#why was there no question on monoclonal antibodies though

[cheatachu-72]

Biology was amazing actually

[mcatmemoranda]

Going through questions:

Chédiak–Higashi syndrome[1] (CHS) is a rare autosomal recessive disorder that arises from a mutation of a lysosomal trafficking regulator protein,[2] which leads to a decrease in phagocytosis. The decrease in phagocytosis results in recurrent pyogenic infections, albinism, and peripheral neuropathy.

Defect in neutrophil phagosome-lysosome fusion. Pyogenic bacteria = staph, strep, pneumococcus.

Cytotoxic (CD8+) T cells have a PD-1 receptor. Tumor cells can express programmed death ligand-1 (PD-L1), which binds to the PD-1 receptors on cytotoxic T cells. PD-L1 binding to the PD-1 receptor prevents cytotoxic T cells from doing their apoptotic function. This is how cancer cells evade destruction by cytotoxic T cells. The binding of PD-L1 to PD-1 receptor causes T cell exhaustion (inability of the T cell to induce apoptosis). Monoclonal antibodies against PD-1 or PD-L1 prevent PD-L1 interaction with PD-1 receptor, so cancer cells can't evade cytotoxic T cell destruction. Pembrolizumab, nivolizumab = PD-1 antibodies. Atezolizumab = PD-L1 antibody.

T lymphocytes release interferon gamma, which activates macrophages to express MHC-> Th1 differentiation. Viral and bacterial infection result in interferon gamma release from T lymphocytes and NK cells. Interferon Gamma Release Assay (IGRA) tests for latent TB; measures amount of interferon gamma released by T lymphs in response to M. tuberculosis antigens; measures cell-mediated immunity.

Mast cells release tryptase. Tryptase is released by mast cells in anaphylactic reactions. Serum tryptase level is used to diagnose anaphylaxis after the pt is stabilized.

The FceRI IgE on mast cells and basophils bind to the Fc portion of circulating IgE antibodies. Antigen binds to multiple IgEs, which causes aggregation of the FceRI receptors (the IgEs on basophils and mast cells)-> degranulation of histamine and tryptase from basophils and mast cells. Ok so this is more complex than I remember learning. I thought it was the IgEs that aggregate. It's specifically the FceRIs (high affinity IgEs) that aggregate. FceRI receptor on mast cells bind to the circulating IgEs. The the FceRIs aggregate via the antigen and that causes degranulation. Aggregation of the FceRIs activates a tyrosine kinase, which then causes degranulation.

Question 14 of my first immunology quiz has an explanation I want to draw a table from

Etanercept is a TNF-alpha inhibitor it links the Fc portion of human IgG1 to soluble TNF alpha receptors, functioning as a fusion protein. It functions as a decoy receptor, which binds all TNF alpha to keep it from binding to TNF alpha receptors. It treats rheumatoid arthritis when MTX fails to work.

Question 13 also has a figure I want to copy.

Azathioprine and mycophenolate inhibit nucleotide synthesis. This prevents B cells and T cells from proliferating. These are immunosuppresants. Azathioprine-> 6 mercaptopurine-> 6 Thioguanine active metabolites; the Thioguauanine metabolites inhibit purine synthesis. If you can't replicate your DNA/RNA, you can't reproduce, so azathioprine prevents B and T cells from proliferating. Activated T lymphs make IL-2, so less IL-2 will be made as well. Immunoglobulins come from plasma cells, which form from B cells. So azathioprine also reduces immunoglobulins (because azathioprine prevents the T cells from proliferating and you need T cells to activate B cells with the costimulatory response).

I got a question right because I remembered from watching an OnlineMedEd video yesterday that MHC Class I receptor is edited in the endoplasmic reticulum. Part of MHC Class I receptor is beta 2 microglobulin. Cells that are infected break up the pathogen in their cytoplasm and then send pieces of the pathogen (antigens) into the endoplasmic reticulum via the TAP receptor. Inside the ER, antigen is added to MHC Class I, then the MHC Class I-Antigen complex is sent to the cell membrane. TAP = Transporter Associated with Antigen Processing. Mutations in the TAP1 gene, which codes for TAP, lead to inability to bring antigen into the ER. So the pt gets granulomatous skin ulcers and respiratory infections even though lymphocyte and immunoglobulin levels are normal.

Pneumococcal conjugate vaccine (PCV13) induces a more robust immune response than the pneumococcal polysaccharide vaccine (PPSV23) because the conjugate vaccine causes B and T cell recruitment-> memory. The polysaccharide vaccine (PPSV23) doesn't create memory cells. PCV13 has a conjugated protein whereas PPSV23 doesn't. Pneumovax = PPSV23; Prevnar = PCV13.

In the blood vessels, bradykinin relaxes smooth muscle, causing vasodilation. But in smooth muscle that is not in the vasculature, bradykinin actually causes contraction of that non-vascular smooth muscle. So, bradykinin dilates blood vessels but constricts smooth muscle that is not in the blood vessels. That’s why it causes cough–it causes constriction of smooth muscle in the bronchi. Since bradykinin is degraded by ACE, when you inhibit ACE with ACEIs such as lisinopril, you stop breakdown of bradykinin–> increased vasodilation and bronchoconstriction. That’s why ACEIs can cause angioedema and cough.

Bradykinin vasodilates-> angioedema (fluid leaves blood vessels).

Hereditary angioedema is AD; can also be due to ACEIs. In hereditary angioedema, pts lack C1 esterase inhibitor, which is normally involved in break down of bradykinin. So no C1 esterase inhibitor-> increased bradykinin-> angioedema. Dx hereditary angioedema with low serum C1 esterase inhibitor and C4 levels. C1 esterase inhibitor suppresses C1-> no classic complement pathway. Kininogen is converted to bradykinin by kallikrein. C1 esterase inhibitor inhibits kallikrein-> decreased bradykinin. So of course without C1 esterase inhibitor, you have increased kallikrein-> more bradykinin.

In germinal centers in lymph nodes, B cells undergo somatic hypermutation, which is what allows the B cells that can respond to a particular antigen to proliferate. Somatic hypermutation = immunoglobulin mutation.

Serum sickness = type III hypersensitivity reaction (antigen-antibody complexes in tissues); occurs 1 to 2 weeks after being exposed to non-human proteins. Pts present with vasculitis, arthralgia, fever, rash, low C3 and C4. Histologically, you see fibrinoid necrosis and infiltrating neutrophils. Low complement occurs because complement-fixing IgM and IgG are in the immune complexes.

Hyper IgM syndrome = X-linked recessive deficiency of CD40L (CD40 Ligand located in T cells and necessary to interact with CD40R on B cells); causes recurrent pulmonary and sinus infections, GI infection, infection with opportunistic bugs (e.g., cryptosporidium), failure to thrive. Pts have lots of IgM, but little IgG, IgA, and IgE. B cells have trouble class switching (because the CD40L-CD40R interaction is necessary to create the costimulatory signal that causes B cell class switching and proliferation). Class switching occurs when heavy chain constant region genes are spliced out so the B cell can create the isotype of immunoglobulin it needs to make. That doesn't happen in Hyper-IgM syndrome because the CD40R-CD40L initeraction necessary to cause that can't happen when there's deficient DC40L. CD40 deficiency is autosomal recessive form of this disease. If B cells don't class switch, they stay as IgM-secreting cells.

Severe Combined Immunodeficiency (SCID) = autosomal recessive adenosine deaminase (ADA) deficiency. Adenosine deaminase deficiency leads to accumulation of adenosine in T cells and B cells (lymphocytes)-> cellular and humoral immunodeficiency. Tx: gene therapy; hematopoietic stem cell transplant. X-linked SCID is more commone than ADA deficiency. No lymphocytes-> bacterial, viral, and fungal infections.

