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Thursday, March 3, 2022

Too early for China to seek 'coexistence' with COVID

 It is still too early for China to consider easing its stringent coronavirus restrictions, with the highly infectious Omicron strain still capable of causing large numbers of deaths, said Liang Wannian, head of an expert group on COVID-19 prevention.

Describing China's so-called 'dynamic clearance' strategy as a "magic weapon", Liang said in an interview with China's state broadcaster CCTV on Wednesday that "coexisting" with the virus was still not an option. He said Omicron was still significantly more deadly than influenza and capable of putting great strain on the country's medical resources.

"In these circumstances, if we relax just a little, it is very probable that the likelihood of a single individual getting severe symptoms or dying will be low, but multiplied by 1.4 billion, it will be a massive number," he said.

Chinese medical experts have been discussing openly the effectiveness and economic impact of its 'dynamic clearance' policies, which aim to shut off transmission routes as soon as new cases are detected.

While foreign analysts suggest the 'zero-COVID' approach could undermine economic growth this year, experts in China say that while lockdowns disrupt individual communities or cities, they also allow the rest of the economy to continue without the risk of further outbreaks.

In comments published on the Twitter-like Weibo platform on Monday, Zeng Guang, former chief epidemiologist with the Chinese Center for Disease Control and Prevention, said 'dynamic clearance' policies would not be in place forever.

China would look for a "flexible and controllable opening-up", he said, though the current risks remained considerable.

"Not far into the future, at an appropriate point in time, a Chinese-style roadmap for coexisting with the virus will present itself," he said.

https://www.swissinfo.ch/eng/too-early-for-china-to-seek--coexistence--with-covid---govt-expert/47397586

Illumina remedies on Grail bid ‘yet to convince’ Eu antitrust regulators

 U.S. life sciences company Illumina’s offer to cut prices and allow rivals continued access to its technologies has ‘yet to convince’ EU antitrust regulators scrutinising its $8 billion cash-and-stock bid for Grail, people familiar with the matter said.

The European Commission opened a full-scale investigation into the deal in July last year and warned that it may hurt innovation and competition in the market for cancer detection tests based on sequencing technologies.

https://whbl.com/2022/03/03/exclusive-illumina-remedies-on-grail-bid-yet-to-convince-eu-antitrust-regulators-sources-say/

No Consensus About Timing of Booster After COVID

 When it comes to knowing how much time should pass between having COVID and getting a booster, there are no set rules or solid findings from comparative studies to look to. In light of the Omicron wave, there are currently, and will continue to be, millions of people in Ibero-America and throughout the world who will need this information.

"There's no clear consensus," Jarbas Barbosa, MD, PhD, assistant director of the Pan American Health Organization, told Medscape Spanish Edition. "Although the vaccine is totally safe to give a person who no longer has any symptoms, every country has its own recommendation as to when to give it. There are other factors at play as well, such as the availability of vaccines."

The prevailing recommendation is to give the dose as soon as the person has recovered when they have the opportunity to access this vaccination. According to the Centers for Disease Control and Prevention (CDC), people with known current SARS-CoV-2 infection should defer any COVID-19 vaccination, including booster vaccination, "at least until recovery from the acute illness (if symptoms were present) and criteria to discontinue isolation have been met."

Still, the CDC acknowledges that "information is lacking" about whether and how the amount of time since infection affects the immune response to vaccination.

"While there are a number of soft recommendations, there still haven't been any randomized studies that have evaluated when the best time to vaccinate people after they've recovered from COVID is so as to stimulate the strongest immune response. So, we don't have any solid, conclusive evidence. However, we know that giving the vaccine to someone after they've had the disease is highly effective and provides hybrid protection, something that's highly desirable. So, people who have recovered from COVID-19 should get vaccinated," noted Armelle Pérez-Cortés Villalobos, MD, a Mexican infectious disease specialist now based in Canada. She is also a member of the editorial board for Medscape Spain.

"My recommendation is in line with the CDC's: people should get the vaccine at any time after the isolation and clinical recovery criteria have been met," she added.

The Sooner, the Better?

For many experts in the region, "give the booster any time" turns into "the sooner the booster's given, the better."

