Study examines the effects of COVID-19 on human kidney cells

Date: June 10, 2021Source:American Society of Nephrology

Summary:

The virus that causes COVID-19 can infect and replicate in human kidney cells, but this does not typically lead to cell death. Kidney cells that already have features of injury may be more easily infected and develop additional injury.

Researchers have studied human kidney cells in the lab to examine the effects of COVID-19 on kidney health. The findings appear in an upcoming issue of JASN.

Many individuals who develop COVID-19 also experience kidney damage, but it’s unclear if this is a direct result of viral infection or a consequence of another condition or the body’s response to the infection. To investigate, a team led by Benjamin Dekel, MD, PhD (Sheba Medical Center, in Israel) cultivated human kidney cells in lab dishes and infected them with the virus that causes COVID-19.

The researchers found that although the virus that causes COVID-19 could enter, infect, and replicate in human adult kidney cells, this did not typically lead to cell death. Prior to infection, the cells contained high levels of interferon signaling molecules, and the infection stimulated an inflammatory response that increased these molecules. In contrast, infection of kidney cells deficient in such molecules resulted in cell death, suggesting a protective effect.

The cells in these experiments were grown as a three-dimensional spheroid that imitates the healthy kidney or as a two-dimensional layer that mimics the cells of an acutely injured kidney. Cells that mimicked an acutely injured kidney were more prone to infection and additional injury but not cell death.

“The data indicate that it is unlikely that the virus is a primary cause of acute kidney injury seen in COVID-19 patients. It implies that if such injury takes place in the kidney by any cause, the virus might jump on the wagon to intensify it. Therefore, if we’re able to limit the common scenario of acute kidney injury in the first place, then there might be the possibility to minimize potential damage caused by the virus,” Dr. Dekel explained.

Study co-authors from the Sheba Medical Center and the Israel Institute for Biological Research include Dorit Omer, PhD, Oren Pleniceanu, MD, PhD, Yehudit Gnatek, MSc, Michael Namestnikov, Osnat Cohen-Zontag, PhD, Sanja Goldberg, PhD, Yehudit Eden Friedman, MD, Nehemya Friedman, PhD, Michal Mandelboim, PhD, Einat B. Vitner, PhD, Hagit Achdout, PhD, Roy Avraham, PhD, Eran Zahavy, PhD, Tomer Israely, PhD, and Haim Mayan, MD.

Disclosures: Dr. Dekel is a co-founder and shareholder at KidneyCure Ltd.make a difference: sponsored opportunity


Story Source:

Materials provided by American Society of NephrologyNote: Content may be edited for style and length.

Another Hidden Covid Risk: Lingering Kidney Problems

September 1, 2021in News

Since the beginning of the pandemic, doctors have found that people who become very ill with Covid-19 often experience kidney problems, not just the lung impairments that are the hallmark of the illness.

Now, a large study suggests that kidney issues can last for months after patients recover from the initial infection, and may lead to a serious lifelong reduction of kidney function in some patients.

The study, published Wednesday in the Journal of the American Society of Nephrology, found that the sicker Covid patients were initially, the more likely they were to experience lingering kidney damage.

But even people with less severe initial infections could be vulnerable.

“You see really, across the board, a higher risk of a bunch of important kidney-associated events,” said Dr. F. Perry Wilson, a nephrologist and associate professor of medicine at Yale, who was not involved in the study. “And what was particularly striking to me was that these persisted.”

Kidneys play a vital role in the body, clearing toxins and excess fluid from the blood, helping maintain a healthy blood pressure, and keeping a balance of electrolytes and other important substances. When the kidneys are not working properly or efficiently, fluids build up, leading to swelling, high blood pressure, weakened bones and other problems.

The heart, lungs, central nervous system and immune system can become impaired. In end-stage kidney disease, dialysis or an organ transplant may become necessary. The condition can be fatal.

The new study, based on records of patients in the Department of Veterans Affairs health system, analyzed data from 89,216 people who tested positive for the coronavirus between March 1, 2020, and March 15, 2021, as well as data from 1,637,467 people who were not Covid patients.

Between one and six months after becoming infected, Covid survivors were about 35 percent more likely than non-Covid patients to have kidney damage or substantial declines in kidney function, said Dr. Ziyad Al-Aly, chief of the research and development service at the V.A. St. Louis Health Care System and senior author of the study.

“People who have survived the first 30 days of Covid are at risk of developing kidney disease,” Dr. Al-Aly, a nephrologist, said.

