It’s not just the lungs: The Covid-19 virus attacks like no other ‘respiratory’ infection
Video created by: HYACINTH EMPINADO/STAT
By SHARON BEGLEY @sxbegle (STAT)
The reports seemed to take doctors by surprise: The “respiratory” virus that causes Covid-19 made some patients nauseous. It left others unable to smell. In some, it caused acute kidney injury.
As the pandemic grew from an outbreak affecting thousands in Wuhan, China, to some 10 million cases and 500,000 deaths globally as of late June, the list of symptoms has also exploded. The Centers for Disease Control and Prevention constantly scrambled to update its list in an effort to help clinicians identify likely cases, a crucial diagnostic aid at a time when swab tests were in short supply and typically took (and still take) days to return results. The loss of a sense of smell made the list only in late April.
“For many diseases, it can take years before we fully characterize the different ways that it affects people,” said nephrologist Dan Negoianu of Penn Medicine. “Even now, we are still very early in the process of understanding this disease.”
What they are understanding is that this coronavirus “has such a diversity of effects on so many different organs, it keeps us up at night,” said Thomas McGinn, deputy physician in chief at Northwell Health and director of the Feinstein Institutes for Medical Research. “It’s amazing how many different ways it affects the body.”
One early hint that that would be the case came in late January, when scientists in China identified one of the two receptors by which the coronavirus, SARS-CoV-2, enters cells. It was the same gateway, called the ACE2 receptor, that the original SARS virus used. Studies going back some two decades had mapped the body’s ACE2 receptors, showing that they’re in cells that line the insides of blood vessels — in what are called vascular endothelial cells — in cells of the kidney’s tubules, in the gastrointestinal tract, and even in the testes.
Given that, it’s not clear why the new coronavirus’ ability to wreak havoc from head to toe came as a surprise to clinicians. Since “ACE2 is also the receptor for SARS, its expression in other organs and cell types has been well-known,” said Anirban Maitra of MD Anderson Cancer Center, who led a study mapping the receptor in cells of the GI tract. (Maitra is an expert in pancreatic cancer and, like many scientists this year, added Covid-19 to his research.)
Infecting cells is only the first way SARS-CoV-2 wreaks havoc. Patients with severe Covid-19 also suffer a runaway inflammatory response and, often, clot formation, said infectious disease physician Rochelle Walensky of Massachusetts General Hospital. That can cause symptoms as different as a lack of blood flow to the intestines and the red, inflamed “Covid toe.”
“We’ve had five cases of patients who’ve had to have their gut removed,” Walensky said. “You see these cases and you say, wait a minute; the virus is doing this, too? It has definitely been keeping us on our toes.”
Venky Soundararajan had a hunch that the extent of ACE2 distribution throughout the body was lying in plain sight. The co-founder and chief scientific officer of nference, which uses artificial intelligence to mine existing knowledge, he and his colleagues turned their system into a hunt for ACE2 knowledge. Combing 100 million biomedical documents from published papers to genomic and other -omics databases, they uncovered multiple tissues and cell types with ACE2 receptors, they reported last month in the journal eLife.
They also calculated what percent of each cell type expresses “reasonable amounts” of ACE2, Soundararajan said. On average, about 40% of kidney tubule cells do, and in a surprise for a “respiratory” virus, cells in the GI tract were “the strongest expressors of ACE2 receptors,” he said.
The data mining found that ACE2 is also expressed in the nose’s olfactory cells. That’s not a new finding per se — the nference system found it in existing databases, after all — but it hadn’t been appreciated by scientists or clinicians. It explains the loss or altered sense of smell that Covid-19 patients experience. Its importance became clear earlier this month, when scientists at the Mayo Clinic and reported that loss of a sense of smell is “the earliest signature of Covid-19,” appearing days before a positive swab test.
That study, using health records of 77,167 people tested for Covid-19, showed how the assumption that infection would first and foremost cause respiratory symptoms was misplaced. In the week before they were diagnosed, Covid-19 patients were 27 times more likely than people who tested negative for the virus to have lost their sense of smell. They were only 2.6 times more likely to have fever or chills, 2.2 times more likely to have trouble breathing or to be coughing, and twice as likely to have muscle aches. For months, government guidelines kept people not experiencing such typical signs of a respiratory infection from getting tested.
Faced with a disease the world had never seen before, physicians are learning as they go. By following the trail of ACE2 receptors, they are more and more prepared to look for, and treat, consequences of SARS-CoV-2 infection well beyond the obvious:
Gut: The coronavirus infects cells that line the inside of the large and small intestine, called gut enterocytes. That likely accounts for the diarrhea, nausea, and abdominal pain that about one-third of Covid-19 patients experience, said MD Anderson’s Maitra: “The GI symptoms reflect physiological [dysfunction] of cells of the lower GI tract.”