"Once the requisite amount of time after the last dose has passed, the booster should be given as soon as the patient no longer has symptoms and their isolation has ended," noted Wilfrido Clara, MD, MPH, a pediatrician and epidemiologist from El Salvador who works for the CDC, in Atlanta, Georgia. He went on to tell Medscape Spanish Edition that, in his opinion, patients treated with monoclonal antibodies only have to wait 90 days.

"When's best? There's no set rule. The CDC recommends that people wait at least until their symptoms have disappeared or 7 days since testing positive and after they've been fever-free for more than 24 hours. So, there's no excuse. Get vaccinated!" as Alfredo Victoria, MD, epidemiologist at Ángeles Hospital Puebla, in Puebla, Mexico, urged on Instagram.

To cite one example, the procedures manual of the Costa Rican Department of Social Security states that the vaccine can be given "immediately after the individual has recovered from the illness." This recommendation is applicable to the first, second, and third doses, as reported in an article in the country's La Nación newspaper.

Chile was the first country in the region to start giving COVID-19 vaccine boosters. Jeannette Dabanch, MD, is an infectious disease specialist at the University of Chile's Clinical Hospital in Santiago. She is also a member of the country's Advisory Committee on Vaccines and Immunizations. As she told Medscape Spanish Edition, "In our booster recommendations, there's no specific recommendation with respect to an interval after infection."

According to the guidelines of Chile's Ministry of Health, "a patient who has had COVID-19 and has recovered can get the vaccine." And Dabanch supported that position. "There's not a lot of evidence, but I believe that the findings of studies on reinfection, as well as the emergence of variants, justify vaccinating on shorter timelines as a matter of public policy."

Other countries recommend longer intervals. In accordance with the advice of its Vaccine Advisory Committee, Colombia suggests that people wait 30 days from the onset of symptoms — or, for those who are asymptomatic, from the date of diagnosis — before getting the booster, said Leonardo Arregocés, MD, PhD, director of medicines and health technologies at the country's Ministry of Health and Social Protection.

As reported in Madrid's newspaper, El Mundo, Spain recommends that, after being diagnosed with COVID, people wait at least 4 weeks — and ensure that they have fully recovered — before getting vaccinated. The United Kingdom adopted the same guidance.

"It Is Confusing"

But the most patient country seems to be Argentina, which this year alone has had over 3 million confirmed new cases of COVID-19 (ie, almost one third of the total cases the country has recorded since the start of the pandemic). In a press conference on January 20 of this year, the country's Minister of Health, Carla Vizzotti, MD, recommended that anyone who has recovered from COVID hold off on getting the booster for 90 days because "the immunity from natural infection is like a booster for our immune system"; the delay will allow "the dose, once it is given, to be more effective and to provide protection for a longer period of time."

This interval is arbitrary ("it could have been 80 days, or 120 days"), but the recommendation is "reasonable," said Pedro Cahn, MD, PhD, scientific director of the Huésped Foundation in Buenos Aires and one of the most prominent infectious disease specialists advising Argentina's government during the pandemic. In his conversation with Medscape Spanish Edition, Cahn pointed out, "There aren't any comparative studies. But we know that acute infection produces a rapid response of antibodies that lasts 4 months. So, while vaccinating immediately doesn't cause anything bad to happen, this approach doesn't take advantage of all of the benefits there are during that time period."

This view was shared by Jorge Geffner, PhD, professor of immunology at the University of Buenos Aires School of Medicine. "The infection essentially acts as an additional dose. And if one immediately administers the third dose of the vaccine — which would be like a fourth dose — it's very likely that there will be only a slight increase in the adaptive immune response. And so it makes sense to wait 60 or 90 days."

Eduardo López, MD, infectious disease specialist and head of the Department of Medicine of the Ricardo Gutiérrez Children's Hospital in Buenos Aires, took a position somewhere in the middle. "There's no global agreement, and even the World Health Organization doesn't indicate what the optimal interval would be. The idea we're currently leaning toward is that if you space the doses out over a longer period of time, when you do give the booster, the antibody levels will increase more. But this is not shown to be true with Omicron. I would fall somewhere in the middle: after a person has been COVID-free for 1 month, the booster doses can be given whenever," he stated on Radio Con Vos.