Henoch-Schonlein Purpura (HSP) = small vessel leukocytoclastic angiitis + deposition of IgA-C3 complexes in skin and GI tract. It's a hypersensitivity reaction related to recent infection. Pts have a purpuric rash, arthralgia, abdominal pain. Can lead to acute glomerulonephritis. Occurs in kids.

[softnow]

paracosm [ii/?]

msr | college au | this chapter: gen | words: 2.2k

she resents the idea that some boy who will no doubt be gone in another week’s time can ruffle her so much.

it’s dana’s turn, folks. necessary shoutout to @o6666666, champion of baby dana and all her emotions. also tagging @today-in-fic.

← last chapter. / ao3.

— — —

Dana has always been good with change. It comes with the territory of being a Navy brat. As a kid, she attended four different elementary schools, two middle schools, and she graduated high school with a class she’d only known for less than a year.

But there is a difference between moving with her family—keeping, if nothing else, the familiarity of her siblings, her parents, the old worn quilt on her old twin bed—and moving alone to the other side of the country, starting college (an exciting but daunting task on its own) nearly 3,000 miles away from everything and everyone she’s ever known.

Granted, she’s handling it better than some—better, for instance, than the girl who lives across the hall and cries on the phone to her parents every night, or the boy in her math class who comes only every third day and reeks of alcohol and pot when he does. Dana, at least, is making an effort.

She has gone to a few welcome mixers, to an underwhelming movie night hosted by her RAs, to a panel discussion on monoclonal antibodies with an audience of serious-looking grad students and old men in sweaters. She leaves her door open while she studies, just in case somebody should like to pop in. On two different weekends, she has allowed her roommate to take her out to parties filled with people who, even if they are new like her, seem to have known each other their whole lives. She has even formed a tentative working friendship with her bio lab partner, and she is frequently invited to have dinner in the dining hall with some of the girls on her floor (although, after a few nights of awkward small talk over rubbery pizza, she has stopped accepting).

But still. Despite the built-in camaraderie of the freshman experience, of being one of many sharing the same anxieties, excitements, and first-time hangovers, she feels…foreign. A little out of her depth.

She tells herself it doesn’t matter. College is, after all, simply a means to an end. But when she calls her parents on Sunday afternoons and her mother asks if she’s making friends, having fun, having the all-American college experience—the one she herself, married and pregnant right out of high school, was denied—well. Dana’s never enjoyed lying.

So she’s glad for the library. She may not know the difference between all the fraternities or where to find the best pizza in town or what a Jägerbomb tastes like, but she has the Dewey Decimal System down pat. She knows all the nicest reading nooks—even the ones the other freshman haven’t found yet—and she gets a startlingly large amount of satisfaction out of booting couples who think they’re sly enough to make out in the fifth-floor economics section. (In the three and a half weeks she’s been working here, she’s kicked out four couples. A rush, every time.)

She likes being the one who, at least for a few hours a day, gets to ask how can I help you? She likes that she has the answers. And she likes—perhaps better than anything—that here, it is perfectly fine to be alone. She doesn’t feel self-conscious behind the circulation desk the way she sometimes does sitting alone at a table meant for four in the student union. There’s nothing sad about it. There’s no pressure to socialize.

Or: there didn’t used to be.

Because now there’s a boy. A persistent boy. A persistent, irritating boy who is tall and lanky with a flop of dark hair and a collection of wrinkled t-shirts, who goes by his last name even though (in Dana’s opinion) his first is actually kind of nice, who, for some unknown reason, has set his sights on her and has made it his life’s mission to not give her a moment’s peace, who has decided that any day she is here, he will be too, hanging all over her desk, following her from floor to floor like a lost puppy, forcing her to listen to his questions and his stories and his inappropriate flirtations which, despite her best efforts, turn her pink as a cherry blossom, damn her Irish heritage.

Even when she tells him to get out—Mulder, I need to work—he will only grin and lean closer like he was never taught about personal space and say something completely disarming like, Dana, has anyone ever told you that you have Cassiopeia right…here? And then he will touch her little constellation of freckles so gently with the tip of his finger, like he’s really not touching her at all, and she will lose track of her filing or her faxing or whatever it was she was doing before he sauntered up, so cool and composed, to lean across her desk in the first place.

It would be easier, she thinks, if he wasn’t so nice. And clever. And handsome. If he was a dumb, ugly jerk, she would have no problem throwing him out (and she’d probably take an even greater amount of satisfaction in it than with the horny couples).

Because she’s not stupid. She knows that pretty, older boys with low, rumbly voices and plush, pink lips don’t seek out girls like her. Not with good intentions, at least. Boys—men, she corrects, because, god, he’s twenty-one—like him go for a different sort of girl. Taller. Older. Louder, funnier, sexier.

So there has to be some ulterior motive, has to, and it’s only a matter of time before his sweet exterior cracks to reveal whatever is really lurking beneath those puppy dog eyes and big smile and soft, gentle hands.

She hopes he just leaves her alone before then. It will be easier, really, for everyone involved.

—

It is a quarter past ten, and Dana lies curled on her lumpy twin bed, her phone cradled in both hands, her back to the wall. The cinderblocks are cool through her thin pajama top.

“He came in again today,” she says, low, like a secret.

“And?” Her sister’s voice is tinny and amused, two thousand-odd miles and a phone line away.

“He said I was beautiful,” she says. “He said I was going to win the Nobel Prize.”

Missy hmms. “For being beautiful?”

Dana shakes her head even though there’s nobody here to see it. Her roommate has been gone for three nights in a row.

“For curing cancer.”

Melissa snorts. “And what’d you say?”

Dana bites the inside of her cheek, the sore patch she’s nibbled raw.

“Nothing.” She draws the blankets tighter around herself. “I told him to leave.”

A pause. Dana thinks her sister might laugh at her, but Missy only sighs.

“Dana.”

“Yeah?”

“Why?”

“Why?”

“Don’t do that. This guy likes you. Why are you—”

“No, he doesn’t,” Dana says. She scrunches the phone cord between her fingers and releases it. Scrunches. Releases.

Melissa does laugh now. “Excuse me, what?”

“He doesn’t like me, Missy. He’s just…playing.”

“Just playing.” Melissa doesn’t sound convinced.

“The way guys do. You know. When they don’t mean it.”

“Oh, my god, Dane.” Melissa laughs again. “‘Just playing’ is calling you after midnight to ask what you’re wearing. It’s…it’s buying you a few drinks, taking you home, and not calling you the next day. This boy is not ‘just playing.’”

When Dana doesn’t say anything, Melissa continues: “Babe,” she says. “Do you honestly believe this guy would be spending that much time in the library if he was ‘just playing?’ Last week, you told me he was there until eleven o’clock on a Friday. Trust me. No guy is spending his Friday night in a library for a girl if he’s just playing.”

Dana bites her cheek again, licks her bottom lip. She thinks about last Friday. He’d shown up a little after eight, fresh from a shower, his hair still damp. She’d been in the fourth floor biology section, pulling books on tree frogs to fill a hold request, and he’d materialized behind her, smiling, with a cup of coffee and a packet of peanut M&Ms. The flip in her stomach had almost knocked her over.

“Hey,” he said. “I was looking for you. Here. Sustenance.”

And he’d thrust the coffee and the candy out at her with a dip of his chin, almost shy. She’d had a lab at eight that morning, and she’d been exhausted. The coffee smelled heavenly—rich and creamy. Exactly what she hadn’t even known she’d needed.

But instead of taking it, she’d folded the books about tree frogs to her chest, lifted her brow, and said, “Mulder, no. You can’t be doing this.”

“Why not?” He seemed genuinely curious. Concerned, maybe, that he was breaking some food-and-drink policy.

She tightened her grip on the books and said, “I don’t need it. I’m working. I need to focus.”

“Exactly,” he said. “Caffeine. Sugar. I only have your best interests at heart.”

