'Boosted Americans seem to be getting more COVID-19 infections'

 As COVID-19 cases began to accelerate again this spring, federal data suggests the rate of breakthrough COVID infections in April was worse in boosted Americans compared to unboosted Americans — though rates of deaths and hospitalizations remained the lowest among the boosted.

The new data do not mean booster shots are somehow increasing the risk. Ongoing studies continue to provide strong evidence of additional protection offered by booster shots against infection, severe disease, and death.

Instead, the shift underscores the growing complexity of measuring vaccine effectiveness at this stage of the pandemic. It comes as officials are weighing key decisions on booster shots and pandemic surveillance, including whether to continue using the "crude case rates" at all.

It also serves to illustrate a tricky reality facing health authorities amid the latest COVID-19 wave: even many boosted Americans are vulnerable to catching and spreading the virus, at a time when officials are wary of reimposing pandemic measures like mask requirements.

"During this Omicron wave, we're seeing an increased number of mild infections — at-home type of infections, the inconvenient, having a cold, being off work, not great but not the end of the world. And that's because these Omicron variants are able to break through antibody protection and cause these mild infections," John Moore, a professor of microbiology and immunology at Weill Cornell Medical College, told CBS News.

"So, one of the dynamics here is that people feel, after vaccination and boosting, that they're more protected than they actually are, so they increase their risks," he said. "That, I think, is the major driver of these statistics."

On the CDC's dashboard, which is updated monthly, the agency acknowledges several "factors likely affect crude case rates by vaccination and booster dose status, making interpretation of recent trends difficult."

The CDC had rolled out the page several months ago, amid demands for better federal tracking of breakthrough cases. It has now grown to encompass data from immunization records and positive COVID-19 tests from 30 health departments across the country

For the week of April 23, it said the rate of COVID-19 infections among boosted Americans was 119 cases per 100,000 people. That was more than double the rate of infections in those who were vaccinated but unboosted, but a fraction of the levels among unvaccinated Americans.

That could be because there is a "higher prevalence of previous infection" right now among those who are unvaccinated and unboosted, the CDC said. More boosted Americans may now have abandoned "prevention behaviors" like wearing masks, leading to an uptick.

Some boosted Americans might be more likely to seek out a lab test for COVID-19, as opposed to relying on over-the-counter rapid tests that go largely unreported to health authorities.

"Home testing has become, I think, the single biggest concern in developed countries that can interfere with our measurements," CDC's Ruth Link-Gelles told a conference hosted by the National Foundation for Infectious Diseases last month. 

Some federal officials have floated the possibility of adopting a survey — similar to those relied on by authorities in the United Kingdom — as an alternative way to track a "ground truth" in COVID-19 cases, though plans to stand up such a system do not appear imminent.

"Moving beyond this crisis, I do think the future is in random sampling. And that's an area that we're looking at closely," Caitlin Rivers, a top official on the agency's disease forecasting team, told an event hosted by the National Academies last week. 

Meanwhile, federal officials are also preparing for key decisions on future COVID-19 vaccine shots, which might up the odds that additional shots might be able to fend off infections from the latest variants. 

In the short term, CDC Director Dr. Rochelle Walensky recently told reporters that her agency was in talks with the Food and Drug Administration about extending the option for second boosters to more adults. 

Right now, only adults 50 and over and some immunocompromised Americans are eligible to receive a fourth dose. 

Next generation of vaccines and boosters

Further down the road, a panel of the Food and Drug Administration's outside vaccine advisers is scheduled to meet later this month to weigh data from new booster candidates produced by Pfizer and BioNTech as well as Moderna. 

BioNTech executives told investors last month that regulators had asked to see data for both shots specifically adapted for the Omicron variant in addition to "bivalent vaccines," which target a blend of mutations. 

Those new vaccines would take about three months to manufacture, the White House's top COVID-19 official Dr. Ashish Jha told reporters.

"It's a little bit of a challenge here because we don't know how much further the virus will evolve over the next few months, but we have no choice because if we want to produce the hundreds of millions of doses that need to be available for a booster campaign, we have to start at risk in the early July timeframe or even somewhat sooner," Dr. Peter Marks, the FDA's top vaccines official, said at a recent webinar hosted by the American Medical Association. 

Marks said that bivalent shots seemed likely to be favored, given the "wiggle room" it could offer for unforeseen variants beyond Omicron. 

