Sunday morning perusals

It was Johnny Cash's birthday last week. I have been a fan from early teenage years after I had stumbled on that recording of the concert in Folsom prison late one night when I had sneaked down to watch tv after everybody had gone to bed. In the 1970s, surrounded by serious Genesis, King Crimson, Led Zeppelin etc. fans, that infatuation was not something to share in public.

Oh. What we considered as troublesome then.

Whereas these days . . .

There's the vaccines, which seem to provide immunity of sorts - very hopeful first data - as well as mild disease course if infected and the potential - highly likely but too early to call - of limited or even halted transmission.

And then there's treatment options. Here is my brief and unskilled summary of a brand new publication on promising drugs to help those infected to recover.

For the full article click here.

SARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic, in which acute respiratory infections are associated with high socio-economic burden.

As a complement to the safe and effective vaccines against SARS-CoV-2, the repurposing of existing drugs represents a pragmatic strategy for the treatment of COVID-19 patients. Drug repurposing (drug repositioning) is advantageous in the face of rapidly-spreading emerging diseases.

Multiple ... clinical trials have been initiated in the search for effective treatments against SARS-CoV-2. The individual drugs or combination treatments for these studies have often been selected based on known activities against SARS-CoV, Ebola virus, HIV or Plasmodium spp. ... However, the search for effective drugs against SARS-CoV-2 could extend beyond known antivirals and anti-infectives ...

 A team of virologists, microbiologist, pharmacologists, infectiologists etc.

... applied high-content screening to a well-defined collection of 5632 compounds including 3488 that have undergone previous clinical investigations across 600 indications. The compounds were screened by microscopy for their ability to inhibit SARS-CoV-2 cytopathicity in the human epithelial colorectal adenocarcinoma cell line, Caco-2. 

Cytopathicity is the ability of a virus to produce detrimental changes in cells. So here, over five thousand established drugs (compounds) that have been used and investigated for their efficacy in six hundred diseases were introduced, separately, to a specific human cell line. This cell line has been used in many drug investigation as it shows how and how fast a drug may enter the body via the small intestine. Basically, the Caco-2 cells are our stand-in in drug trials.

If you are not put off by detailed method descriptions of drug testing and the specifics of testing assays and all the technical stuff, this article reads like a thriller where step by step the villain is surrounded by the good guys.

First, anti malarial drugs:

Among the first group of drugs initially reported to show activity against SARS-CoV were anti-malarial compounds such as chloroquine and its close relative hydroxychloroquine, although larger ...  trials indicated they were largely ineffective. We found that ... other anti-malarial compounds ... were inactive ... whereas the chloroquine analog mefloquine showed concentration-dependent activity at the highest compound concentrations.

Next, anti fungal drugs:

 Our hits also included ... anti fungal compounds  all showing ... effective concentrations ...

Then the HIV drugs: 

Several drugs .. developed for the treatment of HIV ... suggesting a possible mechanism for inhibiting viral replication.

Then a couple of others: 

(drugs used) ... for heart disease, impotence, and psychosis, which also inhibit multiple strains of influenza virus (and those) ... with anti cancer activity (and those) ... developed as oral drugs for the treatment of cancer or inflammation.

And, with stubborn dedication (my interpretation) they came closer and closer and - tada! -

...identified 258 hits that inhibited cytopathicity by more than 75%, most of which were not previously known to be active against SARS-CoV-2 ...

I don't have the first clue about what and how they did all this but I am beginning to love science. 

As a side note, the promising drugs may include viagra. Not that it matters to me.

 

 

Not yet.

Sunday morning reading

Here is my short version of this peer-reviewed review on immunity, vaccines and the covid. 

(for full article with Figures click here)

Any virus that can cause disease in humans must have at least one immune evasion mechanism—at least one immune evasion “trick.” Without the ability to evade the immune system, a virus is usually harmless. Understanding immune evasion by a virus is frequently important for understanding the (...) virus, as well as understanding challenges faced by the adaptive immune system and any candidate vaccine. In the case of SARS-CoV-2, the virus is clearly unusually effective at evading the triggering of early (...)immune responses (...). It is plausible that much of the nature of COVID-19 as an illness is a consequence of this one big trick of SARS-CoV-2.