Her cheeks flamed and she turned away, trying to seem like she was looking for the next book on her list even though all the titles blurred together.

“C’mon, Dana,” he said. “I come in peace.”

“I’m busy.” She didn’t turn around even as he came up behind her, so close she could feel the heat of him, could smell his foresty, manly soap.

“What are you looking for?”

And she’d relented. Something about his closeness, about the way he leaned over her just a little bit, made her weak. She’d shown him the list, and she’d accepted his help.

But she hadn’t accepted the coffee or the candy. Not even when he’d followed her back to the circulation desk and spent the next two hours shifting his weight from one foot to the other, asking her about class, her day, the best book she read that week, her last name, her phone number, and would she like to have dinner one night—any night—he was free any time?

“Good night, Mulder,” she said about ten times before he finally left—not without a few glances over his shoulder—so she could close up.

He’d left the coffee (cold) and the candy (unopened) on the desk. The coffee she poured out in the women’s room. The M&Ms… The M&Ms she ate later, one by one, while she called Melissa, sucking the candy coating off to make them last.

“Dana,” Melissa says now, breaking the silence. “You know he’s not going to wait forever, right?”

Dana frowns against the receiver. “What do you mean?”

“I mean this guy is clearly crazy about you. But if you keep playing hard to get—”

“I’m not!”

“—then he’s going to get bored, okay? It’s fun for a little while, but then it’s like…like running your head into a brick wall, over and over and over again. Eventually, if you keep telling him to get out, he will. And he won’t come back.”

“Good,” Dana says, even though the unexpected ache in her chest doesn’t necessarily agree. “That’s what I want.”

“Hmm.” On the other end of the line, Dana hears the flick of a lighter. “Well. If you really don’t want him, tell him you’ve got a sister in California who would be more than happy to entertain him.”

An image—brief, but not brief enough—flashes through her mind and her stomach clenches.

“I have to go, Missy,” she says. “Good night.”

She recradles the phone on her bedside table and turns out the light. She imagines walking into the library tomorrow, no Mulder. And the day after that, no Mulder. And next week, no Mulder.

She imagines that today was the last day. She imagines him never coming back to lean over the circulation desk and waggle his eyebrows at her, or stand too close to her in the stacks, or surprise her with a little treat ever again.

Maybe she’d spot him on the green one day and he’d point her out to his buddies and laugh. Hey, that’s the girl I messed with last semester. You know, the dumb one who really thought I liked her? Maybe he’d be too busy making puppy dog eyes at some other girl—some tall, willowy, interesting girl—to even notice her.

It would be for the best. This past week has just been a sort of…temporary universal insanity. A paracosm. A Dickensian glimpse into what her life could be if, perhaps, she lived in some alternate reality (which, let the record show, she does not believe in—but hypothetically).

Here, Missy’s voice interrupts, echoing in her head. This guy is clearly crazy about you. She frowns into the darkness. It sounds so simple when her sister says it, so reasonable.

And then there’s Mulder’s voice, too, low and intimate, asking her to coffee, to dinner, to a movie, to anything, really, anything at all. And not just one day. Every day. Several times a day, again and again and again, no matter how many times she says no, says Mulder, please, says I have work to do.

Dana tosses and turns and draws the covers up over her head, curling herself tight against the seductive pull of fantasy. She has always been the level-headed one, never a daydreamer, never impractical. She resents the idea that some boy who will no doubt be gone in another week’s time can ruffle her so much.

Huffing, she hugs a pillow tight to her chest and resolves to put Fox Mulder from her mind. It works, like most nights, only until she begins to dream.

[olko71]

New Post has been published on All about business online

New Post has been published on http://yaroreviews.info/2021/10/merck-pill-intended-to-treat-covid-19-succeeds-in-key-study

Merck Pill Intended to Treat Covid-19 Succeeds in Key Study

Merck MRK 8.37% & Co. and its partner Ridgeback Biotherapeutics LP said their experimental Covid-19 pill helped prevent high-risk people early in the course of the disease in a pivotal study from becoming seriously ill and dying, a big step toward providing the pandemic’s first easy-to-use, at-home treatment.

The pill cut the risk of hospitalization or death in study subjects with mild to moderate Covid-19 by about 50%, the companies said Friday.

The drug, called molnupiravir, was performing so well in its late-stage trial that Merck and Ridgeback said they stopped enrolling subjects after discussions with the U.S. Food and Drug Administration.

The results put molnupiravir on track potentially to be authorized by the end of the year and to finally provide an option for doctors who have spent the pandemic seeking a drug that infected people could easily take at home to prevent them from becoming hospitalized.

Merck plans to ask the FDA to authorize the drug’s use in the coming weeks, Chief Executive Rob Davis said.

If cleared by regulators, the drug would be the first oral antiviral for Covid-19. Within five days of showing symptoms, people would take eight pills daily for five days, if they followed the same protocol used in the study.

Molnupiravir would become a kind of Tamiflu for Covid-19, a medication that can be dispensed to patients when they first develop symptoms, slowing the spread of the virus in the body and potentially preventing people from becoming seriously ill.

Daily reported Covid-19 deaths in the U.S.

Notes: For all 50 states and D.C., U.S. territories and cruises. Last updated Source: Johns Hopkins Center for Systems Science and Engineering

“The ability to take what is a devastating disease like Covid-19 and potentially make it a manageable situation through what is a very convenient round of administration, which is an oral pill you can take at home, has important implications for the ability to manage the ongoing pandemic,” Mr. Davis said.

Together with vaccines, the pill, if authorized, would help transform Covid-19 from a deadly pandemic disease that overwhelms hospitals to a treatable illness as it becomes endemic in the population. “This will help get to that endemic level and maintain that level,” said Gabor Kelen, director of the Department of Emergency Medicine at Johns Hopkins Medicine.

Doctors expressed concern, however, the pill’s promising results might encourage people who are vaccine hesitant to feel emboldened about not getting vaccinated.

“Vaccination is still, first and foremost, the most effective and least risky thing that you can do,” said John Mellors, chair of the Division of Infectious Diseases at the University of Pittsburgh Medical Center and the University of Pittsburgh.

Merck and Ridgeback reported the findings in a press release after an early look at results from the study, which is scheduled to finish in November. The results haven’t been published in a peer-reviewed scientific journal.

The companies said the rate of side effects in study subjects who got molnupiravir and those who got a placebo was similar, though they didn’t say in their news release whether the drug was found in the study to be safe. Mr. Davis, however, said he was confident in the drug’s safety profile.

The drug appeared effective against circulating Covid-19 variants, including highly contagious Delta, according to the companies.

Doctors are increasingly turning to monoclonal-antibody drugs to treat high-risk patients who get sick with Covid-19. WSJ takes a look at how the therapies work and why they’re important for saving lives. Illustration: Jacob Reynolds/WSJ

The results position Kenilworth, N.J.-based Merck, one of the world’s biggest drugmakers, to play a larger role in responding to the pandemic after several setbacks. After its two experimental vaccines failed in testing, Merck agreed to help make Johnson & Johnson’s JNJ -0.64% shot. Merck also halted development of an experimental drug it acquired through a $425 million purchase.

Molnupiravir could generate $10 billion in sales cumulatively through 2025, given potential for stockpiling and its potential for preventing Covid-19, which is still being studied, according to Daina Graybosch, an analyst at Leerink LLC. Merck shares rose more than 9% on the pill news.

Merck said it expects to produce 10 million courses of treatment by the end of the year, with more doses coming next year. If authorized, Merck would begin shipping doses fairly quickly, Mr. Davis said.

The U.S. has agreed to pay Merck $1.2 billion for 1.7 million courses of treatment, should regulators green light use of molnupiravir.

Merck said it plans to make the drug available world-wide and has licensing agreements with generic manufacturers to provide the drug to low-income countries, many of which have had difficulty accessing vaccines to slow the virus’s spread.