Because many people with reduced kidney function do not experience pain or other symptoms, “what’s really important is that people realize that the risk is there and that physicians caring for post-Covid patients really pay attention to kidney function and disease,” he said.

The two sets of patients in the study differed, in that members of one group had all been infected with Covid and members of the other group may have had a variety of other health conditions. Experts cautioned that there were limitations to the comparisons.

The researchers tried to minimize the differences with detailed analyses that adjusted for a long list of demographic characteristics, pre-existing health conditions, medication usage and whether people were in nursing homes.

Another limitation is that patients in the V.A. study were largely male and white, with a median age of 68, so it is unclear how generalizable the results are.

One strength of the research, experts said, is that it involves over 1.7 million patients with detailed electronic medical records, making it the largest study so far on Covid-related kidney problems.

While the results most likely would not apply to all Covid patients, they show that for those in the study, “there’s a pretty notable impact on kidney health in survivors of Covid-19 over the long term, particularly those who were very sick during their acute illness,” said Dr. C. John Sperati, a nephrologist and associate professor of medicine at Johns Hopkins, who was not involved in the study.

Other researchers have found similar patterns, “so this is not the only study suggesting that these events are transpiring after Covid-19 infection,” he added.

He and other experts said that if even a small percentage of the millions of Covid survivors in the United States developed lasting kidney problems, the impact on health care would be great.

To assess kidney function, the research team evaluated levels of creatinine, a waste product that kidneys are supposed to clear from the body, as well as a measure of how well the kidneys filter the blood called the estimated glomerular filtration rate.

Healthy adults gradually lose kidney function over time, about 1 percent or less a year, starting in their 30s or 40s, Dr. Wilson said. Serious illnesses and infections can cause more profound or permanent loss of function that may lead to chronic kidney disease or end-stage kidney disease.

The new study found that 4,757 Covid survivors had lost at least 30 percent of kidney function in the year after their infection, Dr. Al-Aly said.

That is equivalent to roughly “30 years of kidney function decline,” Dr. Wilson said.

Covid patients were 25 percent more likely to reach that level of decline than people who had not had the illness, the study found.

Smaller numbers of Covid survivors had steeper declines. But Covid patients were 44 percent more likely than non-Covid patients to lose at least 40 percent of kidney function and 62 percent more likely to lose at least 50 percent.

End-stage kidney disease, which occurs when at least 85 percent of kidney function is lost, was detected in 220 Covid patients, Dr. Al-Aly said. Covid survivors were nearly three times as likely to receive the diagnosis as patients without Covid, the study found.

Dr. Al-Aly and his colleagues also looked at a type of sudden renal failure called acute kidney injury, which other studies have found in up to half of hospitalized Covid patients. The condition can heal without causing long-term loss of kidney function.

But the V.A. study found that months after their infection, 2,812 Covid survivors suffered acute kidney injury, nearly twice the rate in non-Covid patients, Dr. Al-Aly said.

Dr. Wilson said the new data supported results of a study of 1,612 patients that he and colleagues conducted that found that Covid patients with acute kidney injury had significantly worse kidney function in the months after leaving the hospital than people with acute kidney injuries from other medical conditions.

In the new study, researchers did not directly compare Covid survivors with people infected with other viruses, like the flu, making it hard to know “are you really any sicker than if you just had another bad infection,” Dr. Sperati said.

In a previous study by Dr. Al-Aly’s team, however, which looked at many post-Covid health issues, including kidney problems, people hospitalized with Covid-19 were at significantly greater risk of developing long-term health problems in virtually every medical category, including cardiovascular, metabolic and gastrointestinal conditions, than were people hospitalized with the flu.

Every type of kidney impairment measured in the new study was much more common in Covid patients who were sicker initially — those in intensive care or who experienced acute kidney injury in the hospital.

People who were less ill during their Covid hospitalization were less likely to have lingering kidney problems, but still considerably more likely than non-Covid patients.

“People who are at highest risk are the people who really had it bad to start with,” Dr. Al-Aly said. “But really, no one is spared the risk.”

The study also found that even Covid patients who never needed hospitalization had slightly higher risk of kidney trouble than the general V.A. patient population. But the risk seemed so small, Dr. Sperati said, that “I don’t know that I would hang my hat on” those results.

Dr. Wilson noted that some Covid patients who did not need hospitalization were nonetheless quite ill, needing to stay in bed for days. He said it’s possible that those were the ones who developed long-term kidney dysfunction, rather than people at the mildest end of the Covid spectrum.

Doctors are unsure why Covid can cause kidney damage. Kidneys might be especially sensitive to surges of inflammation or immune system activation, or blood-clotting problems often seen in Covid patients may disturb kidney function, experts said.