In a recent video discussion recorded for Medscape, a couple of renowned specialists from the United States shared the uncertainties they, too, have. Paul Sax, MD, clinical director of the Division of Infectious Diseases at Brigham and Women's Hospital and professor of medicine at Harvard Medical School in Boston, Massachusetts, pointed out that one of the most confusing aspects of COVID-19 — for doctors and for patients — is how durable protection is after natural infection. Part of the reason it's so confusing is that it varies from person to person, there is not a "defined dose" like there is with a vaccine, and it also varies depending on the severity of the illness or even the variant involved.

"There are immunologists who feel like, yes, once you get infected, you can wait. You have 3 months at least and you're not going to get reinfected. There are other immunologists who feel like the infection actually harms some of the immune responses and you should probably get vaccinated as soon as you can. I don't think we have enough data to say what the optimal time to wait is," noted Sax.

For his part, Paul Offit, MD, director of the Vaccine Education Center and professor of pediatrics in the Division of Infectious Diseases at Children's Hospital of Philadelphia, Pennsylvania, agreed that this interval will be understood over time. "It does look like the so-called hybrid immunity, which is induced by a combination of natural infection and immunization, provides maybe a broader protection and possibly longer-lasting protection. We'll see, but it is confusing," he acknowledged.

Pérez-Cortés, Dabanch, Clara, Cahn, and Geffner have disclosed no relevant financial relationships.

https://www.medscape.com/viewarticle/969586

Fibromyalgia Patients See Rapid Benefit From Low-Cal Diet

 For nearly three-quarters of obese patients with fibromyalgia, drastic caloric restriction in a small trial led to 30% or greater reduction in symptom severity in only 3 weeks, researchers reported.

The findings support an emerging hypothesis that caloric restriction has its own analgesic effect independent of weight loss, according to Aaron Stubbs, MD, of Michigan Medicine in Ann Arbor, and colleagues writing in ACR Open Rheumatology.

"Although a larger study with a control group would be the next step in investigating this association, this provides important information for clinicians who counsel patients on alternatives to pharmacologic treatments for pain and other somatic symptoms," the researchers concluded.

A connection between obesity and chronic pain has been well documented, with U.S. national data indicating a 60% increase in prevalence of persistent pain in individuals with obesity compared with the non-obese. That has led to a number of studies seeking to determine whether weight loss would relieve pain in such individuals.

Among these was a Michigan Medicine study published in 2017 with many of the same authors that examined a very low-calorie diet for obese people with pain (not specifically fibromyalgia), finding significant improvement after 12 weeks. Although pain relief was tied to weight loss in that analysis, the relief "was not confined to weight-bearing joints," Stubbs and colleagues noted. That observation suggested that "the benefits seemingly conferred by weight loss cannot be attributed to a reduction in mechanical stress on weight-bearing joints alone; rather, it seems likely that at least a subset of patients experience a global reduction in pain sensitivity."

And if that's the case, then perhaps a low-calorie diet would show benefit long before patients begin to lose significant weight -- hence the current study.

Stubbs and co-authors drew on a weight management program running at the University of Michigan for people with obesity, identifying 195 participants who scored at least 4 on Fibromyalgia Survey Criteria (FSC) at baseline. This score represents at least moderate degrees of pain and pain-related problems. These individuals agreed to a liquid meal replacement diet supplying no more than 800 kcal/day, which was supposed to last 12 weeks. The primary analysis was conducted after 3 weeks, with secondary outcomes assessed in 119 who stayed the 12-week course.

Mean body mass index at baseline was 41.5 (SD 5.2); patients' mean age was 45, and 74% were women. About half also had depressive symptoms.

At week 3, participants had lost an average of about 5.6% of body weight, with mean FSC scores falling from 8.39 at baseline to 4.78 across all participants. Symptom reductions of at least 30% were seen in 72%. There was an ever-so-slight trend toward greater weight loss in patients with very marked improvement (6.0%) and those with moderate improvement (5.5%) compared with those showing little to no improvement (5.2%), which the investigators dismissed as trivial.