Vaccines are the main weapon fighting the pandemic, but doctors and health authorities have long looked for drugs that can help keep people who do get infected from developing severe illness and needing hospitalization.

Nearly two years into the pandemic, however, the drug options are limited. Remdesivir, from Gilead Sciences Inc., GILD -1.85% GILD -1.54% is the only antiviral fully approved by the FDA but is used only to treat hospitalized patients.

The FDA has cleared antibody drugs made by companies like Regeneron Pharmaceuticals Inc. REGN -5.68% and GlaxoSmithKline GSK -0.21% PLC and its partner Vir Biotechnology Inc. VIR -21.07% for people with mild to moderate Covid-19 who aren’t hospitalized. The drugs reduced the risk of hospitalization or death by at least 70% in their trials, a higher efficacy rate than molnupiravir. Yet the antibody drugs are more complicated to administer than swallowing a pill, requiring an intravenous infusion, which initially slowed their uptake.

One of the more effective drugs against Covid-19, a steroid named dexamethasone, is for very sick patients.

“Even though on its face the pill may have shown less benefit than the monoclonal antibodies, because it will be so much easier to use, it will have a much bigger impact on the world stage,” said Daniel Kuritzkes, chief of the division of infectious diseases at Brigham and Women’s Hospital in Boston.

Dr. Mellors said the companies’ results, while encouraging, left him with questions as to how effective the drug is in vaccinated people with breakthrough infections and how its effectiveness compares with monoclonal antibodies. “We need to see the full data set,” he said. He said it would also be important to study the drug’s safety over the long term.

Rajesh Gandhi, an infectious diseases physician at Massachusetts General Hospital and Harvard Medical School, said he would like to know if the pill actually shortened the duration of symptoms and decreased the severity of the disease for those patients who were hospitalized.

He said if the drug is authorized and when more data become available, he would likely prescribe the drug to outpatients with a risk factor, in line with the group that Merck and Ridgeback studied, rather than those at low risk, and that antivirals are best started early in the course of a disease. Yet the drug, he said, would be helpful for those at risk of severe illness.

“You could call in a prescription for the patient, they wouldn’t have to come to get an infusion or a subcutaneous injection, and therefore it would make it easier, kind of like how we treat influenza during flu season,” he said.

Molnupiravir was initially developed by a not-for-profit biotechnology company owned by Emory University. Ridgeback then licensed and formed a collaboration with Emory in early 2020 and later announced a partnership with Merck.

Molnupiravir works by attacking a different portion of the virus than the spike protein on the coronavirus commonly targeted by Covid-19 vaccines and other Covid-19 drugs. The portion attacked by molnupiravir helps the virus reproduce.

“You will now have an oral, easily accessible, easily distributed medicine to keep people out of the hospital and to keep them from dying,” said Wayne Holman, co-founder of Miami-based Ridgeback.

Other companies are also developing Covid-19 antivirals, including Pfizer Inc., PFE -0.19% as well as Roche Holding AG and Atea Pharmaceuticals Inc.

Merck and Ridgeback stopped a study of molnupiravir in hospitalized patients in April, after researchers found that it failed to help them and is unlikely to reduce hospital stays and deaths.

The companies continued studying whether the antiviral was effective early in the course of the disease and in people who are at high risk of Covid-19 complications. Antivirals tend to be most effective when taken soon after infection and become less beneficial over time as patients get sicker, according to doctors and scientists.

The Merck-Ridgeback late-stage, or Phase 3, study enrolled more than 1,400 people who were at high risk of becoming seriously ill with Covid-19. To enroll, participants had to be unvaccinated. About half received an 800-milligram dose of molnupiravir twice a day for five days, with the other participants receiving a placebo.

High risk was defined as having at least one characteristic associated with severe disease or death, such as old age, obesity or diabetes. Treatment began within five days after the participants developed Covid-19 symptoms.

In the interim analysis, 28 of the 385 subjects who received the drug were hospitalized after 29 days, Merck and Ridgeback said, compared with 53 of the 377 subjects in the placebo group who were either hospitalized or died, resulting in an efficacy rate of about 50%.

Through the 29 days, no subjects who received molnupiravir had died, compared with eight deaths in the placebo group, according to the companies.

The interim review of the drug’s effectiveness and safety was performed by an outside panel of independent experts known as a data-safety monitoring committee, which then shared its findings with Merck and Ridgeback.

The panel met late Tuesday to review the data, and then recommended the study stop enrollment because of the positive results, Dr. Holman said. The companies then went to the FDA with that recommendation.

Mr. Davis said that researchers would still perform a final analysis, which could mean the efficacy percentage is adjusted but the overall positive outcome shouldn’t change.

Merck and Ridgeback said in September that they had begun a separate trial studying whether molnupiravir could prevent infection in people after they are exposed to the virus.

Write to Jared S. Hopkins at jared.hopkins@wsj.com and Betsy McKay at betsy.mckay+1@wsj.com

Copyright ©2021 Dow Jones & Company, Inc. All Rights Reserved. 87990cbe856818d5eddac44c7b1cdeb8

[billion-heartbeats]

