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Biology Covid-19 human body

Is ‘happy hypoxia’ in COVID-19 a disorder of autonomic interoception? 


One of the aspects of coronavirus disease 2019 (COVID-19) puzzling clinicians coping with management of the pneumonia that one of the disease’s complications is the presentation of patients with extremely low blood oxygenation, but no sensation of dyspnea [1]. This phenomenon has given rise to the term “happy hypoxemia” [1]. In the Wuhan cohort of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), only 19% complained of shortness of breath; 62% of those with severe disease and 46% of those who ended up intubated, ventilated or dead did not present with dyspnea [2]. What strikes us as odd, is that these patients are tachycardic with tachypnea and respiratory alkalosis. These signs suggest that at least some sensory information must reach the brainstem to elicit a partial compensatory reflex respiratory response that is sufficent to lower the CO2 level, which diffuses more rapidly across the alveoli than oxygen. However, these patients have no conscious awareness of hypoxia.

The homeostatic afferent information emanating from the body forms part of our interoceptive system, which senses the body’s physiological condition, creates awareness, and leads to conscious feelings or symptoms [3]. This process occurs via projections from the brainstem to the cortex that allow the brain to process homeostatic afferent signals. When the brain receives the signal of internal hypoxia, it gives rise to the sensation of “air hunger” and a need to breathe, which is curiously absent in severe COVID-19 patients.

The respiratory responses to hypoxia occur due to the presence of sensory nerves in chemoreceptive areas. These recognize the shift in the internal environment, relay the information to the brainstem, and stimulate an increase in the ventilatory drive. Respiratory pathology elicits autonomic reflexes, such as bronchospasm, secretions, or cough. Dyspnea is the conscious distressing symptom of difficulty in breathing that can be triggered by many clinical conditions [4]. In the setting of cardiopulmonary illness, dyspnea arises from inputs from multiple homeostatic afferents. Interoceptive processing of these signals create a sense of shortness of breath and the urge to breathe. This primitive brainstem reflex is essential for survival as it can respond to a wide range of stimuli, including hypoxia, hypercapnia, irritants, acidosis, airway collapse, and pulmonary vascular congestion.

The glossopharyngeal afferents innervating the carotid body, and the vagal afferents innervating the respiratory tract, play a vital role in monitoring organ function and controlling body homeostasis through activation of the autonomic nervous system. These neurons are the primary sensory inputs of a series of reflex circuits that control key visceral functions, including blood pressure, swallowing, gastrointestinal motility, airway caliber, and tidal volume [4]. They also produce the first afferents for the conscious sensation of dyspnea.

Mechanical or chemical stimuli of pulmonary receptors expressed on afferent vagal nerve terminals in the lung arrive in the brainstem through small-diameter myelinated (Aδ)- or unmyelinated (C)-fiber nerve axons with cell bodies in the jugular or nodose ganglia of the vagus (Fig. 1). Both jugular and nodose pulmonary C-fiber afferents respond to inflammatory mediators and tissue acidification in a graded fashion; these can be considered “nociceptive” fibers as they do not react to eupneic breathing or other regular events, but are excited by “noxious” or “potentially noxious” stimuli. The jugular and nodose nerve fibers of the lung have distinct differences in terms of their embryologic origin, pharmacological responses, and neurochemistry. Thus, they serve different functions–which are hard to tease apart in the intact human. The nodose C-fibers probably play a more prominent role in the genesis of dyspnea and the subjective sensation of breathing difficulty. In contrast, jugular fibers may play a more prominent role in coughing [4]. The vagal C-fiber afferents innervate the larynx response within seconds to laryngeal discomfort and appear to be important in stimulating cough. Meanwhile, the dyspneic sensation is specifically related to the activation of a subgroup of nodose vagal afferent that express adenosine receptors. The afferent information arriving from the vagal and glossopharyngeal nerves converges at the nucleus of the tractus solitarius in the medulla, a key relay site for a variety of other critical homeostatic signals. From here, there are connections to the higher centers of the brain towards the thalamus, somatosensory cortex, insular cortex, and amygdala, all involved in the perception of breathing.

figure 1
Neurophysiology of dyspnea.