Indeed, while weight loss continued over the full 12 weeks, reaching a mean 15% of body weight, further pain relief was not observed among those showing at least moderate improvement at week 3. (Average FSC scores did continue to decline through week 8 in those with little to no initial improvement, dipping below 5.0, and all groups showed a rebound in mean scores after week 8.)

Stubbs and colleagues speculated on potential mechanisms to explain the rapid onset of pain relief. One candidate is that caloric restriction inhibits various inflammatory mediators. Previous studies have found effects on interleukin-10, C-reactive protein, lipopolysaccharide binding protein, and inhibitory factor κB-α, although not consistently. Alternatively, Stubbs' group suggested, caloric restriction might relieve pain "through central alteration of neurotransmission" via action on, for example, neuropeptide Y or opioid receptors.

The study did come with one major limitation, the researchers said: the lack of a control group. "Clearly, randomized controlled clinical trials will be necessary to confirm these results," the team wrote. Stubbs and colleagues also acknowledged that no validated thresholds have been established for FSC score changes that could be considered clinically significant.


Disclosures

Primary Vaccine Series Alone Can't Stop Omicron Infection

 Protection against symptomatic COVID-19 with the Omicron variant shot up after a booster dose among adults who received the two-dose Pfizer vaccine primary series (Comirnaty), though even that faded with time, British researchers found.

While protection against symptomatic disease dwindled to next to nothing (8.8%, 95% CI 7.0-10.5) at 25 or more weeks, vaccine effectiveness jumped to 67.2% (95% CI 66.5-67.8) at 2 to 4 weeks following a booster dose of Pfizer and 73.9% (95% CI 73.1-74.6) following a booster dose of Moderna, reported Jamie Lopez Bernal, PhD, MBBS, of the U.K. Health Security Agency in London, and colleagues.

But this protection declined as well, with vaccine effectiveness falling to 45.7% (95% CI 44.7-46.7) at 10 weeks or more after a Pfizer booster, and to 64.4% (95% CI 62.6-66.1) at 5 to 9 weeks after a Moderna booster, they noted in the New England Journal of Medicine.

Protection was even lower for those who received an initial regimen of AstraZeneca's vaccine, with no detectable protection against Omicron at 20 to 24 weeks after the second dose of vaccine, they added.

"Waning of protection has been observed with time since vaccination, especially with the Delta variant, which is able to at least partially evade natural and vaccine-induced immunity," Lopez Bernal's group wrote.

This adds to the evidence for waning effectiveness of the two-dose vaccine series during the Omicron wave. Data published in an early edition of the Morbidity and Mortality Weekly Report on Tuesday found that vaccine effectiveness against laboratory-confirmed COVID-associated emergency department and urgent care visits among kids ages 5 to 11 was 46% at 14 to 67 days following the second dose.

Lopez Bernal's team examined data from Nov. 27, 2021 to Jan. 12, 2022 using a test-negative design, including 886,774 eligible adults infected with the Omicron variant, 204,154 infected with the Delta variant, and 1,572,621 test-negative controls. They noted that since 90% of sequenced cases on November 27 were Omicron, they used cases tested on or after November 27 "when the positive predictive value was more than 80."

Overall, infection with Omicron occurred a median 39 days after a booster dose. Of all participants, 58.4% were women, and 83.2% were white. Of those who previously tested positive, 11% were infected with Omicron versus 1.8% who were infected with Delta.

Interestingly, the study only measured symptomatic disease, not severe disease. "We are unable to determine protection against severe forms of disease ... owing to the small number of Omicron cases resulting in hospitalization so far in our data set and the natural lag between infection and more severe outcomes," Lopez Bernal and colleagues wrote.

A potential limitation to the study was unique to the U.K., where individuals ages 40 and younger were recommended to receive mRNA vaccines rather than AstraZeneca's vaccine due to the risk of vaccine-induced thrombotic thrombocytopenia, meaning the primary population receiving the Pfizer vaccine was likely "young adults and teenagers." Older populations with more pre-existing conditions were more likely to have received booster doses, the authors noted.

Other limitations included the large proportion of travel-associated cases in the early part of the U.K.'s Omicron wave, which were excluded from the analysis.

"Our findings indicate that two doses of vaccination with [Pfizer's vaccine] are insufficient to give adequate levels of protection against infection with the Omicron variant and mild disease," they concluded.