mic Is this the beginning of the end of the pandemic in India?                     This was an organism unknown to science five months ago. Today it is the subject of study on an unprecedented scale. Antiviral drug trials have been launched. Some 150 vaccine trials are on the anvil! ICUs have been strengthened. Schools closed. To put it simply the World was in a lockdown. This may not be the end! But certainly, the beginning of the End! This is a public-health emergency, and only public health is going to get us out of this. It doesn’t matter how much virus is out there, if people aren’t susceptible to getting it, then the virus will go away. 2021 looks like it will be much better than 2020. India inches closer to the beginning of the end of COVID-19 pandemic. A timely response mitigates the effects of a disaster and India has been spot-on in this regard. The leadership role that India has assumed in dealing with this crisis is now being appreciated across the globe. India has shown the world that it can handle this crisis upfront.   The most tenuous moment is over: The scientific uncertainty at the heart of COVID-19 vaccines is resolved. Vaccines work. And for that, we can breathe a collective sigh of relief. “It makes it now clear that vaccines will be our way out of this pandemic,” The invention of vaccines against a virus identified only 10 months ago is an extraordinary scientific achievement. These are the fastest vaccines ever developed. The coronavirus continued to rip through the country and daily counts of new infections rose to record heights, the seemingly impossible occurred: good news- the beginning of the end of corona virus disease. Following India’s assiduous fight against the rapidly evolving COVID-19 pandemic since the past six months, the country finally sees signs of green shoots with the faster recoveries and sharp decline of new cases. R0 for India is slowly going down to 1.55 from 1.63 in last 20 days. Current R value is at 0.92. Containment zones in the city of Bangalore is down from a whopping 40,000 to Two in the last three months! The recovery rate has gone up to 93%. A year from now, India is likely to be in the midst of a massive vaccination initiative. If I’m getting your hopes up, then there’s good reason. We may be finally turning a corner on a pandemic after a year in which over 1.3 million have already died globally. On 9 November, Pfizer and BioNTech announced that their ribonucleic acid - RNA-based vaccine was 90% successful in preventing symptomatic covid-19. Overview of the corona pandemic The disease caused by the SARS-CoV-2 virus is known as coronavirus disease 2019 – or COVID-19. Coronaviruses are a large family of enveloped, non-segmented, single-stranded, positive-sense RNA viruses that derive their name from their electron microscopic image, which resembles a crown – or corona. There have been 58.7 Million cases of COVID19 world wide with1.39 million deaths. India was home to 9.14 million cases with 134000 deaths. The decline has come in spite of release of lockdowns and other restrictions. 70% of the people with COVID have stopped transmitting the disease. The current India corona numbers are 45209 a day and there is a progressive decline! As the COVID-19 pandemic evolves around the world, it passes through several phases, raising distinct questions and challenges in each Phase 1 An unknown virus emerges 2 A pandemic unfolds 3 The pandemic accelerates 4 State of decline India has carried out 13 crore corona tests so far. This was the sixth consecutive week of falling coronavirus-related deaths in India. The highest deaths from the virus were recorded during the September 14-20 week, when 8,175 people had succumbed to the infection. The current week's toll, at 3,600, is a 56% fall from the peak. Fresh Covid-19 cases continued to fall for the seventh straight week in the country Transcending geographical boundaries — and every socio-economic and political demarcation — the COVID-19 outbreak has caused huge disruptions globally. It has substantially punctured mankind’s vanity. The scourge of nature is far more serious a threat than man-made wars. It is in this context that I see India’s role as exemplary. Among the world leaders, Prime Minister Modi seems to be particularly perspicacious — not only did he ascertain the real nature of the crisis, but he helped to prepare a graded response to it. It is important to step back and think about the monumental achievement of creating effective vaccines that work for a never-before-seen virus causing a disease in under a year. This rapid pace has been due to the technological advances in the last few years and also due to the rational approach used to design the front runner vaccines. Pfizer and Moderna have separately released preliminary data that suggest their vaccines are both more than 90 percent effective, far more than many scientists expected. Neither company has publicly shared the full scope of their data, but independent clinical-trial monitoring boards have reviewed the results, and the FDA will soon scrutinize the vaccines for emergency use authorization. Initial doses of vaccine should be available in December Pfizer and Moderna - they both bet on a new and hitherto unproven idea of using mRNA, which has the long-promised advantage of speed. This idea has now survived a trial by pandemic and emerged likely triumphant. If mRNA vaccines help end the pandemic and restore normal life, they may also usher in a new era for vaccine development. Several COVID-19 vaccines may soon cross the finish line. To vaccinate billions of people across the globe and bring the pandemic to a timely end, we will need all the vaccines we can get. When the Pandemic emerged with murky origins in late 2019 and found naive, unwitting hosts in the human body. science began to unravel many of the virus’s mysteries — how it spreads, how it tricks its way into cells, how it kills? How the body would react? How dangerous was it to life? How would it infect others etc. A fundamental unknown about vaccines hung over the pandemic and our collective human fate: Vaccines can stop many, but not all, viruses. Could they stop this one? The answer, we now know, is yes. A resounding yes. The day Chinese scientists shared the genetic sequence of a new coronavirus in January, researchers began designing vaccines that might train the immune system to recognize the still-unnamed virus. They needed to identify a suitable piece of the virus to turn into a vaccine, and one promising target was the spike-shaped proteins that decorates the new virus’s outer shell. Pfizer and Moderna’s vaccines both rely on the spike protein. Human immune system and the Vaccines! The human immune system is awesome in its power, but an untrained one does not know how to aim its fire. That’s where vaccines come in. Vaccines present a harmless snapshot of a pathogen, that primes the immune system to recognize the real virus when it comes along. Traditionally, this snapshot could be in the form of a weakened virus or an inactivated virus or a particularly distinctive viral molecule. But those approaches take time and expertise. Both are lacking during a pandemic caused by a novel virus. mRNA vaccines offer a clever shortcut. We humans don’t need to intellectually work out how to make viruses; our bodies are already very, very good at incubating them. When the coronavirus infects us, it hijacks our cellular machinery, turning our cells into miniature factories that churn out infectious viruses. The mRNA vaccine makes this vulnerability into a strength. What if we can trick our own cells into making just one individually harmless, though very recognizable, viral protein? The coronavirus’s spike protein fits this description, and the instructions for making it can be encoded into genetic material called mRNA. Several more vaccines using the spike protein are in clinical trials too. They rely on a suite of different vaccine technologies, including weakened viruses, inactivated viruses, viral proteins, and another fairly new concept called DNA vaccines. Never before have companies tested so many different types of vaccines against the same virus, which might end up revealing something new about vaccines in general. The next few months will be a test of one potential downside of mRNA vaccines: their extreme fragility. mRNA is an inherently unstable molecule, which is why it needs that protective bubble of fat, called a lipid nanoparticle. But the lipid nanoparticle itself is exquisitely sensitive to temperature. For longer-term storage, Pfizer/BioNTech’s vaccine has to be stored at –70 degrees Celsius and Moderna’s at –20 Celsius, though they can be kept at higher temperatures for a shorter amount of time. Pfizer/Bio-NTech and Moderna have said they can collectively supply enough doses for 22.5 million people in the United States by the end of the year. The good news is that while we wait, new treatment options for covid-19 are also becoming available. Just last week the first monoclonal antibody (created by Eli Lilly) received emergency use authorization in the US for the treatment of early stage covid-19. There are other monoclonal antibodies which may be approved in the coming days. All of us are united in the hope for a Great Vaccine. But as they say, hope is not a strategy. Prudence demands that decision-makers of all hues have actionable and cost-effective plans to achieve resilience even in the face of a Protracted Covid. People should receive the vaccine on a war footing. It’s a public good and to be treated as such. But the end of the pandemic does not necessarily mean the eradication of COVID-19. The closing act of this public health calamity is likely to be a gradual return to a new normal, with infections, restrictions, and public health fears falling away one by one rather than all at once. Getting there will not be as simple as getting a shot, but with effective vaccines, robust distribution plans, widespread testing, and continued social distancing through the winter — all possible but hardly assured — our exit from the pandemic could come much sooner than many dared hopes. Testing, isolation and contact tracing, however, are all essentially a backup plan for fighting an infectious virus like SARS-CoV-2. The only way to ensure that the virus won’t burn through a global population again is to build a better defence. And the most impenetrable fortress against a virus is immunity by getting vaccinated. The virus is not likely to go away, maybe ever, but certainly not for a long time. “But that said, we’re not going to be living like this forever, and in fact, I expect by springtime that things will start really getting much, much better. And then it’ll continue to get better. And at some point, we will no longer feel like we’re living now. Dr N Prabhudev Former Director Sri Jayadeva institute of Cardiology Former VC of Bangalore university Former Chairman Karnataka state Health Commission nprabhudev@gmail.com

[simonnricketts]

A tunnel and a lit match.

It's been a while since I announced, in perhaps a rather dramatic and arm-waving manner, that I had been diagnosed with terminal cancer. I was then inundated by lovely messages. (If you fancy getting washed warm by that wave of loveliness, then check the tweets I 'liked' on Twitter). Many people have also helpfully hopped on to the running boards of my faltering Facebook jalopy. But how am I doing? I have often felt the need to update you on that front because lots of you ask me.

However, for a long time, I didn't really have too much to tell. I was mainly just getting used to people smiling at me with their heads slightly tilted to one side - the accepted international shorthand for 'sympathy'.

I am still working - and still doing normal things - and embarking on new chemotherapy. In fact, I am writing this from my chemotherapy bed. I'm currently plugged in for six hours of liquid poison.

You know what? I'll tell you about my chemotherapy - that's what I'll do. Other people may be on the same treatment. Some may be about to be. Perhaps I can tell them and you about how my treatment happens.

(Also, don't forget, this saves me from telling all my family and friends the news over and over again - I can just do it here, once and point them to the link.) Spoiler alert - if you haven't got the time, energy or inclination to read about all that you can scroll to the bottom to find out the answer to the question "How are you, Simon?"

My oncologist - an amiable cove who likes to wear a bow tie - told me: "My job is to keep you as healthy as I can, for as long as I can." While admitting he could not "make the cancer go away"- he seems reasonably confident he can keep me toddling along for a while yet.

He told me of a patient who was in similar condition to me. "That guy comes in for chemo once a month and he's been doing it for three years now. He's not getting any better, of course, but he's not getting any worse."

I'll have some of that, I thought. Something to aim for, if nothing else. Bearing in mind, I had been told that I had anything from six months to two years left.

