Anna Sparre @ 4health.se

Det är välkänt att diabetes är en riskfaktor för Covid-19, men det omvända verkar också gälla.

I UK är ungefär 25% av de som behöver sjukhusvård för Covid-19 diabetiker. Men det verkar också vara så att Covid-19 kan skada de insulinproducerande cellerna, så att man kan utveckla diabetes av virusinfektionen.

Många som anländer till sjukhus med svår Covid-19 har skyhöga blodsockernivåer. En antydan om att insulinmekanismen inte fungerar som den ska. För en del av dessa blir tillståndet kroniskt.

Forskning har visat att ACE-2, proteinet/ receptorn som Sars-Cov-2 binder till när det kommer in i den mänskliga cellen, inte bara finns i lungorna. ACE2 finns också i organ och vävnader som är involverade i glukosmetabolismen – såsom bukspottkörteln, tunntarmen, fettvävnaden, levern och njurarna. Experter tror att viruset kan orsaka flera olika och komplexa dysfunktioner av glukosmetabolism genom att komma in i dessa vävnader. Och därmed leda till diabetes.

Men det behövs betydligt mer forskning för att nå ett avgörande svar kring detta. En global databas, CoviDiab Registry-projektet, inrättades i början av juni för att samla information om Covid-19-patienter med höga blodsockernivåer.

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

Not only may diabetes make a coronavirus infection worse, but Covid-19 may also trigger the onset of the chronic condition in some people, emerging evidence suggests. 

It is well known that underlying health issues increase the likelihood of severe illness or death after contracting the coronavirus. 

In the first two months of the UK’s outbreak, roughly 25 per cent of people hospitalised with Covid-19 with already had diabetes, suggesting that the risk of severe illness among diabetics was four times higher than for the general population. 

But Paul Zimmet, a professor of diabetes at Monash University in Melbourne, told Nature that “two pandemics could be clashing”, with Covid-19 also damaging the cells responsible for producing the hormone insulin. 

He said that dozens of patients suffering from severe Covid-19 have arrived at hospital with very high blood sugar levels – a sign that the body is not producing enough of the hormone. 

A handful of these patients have gone on to rapidly develop the chronic condition, where the body produces either no insulin at all, or not enough to work effectively. 

The theory has some precedent as other viruses are known to precipitate autoimmune diseases, including type 1 diabetes. A paper published in Acta Diabetologica journal in 2009 found that damage to the body caused by Sars, a close cousin of the virus that causes Covid-19, triggered the onset of diabetes in some patients.

More recently, an experimental study in miniature lab-grown pancreases published in the Lancet last week concluded that a Covid-19 infection “could induce new onset diabetes” by damaging the cells responsible for control blood sugar levels. 

The findings have not been confirmed in humans and it is unclear whether Covid-19 plays a direct role in the reduced production of insulin.

But on June 12, a group of 17 leading diabetes experts wrote a letter published in the New England Journal of Medicine warning that new-onset diabetes is being observed in some patients who have tested positive for the Covid-19. 

Research has shown that ACE-2, the protein that Sars-Cov-2 binds to as it enters the human cell, is not only located in the lungs. It is also in organs and tissues that are involved in glucose metabolism – such as the pancreas, the small intestine, the fat tissue, the liver and the kidney.

Experts believe that by entering these tissues, the virus may cause multiple and complex dysfunctions of glucose metabolism, triggering diabetes. 

But there are warnings that considerably more research is needed to reach a conclusive answer. Experts hope for clarity in the coming months after a global database, dubbed the CoviDiab Registry project was established in early June to collect information on Covid-19 patients with high blood-sugar levels. 

“As has been stated, we’ve not encountered a virus like Sars-CoV2 before for the breadth of disease it causes,” Prof James Hildreth, president of Meharry Medical College, said. “Now evidence [is] accumulating that Covid-19 virus may cause diabetes. Clearly suggests that people who are pre-diabetic or diabetic should definitely avoid Covid-19 infection.”

https://www.nature.com/articles/d41586-020-01891-8

https://www.sciencedirect.com/science/article/abs/pii/S2213858720301522

https://www.telegraph.co.uk/global-health/science-and-disease/covid-19-may-trigger-diabetes-growing-body-evidence-suggests/

Även om man kan debattera dödstalen och huruvida Covid-19 är en pandemi eller ej, så är det för många en obehaglig sjukdom.

