reviewed. “We need to keep a very open mind as this phenomenon goes forward,” says Nancy Reau, a liver transplant physician who has been treating COVID-19 patients at Rush University Medical Center. “We are still learning.”

The infection begins

When an infected person expels virus-laden droplets and someone else inhales them, the novel coronavirus, called SARS-CoV-2, enters the nose and throat. It finds a welcome home in the lining of the nose, according to a preprint from scientists at the Wellcome Sanger Institute and elsewhere. They found that cells there are rich in a cell-surface receptor called angiotensin-converting enzyme 2 (ACE2). Throughout the body, the presence of ACE2, which normally helps regulate blood pressure, marks tissues vulnerable to infection, because the virus requires that receptor to enter a cell. Once inside, the virus hijacks the cell’s machinery, making myriad copies of itself and invading new cells.

As the virus multiplies, an infected person may shed copious amounts of it, especially during the first week or so. Symptoms may be absent at this point. Or the virus’ new victim may develop a fever, dry cough, sore throat, loss of smell and taste, or head and body aches.

If the immune system doesn’t beat back SARS-CoV-2 during this initial phase, the virus then marches down the windpipe to attack the lungs, where it can turn deadly. The thinner, distant branches of the lung’s respiratory tree end in tiny air sacs called alveoli, each lined by a single layer of cells that are also rich in ACE2 receptors.

Normally, oxygen crosses the alveoli into the capillaries, tiny blood vessels that lie beside the air sacs; the oxygen is then carried to the rest of the body. But as the immune system wars with the invader, the battle itself disrupts this healthy oxygen transfer. Front-line white blood cells release inflammatory molecules called chemokines, which in turn summon more immune cells that target and kill virus-infected cells, leaving a stew of fluid and dead cells—pus—behind. This is the underlying pathology of pneumonia, with its corresponding symptoms: coughing; fever; and rapid, shallow respiration (see graphic). Some COVID-19 patients recover, sometimes with no more support than oxygen breathed in through nasal prongs.

But others deteriorate, often quite suddenly, developing a condition called acute respiratory distress syndrome (ARDS). Oxygen levels in their blood plummet and they struggle ever harder to breathe. On x-rays and computed tomography scans, their lungs are riddled with white opacities where black space—air—should be. Commonly, these patients end up on ventilators. Many die. Autopsies show their alveoli became stuffed with fluid, white blood cells, mucus, and the detritus of destroyed lung cells.

For More Information: https://www.sciencemag.org/news/2020/04/how-does-coronavirus-kill-clinicians-trace-ferocious-rampage-through-body-brain-toes

Asthmatics at no higher risk getting or dying from COVID-19, assessment of studies consisting of 587,000 people shows

Authors: February 19, 2021Source:Taylor & Francis Group

Summary:

A review of 57 studies shows people with asthma had a 14 percent lower risk of getting COVID-19 and were significantly less likely to be hospitalized with the virus.

A new study looking at how COVID-19 affects people with asthma provides reassurance that having the condition doesn’t increase the risk of severe illness or death from the virus.

George Institute for Global Health researchers in Australia analysed data from 57 studies with an overall sample size of 587,280. Almost 350,000 people in the pool had been infected with COVID-19 from Asia, Europe, and North and South America and found they had similar proportions of asthma to the general population.

The results, published in the peer-reviewed Journal of Asthma, show that just over seven in every 100 people who tested positive for COVID-19 also had asthma, compared to just over eight in 100 in the general population having the condition. They also showed that people with asthma had a 14 percent lower risk of acquiring COVID-19 and were significantly less likely to be hospitalized with the virus.

There was no apparent difference in the risk of death from COVID-19 in people with asthma compared to those without.

Head of The Institute’s Respiratory Program, co-author Professor Christine Jenkins said that while the reasons for these findings weren’t clear, there were some possible explanations — such as some inhalers perhaps limiting the virus’ ability to attach to the lungs.

