Virus World

California’s top epidemiologist is warning health providers to delay using a batch of the Moderna COVID-19 vaccine after a “higher-than-usual number of possible allergic reactions” were reported at a Southern Calfiornia vaccination clinic. The affected lot includes 330,000 doses — roughly 1/10th of what the state so far has distributed.  The reaction was observed in fewer than 10 people who required medical attention after receiving the vaccine at one clinic, state epidemiologist Dr. Erica S. Pan said in a statement Sunday night. The conditions of those affected were not released, but health officials described the allergic reaction as “severe.”

The clinic is located in San Diego, the California Department of Public Health reported later. “Out of an abundance of caution and also recognizing the extremely limited supply of vaccine,” read the statement, “we are recommending that providers use other available vaccine inventory and pause the administration of vaccines from Moderna Lot 041L20A until the investigation by the CDC, FDA, Moderna and the state is complete.”  More than 330,000 doses from the affected lot — which arrived in California between Jan. 5 and Jan. 12 — have been distributed to 287 providers across the state, officials said. No other adverse reactions have been reported from that specific lot. “There are not immediate replacement doses during the pause in addition to pending orders scheduled for shipment in the next few days,” public health officials said in the statement sent to health providers. The health department said they would have more information later this week.

Michael Williams is a San Francisco Chronicle staff writer. Email: michael.williams@sfchronicle.com

(Reuters) - A doctor in Boston with a shellfish allergy developed a severe allergic reaction after receiving Moderna’s coronavirus vaccine on Thursday, the New York Times reported on Friday, citing the doctor. Dr. Hossein Sadrzadeh, a geriatric oncology fellow at Boston Medical Center, said he had a severe reaction almost immediately after being vaccinated, feeling dizzy and with a racing heart, the NYT reported. It is the first severe reaction publicly linked to Moderna’s vaccine, which is in its first week of a nationwide rollout. David Kibbe, a spokesman at the Boston Medical Center, said in a statement on Friday that Dr. Sadrzadeh “felt he was developing an allergic reaction and was allowed to self-administer his personal epi-pen. He was taken to the Emergency Department, evaluated, treated, observed and discharged. He is doing well today.” A U.S. Food and Drug Administration official said last week that the FDA is investigating around five allergic reactions that occurred after people were administered Pfizer Inc and BioNTech SE’s COVID-19 vaccine in the United States.

The approval sets the stage for widespread inoculations in the United States with a second coronavirus vaccine.  As the coronavirus continued to surge across the United States, an independent panel of experts advising the Centers for Disease Control and Prevention voted on Saturday to endorse a second coronavirus vaccine for use in the United States. The committee’s recommendation follows an emergency authorization granted by the Food and Drug Administration on Friday. The committee’s endorsement now awaits final approval by Dr. Robert R. Redfield, director of the C.D.C., expected shortly. Some 5.9 million doses of the Moderna vaccine are slated for distribution starting on Sunday, and the first inoculations are expected to begin sometime on Monday. Unlike the Pfizer-BioNTech vaccine, which was authorized for use in people 16 and older, Moderna’s vaccine is approved only for people 18 and older. While Pfizer began clinical trials of its vaccine in children as young as 12 in October, Moderna did not begin its pediatric studies until this month and does not expect to have complete data on safety and efficacy until sometime next year.

Much of the committee’s deliberations centered on the severe allergic reactions reported in several cases following injections of the Pfizer-BioNTech vaccine, which contains ingredients similar to those in Moderna’s recipe. Six cases of anaphylaxis have now been documented in the United States, and two in Britain. Several milder allergic reactions have occurred, as well. More than 272,000 doses of the Pfizer-BioNTech vaccine have already been doled out nationwide as of Saturday, according to the C.D.C. Allergic reactions to vaccines typically occur at a rate of about one in a million. Dr. Grace Lee, a pediatrician and vaccine expert at Stanford University, noted at the committee meeting that the estimates so far seemed to indicate that the risk of these events associated with the Pfizer-BioNTech vaccine “does seem qualitatively higher than for most typical vaccines.” Still, she added, “for me, personally, it doesn’t necessarily change the risk-benefit balance of the Covid-19 vaccine at this time.” Dr. Thomas Clark, an epidemiologist at the C.D.C., noted that people who experience anaphylaxis after getting a shot shouldn’t receive a second dose. It’s still unclear whether an ingredient in Pfizer’s vaccine was the direct cause of the reactions.