Brittiska The Telegraph meddelar bl.a. hur nästan en tredjedel av Covid-patienter kommer tillbaka till sjukhusvård inom fem månader och att en åttondel dör, enligt ny statistik från ONS (Office for National Statistics).
En tidigare studie visade att hela 87 % av de som vårdats på sjukhus för allvarlig covid-19 har långvariga symtom som kvarstår minst två månader – trots att de testar negativt för coronaviruset. Värk i leder eller bröst, andningssvårigheter och utmattning är de vanligaste symtomen.
Allt ovan gäller ju dem som insjuknar så pass svårt att det krävs sjukhusvård. Många gör ju inte det, ska tilläggas.

De som drabbas illa av det nya coronaviruset utvecklar hjärtproblem, diabetes och problem med levern och njurarna.

Dessutom upptäcker man förvånansvärt många nya diabetiker efter Covid-19. Man vet fortfarande inte om det handlar om typ 1 eller typ 2 i huvudsak “We don’t know if it’s because Covid destroyed the beta cells which make insulin and you get Type 1 diabetes, or whether it causes insulin resistance, and you develop Type 2, but we are seeing these surprising new diagnoses of diabetes” Mer om kopplingen mellan Covid-19 och diabetes imorgon.

Forskare uppmanar nu till brådskande tilltag gällande övervakning och kontroller av personer som skrivits ut från sjukhus efter Covid-19.

Mer via https://4health.se/?s=corona och tidigare angående långtids-covid: https://4health.se/?s=lång+covid

The Telegraph skriver:

Almost a third of recovered Covid patients will end up back in hospital within five months and one in eight will die, alarming new figures have shown.

Research by Leicester University and the Office for National Statistics (ONS) found there is a devastating long-term toll on survivors of severe coronavirus, with many people developing heart problems, diabetes and chronic liver and kidney conditions.

Out of 47,780 people who were discharged from hospital in the first wave, 29.4 per cent were readmitted to hospital within 140 days, and 12.3 per cent of the total died.

The current cut-off point for recording Covid deaths is 28 days after a positive test, so it may mean thousands more people should be included in the coronavirus death statistics.

Researchers have called for urgent monitoring of people who have been discharged from hospital.

Study author Kamlesh Khunti, professor of primary care diabetes and vascular medicine at Leicester University, said: “This is the largest study of people discharged from hospital after being admitted with Covid.

“People seem to be going home, getting long-term effects, coming back in and dying. We see nearly 30 per cent have been readmitted, and that’s a lot of people. The numbers are so large.

“The message here is we really need to prepare for long Covid. It’s a mammoth task to follow up with these patients and the NHS is really pushed at the moment, but some sort of monitoring needs to be arranged.”

The study found that Covid survivors were nearly three and a half times more likely to be readmitted to hospital, and die, in the 140 days timeframe than other hospital outpatients.

Prof Khunti said the team had been surprised to find that many people were going back in with a new diagnosis, and many had developed heart, kidney and liver problems, as well as diabetes.

He said it was important to make sure people were placed on protective therapies, such as statins and aspirin.

“We don’t know if it’s because Covid destroyed the beta cells which make insulin and you get Type 1 diabetes, or whether it causes insulin resistance, and you develop Type 2, but we are seeing these surprising new diagnoses of diabetes,” he added.

“We’ve seen studies where survivors have had MRS scans and they’ve cardiac problems and liver problems.

“These people urgently require follow up and the need to be on things like aspirin and statins.”

The new study was published on a pre-print server and is yet to be peer reviewed. However experts described the paper as “important”.

Commenting on the study on Twitter, Christina Pagel, director of the clinical operational research unit at University College London said: “This is such important work. Covid is about so much more than death. A significant burden of long-term illness after hospitalisation for Covid.”

Last year, researchers at North Bristol NHS Trust found that three quarters of virus patients treated at Bristol’s Southmead Hospital were still experiencing problems three months later.

Symptoms included breathlessness, excessive fatigue and muscle aches, leaving people struggling to wash, dress and return to work.