Why don’t all patients have GI symptoms — or indeed, the whole panoply of symptoms suggested by the near ubiquity of ACE2 receptors? For those with mild to moderate Covid-19, “the infectious load in the GI tract may simply not be sufficient to cause symptoms,” Maitra said.
Kidney: The cells lining the tubules that filter out toxic compounds from the blood are rife with ACE2 receptors. Last month, scientists studying 1,000 Covid-19 patients at a New York City hospital reported that 78% of those in intensive care developed acute kidney injury.
Smell: An analysis of 24 studies with data from 8,438 Covid-19 patients from 13 countries found this month that 41% had lost their sense of taste or smell, or both. That shouldn’t be surprising, said Fabio Ferreli of Humanitas University in Milan: “Perhaps the highest levels of ACE2 receptors are expressed in cells in the nasal epithelium.” The sensory loss isn’t due to nasal inflammation, swelling, or congestion, he said, “but to direct damage” to these epithelial cells. Loss of smell also impacts taste, but the virus may also have a direct effect on taste: The nference analysis found high levels of the ACE2 gene in tongue cells called keratinocytes, which contribute to the sense of taste.
There is another implication of the high expression of ACE2 in olfactory epithelium cells, scientists at Johns Hopkins concluded in a paper posted to the preprint site bioRxiv last month: ACE2 levels in the olfactory epithelium of the upper airways that are 200 to 700 times higher than in the lower airways might explain the virus’s high transmissibility. It was weeks before experts recognized that the virus could spread from person to person.
Lungs: This is where a respiratory virus should strike, and SARS-CoV-2 does. The lungs’ type II alveolar cells — among other jobs, they release a compound that allows the lungs to pass oxygen to the blood and take carbon dioxide from it — are studded with ACE2 receptors. Once infected with the coronavirus, they become dysfunctional or die, and are so swarmed by immune cells that this inflammatory response can explode into the acute respiratory distress syndrome (ARDS) that strikes many patients with severe Covid-19, Walensky said.
There is new evidence that the virus also attacks platelet-producing cells, called megakaryocytes, in the lungs. In a study published on Thursday, pathologist Amy Rapkiewicz of NYU Winthrop Hospital found something she had “never seen before”: extensive clotting in the veins and other small blood vessels of patients’ hearts, kidneys, liver, and lungs. She suspects that the platelets produced by infected megakaryocytes travel through the bloodstream to multiple organs, damaging their vasculature and producing potentially fatal clots. “You see that and you say, wow, this is not just a ‘respiratory’ virus,'” Rapkiewicz said.
Pancreas: In April, scientists in China reported that there was higher expression of the gene for ACE2 in the pancreas than in the lungs. Genetic data are an indirect measure of ACE2 receptors themselves, but could have been a tip-off to physicians to monitor patients for symptoms there. As it happens, the Chinese researchers also found blood markers for pancreas damage in Covid-19 patients, including in about 17% of those with severe disease.
Heart: Patients with severe Covid-19 have a high incidence of cardiac arrests and arrhythmias, scientists at the Perelman School of Medicine at the University of Pennsylvania recently found. That’s likely due to an extreme inflammatory response, but there might be more direct effects of the coronavirus, too. A large team of European researchers reported in April that arrhythmia (including atrial fibrillation), heart injury, and even heart failure and pulmonary embolism might reflect the fact that ACE2 receptors are highly expressed in cells along the inside walls of capillaries. When these “vascular endothelial” cells become infected, the resulting damage can cause clots, MGH’s Walensky said, which in turn can cause Covid toe, strokes, and ischemic bowel (too little blood flow to the gut). Studies from around the world suggest that 7% to 31% of Covid-19 patients experience some sort of cardiac injury.
Gallbladder: Specialized cells in this organ, too, have high levels of ACE2 receptors. Damage to the gallbladder (like the pancreas) can cause digestive symptoms.
With the number of Covid-19 patients closing in on 10 million, physicians fervently hope the virus has no more surprises in store. But they’re not counting on it.
“I’ve seen patients every day during this crisis,” said Northwell’s McGinn. “There have been times when I’ve said, wait, the virus can’t do anything new — and then there’s a young woman with a stroke or an older man with myocarditis,” inflammation of the heart muscle. “I keep thinking I’m going to run out of material” for the teaching videos he does on Covid-19, “but it hasn’t happened.”
The battle against COVID-19 has called to action an army of paramedics, healthcare workers, medical researchers, drug makers and many more to the front line of a global pandemic. A team of researchers from MIT have also taken up arms and decided to join the fight against SARS-CoV-2. The MIT...