Some experts have pointed to polyethylene glycol, or PEG, a chemical found in many pharmaceutical products, including laxatives like Miralax, that has very rarely been found to cause allergic reactions. Both the Pfizer-BioNTech and Moderna vaccines contain PEG, though in slightly different formulations.  Dr. Sarah Mbaeyi, a medical officer at the C.D.C., said the agency was recommending that people who know they have severe allergies to any ingredient in the vaccines abstain from getting the shots for now. People with a history of anaphylaxis to other vaccines or injectable therapies should consult their doctors and linger on site for monitoring for 30 minutes after their inoculation in case they start feeling sick. (Everyone else — including people who react strongly to other substances like food, pollen or pet dander, and people with mild allergies of any sort — may leave after 15 minutes.) Three severe allergic reactions were reported in Moderna’s clinical trials, which included more than 30,000 adults, half of whom received a placebo instead of the vaccine. None were believed to be linked to the vaccine.  At the meeting, experts also raised concerns about four cases of a temporary facial paralysis called Bell’s palsy, three of which occurred in the vaccine group in the Moderna trial. (Four cases of Bell’s palsy also arose in Pfizer’s trials, all in the vaccine group.) There’s no evidence yet that directly links the paralysis to either vaccine, and Dr. Jacqueline Miller, a senior vice president at Moderna, said her company was continuing to monitor vaccine recipients for the side effect....

Life-threatening responses seen in at least eight people could be linked to polyethylene glycol, known to trigger reactions to some drugs. Severe allergy-like reactions in at least eight people who received the COVID-19 vaccine produced by Pfizer and BioNTech over the past 2 weeks may be due to a compound in the packaging of the messenger RNA (mRNA) that forms the vaccine’s main ingredient, scientists say. A similar mRNA vaccine developed by Moderna, which was authorized for emergency use in the United States on Friday, also contains the compound, polyethylene glycol (PEG). PEG has never been used before in an approved vaccine, but it is found in many drugs that have occasionally triggered anaphylaxis—a potentially life-threatening reaction that can cause rashes, a plummeting blood pressure, shortness of breath, and a fast heartbeat. Some allergists and immunologists believe a small number of people previously exposed to PEG may have high levels of antibodies against PEG, putting them at risk of an anaphylactic reaction to the vaccine.  Others are skeptical of the link. Still, the U.S. National Institute of Allergy and Infectious Diseases (NIAID) was concerned enough to convene several meetings last week to discuss the allergic reactions with representatives of Pfizer and Moderna, independent scientists and physicians, and the Food and Drug Administration (FDA). NIAID is also setting up a study in collaboration with FDA to analyze the response to the vaccine in people who have high levels of anti-PEG antibodies or have experienced severe allergic responses to drugs or vaccines before. “Until we know there is truly a PEG story, we need to be very careful in talking about that as a done deal,” says Alkis Togias, branch chief of allergy, asthma and airway biology at NIAID. Pfizer, too, says it is “actively seeking follow-up.” A statement emailed to Science noted it already recommends that “appropriate medical treatment and supervision should always be readily available” in case a vaccinee develops anaphylaxis.