In an idealized example of a (...) viral infection, the (...) immune system rapidly recognizes the infection and triggers  “alarm bells”(...). This can occur within a couple of hours of infection.

In a SARS-CoV-2 infection, the virus is particularly effective at avoiding or delaying triggering (...) immune responses (...)  enough to result in asymptomatic infection (...) or clinically mild disease (“mild” is a COVID-19 clinical definition meaning not requiring hospitalization).

If the innate immune response delay is too long—because of particularly efficient evasion by the virus, defective innate immunity, or a combination of both—then the virus (1) gets a large head start in replication in the upper respiratory tract (URT) and lungs, and (2) fails to prime an adaptive immune response for a long time, resulting in conditions that lead to severe enough lung disease for hospitalization (...). These factors can be amplified by challenges of age, as elderly individuals (...) struggle to make a (...) response quickly that can recognize this new virus.

Although lung infection is a major component of severe COVID-19 (and relatively slow), upper respiratory tract (URT) infection is important for transmission. Notably, a vaccine that can prevent severe disease, or even most URT symptomatic diseases, would not necessarily prevent transmission of virus. 

The elderly present particular and important challenges for COVID-19 vaccines. Older individuals are at much higher risk for severe COVID-19. 

One key feature of vaccines is that immunization occurs well in advance of infection, giving the adaptive immune system time to respond, expand, and mature. 

Overall, the interim results from the two COVID-19 RNA vaccine trials were virtually identical, with 94% and 95% efficacy and similar other outcomes. The safety profile of the two vaccines is also excellent, with a combined >70,000 doses administered and no serious adverse events. 

. . . the biggest unknown now is probably the durability of the vaccine-induced immunity. Because there is no licensed RNA vaccine, no clear reference point exists for how durable immunity will be for this vaccine. Are the antibodies durable? Is the T cell memory durable? Is the B cell memory durable? Those are all important questions, and it will take time to answer them.

so many reasons to be cheerful

 

 

And all of a sudden, spring. The blackbirds are singing their hearts out before sunrise and the woodpeckers are screeching and hammering. And there's what my father-in-law would call that good stretch in the evenings now. 

All week the cranes have been returning and it's such a welcome sight and sound. This year more so than ever. When I heard the first flock, late afternoon on Monday, we ran outside to watch the enormous flocks high above in their V-shaped formations flying in from the southwest and I noticed that all the neighbours were out there with us and we all were gazing up and clapping and waving. I got on my bicycle and cycled along with them for a while. It was just the best thing.

In the garden it is winter aconite week. I found just the one snowdrop struggling between the thyme bushes, the last of hundreds which, according to the gardener, is due to shrews eating the bulbs and, according to my own humble opinion - which I wisely keep to myself -, due to the gardener digging up the bulbs because he is not fond of them, their messy green leaves taking up space after too short of a bloom. The gardener hates waste. We disagree.

There's just a bit left to harvest, like these fat fellows, which I roasted (cubed) with a bit of miso butter and honey.

Next will be crocus and grape hyacinth week and before we can take a  breath, the full flowering orgy will be upon us. I have been reading about mast years and now have great hopes for the hazel and various plum trees this year after last summer's dismal harvest.

Meanwhile seed propagation is getting out of hand, we transplanted the first batches and they are now happy in the cold frame and the greenhouse but as always, there's more and even more and soon I will have to do a ring-a-round for takers.

The grandchild asked this morning, can you come to my house granny and granddad? And people, we laughed and held our breath for while.

 

I keep trying to remember that all pandemics are finite. I wonder whether that's a consolation. So history shows that each pandemic ends one way or another. The Spanish flu ended in 1918, as WW I ended, because it was the war that got it going in the first place.

But it's a bit different with the covid. I read and try to understand and what I can figure out is that, yes, we need the vaccines, all of them, but we shouldn't put our hopes on that with a vaccine all will be well.

It doesn't help anyone in the wealthy North/West if we are all vaccinated and the mutations then come to us from Africa because there is a lack of vaccines there.

Most new infectious diseases are transmitted from animals to humans. In recent years alone: Ebola, Sars, Mers,  Zika. You don't need to be an expert to see how this is due to the ongoing destruction of nature, climate change, extinction of species, factory farming. 