So, I go in to the hospital every other Monday. Where I am right now. I sit on a bed and they plug me in to the matrix. You may have seen saw my 'portacath' - it's a brilliant, one-stop shop where they can take blood, give blood, insert chemo, even contrast dye for CT scans. All without the pesky "sharp scratch" phrase the nurse says when taking blood with a needle out of a vein in your arm.

Seriously, everyone should have one. It makes everything so much easier. In fact everyone probably will in the future. We could put food into it. And booze. And vitamins. And software updates. And cheese. Or whatever passes for cheese in the future. Anyway. On that Monday, they don't just pump in chemo. Things have moved a long way forward since the days when - as my doctor said - "we just chucked the poison in you and let you feel ill for days." They now pour in anti-sickness drugs, anti-histamine, loads of stuff to stop you feeling lousy.

Then the strong stuff. The first of the big drugs. The cetuximab. You can click on the link if you want but it's not strictly chemotherapy. It's a 'monoclonal antibody' - a biological drug as opposed to a poison. In terms I can understand, it attaches itself to the cancer cells and turns off the 'signalling bit' - the bit that says to other cancer cells "Hey, let's divide and grow bigger and bigger inside this warm body and then finally make this man's family sad for a really long time."

Then I have irinotecan. This one's also pretty clever. It stops the cancer cells from getting the food they need to divide and grow, That confuses the cancer cells so much that the DNA of the cell gets all tangled and stupid, so it CAN'T divide.

Yes, I just called a cancer cell's DNA stupid. Let nobody tell you I'm not "fighting back" or "battling bravely". I'm practically Spartacus, here. Then the last bit. The nurses attach a cocktail of chemotherapy to me and send me on my way. I wear it around the house and office for two days.

The cocktail is called FOLFIRI. It attacks the cancer cells. Blasts them. And blasts lots of me, too. It remains plugged into my chest for 48 hours. It comes in a little thing called a “Baxter bottle” and the nurses gave me a wee sleeve for it, which attached to - yes, the horror - a bum bag belt. A bum bag. *Oscar Wilde voice* "A bum bag?"

I didn't fancy walking around looking like an American tourist: "Excuse me sir, is this the way to Lie-Cester Square toob station?" so I ditched the bumbag and put the bottle in the hood of my hoodie.

It's perfect, it's discreet and it makes me feel like a benign robot who is being refuelled with special, futuristic oil. I may even bring out a range of natty "cancer hoodies" and go on Dragon's Den. I just need a catchphrase.

(I usually hide it deep in the hood. I made it more visible so you could see it) Two days later, the bottle comes off and I wait for the "tunnel". The chemo tunnel, as I have christened it. Usually, by the Friday, I start to feel really tired. By Saturday, I'm fully exhausted and stay in bed all day. I'm like a mobile phone with 1% battery. I can wake up, tell the time, and then go back to sleep. Nothing else. Same for Sunday, too.  By Monday. I'm usually starting to feel better. And I go back to work.

That's kind of it. The worst of the side-effects. Really. Not so much of a crusading hero now, am I? Sure, there's also this rash that covers all of my upper body. (It looks like this) Sure, trips to the toilet don't make me walk out afterwards with the usual spring-heeled joy. Sure, there is some pain - mainly a low abdominal throb - but so many people have worse.

It would be annoying though, wouldn't it, if I did all that and it made no difference to my chances? If it didn't at least slow down the growth of the tumours? All the pain and no gain? I was sometimes worried that would be the case. Well, that's why I'm writing this today. I have had news. Cautiously positive news. I had a CT scan last week and the results came back today. They compared it to a scan that they took in November 2016. The one that brought the really bad news.

I was nervous, about the results, of course. I had mapped out the possible/feasible outcomes in my head before coming to hospital today. In my opinion, from best to worst, they were:

Tumours are shrinking.

Tumours have stopped growing.

Inconclusive scan.

Tumours are still growing, but slower than expected.

Chemo is not working. Cancer is growing and unaffected and perhaps in new places.

Today, the oncologist told me "it's a good scan". He said many of the tumours* inside me have shrunk a bit. Some of them by a lot. Yes. Good. (*I originally wrote 'my tumours' but fuck that, they're not mine).

So - I got pretty much the “best” news I could feasibly hope for, within the parameters of my situation. I’ll take it. I’ll take it cautiously, but positively.

It is a lit match in the chemo tunnel. Not showing a way out, but showing a way.

We will carry on with this chemo for at least another cycle. A surgeon will look into whether they can cut out some of the tumours (again, to extend life). I may have a break from chemo, or I may go on to a more relaxed regime. We don't know yet. So, there you have it. Cancer is still going to kill me. But not today.

And probably not tomorrow, either. For those who scrolled to the end, here's the question and its answer. Question: How are you Simon?

Answer: "I'm okay. Chemotherapy can be tiring and painful but it has reduced the tumours rather nicely after the first four cycles. While the cancer will never go away, this is a good sign for extending my life for a bit longer. Thank you very much for asking. Your hair looks nice."

[scienceblogtumbler]

Alpacas and antibodies: How scientists hope to stop coronavirus in its tracks

Efforts to design a safe vaccine for Covid-19 are moving forward at full throttle, yet experts agree that it’s likely to be a year, at least, before an immunisation is ready. Meanwhile, scientists around Europe are exploring ingenious ways – including with the help of alpacas – to use the latest techniques in molecular manipulation to repair coronavirus-induced lung damage or to block the virus before it wreaks havoc.

Researchers at the Karolinska Institute in Stockholm, Sweden, are optimistic that at least one of the 124 vaccines in the pipeline will succeed. However, a vaccine needs to be delivered to everyone, and scaling to more than 7 billion doses is extremely challenging. So they have set their research sights on a more accessible goal: ‘neutralising’ antibodies that kill an infection after it has taken hold.

The project CoroNAb was established in mid-February when there were 1,000 known deaths from Covid-19 in the world. ‘Containing the spread of the virus is not our primary objective – that ship has sailed,’ said Dr Benjamin Murrell, assistant professor at the Department of Microbiology, Tumor and Cell Biology at the Karolinska Institute. ‘Our aim is to find therapeutics to stop the progression of disease within a patient.’

Therapeutics

These therapeutics will take the form of antibodies that are infused into a patient through a syringe. When someone is infected with the new SARS-CoV-2 coronavirus, they typically mount an antibody response against it, and in most cases these antibodies contribute to clearing the virus. However, infection-fighting antibodies produced in a lab can also be introduced into the body, resulting in passive immunisation.

So what differentiates a vaccine from imported antibodies?

Vaccines are given to people when they are well, prompting them to develop their own antibodies, whereas antibody therapy is administered when an infection has taken hold and a patient is struggling to mount their own immune response.

Monoclonal antibodies (mAbs) – that is, antibodies that are identical clones of one another – have emerged over the past few decades as effective therapies for various medical conditions, including cancers and autoimmune disorders. Increasingly, they are also considered a major medical tool to fight severe viral infections – such as Covid-19 – though to date, only one mAb been approved for this purpose. Many more are in clinical trials, including one that Dr Murrell has been working on.

At what stage of an infection, exactly, a coronavirus patient would be treated with mAbs remains to be seen. ‘This will need to be studied in animal models, or directly in human trials,’ said Dr Murrell, who is coordinating the CoroNAb project together with partners in Denmark, Switzerland, and the UK.

‘Maybe you can treat someone with monoclonal antibody therapy late in infection and still stop deterioration, but perhaps not,’ he said.

The CoroNAb team at the Karolinska Institute is creating mAbs from animals. An animal is given a specific viral antigen (the molecules that interact with a body’s antibodies) and an immune response is provoked, leading to some of the animal’s immune cells producing antibodies. The cells harbouring these antibodies are then isolated and the genetic sequence of the antibody is cloned from each cell into a circular form of DNA that allows the antibodies to be produced in the lab.