Dr. Sperati said Covid patients in the hospital seemed to have greater need for dialysis, and more protein and blood in their urine, than patients hospitalized with other severe illnesses.

“Covid is probably a little more of a kidney-toxic virus,” Dr. Wilson said. “I do think that the Covid syndrome has some long-term adverse effects on the kidney.”

The post Another Hidden Covid Risk: Lingering Kidney Problems appeared first on New York Times.

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

Clinical determinants of the severity of COVID-19: A systematic review and meta-analysis

PLOS

Abstract

Objective


We aimed to systematically identify the possible risk factors responsible for severe cases.


Methods

We searched PubMed, Embase, Web of science and Cochrane Library for epidemiological studies of confirmed COVID-19, which include information about clinical characteristics and severity of patients’ disease. We analyzed the potential associations between clinical characteristics and severe cases.


Results

We identified a total of 41 eligible studies including 21060 patients with COVID-19. Severe cases were potentially associated with advanced age (Standard Mean Difference (SMD) = 1.73, 95% CI: 1.34–2.12), male gender (Odds Ratio (OR) = 1.51, 95% CI:1.33–1.71), obesity (OR = 1.89, 95% CI: 1.44–2.46), history of smoking (OR = 1.40, 95% CI:1.06–1.85), hypertension (OR = 2.42, 95% CI: 2.03–2.88), diabetes (OR = 2.40, 95% CI: 1.98–2.91), coronary heart disease (OR: 2.87, 95% CI: 2.22–3.71), chronic kidney disease (CKD) (OR = 2.97, 95% CI: 1.63–5.41), cerebrovascular disease (OR = 2.47, 95% CI: 1.54–3.97), chronic obstructive pulmonary disease (COPD) (OR = 2.88, 95% CI: 1.89–4.38), malignancy (OR = 2.60, 95% CI: 2.00–3.40), and chronic liver disease (OR = 1.51, 95% CI: 1.06–2.17). Acute respiratory distress syndrome (ARDS) (OR = 39.59, 95% CI: 19.99–78.41), shock (OR = 21.50, 95% CI: 10.49–44.06) and acute kidney injury (AKI) (OR = 8.84, 95% CI: 4.34–18.00) were most likely to prevent recovery. In summary, patients with severe conditions had a higher rate of comorbidities and complications than patients with non-severe conditions.

Conclusion

Patients who were male, with advanced age, obesity, a history of smoking, hypertension, diabetes, malignancy, coronary heart disease, hypertension, chronic liver disease, COPD, or CKD are more likely to develop severe COVID-19 symptoms. ARDS, shock and AKI were thought to be the main hinderances to recovery.

For More Information: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250602

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

Authors: Sasha Peiris 1 2Hector Mesa 3Agnes Aysola 4Juan Manivel 5Joao Toledo 1 2Marcio Borges-Sa 6Sylvain Aldighieri 1 2Ludovic Reveiz 2 7

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://pubmed.ncbi.nlm.nih.gov/33909679/

Pathophysiology of COVID-19:

Mechanisms Underlying Disease Severity and Progression

Authors: Mary Kathryn Bohn,1,2, Alexandra Hall,1 Lusia Sepiashvili,1,2, Benjamin Jung,1,2 Shannon, Steele,1 and Khosrow Adeli1,2,3

The global epidemiology of coronavirus disease 2019 (COVID-19) suggests a wide spectrum of clinical severity, ranging from asymptomatic to fatal. Although the clinical and laboratory characteristics of COVID-19 patients have been well characterized, the pathophysiological mechanisms underlying disease severity and progression remain unclear. This review highlights key mechanisms that have been proposed to contribute to COVID-19 progression from viral entry to multisystem organ failure, as well as the central role of the immune response in successful viral clearance or progression to death.