Some patients say they have been left needing a wheelchair since contracting the virus, while others claim they can no longer walk up the stairs without experiencing chest pain.

In December, the ONS estimated that one in 10 people who catch coronavirus go on to suffer long Covid with symptoms lasting three months or more.

Overall, roughly 186,000 people in private households in England in the week beginning November 22 were living with Covid-19 symptoms that had persisted for between five and 12 weeks, the most up-to-date ONS data shows.

https://news.yahoo.com/almost-third-recovered-covid-patients-180255388.html

https://www.telegraph.co.uk/global-health/science-and-disease/nine-10-people-have-persistent-symptoms-months-recovering-severe/

https://www.telegraph.co.uk/global-health/science-and-disease/covid-19-may-trigger-diabetes-growing-body-evidence-suggests/

Det är vid det här laget väl känt att män generellt drabbas mer och hårdare än kvinnor av det nya coronaviruset. Fler män blir svårt sjuka, fler män vårdas på IVA och fler män dör med covid-19. I Sverige har 800 fler män dött i covid-19 än kvinnor, trots att fler kvinnor testat positivt för sjukdomen. Om man tittar globalt så är risken för att dö med covid-19 ungefär 1,7 gånger högre för män än för kvinnor. I en ny artikel i Science sammanfattar forskare den kunskap och de teorier som finns hittills om vad det här kan bero på – och många teorier handlar om att det är skillnader i kvinnors och mäns immunförsvar som ligger bakom.

Jag har skrivit om det i tidigare inlägg, bl.a. en del här https://4health.se/hur-hart-vi-drabbas-av-corona-beror-pa-genetiska-skillnader-i-olika-varldsdelar-befolkningar och här https://4health.se/?s=män+drabbas . Läs gärna också om skillnaderna mellan kvinnors och mäns immunsystem: https://4health.se/skillnader-mellan-det-manliga-och-det-kvinnliga-immunsystemet-forklarar-skillnader-i-sjukdomar

Det finns flera skillnader mellan mäns och kvinnors immunförsvar. En sak är att de åldras olika. Hos båda könen försvagas immunförsvaret med åldern, framförallt efter 60 år. Men den försvagningen är kraftigare hos män och sker normalt 5-6 år tidigare än hos kvinnor. Det gör att män, särskilt då äldre män, har svårare att kontrollera virusinfektioner.

Men män har också generellt ett sämre immunförsvar än kvinnor och i alla åldersgrupper över 30 år ser man att män drabbas hårdare och är överrepresenterade när det gäller döda med covid-19. Till och med mer än vid många andra infektioner.

Dessutom finns viktiga immunrelaterade gener på X-kromosomen.

I möss har man sett att receptorn som SARS-Cov2-viruset binder till (ACE2) kan regleras av könshormonet östrogen. Det skulle kunna förklara ytterligare en skillnad i hur man reagerar på infektionen.

Forskarna reflekterar också kring andra kända skillnader mellan män och kvinnors immunsystem, såsom “females generally mount a more robust immune response to vaccines, such as influenza vaccines. However, the heightened immune responses in females can also lead to detrimental immunopathology in infections” Jag reflekterar här över kvinnor som utvecklar långtidssymtom efter covid, samt utvecklar autoimmuna sjukdomar efter infektion generellt.

Läs mer om skillnaderna i immunsystemet i nedan text ur artikeln.

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

Ur artikeln:

“the risk of death in males is ∼1.7 times higher than in females (1). Aging is strongly associated with higher risk of death in both sexes, but at all ages above 30 years, males have a significantly higher mortality risk, rendering older males the most vulnerable group (1). Sex differences are intertwined with differences in gender roles socially and with behavioral factors, which also influence COVID-19 incidence and outcomes. However, there are also possible biological mechanisms of male sex bias that affect the severity of COVID-19, particularly with respect to immune responses.”