‘Since the potency of the antibodies discovered is at least partly down to chance, it makes sense for many groups to be going after the same goal.’

Dr Benjamin Murrell, Karolinska Institute in Stockholm, Sweden

Alpacas

The Stockholm team is focusing its research efforts on mice, rhesus macaques and alpacas. Alpacas are camelids (like camels and llamas) producing particularly interesting antibody fragments, known as ‘single domain’ antibodies, which allow for fast antibody discovery and large-scale antibody production, which is why they are favoured by the CoroNAb team.

One month into the project, these mammals have been injected with lab-created variants of the coronavirus’s spike proteins, and preliminary indications suggest that all animal groups are responding well. Mining the alpaca antibody repertoire is currently underway. Over the next few weeks, the researchers will be testing the neutralising activity of the produced antibodies against SARS-CoV-2.

Dr Murrell said: ‘The coming weeks are both critical and uncertain. Depending on these first results, we’ll either get lucky, or we might have to take a few steps back and repeat.’

Despite all the unknowns, Dr Murrell is confident that neutralising antibodies will emerge from this research. ‘We will make something work,’ he said. The question is, will an effective antibody discovered by the CoroNAb team become a useful addition to Europe’s arsenal of SARS-CoV-2 treatments? Labs around the world are chasing the same prize, working night and day to identify effective antibodies against Covid-19, with some early results already emerging.

To make a contribution in this climate, an antibody will need to have a strong edge over its competition. ‘If one group’s antibody turns out to be 10 times more potent than the next best, you might have to produce far less of it for an effective therapy, reducing the manufacturing burden,’ explained Dr Murrell. He added, ‘Since the potency of the antibodies discovered is at least partly down to chance, it makes sense for many groups to be going after the same goal.’

Bacterium

Professor Luis Serrano from the Centre for Genomic Regulation (CRG) in Spain leads another team engaged in the race against Covid-19. His lab is both supporting global vaccine efforts and probing novel, non-vaccine mechanisms to limit the death toll.

Until two months ago, Prof. Serrano was engaged in the MycoSynVac project, which investigated ways to enlist cellular hosts to transport vaccines around the body. Cellular hosts (known in the field of synthetic biology as chassis) hold great promise as low-cost, scalable and potentially game-changing systems for the targeted delivery of life-saving vaccines.

The chosen chassis in Serrano’s five-year project was a modified form of the bacterium Mycoplasma pneumoniae, which causes respiratory infections. By the project’s conclusion, the researchers were able to show that Mycoplasma makes an excellent universal chassis – meaning all manner of vaccines can safely hitch a ride off it.

Prof. Serrano is optimistic that a vaccine for Covid-19, when it arises, will be among the ingredients that can be safely delivered by his Mycoplasma chassis. The team is in the early stages of testing this hypothesis. Over the next month or so, they will insert synthetic copies of key coronavirus genes into bacterial cells, in the hope that those surface proteins belonging to the virus will trigger a protective immune response from the human body.

As it is engineered from a bacterium that targets the lungs, the chassis may be capable of even more than vaccine transportation, according to Prof. Serrano. ‘We think it can deliver therapeutic molecules directly to receptors in the lungs,’ he said.

These molecules would either counteract inflammation or stop the virus from binding to the alveoli (the cells through which oxygen flows from lungs to bloodstream) by blocking the viral cell receptors, he explains.

With the virus blocked or lung damage repaired, a patient who is not responding to conventional treatments might be spared the worst symptoms of a Covid-19 infection, such as a devastating cytokine storm, where the body mounts a massive, and potentially deadly, immune response – an overreaction triggered by pneumonia.

Spray

‘The idea is to create a spray to deliver our engineered bacteria directly to the lungs, where it will express locally what is needed – the active molecules – and later it will be washed away naturally,’ explained Prof. Serrano.

He added: ‘There are clear advantages to this direct approach. If you apply a drug systemically (affecting the whole body), it might be beneficial where it’s needed but it might also have dangerous effects on other tissue.’

Price is another major benefit to recruiting bacteria to deliver life-saving medications. Producing therapeutic molecules synthetically is expensive. For a fraction of the cost, a host cell can be cloned to produce vast populations of cells containing the same therapeutic molecules.

In the labs of their spin-off company Pulmobiotics, Prof. Serrano’s team is exposing coronavirus proteins to molecules with known anti-inflammatory qualities, to test the molecules’ effectiveness against the virus. They are also engineering mutations of these molecules, hoping to increase the affinity between molecule and human receptor proteins. Data from these experiments is expected by mid-summer.

Prof Serrano is hopeful that his research will yield positive results, however these may not come in time to save lives during the current outbreak. ‘By the time we get (regulatory) approval, the Covid situation may have been resolved,’ he said. ‘But this research will open the way for future therapies during future pandemics.’

The research in this article was funded by the EU. If you liked this article, please consider sharing it on social media.

Published by Horizon

source https://horizon.scienceblog.com/1294/alpacas-and-antibodies-how-scientists-hope-to-stop-coronavirus-in-its-tracks/

[mcatmemoranda]

There was a young female pt who came in complaining of pelvic pain. So I fixated on OB/Gyn causes of pelvic pain. The pt had been to the ER before complaining of pelvic pain and was tested for and negative for gonorrhea and chlamydia. The pt actually had diffuse abdominal pain and the doctor asked more questions about GI etiologies such as PUD and gallstones. Based on the history and physical, it actually seemed more like a GI cause of abdominal pain rather than gynecologic. So he had her follow up with GI. I forgot to not be so myopic in differential diagnoses. Think of other systems that can contribute to the chief complaint. Also, the physical exam helps guide you--in this case, the pt had diffuse abdominal pain, not just pain in the lower abdominal quadrants. So it's less likely a gynecologic etiology. Then the attending asked me how you can clinically distinguish between PUD and gallstones. He said there's really no way to distinguish them clinically. Then he asked about the most common cause of gastric ulcers and I recalled that it's H. pylori and you can do non-invasive testing to diagnose it. I recall when we learned about H. pylori that it's something that the physician shouldn't miss. So it's kind of weird that the pt said her primary care doctor couldn't figure out what was wrong. But then again, the pt didn't seem to be a very good historian. That's another reason why you should think broadly in terms of the differential diagnoses. Then the history and physical can help you to narrow down which things on the ddx it could be.

The diagnosis of H. pylori can be done with a urea breath test (UBT). H. pylori convert urea to CO2 and NH3. So you can give radiolabeled carbon and then detect it in CO2 exhaled but the pt. According to UpToDate:

Noninvasive testing — Noninvasive tests for the diagnosis of H. pylori include urea breath testing (UBT), stool antigen testing, and serology. Of these, UBT and stool antigen assay are tests of active infection. H. pylori serology can be positive in patients with an active or prior infection.

Urea breath testing — UBT is based upon the hydrolysis of urea by H. pylori to produce CO2 and ammonia. Urea with a labeled carbon isotope (non-radioactive 13C or radioactive 14C) is given by mouth; H. pylori liberate labeled CO2 that can be detected in breath samples. The tests can be performed in 15 to 20 minutes and have similar cost and accuracy. The dose of radiation in the 14C test is approximately 1 microCi which is equivalent to one day of background radiation exposure [28]. Even though this dose of radiation is small, the non-radioactive 13C test is preferred in young children and pregnant women. (See "Radiation-related risks of imaging", section on 'Special populations'.)

The sensitivity and specificity of UBT are approximately 88 to 95 percent and 95 to 100 percent, respectively [29]. Thus, false-positive results are uncommon. False-negative results may be observed in patients who are taking PPIs, bismuth, or antibiotics and in the setting of active peptic ulcer bleeding [19,30]. The sensitivity but not specificity of the UBT is reduced in the setting of an active peptic ulcer bleed (67 and 93 percent, respectively) [13]. It is unclear if the reduction in sensitivity is induced by the bleeding process or by changes in the microenvironment of H. pylori to decrease the activity of urease.