Vaccines that might offer even better "mucosal immunity" – actually fighting off the virus where it first infects the respiratory system – are still a ways off, Marks cautioned. 

"I think that we are in a transition time and I, again, will speak openly to the fact that 2022 to 2023 is a year where we have to plan for trying to minimize the effect of COVID-19 with the tools that we have in hand," Marks said at a recent event with the National Foundation for Infectious Diseases. 

"I do believe that, potentially by the 2023-2024 season, we'll start to see second generation SARS-CoV-2 vaccines," he added later.

https://www.cbsnews.com/news/covid-19-vaccine-boosters-infection-rate/

N.J. reports 15 COVID deaths, 3,242 cases. Hospitalizations hit 3-month high

 New Jersey on Thursday reported 3,242 COVID-19 confirmed positive tests and 15 confirmed deaths as hospitalizations increased to the highest number of patients in more than three months.

The state’s seven-day average for confirmed cases was 3,043 on Thursday, down 21% from a week ago, but still up 40% from a month ago.

The statewide rate of transmission for Wednesday was 1. When the transmission rate is 1, that means cases have leveled off at the current numbers.

New Jersey 71 hospitals reported 928 patients with confirmed or suspected coronavirus cases as of Wednesday night, the most since Feb. 22 when the winter omicron variant wave was receding.

Of those hospitalized, 117 were in intensive care and 46 were on ventilators. There were at least 180 people discharged in the 24-hour period ending Wednesday, according to state data.

The positivity rate for tests conducted on Saturday, the most recent day with available data, was 16.12%.

The Centers for Disease Control and Prevention now lists 11 New Jersey counties with “high” transmission rates — Atlantic, Burlington, Camden, Cape May, Gloucester, Mercer, Monmouth, Morris, Ocean, Salem and Sussex.

Those in high-risk areas are recommended to wear a mask indoors in public and on public transportation and stay up-to-date on vaccinations, according to the CDC.

Ten counties are in the medium risk category: Bergen, Cumberland, Essex, Hudson, Hunterdon, Middlesex, Passaic, Somerset, Union and Warren. Masks are not recommended in the medium and low regions.

TOTAL NUMBERS

New Jersey has reported 2,061,154 total confirmed COVID-19 cases out of more than 17.8 million PCR tests conducted in the more than two years since the state reported its first known case March 4, 2020.

The Garden State has also recorded about 341,738 positive antigen or rapid tests, which are considered probable cases. And there are numerous cases that have likely never been counted, including at-home positive tests that are not included in the state’s numbers.

The state of 9.2 million residents has reported 33,742 COVID-19 deaths — 30,673 confirmed fatalities and 3,069 probable ones.

New Jersey has the eighth-most coronavirus deaths per capita in the U.S. — behind Mississippi, Arizona, Oklahoma, Alabama, Tennessee, Arkansas and West Virginia — as of the latest data reported Wednesday. Last summer, the state had the most deaths per capita in the country.

The latest numbers follow a major study that revealed even a mild case of COVID-19 can significantly affect the brain. Long COVID — the term commonly used to describe symptoms stemming from the virus long after a person no longer tests positive — has been found to affect between 10% and 30% of those who contract the infection, regardless of whether they have a mild or serious case. In New Jersey, that would mean that roughly 600,000 of the more than 2 million who have tested positive for COVID since the onset of the pandemic either have or have had long COVID.

VACCINATION NUMBERS

More than 6.93 million of the 8.46 million eligible people who live, work or study in New Jersey have received the initial course of vaccinations and more than 7.8 million have received a first dose since vaccinations began here on Dec. 15, 2020.

More than 3.79 million people in the state eligible for boosters have received one. That number may rise after the FDA on Tuesday approved booster shots for healthy children between the ages of 5 and 11. U.S. regulators authorized the booster for kids hoping an extra vaccine dose will enhance their protection as infections once again creep upward.

SCHOOL AND LONG-TERM CARE NUMBERS

For the week ending May 22, with 57.8% of schools reporting data, another 10,948 COVID-19 cases were reported among staff (3,066) and students (7,882) across New Jersey’s schools.

Since the start of the academic year, there have been 135,409 students and 40,649 school staff members who have contracted COVID-19 in New Jersey, though the state has never had more than two-thirds of the school districts reporting data in any week.

The state provides total student and staff cases separately from those deemed to be in-school transmission, which is narrowly defined as three or more cases linked through contact tracing.

