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En studie som publicerats i the Lancet den här veckan går igenom hur en person återinfekterats och insjuknat mer än en gång i covid-19. Såvida inte testerna däremellan varit falskt negativa. MEN forskarna säger att virusets gener såg så pass olika ut i de två positiva testerna, att det inte kan ha varit samma infektion som fortsatt. De menar att viruset inte kan förändras så mycket i kroppen på en och samma person under denna tid. Utan konstaterar att den här personen infekterats två gånger med CoV-SARS-2. Ett tecken på att immuniteten mot viruset kanske inte alltid är så bra eller särskilt långvarig.

Fallet beskrivs bl.a. såhär:

“The patient had two positive tests for SARS-CoV-2, the first on April 18, 2020, and the second on June 5, 2020, separated by two negative tests done during follow-up in May, 2020“

“Genetic discordance of the two SARS-CoV-2 specimens was greater than could be accounted for by short-term in vivo evolution. These findings suggest that the patient was infected by SARS-CoV-2 on two separate occasions by a genetically distinct virus.“

Ur studien:

The degree of protective immunity conferred by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently unknown. As such, the possibility of reinfection with SARS-CoV-2 is not well understood. We describe an investigation of two instances of SARS-CoV-2 infection in the same individual.

A 25-year-old man who was a resident of Washoe County in the US state of Nevada presented to health authorities on two occasions with symptoms of viral infection, once at a community testing event in April, 2020, and a second time to primary care then hospital at the end of May and beginning of June, 2020. Nasopharyngeal swabs were obtained from the patient at each presentation and twice during follow-up. Nucleic acid amplification testing was done to confirm SARS-CoV-2 infection. We did next-generation sequencing of SARS-CoV-2 extracted from nasopharyngeal swabs. Sequence data were assessed by two different bioinformatic methodologies. A short tandem repeat marker was used for fragment analysis to confirm that samples from both infections came from the same individual.

The patient had two positive tests for SARS-CoV-2, the first on April 18, 2020, and the second on June 5, 2020, separated by two negative tests done during follow-up in May, 2020. Genomic analysis of SARS-CoV-2 showed genetically significant differences between each variant associated with each instance of infection. The second infection was symptomatically more severe than the first.

Genetic discordance of the two SARS-CoV-2 specimens was greater than could be accounted for by short-term in vivo evolution. These findings suggest that the patient was infected by SARS-CoV-2 on two separate occasions by a genetically distinct virus. Thus, previous exposure to SARS-CoV-2 might not guarantee total immunity in all cases. All individuals, whether previously diagnosed with COVID-19 or not, should take identical precautions to avoid infection with SARS-CoV-2. The implications of reinfections could be relevant for vaccine development and application.

Mer via https://4health.se/?s=corona

https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30764-7/fulltext

Världens näst snabbaste dator har tagit fram en modell som kan förklara nästan allt gällande hur det nya coronaviruset, SARS-CoV-2, påverkar våra kroppar när vi insjuknar i Covid-19. Man har låtit datorn analysera över 40 000 gener från 17 000 prover – och 2,5 miljarder genetiska kombinationer. Forskare har sedan analyserat resultaten.

Resultatet: bradykinin-hypotesen. En hypotes som förklarar nästan alla symtom och dessutom ger förslag på behandlingar.

Hypotesen är i linje med tidigare förklaringar om hur viruset infekterar via ACE2-recptorer. Men viruset nöjer sig inte med att infektera celler som har rikligt med ACE2-receptorer, utan lurar kroppen att uppreglera ACE2 även på andra ställen (läs den engelska texten nedan som förklarar detta på ett utmärkt sätt).

RAS, “the renin–angiotensin system”, kontrollerar många aspekter av vår blodcirkulation, inklusive ett ämne som kallas bradykinin som normalt är involverat i att reglera blodtryck. Enligt de här nya uppgifterna, så är det så att när det nya coronaviruset förändrar RAS, så gör det att den normala regleringen av just bradykinin blir helt utslagen. Bradykininreceptorerna påverkas och kroppen slutar bryta ner bradykinin ordentligt. ACE bryter normalt ner bradykinin, men när viruset nedreglerar detta, så slutar den här mekanismen fungera som den ska. Slutresultatet blir att mängden bradykinin i kroppen blir oreglerad och ämnet ansamlas.

Och just denna ansamling av bradykinin kan förklara alla möjliga udda symtom som viruset skapar. Forskarna konkluderar att “the pathology of Covid-19 is likely the result of Bradykinin Storms rather than cytokine storms,”

Bradykinin skapar läckande blodkärl, kan bryta ner blod-hjärn-barriären mm, vilket förklarar många symtom. Läs mer i nedan citat ur texten.