“male sex is more often associated with lower immune responses and higher susceptibility and/or vulnerability to infections in animals. This is generally also the case in humans (2): Male patients have higher viral loads for hepatitis B virus (HBV) and HIV (2). Conversely, females generally mount a more robust immune response to vaccines, such as influenza vaccines. However, the heightened immune responses in females can also lead to detrimental immunopathology in infections”

“The physiological response to virus infection is initiated when virus replication is detected by pattern recognition receptors. This leads to two antiviral programs by the infected cells: (i) cellular antiviral defense programs mediated by type I and type III interferons (IFNs) to limit viral replication and spread, and (ii) cytokine and chemokine production to recruit and coordinate immune cells, such as monocytes and neutrophils that can phagocytose and eliminate infected cells. Notably, COVID-19 is characterized by strong innate immune cytokine and chemokine responses despite the disproportionately low antiviral defense signature mediated by IFNs (3). Patients with severe COVID-19 exhibit high serum concentrations of proinflammatory cytokines and chemokines, with particularly high concentrations of interleukin-6 (IL-6) and the inflammasome-associated cytokines IL-1β and IL-18 (4). Exacerbated systemic inflammation is associated with extensive pulmonary pathology, including massive infiltration of monocytes and neutrophils. Increased neutrophil count is associated with poor clinical outcome (5). The robust induction of these inflammatory cytokines and cells may be a compensatory response to the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to evade IFN responses, which necessitates the engagement of IFN-independent defense mechanisms (6).

The plasma concentrations of several key innate immune cytokines and chemokines, such as IL-8 and IL-18, are increased in male patients compared with female patients in the early phase of COVID-19. Conversely, female patients have higher plasma concentrations of type I IFN (IFNα) over the disease course (7). Notably, autoantibodies that inhibit type I IFN signaling have been reported in a subset of severely ill patients, the majority (94%) of whom were older males (8). By contrast, T cell activation at the early phase of SARS-CoV-2 infection is robust even in older female patients, whereas male patients have a significant decline with age. Male patients with poor T cell activation at the early phase of disease onset have worse COVID-19 outcomes, whereas no such difference is observed in female patients (7).

What could be the potential underlying mechanism of this sex dimorphism in immune response? One culprit is the sex chromosomes: A substantial number of important immune-related genes are encoded on the X chromosome. Although one of the two copies of the X chromosome in females is usually epigenetically silenced [X chromosome inactivation (XCI)], some critical immune-related genes, including Toll-like receptor 7 [TLR7, whose viral RNA sensing elicits strong type I IFN production in its major producer, plasmacytoid dendritic cells (pDCs)], can escape from XCI in some proportion of cells. This makes the population “mosaic” for biallelic expression, which leads to higher gross expression of some immune-related genes in females (9). Human pDCs have also been reported to have higher expression of interferon regulatory factor 5 (IRF5) in females. Higher expression of these genes leads to more robust type I IFN responses in females, and this is one of the potential mechanisms involved in females’ enhanced protection against viral infections, including COVID-19 (1, 2).

Sex has a major impact on immune cell transcriptomes; immune cells or even the immune system are differentially affected by aging, depending on sex. Aging induces a decline in the proportion of naïve T cells that is more prominent in males, and B cells decline after age 65 only in males (10). Males have abrupt and drastic changes in the epigenetic landscape of their immune cells between ages 62 and 64, and subsequently males exhibit an accelerated immunosenescence phenotype that is characterized by enhanced innate proinflammatory gene expression and lower gene expression related to adaptive immunity, which could potentially predispose older males to hyperinflammation and poor adaptive immune responses.

By contrast, major changes in the epigenetic landscape of immune cells occur in females 5 to 6 years later than in males, with this gap largely corresponding to the life span differences between sexes (10). It is notable that females generally mount more pronounced cytokine responses in viral infections, although this is not the case with COVID-19. Instead, males have higher plasma concentrations of innate proinflammatory cytokines such as IL-8 and IL-18 (7). This could be because patients who have severe disease are generally of older age, and the background transcriptomic and epigenetic sex differences in immune cells in these older individuals are possibly amplified and more explicitly manifested in the context of SARS-CoV-2 infection (see the figure).