New Jersey has reported 924 total in-school outbreaks, including 6,631 cases among students and staff. That includes 48 new outbreaks in the latest weekly report ending May 31. The state reported 69 in-school outbreaks the previous week.

At least 9,122 of the state’s COVID-19 deaths have been among residents and staff members at nursing homes and other long-term care facilities, according to state data.

There were active outbreaks at 363 facilities, resulting in 4,031 current cases among residents and 3,702 cases among staff, as of the latest data.

GLOBAL NUMBERS

As of Thursday, there have been more than 531 million COVID-19 cases reported across the globe, according to Johns Hopkins University, and more than 6.29 million people died due to the virus.

The U.S. has reported the most cases (more than 84.4 million) and deaths (at least 1,007,735) of any nation.

There have been more than 11.38 billion vaccine doses administered globally.

https://www.nj.com/coronavirus/2022/06/nj-reports-15-covid-deaths-3242-cases-hospitalizations-hit-3-month-high.html

Metformin Bombs in Breast Cancer in Landmark Trial

 In the largest investigation into the issue to date, metformin did not improve survival of patients with high-risk, operable breast cancer when added to standard adjuvant treatments.

Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients, as reported by Medscape Medical News. Those studies mostly involved older patients with cancer who also had diabetes.

These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.

Now this latest trial in breast cancer, which included 3649 patients with hormone receptor–positive or –negative disease and who did not have diabetes, also found that metformin had no effect on survival.

These results "tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped," lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, Canada, said in a press release.

The negative results "underscore the need for well-conducted randomized trials" before observational studies are put into practice, Goodwin and her team said.

However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that "because metformin is effective in type 2 diabetes, the results...should not affect the use of metformin" in breast cancer patients who have diabetes.

The study was published online on May 24 in JAMA.

Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment ― chemotherapy, radiotherapy, hormone therapy, and/or others ― following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.

Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.

Among 2533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs 1.32 with placebo (HR, 1.10, P = .47).

Metformin was stopped early at about 3 years for the 1116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs 2.15 in the group that received placebo (HR, 0.89, P = .46).

However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).

The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.

This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it's possible that metformin "could provide an additional treatment option for HER2-positive breast cancer," Goodwin said.

Grade 3 or higher adverse events were more common with metformin (21.5% vs 17.5%). The most common such events were hypertension (2.4% vs 1.9%), irregular menses (1.5% vs 1.4%), and diarrhea (1.9% vs 0.8%).

The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Goodwin has disclosed no relevant financial relationships. Several co-authors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One co-author is an AstraZeneca employee.

JAMA. Published online May 24, 2022. Full text

https://www.medscape.com/viewarticle/974579

Low Vitamin D Links With Increased Diabetic Foot Ulcers

 Researchers published the study covered in this summary on researchsquare.com as a preprint that has not yet been peer reviewed.

Key Takeaways

• Low serum levels of vitamin D were significantly associated with a higher prevalence of diabetic foot ulcers in elderly patients with diabetes.

• Average serum levels of 25-hydroxy-vitamin D (25-OH-D) (vitamin D₃, the major circulating form of vitamin D in people) steadily decreased as the severity of diabetic foot ulcers increased, as measured by the Wagner classification.

• Elderly people with diabetes should undergo routine vitamin D screening or receive vitamin D supplementation to prevent the onset or improve the prognosis of diabetic foot ulcers, the authors say.

Why This Matters

• Vitamin D deficiency is common in elderly patients with diabetes.

• The relationship between diabetic foot ulcers and vitamin D levels is controversial, with conflicting data. 

• This is the first study to assess vitamin D levels in elderly patients hospitalized with a diabetic foot ulcer, the authors say.

Study Design

• This was a retrospective analysis of 339 hospitalized patients with type 2 diabetes aged 60-90 years seen between January 2020 and March 2020, including 204 with and 135 without diabetic foot ulcers.

• The study included patients who met the 1999 diagnostic criteria of the World Health Organization for diabetes and diabetic foot ulcers, but excluded those taking an agent that can affect serum vitamin D levels.

Key Results

• The average age of participants was 67 years old and nearly two thirds were men.

• In the multivariate analysis, independent significant protective factors for diabetic foot ulcer were higher levels of 25-OH-D, triglycerides, and HDL-C.

• Factors that independently linked with an increased diabetic foot ulcer risk were prolonged diabetes duration and elevated systolic blood pressure.