Introduction

Coronavirus disease 2019 (COVID-19) is caused by a novel beta-coronavirus known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). As of June 15, 2020, the number of global confirmed cases has surpassed 8 million, with over 400,000 reported mortalities. The unparalleled pathogenicity and global impact of this pandemic has rapidly engaged the scientific community in urgently needed research. Preliminary reports from the Chinese Center for Disease Control and Prevention have estimated that the large majority of confirmed SARS-CoV-2 cases are mild (81%), with ~14% progressing to severe pneumonia and 5% developing acute respiratory distress syndrome (ARDS), sepsis, and/or multisystem organ failure (MOF) (144). Although more data is urgently needed to elucidate the global epidemiology of COVID-19 (80), a wide spectrum of clinical severity is evident, with most patients able to mount a sufficient and appropriate immune response, ultimately leading to viral clearance and case resolution. However, a significant subset of patients present with severe clinical manifestations, requiring life-supporting treatment (51). The pathophysiological mechanisms behind key events in the progression from mild to severe disease remain unclear, warranting further investigation to inform therapeutic decisions. Here, we review the current literature and summarize key proposed mechanisms of COVID-19 pathophysiological progression (FIGURE 1). Key Pathophysiological Mechanisms: Our Current Understanding Viral Invasion The first step in COVID-19 pathogenesis is viral invasion via its target host cell receptors. SARSCoV-2 viral entry has been described in detail elsewhere (138). In brief, SARS-CoV-2 consists of four main structural glycoproteins: spike (S), membrane (M), envelope (E), and nucleocapsid (N). The M, E, and N proteins are critical for viral particle assembly and release, whereas the S protein is responsible for viral binding and entry into host cells (33, 76, 89, 143, 148). Similar to SARS-CoV, several researchers have identified human angiotensin converting enzyme 2 (ACE2) as an entry receptor for SARS-CoV-2 (75, 99, 148, 156). SARSCoV-2 is mostly transmissible through large respiratory droplets, directly infecting cells of the upper and lower respiratory tract, especially nasal ciliated and alveolar epithelial cells (161). In addition to the lungs, ACE2 is also expressed in various other human tissues, such as the small intestine, kidneys, heart, thyroid, testis, and adipose tissue, indicating the virus may directly infect cells of other organ systems when viremia is present (77). Interestingly, although the S proteins of SARS-CoV-2 and SARSCoV share 72% homology in amino acid sequences, SARS-CoV-2 has been reported to have a higher affinity for the ACE2 receptor (18, 21, 143). Following host cell binding, viral and cell membranes fuse, enabling the virus to enter into the cell (89). For many coronaviruses, including SARS-CoV, host cell binding alone is insufficient to facilitate membrane fusion, requiring S-protein priming or cleavage by host cell proteases or transmembrane serine proteases (9, 10, 90, 94, 108). Indeed, Hoffman and colleagues demonstrated that S-protein priming by transmembrane serine protease 2 (TMPRSS2), which may be substituted by cathepsin B/L, is required to facilitate SARS-CoV-2 entry into host cells (58). In addition, unlike other coronaviruses, SARS-CoV-2 has been reported to possess a furin-like cleavage site in the S-protein domain, located between the S1 and S2 subunits (31, 138). Furin-like proteases are ubiquitously expressed, albeit at low levels, indicating that S-protein priming at this cleavage site may contribute to the widened cell tropism and enhanced transmissibility of SARS-CoV-2 (123). However, whether furin-like protease-mediated cleavage is required for SARS-CoV-2 host entry has yet to be determined. Blocking or inhibiting these processing enzymes may serve as a potential antiviral target (130). Interestingly, SARS-CoV-2 has developed a unique S1/S2 cleavage site in its S protein, characterized by a four-amino acid insertion, which seems to be absent in all other coronaviruses (4). This molecular mimicry has been identified as an efficient evolutionary adaptation that some viruses have acquired for exploiting the host cellular machinery. Once the nucleocapsid is deposited into the cytoplasm of the host cell, the RNA genome is replicated and translated into structural and accessory proteins. Vesicles containing the newly formed viral particles are then transported to and fuse with the plasma membrane, releasing them to infect other host cells in the same fashion (33, 89, 105). Although much progress has been made in our understanding of the mechanisms underlying SARS-CoV-2 invasion, additional research is needed to delineate exactly how cleavage of the S proteins by TMPRSS2 confers viral particle entry as well as how S-protein cleavage by membrane proteases contributes to viral penetration.

For More Information: https://journals.physiology.org/doi/pdf/10.1152/physiol.00019.2020

High sensitivity troponin and COVID-19 outcomes

Authors: Nikolaos Papageorgiou,a,bCatrin Sohrabi,aDavid Prieto Merino,c,dAngelos Tyrlis,aAbed Elfattah Atieh,aBunny Saberwal,aWei-Yao Lim,aAntonio Creta,aMohammed Khanji,aReni Rusinova,aBashistraj Chooneea,aRaj Khiani,d,eNadeev Wijesuriya,e,fAnna Chow,e,fHaroun Butt,e,fStefan Browne,e,fNikhil Joshi,e,fJamie Kay,e,fSyed Ahsan,a and Rui Providenciaa,g

Abstract

Background

Recent reports have demonstrated high troponin levels in patients affected with COVID-19. In the present study, we aimed to determine the association between admission and peak troponin levels and COVID-19 outcomes.