Unseen Origin? SARS-CoV-2 Abandoned Search for Patient Zero and Crisis of Institutional Silence
On https://www.monkeyandelf.com/unseen-origin-sars-cov-2-abandoned-search-for-patient-zero-and-crisis-of-institutional-silence/
Unseen Origin? SARS-CoV-2 Abandoned Search for Patient Zero and Crisis of Institutional Silence
In the long, relentless story of human plague, every great contagion begins with a singularity. The identification of the first infected individual—the one known simply as patient zero—is more than a formal step in a procedural checklist; it is the cornerstone of epidemiology itself. From the methodical reasoning of Hippocrates to the molecular tracing of Louis Pasteur, the science of infectious disease rests upon the premise of discovering a causal beginning. Without this initial point of contact, the chain of transmission remains broken, the cause floats in uncertainty, and any containment strategy is built upon the shifting sands of assumption.
Yet, in the case of the SARS-CoV-2 virus, which triggered the most extensive global crisis of the 21st century, the search for that indispensable beginning was not merely difficult—it was seemingly abandoned. The absence of the inaugural case is not a scientific failure but an institutional paradox, a vacuum that speaks volumes about the priorities of global power. A truly independent and transparent international investigation was never permitted to take root. No external, unaffiliated laboratory gained unfettered access to the original clinical samples, the primary data logs, or the raw documentation required for definitive answers. The world was mobilized into historic action, enforcing unprecedented societal controls, without ever knowing the precise nature or origin of the pathogen it was facing. The very institutions tasked with ensuring international transparency chose, instead, the impenetrable veil of institutional silence.
Wuhan’s Paradox Laboratory. Proximity and the Shadow of Gain-of-Function
The city of Wuhan, the sprawling capital of Hubei province, stands as the indisputable ground zero for the first cluster of unusual pneumonia cases detected in late 2019. This same city is home to the Wuhan Institute of Virology (WIV), a facility renowned globally for its advanced, years-long research into the intricate dynamics of coronaviruses sourced from bats. For a decade, scientists at the institute conducted intense, high-risk experiments, studying the mechanisms of cross-contamination between animal reservoirs and human populations.
This research necessarily involved the application of controversial and ethically strained techniques: specifically, gain-of-function studies. This practice involves deliberate genetic manipulation to increase the infectivity or pathogenicity of a virus, often to predict and prepare for future natural outbreaks. While accepted under the strictest of safety protocols, the technique has been the subject of decades of profound bioethical controversy, carrying the intrinsic risk of creating artificial, highly virulent strains with unpredictable behavior.
The prophetic warning arrived years before the crisis. In 2015, a study published in Nature Medicine, co-signed by Chinese and American researchers, described the successful construction of a chimeric bat virus capable of efficiently infecting human respiratory cells via the crucial ACE2 receptor. This finding, which demonstrated the stunning technical feasibility of creating such a menace, prompted immediate calls from other scientific bodies for a reconsideration of the risks involved. When, four years later, the SARS-CoV-2 origin mystery unfolded with terrifying speed, the circumstantial associations were, for many, too compelling to ignore.
The Viral Signature and the Lack of an Intermediate Host
The original strain of SARS-CoV-2 exhibited a chilling, impressive adaptation to the human ACE2 receptor—the molecular gateway that facilitates infection of the respiratory tract. This adaptation suggested either a long, hidden evolutionary path through an unknown chain of hosts or, critically, a highly optimized genetic blueprint.
The search for an intermediate host, which proved decisive in the containment of previous outbreaks like SARS-CoV-1 in 2002 or MERS, failed completely. No animal link was definitively and credibly identified that bridged the gap between bats and humans. Simultaneously, several key biological samples, internal databases, and primary clinical information were suddenly withdrawn or rendered inaccessible to foreign researchers. Instead of welcoming a full, transparent international inquiry, a definitive veil of official suppression was imposed, turning the scientific question into a geopolitical security issue.
Institutional Veil – The Architecture of Managed Ignorance
The state of medical inquiry—which requires causation as its fundamental premise—was thus paralyzed. In January 2021, nearly two years into the pandemic, the World Health Organization (WHO) finally sent a mission to the Wuhan laboratory. The team operated under the heavy, strict supervision of the Chinese authorities, a fact which immediately compromised the investigation’s independence. The resulting report casually dismissed the possibility of a laboratory leak as “highly unlikely,” yet provided no transparent, verifiable evidence to support this conclusion.
The inherent weakness of this position was acknowledged even by the institution’s own leadership. The WHO director-general, Tedros Adhanom Ghebreyesus, was shortly forced to walk back the report’s finality, declaring that “all cases remain on the table,” a tacit admission that the investigation was incomplete and politically compromised. This institutional stance only reinforced a climate of mistrust.