• Overall, 80.5% had vitamin D deficiency (defined as < 50 nmol/L or < 20 ng/mL).

• Among the people without a diabetic foot ulcer, 3% had vitamin D levels that were sufficient (> 75 nmol/L or > 30 ng/mL), 24% had levels defined as insufficient (50-75 nmol/L or 20-30 ng/mL), and 73% were deficient.

• Among those with a diabetic foot ulcer, 2% had sufficient vitamin D levels, 13% had insufficient levels, and 85% had deficient levels. The differences between these rates and those among the people without a diabetic foot ulcer were significant.

• Level of 25-OH-D significantly decreased with increasing severity of diabetic foot ulcer based on Wagner grade. People with the lowest grade diabetic foot ulcer, Wagner 1, had on average more than twice the serum level of 25-OH-D compared to those with the most severe diabetic foot ulcer, rated as Wagner 5.

Limitations

• The study was cross-sectional. Well-designed, prospective studies are needed to assess the causal relationship between vitamin D and diabetic foot ulcer risk, and to explore whether vitamin D supplementation has any effect on diabetic foot ulcer treatment, the authors said. The results could provide clear evidence for using vitamin D supplementation for prevention and treatment of diabetic foot ulcer in elderly people with diabetes.

Disclosures

• The study received no commercial funding.

• The authors reported no disclosures.

This is a summary of a preprint research study, "Correlation between serum 25-OH-vitamin D level and diabetic foot ulcer in elderly diabetic patients," written researchers at the Air Force Medical Center, Beijing, China, and colleagues on Research Square and brought to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on researchsquare.com.

https://www.medscape.com/viewarticle/975027

IV Lidocaine Relieves Pain in Refractory Migraine

 Lidocaine infusions yield both short- and medium-term pain relief in treatment-resistant chronic migraine, new research suggests.

Investigators analyzed data for more than 600 hospitalized patients with refractory chronic migraine receiving continuous multiday lidocaine infusions. Results showed median pain rating decreased by 6 points on the Numerical Rating Scale (NRS) from admission to end of hospitalization.

In addition, almost 90% of patients responded acutely, with 43% achieving sustained improvement at 1 month.

"Our main messages are that lidocaine can produce acute relief of headache pain, and on average, patients in the study reported some relief up to a month or greater after treatment," study investigator Eric Schwenk, MD, associate professor of anesthesiology and orthopedic surgery and director of orthopedic anesthesia, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, told Medscape Medical News.

The findings were published online May 23 in BMJ Regional Anesthesia and Pain Medicine.

Adequate Evidence?

Inpatient hospitalization for treatment with multiday intravenous infusions is indicated for patients with refractory chronic migraine, the investigators note.

Continuous multiday lidocaine infusion has been suggested for these patients. Although the exact mechanism of action is unknown, it appears its anti-nociceptive, anti-hyperalgesic, and anti-inflammatory effects "play a key role," the researchers write.

Schwenk said he conducted the study because patients with resistant migraine "have very few treatments to turn to that can produce meaningful improvement in their headache pain." He added that this type of migraine is usually associated with some degree of disability.

At Thomas Jefferson, intravenous therapies such as lidocaine infusions "have been used successfully for several decades, but very few studies have been published that show any benefit of lidocaine," he said.

"We wanted to describe our experience with lidocaine and demonstrate the benefits on headache pain that occur. We also wanted to show that there is adequate evidence to support a clinical trial, which is the gold standard in medicine, that examines lidocaine in chronic migraine," Schwenk added.

The researchers assessed the electronic records of all consecutive inpatients with refractory chronic migraine who had sufficient information in their charts and who were treated with continuous lidocaine infusion between April 1, 2017 and April 1, 2020. The analysis included 609 patients (mean age, 46  years; 81.1% women; 89.8% White, 6.4% Black, 2% Hispanic).

In addition to the infusion, patients received other migraine medications during hospitalization, including ketorolac, magnesium, dihydroergotamine, methylprednisolone, and neuroleptics.

The primary outcome was change in headache pain from baseline to hospital discharge. Secondary outcomes, measured at the postdischarge office visit 25 to 65 days after treatment, included headache pain, number of headache days, percentage of sustained and acute responders, plasma lidocaine levels, and drug-related adverse effects (AEs).