Methods

This was an observational multi-ethnic multi-centre study in a UK cohort of 434 patients admitted and diagnosed COVID-19 positive, across six hospitals in London, UK during the second half of March 2020.

Results

Myocardial injury, defined as positive troponin during admission was observed in 288 (66.4%) patients. Age (OR: 1.68 [1.49–1.88], p < .001), hypertension (OR: 1.81 [1.10–2.99], p = .020) and moderate chronic kidney disease (OR: 9.12 [95% CI: 4.24–19.64], p < .001) independently predicted myocardial injury. After adjustment, patients with positive peak troponin were more likely to need non-invasive and mechanical ventilation (OR: 2.40 [95% CI: 1.27–4.56], p = .007, and OR: 6.81 [95% CI: 3.40–13.62], p < .001, respectively) and urgent renal replacement therapy (OR: 4.14 [95% CI: 1.34–12.78], p = .013). With regards to events, and after adjustment, positive peak troponin levels were independently associated with acute kidney injury (OR: 6.76 [95% CI: 3.40–13.47], p < .001), venous thromboembolism (OR: 11.99 [95% CI: 3.20–44.88], p < .001), development of atrial fibrillation (OR: 10.66 [95% CI: 1.33–85.32], p = .026) and death during admission (OR: 2.40 [95% CI: 1.34–4.29], p = .003). Similar associations were observed for admission troponin. In addition, median length of stay in days was shorter for patients with negative troponin levels: 8 (5–13) negative, 14 (7–23) low-positive levels and 16 (10–23) high-positive (p < .001).

Conclusions

Admission and peak troponin appear to be predictors for cardiovascular and non-cardiovascular events and outcomes in COVID-19 patients, and their utilization may have an impact on patient management.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970632/

Long covid: Damage to multiple organs presents in young, low risk patients

Authors: Gareth Iacobucci BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m4470 (Published 17 November 2020)Cite this as: BMJ 2020;371:m4470

Young, low risk patients with ongoing symptoms of covid-19 had signs of damage to multiple organs four months after initially being infected, a preprint study has suggested.1

Initial data from 201 patients suggest that almost 70% had impairments in one or more organs four months after their initial symptoms of SARS-CoV-2 infection.

The results emerged as the NHS announced plans to establish a network of more than 40 long covid specialist clinics across England this month to help patients with long term symptoms of infection.

The prospective Coverscan study examined the impact of long covid (persistent symptoms three months post infection) across multiple organs in low risk people who are relatively young and had no major underlying health problems. Assessment was done using results from magnetic resonance image scans, blood tests, and online questionnaires.

The research has not yet been peer reviewed and could not establish a causal link between organ impairment and infection. But the authors said the results had “implications not only for [the] burden of long covid but also public health approaches which have assumed low risk in young people with no comorbidities.”

The study enrolled participants at two UK sites in Oxford and London between April and August 2020. Two hundred and one individuals (mean age 44 (standard deviation 11.0) years) completed assessments after SARS-CoV-2 infection a median of 140 days after initial symptoms.

Participants were eligible if they tested positive for SARS-CoV-2 by random polymerase chain reaction swab (n=62), a positive antibody test (n=63), or had typical symptoms and were determined to have covid-19 by two independent clinicians (n=73).

The prevalence of pre-existing conditions was low (obesity: 20%, hypertension: 6%, diabetes: 2%, heart disease: 4%), and less than a fifth (18%) of individuals had been hospitalised with covid-19.

The most commonly reported ongoing symptoms—regardless of hospitalization status—were fatigue (98%), muscle ache (88%), shortness of breath (87%), and headache (83%). There was evidence of mild organ impairment in the heart (32% of patients), lungs (33%), kidneys (12%), liver (10%), pancreas (17%), and spleen (6%).

For More Information: https://www.bmj.com/content/371/bmj.m4470

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

Alert — EU looking into new side effects of Vaccine…

Authors: By citizenfreepress.com

Three new conditions reported by people after vaccination with shots from Pfizer and Moderna are being studied to assess if they may be possible side effects, Europe’s drug regulator said on Wednesday.

Erythema multiforme, a form of allergic skin reaction; glomerulonephritis or kidney inflammation; and nephrotic syndrome, a renal disorder characterised by heavy urinary protein losses, are being studied by the safety committee of the European Medicines Agency (EMA), according to the regulator.

Last month, the EMA found a possible link between heart inflammation and the mRNA vaccines.

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