“Chemical receptors in the lungs that the virus binds to are less active in people with a particular type of asthma and some studies suggest that inhaled corticosteroids — commonly used to treat asthma — can reduce their activity even further,” she said.

“Also, initial uncertainty about the impact of asthma on COVID-19 may have caused anxiety among patients and caregivers leading them to be more vigilant about preventing infection.”

Lead author Dr Anthony Sunjaya added that while this study provides some reassurance about the risks of exposure to COVID-19 in people with asthma, doctors and researchers were still learning about the effects of the virus.

“While we showed that people with asthma do not seem to have a higher risk of infection with COVID-19 compared to those without asthma and have similar outcomes, we need further research to better understand how the virus affects those with asthma,” he said.

For More Information: https://www.sciencedaily.com/releases/2021/02/210219091850.htm

Histopathological observations in COVID-19: a systematic review

  1. Authors: Vishwajit Deshmukh1, Rohini Motwani, Ashutosh Kumar3, Chiman Kumari4, Khursheed Raza5
  2. Correspondence to Dr Rohini Motwani, Department of Anatomy, ESIC Medical College and Hospital, Sanathnagar, Hyderabad, Telangana, India; rohinimotwani@gmail.com

Abstract

Background Coronavirus disease-2019 (COVID-19) has caused a great global threat to public health. The World Health Organization (WHO) has declared COVID-19 disease as a pandemic, affecting the human respiratory and other body systems, which urgently demands for better understanding of COVID-19 histopathogenesis.

Objective Data on pathological changes in different organs are still scarce, thus we aim to review and summarise the latest histopathological changes in different organs observed after autopsy of COVID-19 cases.

Materials and methods Over the period of 3 months, authors performed vast review of the articles. The search engines included were PubMed, Medline (EBSCO & Ovid), Google Scholar, Science Direct, Scopus and Bio-Medical. Search terms used were ‘Histopathology in COVID-19’, ‘COVID-19’, ‘Pathological changes in different organs in COVID-19’ or ‘SARS-CoV-2’. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 guidelines were used for review writing.

Result We identified various articles related to the histopathology of various organs in COVID-19 positive patients. Overall, 45 articles were identified as full articles to be included in our study. Histopathological findings observed are summarised according to the systems involved.

Conclusion Although COVID-19 mainly affects respiratory and immune systems, but other systems like cardiovascular, urinary, gastrointestinal tract, reproductive system, nervous system and integumentary system are not spared, especially in elderly cases and those with comorbidity. This review would help clinicians and researchers to understand the tissue pathology, which can help in better planning of the management and avoiding future risks.

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

For More Information: https://jcp.bmj.com/content/74/2/76

Pathological findings in organs and tissues of patients with COVID-19: A systematic review

  1. Authors: Sasha Peiris, Hector Mesa, Agnes Aysola, Juan Manivel, Joao Toledo, Marcio Borges-Sa, Sylvain Aldighieri, Ludovic Reveiz

Abstract

Background

Coronavirus disease (COVID-19) is the pandemic caused by SARS-CoV-2 that has caused more than 2.2 million deaths worldwide. We summarize the reported pathologic findings on biopsy and autopsy in patients with severe/fatal COVID-19 and documented the presence and/or effect of SARS-CoV-2 in all organs.

Methods and findings

A systematic search of the PubMed, Embase, MedRxiv, Lilacs and Epistemonikos databases from January to August 2020 for all case reports and case series that reported histopathologic findings of COVID-19 infection at autopsy or tissue biopsy was performed. 603 COVID-19 cases from 75 of 451 screened studies met inclusion criteria. The most common pathologic findings were lungs: diffuse alveolar damage (DAD) (92%) and superimposed acute bronchopneumonia (27%); liver: hepatitis (21%), heart: myocarditis (11.4%). Vasculitis was common only in skin biopsies (25%). Microthrombi were described in the placenta (57.9%), lung (38%), kidney (20%), Central Nervous System (CNS) (18%), and gastrointestinal (GI) tract (2%). Injury of endothelial cells was common in the lung (18%) and heart (4%). Hemodynamic changes such as necrosis due to hypoxia/hypoperfusion, edema and congestion were common in kidney (53%), liver (48%), CNS (31%) and GI tract (18%). SARS-CoV-2 viral particles were demonstrated within organ-specific cells in the trachea, lung, liver, large intestine, kidney, CNS either by electron microscopy, immunofluorescence, or immunohistochemistry. Additional tissues were positive by Polymerase Chain Reaction (PCR) tests only. The included studies were from numerous countries, some were not peer reviewed, and some studies were performed by subspecialists, resulting in variable and inconsistent reporting or over statement of the reported findings.

