Astride Veinianie, Lady-Consort Lorenne, breathed in deeply before she stepped forwards to address the assembly full of healers.
"Welcome everyone to this first healing seminar organised by the House of Lorenne and Veinianie in the Orage Mountains. As we all know, Healing has never been a very collaborative field, and this has greatly impacted medical advances. I hope that by organising this seminar and similar ones in the future, we will be able to better exchange information and debate potential treatments, resulting in better quality of healing through the region.
"For our first session, I thought it best to start with an old disease endemic in the region, the sweats. You all have undoubtedly heard about it, if only from warnings from your parents as a child. The sweats are caused by a virus transmitted by the bite of yellow gnats, magic-resisting living at the threshold between the magical storms areas and the rest of the region. The characteristics symptoms are an intense and debilitating fever and a disorder of the pain processing pathways.
"I will start by reviewing what we know about the virus, as well as new discoveries I have made recently, before finally discussing treatment and new therapeutic targets. I hope that by the end of this session, we can all have a productive discussion concerning them, so that we can leave with plans for treatment trials."
She looked around at the crowd to survey the reception of her words. Most of them were frowning dubiously. That was unsurprising. All anyone could ever see and remember was her young age, not all that she had already accomplished for the healing field. They would not believe she could teach them anything new today. Gathering them all had been hard enough, she had to be impressive if she wanted her seminar idea to be successful and to have the opportunity to make durable changes in the region.
"As I have already said, this disease starts with the bit of a yellow gnat carrying the sweat virus. The gnats themselves are unaffected by the virus, but they are the only blood-sucking insects able to carry it when they feed on the blood of contaminated humans. They can then transmit it to others with their next bite."
Someone muttered not so discreetly, "We just have to be careful not to go close to the mountains. Everyone knows the sweats are a peasant's disease!"
Astride's polite smile strained. Experience told her nothing she said would be able to change the healers' views on the value of life. Everyone with power looked down on their inferiors, and to be a good healer one had to be powerful. She forced herself to go on as if she had not heard anything.
"The virus life cycle in the human body has been known to our community for many centuries already. From the site of contamination, the virus spread in the body until it reaches neurons of the peripheral or central nervous systems. Once there, it starts its replication cycle."
She marked a pause to highlight the importance of her next words. "The danger of virus comes from the fact that it is surrounded by a protective envelope made of magic-binding proteins binding magic. Those proteins bind magic very tightly and so this envelope is completely unbreachable from the outside. This mechanism evolved as an adaptation to the magical storms, but for the virus it also has the benefit of protecting it from our immune system."
"We would not have any problem if people did not insist on continuing to go into the mountains!" This time the remark was loud, and everyone turned towards the person in question, an old woman with greying hair Astride did not recognise. "Why can't all the lords and ladies forbid it? If the lifeforms there do not meet any human, they will cease to turn their magic-resistance mechanism against us! Do we really want to taunt them and see what else they could come up with?"
Astride nodded politely to acknowledge her words. Hopefully she would not get too many of those interruptions. Her back was already hurting despite how shortly she had been standing in front of them and she would not able to last an hour.
"You should make the suggestion to the ruler of your Estate. I am afraid, however, that this is beyond the scope of today's seminar. Unfortunately for us, the virus is already among us and it will not leave any time soon.
"To continue on their life cycle, the envelope is only opened from the inside once the virus has penetrated inside neurons, at which point it is undetectable by the immune cells. This allows it to replicate peacefully until the number of viruses contained in the cell becomes too great and makes it burst open, freeing the virus to go contaminate other cells.
"When looking at most cases of the sweats, we can say that the replication of the virus inside the body is normally slow. Indeed, symptoms can take weeks to appear, and contaminated individuals can wither for months before the central nervous system is too badly affected and the autonomic system breaks down and patients die."
Virus bursting from a cell by AmélieIS
A young man raised his hand and Astride gesture for him to speak. "What about all the stories we've heard about the epidemic? The sweats suddenly killing people in just days and propagating to everyone before just disappearing? Is it really due to people not paying proper respect to our ancestors?"
Astride nodded with approval. "Indeed, we have all heard those stories. The last epidemic occurred a few centuries ago, and we do not have perfect records of the observations of the healers of the time. By what we can tell, new strains of the virus with a fast replication rate evolve periodically and spread quickly through the population thanks to this advantage. In such cases, symptoms show up to only a few hours after the insect bite, and patients die in a matter of days or weeks. Thankfully for us, such epidemic kills people too fast for the disease to really be able to propagate for very long, and soon those strains of the virus die out, leaving only their slowest cousins behind."
"Let us now look at the symptoms in more details," Astride continued. "This is where I can bring to you brand new information on the exact mechanism of the disease from the results of my own research in the past few months."
As expected, everyone stood straighter and some even leaned forwards in impatience. They still sported dubious expression, of course, but that would change quickly.
"What I have discovered is that the characteristics symptoms do not come from the virus itself, but rather from the toxins that it releases when it burst from dead cells in the central nervous system. Indeed, those toxins do not stay locally but spread through the whole of the peripheral and central nervous systems, resulting in a high inflammation and fever. While at first this is manageable, the intensity progressively increases over the course of the disease until the symptoms become debilitating and force the patient to be bedridden and mostly unconscious for what little time they have left to live."
She paused again and swept her gaze through the room to meet everyone's eyes. "Those are the symptoms that we all recognise and accept. What has been a lot more controversial concern the sensation of terrible pain reported by many patients. Many among our healing community have dismissed them as being solely in patients' head and imagination. However, I can tell you today that I have found direct proof of their existence. This is really revolutionary and must change the way in which we handle this disease."
Mutters broke everywhere and expressions morphed from dubious to openly scandalised. Astride noted who was reacting how but did not challenge them directly. For now.