Neurophysiology of dyspnea. Main afferent (sensory) homeostatic information arising from areas of the vasculature and lungs give rise to the sensation of dyspnea. When stimulated, the chemoreceptive and mechanoreceptive signals are transmitted to the brainstem via the glossopharyngeal and vagus nerves, converging at the nucleus of the tractus solitarus (NTS). Subsequent projections continue to the somatosensory cortex and other higher brain regions, which provide the interoceptive sense of the internal environment of the body. The processing of these signals within the cortex gives rise to sensations such as air hunger, dyspnea, or shortness of breath. This interceptive processing appears to be abnormally blunted in patients with coronavirus disease 2019

The pathophysiology underlying the dissociation between profound hypoxemia and overt dyspnea in COVID-19 pneumonia is, at this point, unclear. In our experience, this disassociation exists in patients with severe lesions in the glossopharyngeal or vagus nerves due to damage to the cranial nerve after neck cancer or congenital neuropathies, but these findings are unexpectedly absent in the autopsy reports that are now emerging in COVID-19 cases.

The possibility that the novel SARS-COV-2 is neuro-invasive remains controversial. On one hand, in severe COVID-19 cases, neurological symptoms, such as anosmia, headache, altered mental status, seizures, and delirium, are common; and SARS-COV-2 is found in the cerebral spinal fluid and thought to enter the brain through synapse-connected routes [1]. The possible damage to the afferent hypoxia-sensing neurons in persons with COVID-19 could be due to the intense cytokine storm or the direct effect of SARS-COV2 on mitochondria or on the nerve fibers [1]. On the other hand, the findings from brain magnetic resonance imaging (MRI) studies and pathology reports in lethal COVID-19 cases are inconsistent and do not provide a pathophysiological correlate to explain the absence of dyspnea [5]. The common brain pathology findings in fatal COVID-19 cases are multiple areas of ischemic and micro-bleeding hemorrhagic strokes with only small regions of inflammation; however, it is worth noting that at least 40% of cases brain imaging studies were normal and there were no signals of brainstem abnormalities on the MRI scans. The neurological manifestations of other coronaviruses are even less well studied, but neuropathy and myopathy are reported in a handful of cases of both severe acute respiratory syndrome (SARS-CoV) and middle eastern respiratory syndrome (MERS-CoV). What makes COVID-19 most intriguing at this point is what the patient does not sense and what the brain does not show in terms of pathology.

Regardless of the uncertain underlying pathology, reduced perception of dyspnea is a disorder of blood-gas interoception. It may mask the severity of the medical status and ultimately delay patients from seeking urgent medical care. Patients admitted with COVID-19 can suffer sudden death after voluntary “breaks” from the oxygen supplementation. Recognizing “happy hypoxia” as a feature of COVID-19 pneumonia has led to better patient care, with physicians relying on other markers of disease, such as tachycardia, fever, or serum inflammatory acute reactants, to guide treatment or discharge patients from the hospital. Continuing research on how the novel coronavirus impacts peripheral sensors and neural pathways holds the promise of further clarifying its mechanisms.

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Covid-19 environment

India braces for powerful cyclone amid deadly virus surge!!

A powerful cyclone roaring in the Arabian Sea was moving toward India’s western coast on Monday as authorities tried to evacuate hundreds of thousands of people and suspended COVID-19 vaccinations in one state.

Cyclone Tauktae, which has already killed six people in parts of southern India, is expected to make landfall on Monday evening in Gujarat state with winds of up to 175 kph (109 mph), a statement by the India Meteorological Department said.

After the cyclone slams ashore, forecasters warn of the potential for extensive damage from high windsheavy rainfall and flooding in low-lying areas.