Not For Everyone

Results showed baseline current pain ratings for all hospitalized patients decreased from a median of 7.0 (5 - 8) on admission to 1.0 (0 - 3) on discharge (P < .001) on the NRS. On the scale, a zero is defined as "no pain" and a 10 is "worst pain imaginable."

The average pain at the post-discharge office visit likewise decreased from baseline (5.5 vs 7.0 [5.0 - 8.0], P < .001). Moreover, the number of headache days decreased from baseline to the postdischarge office visit (26.8 vs 22.5 day, P < .001).

The researchers also distinguished between "acute" (86.8%) and "sustained" (46.2%) responders, with some overlap. Acute responders reported a decreased of 2 points or more on the NRS from beginning to end of treatment. Sustained responders were "those acute responders whose average pain remained at a level 2 points below baseline at 1 month," the investigators write.

A subgroup analysis of 244 patients who had received lidocaine previously showed no difference in headache days at the postdischarge office visit between them and the participants who had not previously received lidocaine.

Patients who received ketorolac or methylprednisolone during their hospitalization had a smaller change in pain compared with those who did not receive these agents. There were no significant differences in patients who received other headache medications.

The most common adverse event was nausea/vomiting. This was followed by cardiovascular changes, hallucinations/nightmares/visual changes, sedation/sleepiness, anxiety, dizziness/lightheadedness, cerebrovascular accident-like symptoms, urinary retention, and paresthesias.

"Lidocaine is not for everyone and does have some side effects such as nausea/vomiting, heart rhythm changes, and vision changes," said Schwenk.

Additionally, "in our study it required an average of 5 days of continuous infusion through an intravenous line to be effective and has not been well studied in patients with less severe disease," he noted.

Nevertheless, "for patients with refractory chronic migraine and their physicians, it may be worth considering referral to an experienced center that can offer aggressive intravenous treatments such as lidocaine if relief cannot be obtained from other medications," he said.

The investigators add that a "prospective, randomized, double-blind trial is needed to confirm these results but may be challenging, given the refractory nature of the disease and the associated ethical dilemmas."

"Valuable Evidence"

Commenting for Medscape Medical News, Samer Narouze, MD, PhD, professor and chair, Center for Pain Medicine, Western Reserve Hospital, Cuyahoga Falls, Ohio, "congratulated" the investigators on the research. He was not involved with the study.

He described the paper as "an important step in the search for an effective treatment for intractable chronic migraine headaches, which are otherwise refractory to other medications."

However, Narouze, who is also the president of the American Society of Regional Anesthesia and Pain Medicine, pointed to several limitations to adopting the described protocol.

First, the researchers used continuous infusions for several days with hospitalization, which "may significantly add to the treatment costs and may not be feasible or practical for wide adoption by many," he said. In addition, the "great outcomes reported in this study" may not be reproducible with outpatient infusions.

"It would have been helpful if the authors could identify who will benefit from IV lidocaine therapy and who won't, although this could be impossible to achieve, as most of these patients are on so many diverse preventive medications," Narouze noted.

Nevertheless, given the challenges of conducting a large, prospective randomized controlled trial, "we need to count on other available data sources, and the current study by Schwenk's team represents the real-world data," said Narouze.

Also commenting for Medscape Medical News, Jason Ray, MBBS, consultant neurologist in the Department of Neurology at Alfred Hospital and Monash University, Melbourne, Australia, and at Austin Health, Heidelberg, Australia, noted the study provides "valuable evidence of the efficacy and safety of intravenous lidocaine, publishing the largest series to date in the literature detailing the inpatient and 1-month response rates." Ray was not associated with the research.

No study funding was listed. Schwenk has been a consultant, advisory panel member, or received honoraria from AbbVie, Amgen, Aeon BioPharma, Axsome Therapeutics, Curelator, Epalex, GlaxoSmithKline Consumer Health Holdings, electroCore Medical, Impel NeuroPharma, Lilly USA, Medscape, Lundbeck, Nocera, Pulmatrix, Revance, Salvia, Bioelectronics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, Thermaquil, and Trillen Medical.

Narouze reports no relevant financial relationships. Ray reports receiving funding from the Pharmaceutical Society of Australia and the Limbic and has been supported by unrestricted funding grants from Viatris and Novartis for educational material. He has also received support from Lundbeck for the running of a trial of eptinezumab vs lidocaine.

BMJ Reg Anesth Pain Med. Published online May 23, 2022. Full text

https://www.medscape.com/viewarticle/975011