She resumed her explanation. "Indeed, another effect of the toxin on the central nervous is a change in the balance of neurotransmitters and hormones that greatly mess up with the signalling pathway of pain stimuli. Normally, after a pain stimulus is detected by the nociceptors, the signal is transmitted to the peripheral nervous system, then the central nervous system. Once there, inhibitory signals are sent back to the receptors to acknowledge the reception of the signal and stop it.
"In patients affected by the virus, two changes occur: 1) the threshold for the feeling of pain in the receptors is lower, 2) the pain signal is amplified during transmission because of an excess of signalling neurotransmitters in the cerebrospinal fluid and brain, 2) the inhibitory signal is reduced because of a decreased level of the required neurotransmitters. Please take note that those changed levels are directly measurable with our magic. If you would insult me by not believing my words, I would hope that your professional conscientiousness would incite you to check them yourselves."
Despite her level tone and her attempt to contain her glare, more than a few people shifted uncomfortably.
"What all of those changes result in is affected individuals having a much lower pain threshold. Concretely, this means that they feel pain from stimuli that are not normally painful—allodynia—as well as feeling a much more important pain compared to the objective intensity of pain stimuli—hyperalgesia."
There. Black-on-white proof. She once again swept her eyes through the room to meet as many as she could, daring anyone to directly opposed her.
The first to interrupt the silence, however, was someone she recognised as being one of the more open-minded healers of the region. A middle-age woman from the coastal region. "Those neurotransmitters would also affect other biological processes, would they not? Like mood, energy level and sleep quality. Can we see effects in patients?"
"Indeed, this is a good remark." Astride smiled warmly at the woman. "The changes in neurotransmitter also have secondary effects on all of those processes, and this does further weaken the patients and prevent them from adequately fight against the virus infestation."
Average stimulus-pain threshold in humans by AmélieIS
Astride shifted on her feet, attempting to relieve the pain in her spine. Seeing as nobody else felt the need to contradict her immediately, she hurried to go on to the last part of her talk. As soon as she was done, she would be able to sit.
"Healing magic is not currently able to properly treat individual affected by this virus. As all of you who have attempted to do so will know, the capsule protecting the virus makes it resistant to both the patient's and the healer's magic.
"The only thing we have been able to do so far is use pain medication to mitigate the symptoms, but there too we have encountered difficulties: our medication affects the whole body, not just the specific pain process. Thus, taking them results in wild mood changes in the patients. In addition, not all patients have the exact same changes in neurotransmitters, and so medicines having some mild beneficial effects in a patient will do nothing in others.
"Of course, we all know the legend of Lady Oriane Merisse who ventured in the Orage Mountain in an attempt to find a remedy against the disease after her son became affected, correctly deducing that only the adaptations against strong magic that all the local lifeforms carry would have a chance of being effective against the envelope of the virus.
"The stories are already a few century-old and they do get a bit confused about whether she was successful or not, only agreeing that she came back alive and with many samples to test. Unfortunately for us, regular expeditions in the mountains are not a possibility, and so we must look somewhere else for treatments.
"What I bring you today is a new therapy target for us to look at: finding a way to mop up the toxins away from the body so as to limit the symptoms. Once greatest part of them will be gone, we will then be able to use the appearance of new toxins as an indicator of which region of the body is contaminated, destroy all neurons there, and only once the patient will be confirmed free of the virus, regenerate all lost neurons."
"I have come up with a number of chemical strategies to target the toxin and develop a few elixirs that promise to be effective. What I expect from all of you today is a discussion on how to come up with more of them, as well as the establishment of trials through the region to test their efficiency. I will furnish you all with the elixirs and you will administer them to your patients, proceed with the treatment I have highlighted and report on the results."
Before she could go on, she was finally interrupted by the oppositions she had been expecting from the start. Great, that meant she would be able to shut them down and sit down soon afterwards.
The head healer from Sarenne stood to all of his height, his chin rosing in the air so that he was looking down at her despite the distance between them. "It would appear, Lady-Consort Lorenne, that you are operating on a misunderstanding: that you are some kind of leader over us because of your status and that any of us have any incentive to listen to you. House Laresse surely cannot hope into intimidating us all just because of their recent conquest of an Estate. You will find that we are made of much stronger mettle."
The man's tone was perfectly calm and cool, as if he was discussing the flowering of his garden and not delivering a deadly insult.
Movement at the back of the room caught Astride's attention. Shockingly, her husband seemed to have found the time and curiosity of investigating what she was up to.
Astride smiled sweetly at him and the rest of the room. She certainly did not require anyone else to make herself respected.
"If any of you do not have the good sense of being intimidated by House Laresse and my husband nor the politeness of using the etiquette I am sure you must have been taught at some point in your life, then do consider who I am. I am the only one among who came up with any effective new medicine in my life, no matter how short it has been until now. I am also the one who, despite having made the recipe of those pain medications public, still provides you all with those elixirs and balms and many others too. If you insist on forgetting your manners and wallowing in your mediocrity, you can be sure there will be strong consequences for you and the Estate that you represent today."
A chill came over the room and many of the healers gathered shivered. The Sarenne head healer pinched his lips and sat down slowly, finally seeing the good sense of deferring to Astride. Her smile widened as she met her husband's surprised expression. Being a healer did not mean she was a delicate flower unable to arm anyone, and he too would do well to remember it.
The Empire of the Covenant is a millennia-old federal empire spread over a whole continent and gathering around 600 independent Estates. Those are ruled by powerful mages, lords and ladies who are the Heads of their Houses and who are linked to the ancestral magic of their Lands. Estates are divided by their affilitation with the Light or Dark political factions.
See Geography, Climate and Demography of the Empire and Political Organisation of the Empire.