The massive storm comes as India is battling with a devastating coronavirus surge—and both the storm and the virus could exacerbate the effects of the other. The storm has already led to the suspension of some vaccination efforts and there is greater risk of virus transmission in crowded evacuation shelters

Virus lockdown measures, meanwhile, could slow relief work after the storm, and damage from the storm could potentially destroy roads and cut vital supply lines for things like vaccines and medical supplies needed for virus patients.

In Gujarat, vaccinations were suspended for two days and authorities worked to evacuate hundreds of thousands of people to temporary relief shelters. The state’s Chief Minister Vijay Rupani Monday asked officials to ensure that the oxygen supplies to hospitals are not disrupted.

In Maharashtra, operations at Mumbai city’s Chhatrapati Shivaji Maharaj International Airport were suspended for three hours.

Already, thousands of rescue and relief teams from the army, navy and coast guard, along with ships and aircraft, have been deployed for recovery operations.

India’s western coast no stranger to devastating cyclones, but changing climate patterns have caused them to become more intense, rather than more frequent.

In May 2020, nearly 100 people died after Cyclone Amphan, the most powerful storm to hit eastern India in more than a decade, ravaged the region and left millions without power.

Hoping that everything ends well this time.😟

Stay home, Stay safe 🙏🏼🙏🏼

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Covid-19 environment

Let’s go BLUE for a COVID-19 recovery!!

“The ocean economy may be a victim of the impacts of the COVID-19 crisis, but it also holds solutions for rebuilding a more resilient, sustainable and equitable post-COVID world.”

– A Sustainable & Equitable Blue Recovery to the COVID-19 Crisis Report

Ocean and coastal habitats provide an essential workplace for the world’s small-scale fishers, and coastal communities rely on the ocean for jobs, food, health, and cultural traditions. In fact, the ocean economy adds approximately US$1.5 trillion in value globally (OECD 2016). But the COVID-19 pandemic disproportionally impacts the ocean economy and these communities, especially those from Small Island Developing States (SIDS).

new special report commissioned by the High-Level Panel for a Sustainable Ocean Economy (the Ocean Panel) recognizes the ocean economy’s vital role and the pandemic’s devastating impacts on ocean workers and the marine sector—and importantly, offers recovery solutions.

“A Sustainable and Equitable Blue Recovery to the COVID-19 Crisis”, as the name implies, recognizes the power of nature to help solve daunting global issues like climate change and pandemics. The report was released ahead of Climate Week NYC and a Rare-facilitated high-level roundtable meeting of coastal countries, where officials issued a joint message acknowledging the importance of the small-scale fishing sector to a blue (or green) recovery: that by implementing coastal and marine nature-based solutions, small-scale fishers can improve food security, nutrition, and the local economies of coastal nations, and enhance coastal resilience from climate change.

As a member of the Ocean Panel’s Advisory Network, Rare supports the five blue stimulus opportunities for government investment in COVID-19 crisis recovery outlined in the report. These proposed solutions deliver short-term relief to the economy and long-term economic, social, and environmental resilience. Moreover, they are considered a win-win for immediate assistance and forward-looking sustainable planning, known as a ‘no regrets’ investment strategy.

Fish Forever, Rare’s coastal fisheries program, prioritizes the report’s solution related to coastal and marine ecosystems: Invest in Coastal and Marine Ecosystem Restoration and Protection. Fish Forever uses behavioral insights to inspire fishing communities — fishers, fish buyers and traders, community members, and their local government — to adopt more responsible behaviors related to coastal fishing and implement nature-based solutions to protect their natural resources.