We humans penetrate ever deeper into the natural habitat of wild animal populations. This increases the likelihood that new viral diseases will pass from animals to humans. Even if the fight against this pandemic is currently overshadowing everything, we have to face the larger ecological crisis behind it at the same time.

This is a long-term epidemic, after 12 months, obviously so and it has and will continue to change society and daily life. That's a good thing. I read that the bubonic plague which killed at least a third of the population of Europe in the 14th century (??) is responsible for our concept of public health. Pandemic as formative event, so to speak.

People ask me what I miss most and I am at a loss. Travel, eating out, going to a bookshop, a museum, it all sounds so trivial and vain when I hear of terrible cases of long covid, of family members dying within hours of each other. Of course, I want to visit my daughter, my grandchild. But for much longer than this pandemic, we have been talking about how things were spiralling out of control, have been plotting ways and campaigns and actions to enable our children's and grandchildren's future on a livable planet away from the old destructive normal. 

Because the old normal has put us here, I want to shout. Our silly arrogance, our superiority complex. Let's be a tad more humble here and take our place, our teeny tiny place on the planet with care and responsibility.

 

this is what I would call honest leadership in a pandemic

 

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First the river flooded and it rained for ever an entire week, then the cold front moved in with an entire week of frost and sunlight and strong northerly wind. The house is pretty crowded with various potted lemon and fig trees sheltering indoors, the window sills are filling up with seed trays. We started six new varieties of tomatoes and a couple of peppers from a seed sharing group. This is what excitement looks like at the onset of year 2 with covid. On Tuesday, I had my first jab (Moderna). I admit that I was watching out for side effects but none appeared.

Yesterday, I just had to cycle, two no-bicycle weeks is a long stretch for me, and I wrapped up in very many layers but had to turn back after maybe six kilometers as my fingers were frozen numb and no amount of cursing and scarf wrapping and hood tightening could get that freezing wind out of my nose and face and neck. I never liked the cold. I don't even like the look of it, the godawful frosty sunlit crunchy lawn with all that stupid glitter.

My childhood winters were snowy and cold, long weeks of ice skating and tobogganing and skiing and snow ball fights. I didn't know it at the time, but I hated it. Truly hated it. What a miserable time! I was often the one who turned back first, walking home through the thick snow banks along the road, stumbling and crying. My feet white and numb, my mother sat me in front of two buckets, one filled with cold water, one with warm water, gave me her watch and I would stick my feet for five minutes first in the warm and then in the cold bucket and back and forth until they started to itch and tingle and come back to life. 

While my siblings could not get outside fast enough, I welcomed every inkling of a sore throat or runny nose, any excuse to be allowed to stay indoors. Looking out into what my mother would call her winter wonderland garden, only let my heart sink. Still does.

I read somewhere something to the effect that we are confirmed, consoled and troubled by the landscapes through which we move in life and the places in which we live and have lived. About the ways our mood and our imagination and our identity has become influenced by the weather and the shapes and the textures and also the people, animals, plants, hills and shores (remembered and actual) of all the places we have inhabited.

It was always the sea I wanted. Even long before I knew much about it. It must have been from a book I read, maybe Pippi Longstocking's father in the South Seas, or one of those Sunday school missionary stories with pictures of children in fishing boats off the coast of Madagascar. Anyway, I would proclaim that I wanted to live by the sea. My parents were amused, what imagination she has and so on.

And then I lived by the sea, within walking distance to two different oceans, one after the other, one more spectacular than the other, for over a decade and it was just, well, normal. Then, I moved to this river valley, which was alien to me for so many years. Every aspect about life here was uninviting, the closeness, the dark hills, the way this big river cut across the landscape so carelessly, flooding and drying out in turn, messing things up. And for a while, occasionally even now, I so much wanted to be back by the sea, move away from what felt so claustrophobic at the time.

Yet, my parents and their parents, my grandparents, had no such longings. In their different ways, they were fiercely attached to a life that included forests and fields and orchards and riverbanks and carp ponds and vegetable gardens. 