Dessutom ökar viruset kroppens produktion av HLA (hyaluronic acid) i lungorna. Ett ämne som används I tvål och lotion eftersom det kan absorbera extremt mycket vätska. När vätska läcker in i lungorna, pga effekter av bradykinin, så bildas en sorts gel i lungorna. Det är denna som ger andningssvårigheter och som gör att respiratorer inte lyckas hjälpa patienterna.

Man jämför Covid-19 med vissa blodtryckssänkande läkemedel som fungerar just genom att öka bradykininnivåerna. Intressant nog är biverkningarna från dessa läkemedel exakt samma som symtomen i Covid-19…

Igår skrev jag ett populärt inlägg om en framgångsrik studie på D-vitamin i Covid-19-patienter. https://4health.se/studie-d-vitamin-effektiv-behandling-av-covid-19 Även dessa slående resultat kan förklaras med bradykinin-hypotesen. D-vitamin är involverat i RAS-systemet och kan sänka ett ämne som kallas REN. Denna mekanism skulle kunna hindra sådana här bradykinin-stormar.

Som sagt, läs även texten här nedan:

Earlier this summer, the Summit supercomputer at Oak Ridge National Lab in Tennessee set about crunching data on more than 40,000 genes from 17,000 genetic samples in an effort to better understand Covid-19. Summit is the second-fastest computer in the world, but the process — which involved analyzing 2.5 billion genetic combinations — still took more than a week.

When Summit was done, researchers analyzed the results. …
..
The computer had revealed a new theory about how Covid-19 impacts the body: the bradykinin hypothesis. The hypothesis provides a model that explains many aspects of Covid-19, including some of its most bizarre symptoms. It also suggests 10-plus potential treatments, many of which are already FDA approved. …

According to the team’s findings, a Covid-19 infection generally begins when the virus enters the body through ACE2 receptors in the nose, (The receptors, which the virus is known to target, are abundant there.) The virus then proceeds through the body, entering cells in other places where ACE2 is also present: the intestines, kidneys, and heart. This likely accounts for at least some of the disease’s cardiac and GI symptoms.

But once Covid-19 has established itself in the body, things start to get really interesting. …
… Covid-19 isn’t content to simply infect cells that already express lots of ACE2 receptors. Instead, it actively hijacks the body’s own systems, tricking it into upregulating ACE2 receptors in places where they’re usually expressed at low or medium levels, including the lungs.

In this sense, Covid-19 is like a burglar who slips in your unlocked second-floor window and starts to ransack your house. Once inside, though, they don’t just take your stuff — they also throw open all your doors and windows so their accomplices can rush in and help pillage more efficiently.

The renin–angiotensin system (RAS) controls many aspects of the circulatory system, including the body’s levels of a chemical called bradykinin, which normally helps to regulate blood pressure. According to the team’s analysis, when the virus tweaks the RAS, it causes the body’s mechanisms for regulating bradykinin to go haywire. Bradykinin receptors are resensitized, and the body also stops effectively breaking down bradykinin. (ACE normally degrades bradykinin, but when the virus downregulates it, it can’t do this as effectively.)

The end result, the researchers say, is to release a bradykinin storm — a massive, runaway buildup of bradykinin in the body. According to the bradykinin hypothesis, it’s this storm that is ultimately responsible for many of Covid-19’s deadly effects. Jacobson’s team says in their paper that “the pathology of Covid-19 is likely the result of Bradykinin Storms rather than cytokine storms,” which had been previously identified in Covid-19 patients, but that “the two may be intricately linked.” Other papers had previously identified bradykinin storms as a possible cause of Covid-19’s pathologies.

Covid-19 is like a burglar who slips in your unlocked second-floor window and starts to ransack your house.

As bradykinin builds up in the body, it dramatically increases vascular permeability. In short, it makes your blood vessels leaky. This aligns with recent clinical data, which increasingly views Covid-19 primarily as a vascular disease, rather than a respiratory one. But Covid-19 still has a massive effect on the lungs. As blood vessels start to leak due to a bradykinin storm, the researchers say, the lungs can fill with fluid. Immune cells also leak out into the lungs, Jacobson’s team found, causing inflammation.

And Covid-19 has another especially insidious trick. Through another pathway, the team’s data shows, it increases production of hyaluronic acid (HLA) in the lungs. HLA is often used in soaps and lotions for its ability to absorb more than 1,000 times its weight in fluid. When it combines with fluid leaking into the lungs, the results are disastrous: It forms a hydrogel, which can fill the lungs in some patients. According to Jacobson, once this happens, “it’s like trying to breathe through Jell-O.”