Investing in a nature-based solution like restoring and protecting coastal and marine ecosystems benefits coastal fishing households and their communities. This solution also has a host of benefits critical for a blue recovery, including the following five:

  1. Improves Food Security – Protecting coastal ecosystems supports ample fish resources and fish breeding habitat, which safeguards fishing communities by strengthening food security during times of crisis. Technology innovations, like Rare’s OurFish App referenced in the report, show how a nature-based approach to resource management benefits the community and improves food security: the app digitally helps to manage and understand fish stock and finance trends and enables fishing communities to monitor the value, type and local amount of fish caught.
  2. Enables Sound Financial and Household Decision-Making – Establishing Savings Clubs led by small-scale fishers empowers its members, often majority women, to manage their long-term household finances. It also raises awareness of the actions needed to enforce fish sanctuaries for coastal habitat protection and community livelihoods’ sustainability. This approach to behavior change “can powerfully affect the long-term strategy behind coastal fisheries conservation and the goal of ending overfishing,” as the report explains.
  3. Enhances Economic, Social, and Environmental Resilience – Investing in coastal and marine ecosystem restoration and protection can also expand job opportunities, such as protected areas enforcement officers, development planners, environmental engineers, and ecological restoration scientists. In addition to job security, nature-based solutions support the healthy natural resources that protect small-scale fishers’ livelihoods.
  4. Manages Natural Resources Sustainably – Ensuring coastal and marine ecosystem integrity further increases economic productivity by improving fisheries and tourism opportunities. Sustainable management also allows for more significant investment opportunities in blue carbon activities focused on climate mitigation and adaptation benefits from mangroves, seagrasses, and tidal salt marshes.
  5. Builds Community Pride – Stakeholder engagement and collaboration with public and private sectors, including small-scale fishers and their families, are critical for building pride in and ownership of more sustainable behaviors and community-based programs. Co-owning and managing natural resources and ensuring the inclusion of women and Indigenous communities has also demonstrated long-lasting benefits and delivers on many of the UN’s sustainable development goals.

Farmers and fishers rely on healthy ecosystems and strong local governance and management to thrive. Building back better from the impacts of COVID-19 will require a global blue recovery effort that not only prioritizes nature-based solutions but empowers coastal communities and their leaders to champion blue solutions.

BLUE solutions for COVID-19 recovery

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Biology Covid-19 human body

Covid 19’s lingering problem : Heart damage

Massachusetts General Hospital pathologist James Stone can tell that most of the hearts he’s examined from COVID-19 patients are damaged from the first moment he holds them. They’re enlarged. They’re heavy. They’re uneven.

What he can’t tell—at least until he starts looking at samples of the tissue under a microscope—is exactly how those hearts were damaged, and whether it is a direct result of SARS-CoV-2 infection.

Early in the pandemic, other clinicians noted that even some patients who didn’t have preexisting heart conditions experienced cardiovascular damage while fighting COVID-19 infections, pointing to a possible causative link. Researchers had found, for example, that 8–12 percent of hospitalized COVID-19 patients had elevated levels of muscle contraction–regulating proteins called troponins—a sign of heart damage—and that these patients had an increased risk of mortality compared with those who didn’t have excess troponins. And early observations of patients in China who suffered reduced ejection fraction—the amount of blood getting pumped out of the heart each time it contracts—led researchers to suggest that these individuals were likely experiencing myocarditis, a severe form of inflammation that can weaken the heart and is commonly associated with infections.

But Stone and his collaborators’ analysis of heart tissue from 21 patients who died of COVID-19, published today (September 24) in the European Heart Journal, shows that while 86 percent of the patients did have inflammation in their hearts, only three had myocarditis. Several had other forms of heart injury, such as right ventricular strain injuries.

“The problem we identified in this study is that there’s other types of myocardial injury in these patients that is also causing elevated troponins,” says Stone. His international team sought to determine the mechanisms through which the disease damaged the heart and found that some conditions “really haven’t been talked about at all in the [COVID-19] papers that have previously been published.”

The pathologists observed a median of 20 slides from each heart, which is more than are included in most other studies regarding COVID-19’s cardiac effects. George Abela, a cardiologist at Michigan State University who was not involved in the study, tells The Scientist in an email, “This provides a more in-depth view of the extent of injury.”