Conclusions

The main pathologic findings of severe/fatal COVID-19 infection are DAD, changes related to coagulopathy and/or hemodynamic compromise. In addition, according to the observed organ damage myocarditis may be associated with sequelae.

For More Information: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250708

Late Complications of COVID-19; a Systematic Review of Current Evidence

Authors: SeyedAhmad SeyedAlinaghi,1Amir Masoud Afsahi,2Mehrzad MohsseniPour,1Farzane Behnezhad,3Mohammad Amin Salehi,1Alireza Barzegary,4Pegah Mirzapour,1Esmaeil Mehraeen,5,* and Omid Dadras6

Introduction

Introduction:

COVID-19 is a new rapidly spreading epidemic. The symptoms of this disease could be diverse as the virus can affect any organ in the body of an infected person. This study aimed to investigate the available evidence for long-term complications of COVID-19.

Methods:

This study was a systematic review of current evidence conducted in November 2020 to investigate probable late and long-term complications of COVID-19. We performed a systematic search, using the keywords, in online databases including PubMed, Scopus, Science Direct, Up to Date, and Web of Science, to find papers published from December 2019 to October 2020. Peer-reviewed original papers published in English, which met the eligibility criteria were included in the final report. Addressing non-human studies, unavailability of the full-text document, and duplicated results in databases, were characteristics that led to exclusion of the papers from review.

Results:

The full-texts of 65 articles have been reviewed. We identified 10 potential late complications of COVID-19. A review of studies showed that lung injuries (n=31), venous/arterial thrombosis (n=28), heart injuries (n=26), cardiac/brain stroke (n=23), and neurological injuries (n=20) are the most frequent late complications of COVID-19.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927752/

Severe covid-19 pneumonia: pathogenesis and clinical management

Authors: Amy H Attaway, assistant professor of medicine, associate director, COPD center1,  Rachel G Scheraga, assistant professor of medicine2,  Adarsh Bhimraj, head, section of neurological infections; staff, infectious diseases1,  Michelle Biehl, associate staff, pulmonary and critical care medicine; director, post ICU recovery clinic1,  Umur Hatipoğlu, associate professor of medicine; director, respiratory therapy; director, COPD center1

Abstract

Severe covid-19 pneumonia has posed critical challenges for the research and medical communities. Older age, male sex, and comorbidities increase the risk for severe disease. For people hospitalized with covid-19, 15-30% will go on to develop covid-19 associated acute respiratory distress syndrome (CARDS). Autopsy studies of patients who died of severe SARS CoV-2 infection reveal presence of diffuse alveolar damage consistent with ARDS but with a higher thrombus burden in pulmonary capillaries. When used appropriately, high flow nasal cannula (HFNC) may allow CARDS patients to avoid intubation, and does not increase risk for disease transmission. During invasive mechanical ventilation, low tidal volume ventilation and positive end expiratory pressure (PEEP) titration to optimize oxygenation are recommended. Dexamethasone treatment improves mortality for the treatment of severe and critical covid-19, while remdesivir may have modest benefit in time to recovery in patients with severe disease but shows no statistically significant benefit in mortality or other clinical outcomes. Covid-19 survivors, especially patients with ARDS, are at high risk for long term physical and mental impairments, and an interdisciplinary approach is essential for critical illness recovery.