The other important biological factors are sex hormones. In a mouse model of SARS-CoV infection, higher mortality in male mice was observed and was attributed to the protective roles of the female sex hormone estrogen (1). Studies using various cell types and animal models have shown that the expression of angiotensin-converting enzyme 2 (ACE2), the host cell entry receptor for SARS-CoV-2, is modulated by estrogen (1). This likely occurs through transcriptional regulation by estrogen receptor signaling, although the detailed molecular mechanisms are yet to be identified and the consequences of the type of ACE2 modulation (up- or down-regulation) could be cell type– and context-dependent. Estrogen receptors are widely expressed by many cell types, including immune cells, and estrogen is a critical regulator of gene expression and functions in innate immune cells, including monocytes, macrophages, and dendritic cells, as well as in lymphocytes such as T helper 1/2 (T_H1/2) cells, regulatory T cells (T_regs), and B cells. One of the major forms of estrogen, estradiol, has been shown to dampen the production of excessive innate inflammatory cytokines by monocytes and macrophages (1). Menopause is an independent risk factor for female patients, and concentrations of estradiol and anti-Müllerian hormone, which is produced by cells in developing follicles and is an endocrine marker for oocytes remaining in the ovaries (ovarian reserve), are inversely correlated with COVID-19 severity (11). Conversely, androgen-deprivation therapies for prostate cancer have been reported to reduce the risk for SARS-CoV-2 infection (12). Like estrogen receptors, androgen receptors are expressed widely among immune cells, regulating the transcription of various genes, and the outcome of their signaling has been shown to be generally immunosuppressive (1).

Despite the emerging understanding of sex differences of immune responses in COVID-19, many questions remain. Sex is not binary, and little is known regarding immune responses to viral infections, including COVID-19, in individuals with disorders of sex development (DSD) or transgender individuals. DSD describes congenital conditions in which the development of chromosomal, gonadal, and anatomical sex is atypical. For example, Klinefelter syndrome (also known as 47, XXY) results in phenotypes such as gynecomastia (enlarged breast tissue in males) and small testes with hypogonadism. This condition accompanies a series of comorbidities, in particular a high frequency of autoimmune diseases, such as systemic lupus erythematosus (SLE). The prevalence of SLE among Klinefelter syndrome patients is higher by a factor of 14 than among 46, XY males; this is comparable to its prevalence among 46, XX females, which suggests a gene dosage effect of the X chromosome (13). Additionally, transgender is a collective term encompassing those whose gender identities or gender roles differ from those typically associated with the sex they were assigned at birth. Little is known about the immune responses in these individuals, some of whom are undergoing gender reassignment hormone therapies. It is possible that DSD and transgender individuals mount distinct immune responses to viral infection in general and also in COVID-19.

Sex differences in immunity also have implications for responses to SARS-CoV-2 vaccination or reinfection. Analysis of convalescent plasma showed that male sex, older age, and hospitalization for COVID-19 were associated with greater SARS-CoV-2 antibody titers (14). This could be related to increased disease severity in this demographic of patients, with increased viral load driving more B cell activation and antibody production. Alternatively, higher amounts of antiviral antibodies could be due to compensatory increases in antibody production due to suboptimal qualities of antibodies generated in older males, which are unable to neutralize the virus effectively. Antibodies with suboptimal neutralizing ability have the capacity to promote viral invasion into host cells such as macrophages [called antibody-dependent enhancement (ADE)]. However, there has been no clear evidence of ADE in COVID-19. With other viral infections, fatal diseases in dengue virus infection (dengue hemorrhagic fever and dengue shock syndrome) have been associated with ADE. Upon secondary infection with a virus of a serotype different from that of the primary infection, the fatalities from these severe diseases were primarily seen in adult females despite the male dominance in dengue hemorrhagic fever prevalence (15). The mechanism remains unknown but may be due to heightened inflammation in females, leading to capillary permeability.

It is important that studies of COVID-19 patients report results in a sex-disaggregated manner, not only to elucidate differential disease pathogenesis, but also to enable a deeper understanding of this disease and the eventual development of better treatment and preventive strategies. It should be standard practice to collect and report sex-disaggregated data for this and for all infectious disease and vaccine studies in the future.”

https://science.sciencemag.org/content/371/6527/347

https://www.dn.se/vetenskap/forskare-nya-teorier-om-varfor-man-drabbas-hardare-av-covid-19/

https://sverigesradio.se/artikel/7652493