The researchers expected to find some macrophages, a type of white blood cell that indicates inflammation, as pathologists had observed macrophages in the hearts of SARS patients during the 2003 outbreak. But Stone says he was surprised to see just how common these were—18 out of 21 COVID-19 patients’ hearts harbored macrophages that exhibited this type of inflammation. “It was really quite extensive,” he says.

As they analyzed the hearts further, the pathologists noted that only three patients had myocarditis, while four showed signs of heart injury due to right ventricular strain and another four had small blood clots in the vessels in the heart. It’s not clear why patients experience such inconsistent cardiac issues.

Abela says these findings have implications for treatment. For example, if the patient has right heart failure, a condition where the right side of a patient’s heart is not pumping enough blood to the lungs, a device that mechanically helps the heart pump blood might help, rather than drugs that target the inflammation or infection, which could be used to treat myocarditis.

Because so many of the hearts were infiltrated by macrophages, the researchers say that it may be difficult to discern who is experiencing myocarditis, which is characterized by different inflammatory cells—lymphocytes—while patients are alive. The two cell types would appear similar on tests that image the hearts of living patients. So, the team looked back at the patients’ medical records to see if they could find patterns in clinical tests that would reveal the type of heart damage when it still might be treatable. The three patients with myocarditis all had both troponin levels above 60 ng/mL and abnormal ECG readings while in the hospital. Only 15 percent of the patients without myocarditis had this combination.

The findings need to be replicated in larger groups of patients but could help doctors determine the best course of treatment for heart damage due to COVID-19, Stone says. The study is “giving the cardiologists and the ICU doctors that are taking care of these patients a roadmap of the changes that are going on in the heart.”

“Novel disease entities like SARS-CoV-2 reinforce the tremendous importance of continuing our efforts at continuing to facilitate autopsy evaluations,” says Allan Jaffe, a cardiologist at the Mayo Clinic, in an email. “This consortium of hospitals have added substantially to our knowledge of Covid disease.”

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Biology Covid-19

What Does Asymptomatic COVID-19 Look Like Under the Surface?

— Many individuals show subclinical abnormalities as well as differences from symptomatic patients

Asymptomatic individuals carrying SARS-CoV-2 shed the virus longer than those with COVID-19 symptoms, with other lab findings suggesting the symptomatic patients mounted more robust immune responses, a small study in China found.

Median duration of viral shedding among 37 asymptomatic patients was 19 days (interquartile range 15-26; range 6-45) versus 14 days among 37 matched symptomatic patients (IQR 9-22; log-rank P=0.028), reported Jing-Fu Qiu, PhD, of Chongqing Medical University, and colleagues, though viral shedding does not necessarily mean the patients were infectious.

Virus-specific IgG antibody titers and cytokine levels were also significantly lower among asymptomatic patients in the acute phase of infection, when viral RNA can be found in respiratory specimens, the authors wrote in Nature Medicine — both of which indicated that immune responses weren’t as strong in the asymptomatic group.

Asymptomatic transmission of COVID-19 is one of its biggest mysteries, with the World Health Organization recently reminding the public of the distinction between asymptomatic patients, who never develop symptoms, and presymptomatic patients, who go on to develop symptoms later in the course of disease.

Qiu and colleagues characterized asymptomatic carriers as the “silent spreaders” of COVID-19.

“However, our understanding of the clinical features and immune responses of asymptomatic individuals with SARS-CoV-2 infection is limited,” the researchers added.

For the study, they examined data from 178 patients with PCR-confirmed SARS-CoV-2 infection in the Wanzhou District in China, including 37 without symptoms. Median age in the latter was 41, and 22 were women. These individuals were matched by age, sex, and comorbidity with 37 symptomatic patients for antibody detection and cytokine measurement. Qiu and colleagues also included a group of 37 individuals who tested negative via RT-PCR for cytokine comparisons.

Lab values and imaging were not entirely normal for the asymptomatic group. Eleven had increased C-reactive protein levels and six had elevated levels of alanine aminotransferase. Chest CT found “focal ground-glass opacities” in 11 and “stripe shadows and/or diffuse consolidation” in another 10 of the group; in two-thirds of these 21 patients, the abnormalities were in only one lung. The remaining 16 showed entirely normal imaging.