Introduction

The ongoing outbreak of the coronavirus disease 2019 (covid-19) has posed immense challenges for the research and medical communities. This review focuses on the epidemiologic and clinical features of covid-19, the pathophysiologic mechanisms, inpatient respiratory support, and the evidence to date on drug treatments. It also covers the recovery and long term management of patients with covid-19 pneumonia. The review is aimed at clinicians and intensivists caring for patients with severe covid-19 pneumonia as defined by the National Institutes of Health,1 referring to individuals with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) testing who have SpO2 <94% on room air at sea level, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mm Hg, respiratory frequency >30 breaths/min, or lung infiltrates >50%.

For More Information: https://www.bmj.com/content/372/bmj.n436

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19) – anatomic pathology perspective on current knowledge

Authors: Sambit K. MohantyAbhishek SatapathyMachita M. NaiduSanjay MukhopadhyayShivani SharmaLisa M. BartonEdana StrobergEric J. DuvalDinesh PradhanAlexandar Tzankov & Anil V. Parwani 

Abstract

Background

The world is currently witnessing a major devastating pandemic of Coronavirus disease-2019 (COVID-19). This disease is caused by a novel coronavirus named Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). It primarily affects the respiratory tract and particularly the lungs. The virus enters the cell by attaching its spike-like surface projections to the angiotensin-converting enzyme-2 (ACE-2) expressed in various tissues. Though the majority of symptomatic patients have mild flu-like symptoms, a significant minority develop severe lung injury with acute respiratory distress syndrome (ARDS), leading to considerable morbidity and mortality. Elderly patients with previous cardiovascular comorbidities are particularly susceptible to severe clinical manifestations.

Body

Currently, our limited knowledge of the pathologic findings is based on post-mortem biopsies, a few limited autopsies, and very few complete autopsies. From these reports, we know that the virus can be found in various organs but the most striking tissue damage involves the lungs resulting almost always in diffuse alveolar damage with interstitial edema, capillary congestion, and occasional interstitial lymphocytosis, causing hypoxia, multiorgan failure, and death. A few pathology studies have also reported intravascular microthrombi and pulmonary thromboembolism. Although the clinical presentation of this disease is fairly well characterized, knowledge of the pathologic aspects remains comparatively limited.

Conclusion

In this review, we discuss clinical, pathologic, and genomic features of COVID-19, review current hypotheses regarding the pathogenesis, and briefly discuss the clinical characteristics. We also compare the salient features of COVID-19 with other coronavirus-related illnesses that have posed significant public health issues in the past, including SARS and the Middle East Respiratory Syndrome (MERS).

For More Information: https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-020-01017-8

The role of extracorporeal membrane oxygenation in critically ill patients with COVID-19: a narrative review

Authors: Shiqian HuangShuai ZhaoHuilin LuoZhouyang WuJing WuHaifa Xia & Xiangdong Chen BMC Pulmonary Medicine volume 21, Article number: 116 (2021)

Abstract

Extracorporeal life support treatments such as extracorporeal membrane oxygenation (ECMO) have been recommended for the treatment of severe acute respiratory distress syndrome (ARDS) patients with coronavirus disease 2019 (COVID-19). To date, many countries, including China, have adopted ECMO as a treatment for severe COVID-19. However, marked differences in patient survival rates have been reported, and the underlying reasons are unclear. This study aimed to summarize the experience of using ECMO to treat severe COVID-19 and provide suggestions for improving ECMO management. The effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the pathophysiology of COVID-19 and the effects of ECMO on the clinical outcomes in patients with severe cases of COVID-19 were reviewed. Recent data from frontline workers involved in the use of ECMO in Wuhan, China, and those experienced in the implementation of artificial heart and lung support strategies were analyzed. There is evidence that ECMO may complicate the pathophysiological state in COVID-19 patients. However, many studies have shown that the appropriate application of ECMO improves the prognosis of such patients. To expand our understanding of the benefits of ECMO for critically ill patients with COVID-19, further prospective, multicenter clinical trials are needed.

For More Information: https://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-021-01479-6