Tedros himself, a former Ethiopian minister and biologist, had faced prior accusations—publicized in major media outlets—of obscuring large-scale cholera outbreaks in his own country by rebranding them as less severe “acute watery diarrhea,” allegedly to protect his government’s international image. In this light, the WHO’s posture regarding the WIV—an organization ostensibly embodying the independence of science aligning itself with the political expediencies of an authoritarian state—was seen by critics not as a necessary compromise, but as a definitive crisis of legitimacy.
The Great Inversion Epidemiology as Control Mechanism
The failure to establish the SARS-CoV-2 origin marked a profound inversion in the function of modern medicine. For the first time in the post-20th-century era, epidemiology stopped looking for the cause and aggressively limited itself to managing the consequences. The tracing of the first case—which was decisive for controlling the spread of Ebola or the original SARS—was abandoned.
Instead of foundational knowledge, an urgent, often poorly documented need for action took precedence. Governments implemented restrictive measures based on statistical modeling and projections of fear, not on real source data. The medical community operated in a landscape of guesswork, lacking a full understanding of the pathogen’s initial mechanism. This absence of principle was replaced by the imperative of state paternalism. The clinical paradox emerged: doctors were forced to prescribe, and public health policies were enacted, with surprisingly weak documentation regarding the virus’s genesis. Ignorance was not only tolerated but effectively legitimized, so long as it ensured public compliance.
Cultural Paradox – Weaponization of Fear and Obedience
The pandemic became more than a biological test; it was a crisis of knowledge, revealing a profound new cultural phenomenon: the transformation of fear into a criterion of truth. In the face of radical uncertainty, governments and societies adopted a logic of “necessary discipline.” Questions about the virus’s origins were quickly labeled as suspicious, criticisms of the WHO were dismissed as “conspiracy theories,” and any search for accountability was interpreted as a direct threat to collective security.
The phrase “follow the science” was swiftly converted into a political slogan—a catchphrase used not to strengthen rigorous research, but to unilaterally close the debate. Disagreement was reframed as moral deviance. As the economist Thomas Sowell observed in another context, in such environments, actions are often judged not by their verifiable results, but by the projected intentions behind them. Thus, the deliberate institutional silence about the virus’s birth ceased to be a problem to be solved and became, disturbingly, an ethical stance—an alleged act of scientific responsibility. The simple act of “not asking” became synonymous with “contributing to the collective good.”
Flight from Authenticity and the Dogma of Authority
This new ethics of managed ignorance was executed on three interconnected levels. At the governmental level, political leaders avoided any investigation that might embarrass global allies or powerful institutions. Within the scientific field, individual researchers often practiced self-censorship under the tangible threat of institutional sanctions or the complete loss of crucial funding. And perhaps most importantly, at the social level, a population overwhelmed by anxiety overwhelmingly preferred the comfortable certainty of official narratives over the demanding, complex truth of uncertainty.
The philosopher Martin Heidegger described this as the flight from authenticity—the refusal to confront the difficult truth when faced with the anxiety of personal and institutional responsibility. Fear was quickly adopted as a refuge, and compliance became the new, simplified form of security.
In this climate, the very nature of science was inverted. It became a mechanism of obedience, not of independent knowledge. An authority that vehemently refuses to be questioned and controlled ceases to be an authority; it solidifies into a dogma. The economist Jesús Huerta de Soto correctly warned that a state monopoly on knowledge is not merely dangerous—it is fundamentally unscientific. When the search for truth is driven by political mandates, it loses its defining characteristic as a free inquiry and morphs into a tool of state control, transforming health policy into a vehicle for authoritarianism cloaked in the guise of compassion.
The silence surrounding the patient zero of SARS-CoV-2, therefore, acquires a deeper, darker significance. It is not a technical oversight; it is the definitive symptom of an era where power actively favors control over transparency. The orphan virus was born, spread, and resulted in millions of deaths, yet its origins were never fully investigated because the answer was politically dangerous. The refusal to answer that fundamental question marks our entry into a new post-scientific era—one where logic is secondary to power, and the right to ask is the most radical act remaining.
Antibody that may protect against Covid-19 identified - Times of India
Antibody that may protect against Covid-19 identified – Times of India
[ad_1]
BOSTON: Scientists have identified a human antibody that they say may potentially prevent or limit SARS-CoV-2 infection that causes Covid-19 disease.
The researchers from the University of Massachusetts Medical School (UMMS) in the US discovered and characterised a cross-reactive human monoclonal antibody (MAB) to SARS-CoV-2 spike proteins which blocks ACE2 receptorbinding on the mucosal…
Frequent complications of COVID-19 include purple rashes, swollen legs, clogged catheters and sudden death. Anyone with a severe illness is at risk of developing clots, but hospitalized patients with COVID-19 appear to be more susceptible. Blood clots in the deep veins of the body can occur due to injury/damage, inactivity,…