The effect of PPIs, which is presumably due to suppression of H. pylori, was illustrated in a series of 93 patients who had H. pylori infection documented by UBT [30]. Treatment with lansoprazole was associated with a negative result on subsequent UBT in 33 percent of patients. Repeat breath test results 3, 7, and 14 days after stopping lansoprazole were positive in 91, 97, and 100 percent, respectively. In another study of 60 patients with biopsy-proven H. pylori infection who underwent UBT testing 7 and 14 days after treatment with lansoprazole false-negative rates with lansoprazole and bismuth were 40 and 55 percent, respectively [31]. It is controversial whether H2RAs affect the sensitivity of the UBT [19,32-34].

Stool antigen assay — The detection of bacterial antigen indicates an ongoing H. pylori infection. Stool antigen testing can therefore be used to establish the initial diagnosis of H. pylori and to confirm eradication [3]. Of the available tests, stool antigen testing is the most cost-effective in areas of low to intermediate prevalence of H. pylori [35]. (See 'Patients not undergoing upper endoscopy' above and 'Confirmation of eradication' below.)

The sensitivity and specificity of the laboratory-based monoclonal enzyme immunoassay (94 and 97 percent, respectively) are comparable to the UBT [36-47]. Stool antigen testing is affected by the recent use of bismuth compounds, antibiotics, and PPIs. Although some data suggest that stool antigen test is predictive of eradication as early as seven days after completion of therapy, to reduce false-negative results, patients should be off antibiotics for four weeks, and PPIs for one to two weeks, prior to testing [19,31,39,48,49]. In the setting of active bleeding from peptic ulcers, the specificity of the stool antigen testing may decrease [50,51]. However, the sensitivity of the monoclonal enzyme immunoassay remains high in the setting of a recent peptic ulcer bleed. This was illustrated in a study in which 34 patients underwent inpatient stool antigen testing a mean of 2.8 days (range 0 to 8 days) after hospitalization for a bleeding peptic ulcer. The sensitivity of the monoclonal enzyme immunoassay in this study was 94 percent, significantly higher than a polyclonal enzyme immunoassay and a rapid monoclonal immunochromatographic stool test (74 and 60 percent, respectively). (See 'Patient undergoing upper endoscopy' above and 'Medications that should be discontinued prior to testing' above.)

Stool antigen testing using the polyclonal enzyme immunoassay is no longer used given its low sensitivity. The rapid in-office monoclonal immunochromatographic stool antigen tests has high specificity but its adoption has been limited by its low sensitivity (96 and 50 percent, respectively) [52]. (See 'Confirmation of eradication' below.)

Serology — Laboratory-based ELISA test to detect immunoglobulin G (IgG) antibodies is inexpensive and noninvasive. However, serologic tests require validation at the local level, which is impractical in routine practice. In addition, concerns over its accuracy have limited its use. Guidelines recommend that serologic testing should not be used in low prevalence populations as the low accuracy of serology would result in inappropriate treatment in significant numbers of patients [2,3,11].

One meta-analysis that evaluated the performance of several commercially available serologic assays found an overall sensitivity and specificity of 85 and 79 percent, respectively [53]. Inaccurate serological tests are more common in older adults and in patients with cirrhosis in whom specificity can be decreased [54,55]. Local prevalence of H. pylori affects the positive predictive value of antibody testing. In areas where the prevalence of H. pylori is less than 20 percent, as in much of the United States, a positive serologic test is more likely to be a false positive. As a result, secondary testing with a stool or breath test to confirm the initial result is appropriate before initiating treatment. However, a negative test in a patient with a low pretest probability for infection, is helpful to exclude infection. An example would be a young individual with dyspepsia and no evidence of peptic ulcer disease, especially in an area where the prevalence of H. pylori is low.

Serology does not reliably distinguish between active and past infection. A quantitative ELISA test is generally used in research settings. It allows for determination of IgG titers of paired sera from the acute and convalescent (three to six months or longer) phase and can confirm eradication of the infection. However, this is not performed in clinical practice.

[adr-and-fit-blog]

Moon is a harsh mistress.

"suna hai, sunaa hai...", The phone sang into the ear of an air-headed simpleton who is the sixteen year old in me, as I stood there on the balcony of a gloomy library, grasping the caging installed on the parapet. I prefer to call it caging as in my view it isn't a grill or a railing put up for safety. Rather an insurance for the institution, in case one of these sorry bastards (read MBBS doctors trying to get a post graduation), including yours truly, tried to off themselves. That Hindi song, inspite of my bare minimum Hindi knowledge, was serving as the ray of sunshine I needed that blue day.

"Hi! Adi!!"

Hundreds of guys would give their left testicle to have their names called by that chirpy voice. But, I think I'm just lucky!

"Hey, how's my favorite girl today?"

"sad, Adi.."

'As expected', thought the mediocre intellectual in me.

Even though the Himalayan problems faced by the ravishing yet naive second year damsel failed to provoke sadness, fear or happiness in me, the likes of which were expected by her, I still played along, controlled entirely by the horny sixteen year old, who am not sure if lives in my head or further down south. I'm starting to feel down south it is.

"Sharma won't say if she can come to Bangalore or not, yet! But, I wanna come. To be with you. I don't know what to do now!"

"There's one other way, you can come with me with or without Sharma."

"How Adi? Won't she doubt something is up between us if I do that?"

'Oh something will be UP between US alright.', thought the sixteen year old imbecile.

"Okay that might be a problem."

"But, I wanna party. With you! Srisha goes out to pubs and clubs with her boyfriend, Sharma hates going out and I hate Srisha's boyfriend, so I can't go out with them either."

"Why do you hate the guy?", I asked, with a little nonsensical happiness that she hates another guy.

"Two reasons. One, I personally think he's an asshole and two, I'm envious of them both since YOU aren't free"

Behind my small thought process of thinking what to tell her, I was more surprised that she knew what 'envious' meant.

"Haha, twenty more days darling. I'm all yours."

"Yeah, I've made a list. You're taking me to every one of those places."

"Wow, how are you so sure we'll ever get out of your room?"

"Adi! You're horrible!!"

"Guilty as charged."

"What?"

"Nothing, nothing. I am horrible, yes."

"No you're not, I'm not sure I'll let you leave the room either."

As the imbecile in me was beginning to smirk, the gateway to sunshine (my phone), gave a little vibration.

"One second, I'm getting another call."

Leena calling... Read the dim screen under the now bright sun.

'Let it go on call waiting, you can tell you were on a call with mom. People always eat that shit up!' begged the imbecile.

"Darling, I'll call you back. My mom is calling on the other line."

'You stupid fuck, why would you give up a call with a horny girl on the other side to talk to your boring as fuck girlfriend?', screamed the frustrated sixteen year old. What he did not understand is that, if I had the capability of making rational decisions, I wouldn't be in this position in the first place.

'What does he know? He's after all a stew of hormones.' I said to myself.

HORMONES! SHIT!! I've to cover entire hormone physiology before 6 and it's already 4!

"Hey baby!" I cooed to the girlfriend.

"Hey love! Listen, mom told me to come work in the hospital.. I said I....."

As I tuned out the rambling voice in my phone and started mumbling the mindless, punctuated "hmmm", I thought, 'அவளா இல்ல இவளா?' (Roughly translating to that girl or this girl?). I also knew one more thing. If I told this to anyone else, they'll have only one question, "அவளுமா?" ("Avalumaa?" Or, in English "She too?").

Hence, Avelumab.

(Avelumab is a fully human monoclonal antibody drug for use in immunotherapy, originally for the treatment of non-small-cell lung carcinoma.)