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.

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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;


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.

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COVID-19 pathophysiology: A review

Authors: COVID-19 pathophysiology: A review Koichi Yuki, Miho Fujiogi, and Sophia Koutsogiannaki


In December 2019, a novel coronavirus, now named as SARS-CoV-2, caused a series of acute atypical respiratory diseases in Wuhan, Hubei Province, China. The disease caused by this virus was termed COVID-19. The virus is transmittable between humans and has caused pandemic worldwide. The number of death tolls continues to rise and a large number of countries have been forced to do social distancing and lockdown. Lack of targeted therapy continues to be a problem. Epidemiological studies showed that elder patients were more susceptible to severe diseases, while children tend to have milder symptoms. Here we reviewed the current knowledge about this disease and considered the potential explanation of the different symptomatology between children and adults.

1. Introduction

In December 2019, a series of acute atypical respiratory disease occurred in Wuhan, China. This rapidly spread from Wuhan to other areas. It was soon discovered that a novel coronavirus was responsible. The novel coronavirus was named as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, 2019-nCoV) due to its high homology (~80%) to SARS-CoV, which caused acute respiratory distress syndrome (ARDS) and high mortality during 2002–2003 [1]. The outbreak of SARS-CoV-2 was considered to have originally started via a zoonotic transmission associated with the seafood market in Wuhan, China. Later it was recognized that human to human transmission played a major role in the subsequent outbreak [2]. The disease caused by this virus was called Coronavirus disease 19 (COVID-19) and a pandemic was declared by the World Health Organization (WHO). COVID-19 has been impacting a large number of people worldwide, being reported in approximately 200 countries and territories [3,4]. As of April 7th, 2020, around 1,400,000 cases worldwide have been reported according to the Center for Systems Science and Engineering (CSSE) at John Hopkins University [5].

SARS-CoV-2 virus primarily affects the respiratory system, although other organ systems are also involved. Lower respiratory tract infection related symptoms including fever, dry cough and dyspnea were reported in the initial case series from Wuhan, China [6]. In addition, headache, dizziness, generalized weakness, vomiting and diarrhea were observed [7]. It is now widely recognized that respiratory symptoms of COVID-19 are extremely heterogeneous, ranging from minimal symptoms to significant hypoxia with ARDS. In the report from Wuhan mentioned above, the time between the onset of symptoms and the development of ARDS was as short as 9 days, suggesting that the respiratory symptoms could progress rapidly [6]. This disease could be also fatal. A growing number of patients with severe diseases have continued to succumb worldwide. Epidemiological studies have shown that mortalities are higher in elder population [8] and the incidence is much lower in children [9,10]. Current medical management is largely supportive with no targeted therapy available. Several drugs including lopinavir-ritonavir, remdesivir, hydroxychloroquine, and azithromycin have been tested in clinical trials [8,11,12], but none of them have been proven to be a definite therapy yet. More therapies are being tested in clinical trials. A large number of countries have implemented social distancing and lockdown to mitigate further spread of the virus. Here we will review our current knowledge of COVID-19 and consider the underlying mechanism to explain the heterogeneous symptomatology, particularly focusing on the difference between children and adult patients.

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What Does COVID Do to Your Blood?

Authors: Panagis Galiatsatos, M.D., M.H.S., Robert Brodsky, M.D.

COVID-19 is a very complex illness. The coronavirus that causes COVID-19 attacks the body in many different ways, ranging from mild to life threatening. Different organs and tissues of the body can be affected, including the blood.

Robert Brodsky, a blood specialist who directs the Division of Hematology, and Panagis Galiatsatos, a specialist in lung diseases and critical care medicine, talk about blood problems linked to SARS-CoV-2 — the coronavirus that causes COVID-19 — and what you should know.

Coronavirus Blood Clots

Blood clots can cause problems ranging from mild to life threatening. If a clot blocks blood flow in a vein or artery, the tissue normally nourished by that blood vessel can be deprived of oxygen, and cells in that area can die.

Some people infected with SARS-CoV-2 develop abnormal blood clotting. “In some people with COVID-19, we’re seeing a massive inflammatory response, the cytokine storm that raises clotting factors in the blood,” says Galiatsatos, who treats patients with COVID-19.

“We are seeing more blood clots in the lungs (pulmonary embolism), legs (deep vein thrombosis) and elsewhere,” he says.

Brodsky notes that other serious illnesses, especially ones that cause inflammation, are associated with blood clots. Research is still exploring if the blood clots seen in severe cases of COVID-19 are unique in some way. 

The Impact of Coronavirus Blood Clots Throughout the Body

In addition to the lungs, blood clots, including those associated with COVID-19, can also harm:

The nervous system. Blood clots in the arteries leading to the brain can cause a stroke. Some previously young, healthy people who have developed COVID-19 have suffered strokes, possibly due to abnormal blood clotting.

The kidneys. Clogging of blood vessels in the kidney with blood clots can lead to kidney failure. It can also complicate dialysis if the clots clog the filter of the machine designed to remove impurities in the blood.

Peripheral blood vessels and “COVID toe.” Small blood clots can become lodged in tiny blood vessels. When this happens close to the skin, it can result in a rash. Some people who test positive for COVID-19 develop tiny blood clots that cause reddish or purple areas on the toes, which can itch or be painful. Sometimes called COVID toe, the rash resembles frostbite.

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Platelets Promote Thromboinflammation in SARS-CoV-2 Pneumonia

Authors: Francesco TausGianluca SalvagnoStefania CanèCristiano FavaFulvia MazzaferriElena CarraraVarvara PetrovaRoza Maria BarouniFrancesco DimaAndrea DalbeniSimone Romano,



Pulmonary thrombosis is observed in severe acute respiratory syndrome coronavirus 2 pneumonia. Aim was to investigate whether subpopulations of platelets were programmed to procoagulant and inflammatory activities in coronavirus disease 2019 (COVID-19) patients with pneumonia, without comorbidities predisposing to thromboembolism.

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