Around 80% of both symptomatic and asymptomatic patients tested positive for IgG antibodies about 3-4 weeks after exposure. The difference was greater when examining IgM antibodies, with positive findings in 78.4% of symptomatic patients and 62.2% of asymptomatic patients.

In the early convalescent phase, defined as 8 weeks after hospital discharge, symptomatic patients had higher IgG levels, though both groups experienced over 90% decreases in IgG levels. A larger proportion of asymptomatic patients had decreases in neutralizing serum antibody levels versus symptomatic patients (81.1% vs 62.2%, respectively).

These findings should serve as a caution against assuming prior infection confers immunity to future infection, Qiu and colleagues said.

“These data might indicate the risks of using COVID-19 ‘immunity passports’ and support the prolongation of public health interventions, including social distancing, hygiene, isolation of high-risk groups, and widespread testing,” the team wrote.

Plasma levels of cytokines were also similar between asymptomatic patients and healthy controls, though significantly higher levels of stem cell factor and leukemia inhibitory factor were found in the asymptomatic group, the researchers noted, calling this a “reduced inflammatory response characterized by low circulating concentrations of cytokines and chemokines.”

Qiu and co-authors cited the varying sensitivity and specificity of antibody tests (obtained from a company called Bioscience) as a limitation to their study, adding that the results may be confounded by existing antibodies to other coronaviruses, such as SARS or MERS, as well as common cold viruses.

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Biology Covid-19

Covid -19 : An Enigma for researchers

Coronaviruses were first identified as human respiratory pathogens, in the year 1965, and were known to demonstrate very high rate of mutation. Coronaviruses are enveloped (+) RNAs, that replicate in the cytoplasm. To deliver their nucleocaspid into the host cell, they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates this entry of the virus and acts as the primary determinant of cell tropism and pathogenesis. Glycoprotein (S) is classified as a class I fusion protein and is reponsible for binding to the receptor on the host cell, whilst mediating the fusion of the host and viral membranes. This is a process driven by major conformational changes of the S protein. On more technical terms, Corona viruses are the containers of the largest ssRNA genome of 33kb. Structurally, coronaviruses are enveloped viruses with round or pleomorphic virions which are 80 to 120 nm in diameter

This 1st generation of coronaviruses could not survive for long, owing to the host resistance. However, in 2002, new strains of these coronaviruses emerged. These strains of Coronaviruses had very similar genome sequences, and had been isolated from animals sold at markets, in China, where the first SARS cases had appeared. Antibodies to these viruses were found in people in China and some bat species. This small outbreak of corona can be consideed as one due to the 2nd generation of Corona viruses.

Finally, the Coronavirus outbreak of 2020-this outbreak had presented itself in the form of pneumonia of an unknown etiology, in Wuhan, China. This is named as SARS-CoV-2. It can be implied that recombination could have occurred, either by viral-viral or viral-host genes committing acts of “molecular piracy” to invade vertebrates and render them immunocompromised. This pandemic begets an extensive line of research by the world’s brightest to solve this enigma, consequently putting an end to it.

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Covid-19 environment

Covid-19 and our Environment

After the lockdown due to Covid-19 in many countries, there was lesser travelling done by people, whether by cars, trains or flights. Even many industries were non-functional. This led to the significant decrease in air pollution, as there was a marked reduction in nitrous oxide emission.

Lockdown has decreased the fishing activity, hence the fish biomass will increase. Even the sea turtles have been spotted returning to areas they once avoided to lay their eggs, all due to the lack of human interference.

Plants are growing better because there is cleaner air and water, yet again there is no human interference.

Less litter means lesser clogging of river systems, which is good in the long run for the environment.

In conclusion, though there has been a positive impact on the environment due to the lockdown, there is a fear that once people start travelling, all these positive impacts will soon disappear.