Anaphylactic reactions can occur with any vaccine, but are usually extremely rare—about one per 1 million doses. As of 19 December, the United States had seen six cases of anaphylaxis among 272,001 people who received the COVID-19 vaccine, according to a recent presentation by Thomas Clark of the U.S. Centers for Disease Control and Prevention (CDC); the United Kingdom has recorded two. Because the Pfizer and Moderna mRNA vaccines use a new platform, the reactions call for careful scrutiny, says Elizabeth Phillips, a drug hypersensitivity researcher at Vanderbilt University Medical Center who attended an NIAID meeting on 16 December. “This is new.”  News reports about the allergic reactions have already created anxiety. “Patients with severe allergies in the US are getting nervous about the possibility that they may not be able to get vaccinated, at least with those two vaccines,” Togias wrote in an invitation to meeting participants. “Allergies in general are so common in the population that this could create a resistance against the vaccines in the population,” adds Janos Szebeni, an immunologist at Semmelweis University in Budapest, Hungary, who has long studied hypersensitivity reactions to PEG and who also attended the 16 December gathering. Scientists who believe PEG may be the culprit stress that vaccination should continue. “We need to get vaccinated,” Phillips says. “We need to try and curtail this pandemic.” But more data are urgently needed, she adds: “These next couple of weeks in the U.S. are going to be extremely important for defining what to do next.”

Toothpaste and shampoo

Pfizer’s and Moderna’s clinical trials of the vaccines, which involved tens of thousands of people, did not find serious adverse events caused by the vaccine. But both studies excluded people with a history of allergies to components of the COVID-19 vaccines; Pfizer also excluded those who previously had a severe adverse reaction from any vaccine. People with previous allergic reactions to food or drugs were not excluded, but may have been underrepresented. The two vaccines both contain mRNA wrapped in lipid nanoparticles (LNPs) that help carry it to human cells but also act as an adjuvant, a vaccine ingredient that bolsters the immune response. The LNPs are “PEGylated”—chemically attached to PEG molecules that cover the outside of the particles and increase their stability and life span. PEGs are also used in everyday products such as toothpaste and shampoo as thickeners, solvents, softeners, and moisture carriers, and they’ve been used as a laxative for decades. An increasing number of biopharmaceuticals include PEGylated compounds as well. PEGs were long thought to be biologically inert, but a growing body of evidence suggests they are not. As much as 72% of people have at least some antibodies against PEGs, according to a 2016 study led by Samuel Lai, a pharmaco-engineer at the University of North Carolina, Chapel Hill, presumably as a result of exposure to cosmetics and pharmaceuticals. About 7% have a level that may be high enough to predispose them to anaphylactic reactions, he found. Other studies have also found antibodies against PEG, but at lower levels. “Some companies have dropped PEGylated products from their pipeline as a result,” Lai says. But he notes that the safety record of many PEGylated drugs has persuaded others that “concerns about anti-PEG antibodies are overstated. Szebeni says the mechanism behind PEG-conjugated anaphylaxis is relatively unknown because it does not involve immunoglobulin E (IgE), the antibody type that causes classical allergic reactions. (That’s why he prefers to call them “anaphylactoid” reactions.) Instead, PEG triggers two other classes of antibodies, immunoglobulin M (IgM) and immunoglobulin G (IgG), involved in a branch of the body’s innate immunity called the complement system, which Szebeni has spent decades studying in a pig model he developed...

Two workers at an Alaska hospital suffered allergic reactions after receiving Pfizer's Covid-19 vaccine this week, and one was kept for observation for at least two nights, hospital representatives said.  The hospitalized worker's reaction was more serious but not life-threatening, doctors said: She felt flushed within the first 10 minutes of receiving the vaccine Tuesday at Bartlett Regional Hospital in Juneau and later reported symptoms including shortness of breath and elevated heart rate. The second Bartlett health care worker was treated for less severe symptoms after being injected Wednesday, felt fine within an hour and was released, hospital officials said.  The cases are the first allergic reactions to the vaccine to be widely reported in the US, although health officials said they are expecting the occasional allergic reaction -- and are prepared to treat anyone suffering from one. The two workers were among staff being vaccinated at Bartlett Regional Hospital as part of the rollout of Pfizer's vaccine across the country this week. State health officials reported the first one Wednesday, and the hospital publicized the second later in the day. "We expected that a side effect like this could occur after reports of anaphylaxis were made in England after people there received the Pfizer-BioNTech Covid-19 vaccine," Alaska's Chief Medical Officer Dr. Anne Zink said after the first reaction was reported. "All sites that are approved to provide vaccinations in Alaska must have medications on hand to deal with an allergic reaction and that was the case in Juneau."