In her last years, when she was 100 years old, my grandmother, who then lived in a care home, would still oversee the apple harvest in her garden with angry instructions over the phone to my brother and cousins as to who would get how much and when and where to collect the windfalls for juice making. There were seven varieties of apple trees. I still know their names: Klarapfel, Gravensteiner, one early and one late Renette, Goldparmäne, Boskoop and Berlepsch. On one of my visits, the summer before her death, she scolded me for wearing flimsy sandals. Total waste of money, she told me, not made for walking and certainly useless for working in the garden. in other words, good for nothing.

Years ago, when I was very ill the summer after I had oral surgery, my father took me for a long drive through the hills and forests of Hohenlohe, an area just west of his Franconian homeland, where he had spent many childhood summers with relatives. As we drove through small villages with storks nesting on church steeples and past moated medieval castles, he pointed out the old apple orchards everywhere. See the wealth, the riches, he said. And he was not only referring to the soil that had produced such abundant trees for centuries. What he noted was the windfall apples. In fact, piles of it under every tree. There are so many apples this year, he told me, too many. The farmers won't harvest this year, not worth the effort, better to leave them rot, for the birds, the deer and the soil. 

I could go on, memories of following my grandfather in his three-piece suit, his fob watch and walking stick with the shiny knobbly handle, while he walked deeper and deeper into the forest, pointing out adders and salamander skins, blue jay feathers and broken bird egg shells. My mother and her herb garden, her bean stalks and the way she could imitate bird song.

We are all shaped by the sound of wind, the slant of sunlight by streams of scent flowing faint or sharp in the larger ocean of air.

Barry Lopez

the wheel

 

 

. . . in the pagan year, there is a ceremony or a ritual or something being marked, every six weeks, across the year, and that that gives hope for anybody who is currently suffering, because you are never far away from the next moment when you can get together and when you can celebrate. But also, it gives you a sense of time passing, which is really helpful when you’re struggling, because time can begin to drag, and you can get mired in hopelessness. But actually, you get a kind of marker of your progress, so the next time that something comes up in the calendar, you can feel how far away you actually are from the last time you celebrated, and that that helps you to move through, and you can start to look towards the next one, and a pleasure in the next one, perhaps, as a way of dividing up those long months.

 

Katherine May (speaking in "on being" -  a lovely podcast episode)

Time flies, Imbolc is past us. The German feast day on the 2nd of February is called Maria Lichtmess (Mary's candlemass), the day Mary blows out the candle that was lit by St. Martin in November - yet another pagan ritual customized by the churches. Godlovethem. 

My Franconian grandmother would declare, an Lichtmess ich mein Brot bei Licht ess' (on the day of candlemass I can eat dinner by daylight). It is also my sister's birthday and we managed a polite phone call. Even laughter.

My year is usually split into quarter sections dictated by my health insurance. Every three months, I have to show my face and my insurance card to my GP to prove my existence and to collect prescriptions and referrals. And there's the one brief immunologist appointment every three  months.

When I was first diagnosed with my shitty disease, I was in despair about this, waiting from one of these appointments to the next, the gap seemed enormous and so much could happen, what if I go deaf or blind or the kidneys pack it in or what if I die, until I finally accepted that checking on a chronic condition every three months or so is the way it's done. In between, nobody is holding your hand, you just have to make the best of it. (And you are supposed to keep a record of symptoms.)

So, you get quite blasé about it all after a while, you forget about the record soon enough, nothing life threatening happens, and by now you barely register the clumps of blood on your tissue every morning after your sinuses start to clear. Because even if it's a fair bit and has been going on for what, weeks, months (?), it's not a nose bleed, just lumpy stuff, and you know, it's crusts that count. Crusts, you have been told, mean vascular tissue damage, lumpy clumpy stuff is just plain boring bleeding sinus membranes.

Also, the digestive system can be far more variable than you were told to believe. Two weeks of painful bloating nausea is considered acceptable under the circumstances unless it's accompanied by constant constipation and, here we go again, blood. Don't bother to get alarmed.

And anyway, the date for the annual full colonoscopy/endoscopy is set (for June).

Fatigue? Brain fog? Rest is a good thing and don't expect too much at your age. After all, this is a chronic illness.

You scrape by, from day to day, to week to week, quarter to quarter. From Imbolc to Ostara to Beltaine to midsummer. On and on.