Disclosures

This study was supported by the U.K. Health Security Agency.

Andrews disclosed no conflicts of interest.

Lopez Bernal disclosed no conflicts of interest.

Other co-authors disclosed support from the U.K. government and various ties to industry.

COVID Patients Fared Better at Dedicated Hospitals for It

 Hospitals dedicated to treating only COVID-19 patients appeared to yield better outcomes for them than other, mixed-use hospitals, a study showed.

At the two M Health Fairview hospitals converted to treat COVID-19 starting in March and November 2020, overall mortality with COVID-19 was higher than in the health system's other nine Minnesota hospitals (11.6% vs 8.0%, P<0.001).

But after accounting for the generally sicker patients treated at the dedicated hospitals, in-hospital mortality was a relative 22% to 25% less likely, which was significant in both unmatched and propensity-matched comparisons.

Complications were a relative 19% less likely than at mixed-use hospitals, Elizabeth Lusczek, PhD, of the University of Minnesota in Minneapolis, and colleagues reported in JAMA Network Open.

The mechanism appeared to be higher use of COVID-specific therapies that have been proven in clinical trials.

"This experience suggests improved in-hospital mortality for patients treated at dedicated hospitals owing to improved processes of care and supports the use of establishing cohorts for future pandemics," which are likely only to increase given ongoing globalization and zoonosis, Lusczek's group wrote.

It's a time-honored strategy -- from whole cities established to isolate people infected with leprosy over the centuries to tuberculosis sanatoriums and even South Korean hospitals dedicated to treating the Middle Eastern respiratory syndrome (MERS) outbreak.

M Health Fairview converted two of its hospitals with building modifications to enhance remote telemetry, create negative airflow rooms with HEPA filters, and update interventional radiology and procedural suites and ensure that the healthcare workers there would have easy access to personal protective equipment (PPE) even in times of general shortage.

Protocols also kept up with evolving evidence, in part through dedicated order sets and documentation templates, along with participation in major trials and prospective databases.

Those hospitals saw 2,077 consecutive adults with RT-PCR-confirmed SARS-CoV-2 infection admitted from March 1, 2020 through June 30, 2021. The other nine hospitals in the system had 3,427 such patients admitted during the same period.

The two groups of hospitals differed on nearly every evaluated aspect, with COVID-dedicated hospitals having patients with more factors associated with poor outcomes -- higher median BMI, fewer English-speaking patients, fewer women, higher comorbidity scores (median 6 vs 5 on the Elixhauser index) -- and sicker by everything from baseline oxygen saturation to mechanical ventilation rate (15.9% vs 6.1%) and ICU admission rate (41.1% vs 18.2%).

Quality metrics in treatment of these patients also showed the advantage of the COVID-dedicated hospitals, with significantly higher rates of use of the following:

Sensitivity analyses suggested an even greater effect in patients hospitalized for longer than 3 days (OR 0.70, 95% CI 0.54-0.90), which the researchers said was "not surprising because patients who died from early complications of COVID-19 were likely to die despite any possible intervention, but those with prolonged hospitalization likely benefit from improved care provided by the COVID-19-dedicated hospitals."

Another sensitivity analysis excluding patients treated in the first 3 months of the pandemic showed the same thing, which Lusczek's group called likely "in part from intangible and unmeasurable variables," like early identification and treatment of multiorgan failure and transfer to ICU care.

But staff camaraderie, decreased anxiety from universal PPE use, and such factors might have played a role too, they said.

One key limitation of the study was not comparing results in dedicated COVID-19 wards within hospitals to those of entirely COVID-dedicated hospitals.

But the study was also retrospective, relied on some imputed data and lacked other information on nursing care, like prone positioning.

"There also was clearly bias in the patients who were selected for transfer to the COVID-19-dedicated hospitals by the clinicians at the admitting hospital," Lusczek and colleagues noted.


Disclosures

The research was supported by AHRQ/PCORI and National Institutes of Health National Center for Advancing Translational Sciences grant funds, with additional support from the University of Minnesota.

Lusczek disclosed no relevant relationships with industry. One coauthor disclosed grants from the Ultran Group related to COVID-19 therapeutics.