This may explain why ventilators have proven less effective in treating advanced Covid-19 than doctors originally expected, based on experiences with other viruses. “It reaches a point where regardless of how much oxygen you pump in, it doesn’t matter, because the alveoli in the lungs are filled with this hydrogel,” Jacobson says. “The lungs become like a water balloon.” Patients can suffocate even while receiving full breathing support.

The bradykinin hypothesis also extends to many of Covid-19’s effects on the heart. About one in five hospitalized Covid-19 patients have damage to their hearts, even if they never had cardiac issues before. Some of this is likely due to the virus infecting the heart directly through its ACE2 receptors. But the RAS also controls aspects of cardiac contractions and blood pressure. According to the researchers, bradykinin storms could create arrhythmias and low blood pressure, which are often seen in Covid-19 patients.

The bradykinin hypothesis also accounts for Covid-19’s neurological effects, which are some of the most surprising and concerning elements of the disease. These symptoms (which include dizziness, seizures, delirium, and stroke) are present in as many as half of hospitalized Covid-19 patients. According to Jacobson and his team, MRI studies in France revealed that many Covid-19 patients have evidence of leaky blood vessels in their brains.

Bradykinin — especially at high doses — can also lead to a breakdown of the blood-brain barrier. Under normal circumstances, this barrier acts as a filter between your brain and the rest of your circulatory system. It lets in the nutrients and small molecules that the brain needs to function, while keeping out toxins and pathogens and keeping the brain’s internal environment tightly regulated.

If bradykinin storms cause the blood-brain barrier to break down, this could allow harmful cells and compounds into the brain, leading to inflammation, potential brain damage, and many of the neurological symptoms Covid-19 patients experience. Jacobson told me, “It is a reasonable hypothesis that many of the neurological symptoms in Covid-19 could be due to an excess of bradykinin. It has been reported that bradykinin would indeed be likely to increase the permeability of the blood-brain barrier. In addition, similar neurological symptoms have been observed in other diseases that result from an excess of bradykinin.”

Increased bradykinin levels could also account for other common Covid-19 symptoms. ACE inhibitors — a class of drugs used to treat high blood pressure — have a similar effect on the RAS system as Covid-19, increasing bradykinin levels. In fact, Jacobson and his team note in their paper that “the virus… acts pharmacologically as an ACE inhibitor” — almost directly mirroring the actions of these drugs.

By acting like a natural ACE inhibitor, Covid-19 may be causing the same effects that hypertensive patients sometimes get when they take blood pressure–lowering drugs. ACE inhibitors are known to cause a dry cough and fatigue, two textbook symptoms of Covid-19. And they can potentially increase blood potassium levels, which has also been observed in Covid-19 patients. The similarities between ACE inhibitor side effects and Covid-19 symptoms strengthen the bradykinin hypothesis, the researchers say.

ACE inhibitors are also known to cause a loss of taste and smell. Jacobson stresses, though, that this symptom is more likely due to the virus “affecting the cells surrounding olfactory nerve cells” than the direct effects of bradykinin.

Though still an emerging theory, the bradykinin hypothesis explains several other of Covid-19’s seemingly bizarre symptoms. Jacobson and his team speculate that leaky vasculature caused by bradykinin storms could be responsible for “Covid toes,” a condition involving swollen, bruised toes that some Covid-19 patients experience. Bradykinin can also mess with the thyroid gland, which could produce the thyroid symptoms recently observed in some patients.

The bradykinin hypothesis could also explain some of the broader demographic patterns of the disease’s spread. The researchers note that some aspects of the RAS system are sex-linked, with proteins for several receptors (such as one called TMSB4X) located on the X chromosome. This means that “women… would have twice the levels of this protein than men,” a result borne out by the researchers’ data. In their paper, Jacobson’s team concludes that this “could explain the lower incidence of Covid-19 induced mortality in women.” A genetic quirk of the RAS could be giving women extra protection against the disease.

The bradykinin hypothesis provides a model that “contributes to a better understanding of Covid-19” and “adds novelty to the existing literature,” according to scientists Frank van de Veerdonk, Jos WM van der Meer, and Roger Little, who peer-reviewed the team’s paper. It predicts nearly all the disease’s symptoms, even ones (like bruises on the toes) that at first appear random, and further suggests new treatments for the disease.

As Jacobson and team point out, several drugs target aspects of the RAS and are already FDA approved to treat other conditions. They could arguably be applied to treating Covid-19 as well. Several, like danazol, stanozolol, and ecallantide, reduce bradykinin production and could potentially stop a deadly bradykinin storm. Others, like icatibant, reduce bradykinin signaling and could blunt its effects once it’s already in the body.