Are Americans Aware of the Extended COVID Vax Dosing Interval?

 We applaud the CDC's decision last week to update its guidelines to incorporate an extended dosing interval (with 8 weeks between initial mRNA vaccine doses) for younger individuals (12-39 years old) who are not moderately or severely immunocompromised. This decision follows the favorable discussion by the agency's Advisory Committee on Immunization Practices. As we outlined in our recent MedPage Today opinion piece, the evidence strongly supports extended intervals between vaccine doses on the basis of 1) immunological research 2) vaccine effectiveness and 3) safety.

The extended interval dosing signals the CDC is leading with evidence-based guidelines. However, the change still requires more clear messaging and more robust efforts by the CDC to publicize this recommendation to reach as many people as possible.

Make 8 Weeks the Default Interval

The interim update was made on February 22 as a footnote to one of the tables on the CDC's webpage that is geared toward healthcare professionals: "Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Approved or Authorized in the United States." However, we have a few suggestions. In Table 2 on the professionals-focused webpage, CDC should remove the "3-8 weeks" for the Pfizer vaccine interval and the "4-8 weeks" for the Moderna vaccine interval and make "8 weeks" as the default. The footnote under the table indicates who should receive the vaccines using a shorter dosing interval (e.g. people who are moderately to severely immunocompromised; adults ages 65 years and older; and others who need rapid protection due to increased concern about community transmission or risk of severe disease).


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Table 2 from CDC webpage

We also recommend the CDC consider extending the dosing interval for the 5-11 age group (currently 3 weeks between Pfizer doses) after performing research to evaluate the safety and effectiveness of this approach. The National Advisory Committee on Immunization in Canada currently recommends a longer (8-week) dosing interval for this group based on principles of immunology.

By making these changes, the CDC would be accentuating that an 8-week interval of the primary series should be the default and will clarify that the shorter dosing interval is more appropriate only for select groups.

Publicize the Longer Dosing Interval

The CDC should also more publicly promote the modified recommendation by updating the guidelines on its webpage for the general public ("Vaccines for COVID-19") and in press releases to the media, both of which have been noticeably absent.

Greater transparency of these updated evidence-based guidelines can encourage vaccination among those who remain vaccine hesitant or parents who have not yet vaccinated their children due to concerns of myocarditis. With the extended 8-week dosing interval showing evidence of a lower risk of myocarditis, emphasizing this message may be the push parents need to vaccinate their kids.

The extended dosing interval recommendation has become even more urgent with newly emerging evidence around the vaccine for kids. A large analysis from New York showed that vaccine effectiveness against infection among children 5 to 11 years old declined considerably in the Omicron era. While protection against hospitalization declined too, it still remained fairly high (48% in kids 5-11 and 73% in kids 12-17). Of note, this analysis of administrative data could not determine prior infection status among the unvaccinated so the calculated vaccine effectiveness may appear lower since those with previous infection will have some immunity. CDC data released on Tuesday from 10 states, including New York, had somewhat different findings for the 5-11 group, with two doses of Pfizer vaccine showing 51% protection against emergency department and urgent care visits during Omicron, and 74% effectiveness against hospitalization across the Delta and Omicron waves. While more research is needed, both studies point to decreasing protection against Omicron for younger age groups. Increasing the duration between doses for younger children can increase immunogenicity, as evidenced by this Cell paper showing increased antibody and T cell responses with longer intervals of the Pfizer vaccine and this JAMA paper showing similar findings. While these studies look at the response in adults, studies have verified that longer intervals between vaccine doses for other infections in children increase immunogenicity, forming the basis for the childhood vaccination schedule.

In light of this emerging data, what's the best next step? Vaccine safety remains high with the 8-week dosing interval, and while vaccine protection against infection appears to have declined among kids, the COVID-19 vaccine still offers important protection against severe illness and hospitalization. With a more strongly worded and publicized recommendation from the CDC, doctors can discuss this with their patients and help convince them to get vaccinated.

Michael Daignault, MD, is an emergency physician at Providence Saint Joseph Medical Center in Burbank, California. Monica Gandhi, MD, MPH, is a professor of medicine in the school of medicine at University of California San Francisco.

https://www.medpagetoday.com/opinion/second-opinions/97475