Interestingly, Jacobson’s team also suggests vitamin D as a potentially useful Covid-19 drug. The vitamin is involved in the RAS system and could prove helpful by reducing levels of another compound, known as REN. Again, this could stop potentially deadly bradykinin storms from forming. The researchers note that vitamin D has already been shown to help those with Covid-19. The vitamin is readily available over the counter, and around 20% of the population is deficient. If indeed the vitamin proves effective at reducing the severity of bradykinin storms, it could be an easy, relatively safe way to reduce the severity of the virus.

Other compounds could treat symptoms associated with bradykinin storms. Hymecromone, for example, could reduce hyaluronic acid levels, potentially stopping deadly hydrogels from forming in the lungs. And timbetasin could mimic the mechanism that the researchers believe protects women from more severe Covid-19 infections. All of these potential treatments are speculative, of course, and would need to be studied in a rigorous, controlled environment before their effectiveness could be determined and they could be used more broadly.

Mer via https://4health.se/?s=corona

https://elemental.medium.com/a-supercomputer-analyzed-covid-19-and-an-interesting-new-theory-has-emerged-31cb8eba9d63

Jag har fått frågor om det där med T-cellssvar och coronavirus. Generellt är det ju så att har man haft en viss infektion, tex av det nya coronaviruset CoV-SARS-2, så har man antikroppar mot detta specifika virus. Vårt immunförsvar består bl.a. av vita blodkroppar i form av B- och T-celler. De vita blodkroppar som kallas B-celler, producerar antikroppar som gör att kroppen kan känna igen och bekämpa farliga inkräktare, som bakterier och virus.

Det finns också olika sorters T-celler i vårt immunförsvar. Vissa T-celler är mer generella försvarare, men minnes-T-celler lär sig också, som antikroppar, att känna igen vissa smittämnen för att kunna angripa dem om vi smittas igen. En hyfsat förenklad beskrivning.

Immunförsvarets minnen av gamla förkylningar orsakade av snällare coronavirussläktingar kan vara en förklaring till varför covid-19 slår så olika hos olika personer.

Forskare har nämligen sett tydliga bevis för att personer som inte varit utsatta för covid-19-smitta, ändå kan bära på T-celler som redan är programmerade att svara på det nya viruset.

I en studie tidigare i år upptäckte de här forskarna, från La Jolla Institute of Immunology i USA, att mellan 20 och 50 procent av personer som inte varit utsatta för Sars-cov-2-viruset ändå bär på T-celler som verkar känna igen och svara på det. Det är alltså minnes-T-celler.

Teorin var att de här personerna tidigare varit smittade av covid-19-virusens snällare kusiner, coronavirus som orsakar förkylning, och att de har kvar ett T-cells-försvar mot dem, som också reagerar på covid-19.

Nu har samma forskare gått vidare. För att vara helt säkra på att deras prover verkligen kom från personer som inte varit utsatta för covid-19-smitta använde de prover från mellan 2015 och 2018, då sjukdomen inte fanns. Och i dem hittade de T-celler som reagerade både på virussekvenser hos de snällare förkylningsvirusen och sars-cov-2.

Det kan alltså vara så att en del av befolkningen som tidigare haft den här sortens förkylningar, bär på ett vilande immunförsvar, som ger dem ett försprång – ett skydd som gör att de inte blir lika sjuka, eller kanske rentav inte får några symtom alls. Men innan vi vet säkert behövs det mer studier på både människor och djur. Om det är fullständigt skydd, eller att somliga blir asymptomatiska, det är det vi inte vet i dagsläget.

I juni kom en uppmärksammad svensk studie som visade att siffran på hur många som utvecklat T-celler mot SARS-CoV-2 kan vara betydligt högre än de som utvecklat antikroppar.

Det tolkades då som att smittspridningen, och kanske immuniteten, i samhället var större än vad man kunde se bara genom att testa för antikroppar. Men den här amerikansk studien tyder på att personer som har T-celler som reagerar på covid-19 kan ha utvecklat dem när de exponerats för andra snällare förkylningsvirus.

Den svenska studien har fått uppdateras med informationen att man inte vet om T-cellerna kommer från SARS-CoV-2 eller från andra besläktade virus. Man kan inte veta till hundra procent att det inte är korsreaktiva svar. Det kan vara både och.

Mer via https://4health.se/?s=corona

https://science.sciencemag.org/content/early/2020/08/04/science.abd3871

https://sverigesradio.se/sida/artikel.aspx?programid=406&artikel=7528440

https://sverigesradio.se/artikel/7527650