Tough Pain Relief Choices in the COVID-19 Pandemic

 More people with fever and body aches are turning to nonsteroidal anti-inflammatory drugs (NSAIDs) to ease symptoms, but the drugs have come under new scrutiny as investigators work to determine whether they are a safe way to relieve the pain of COVID-19 vaccination or symptoms of the disease.

Early on in the pandemic, French health officials warned that NSAIDs, such as ibuprofen, could worsen coronavirus disease, and they recommended switching to acetaminophen instead.

The National Health Service in the United Kingdom followed with a similar recommendation for acetaminophen.

But the European Medicines Agency took a different approach, reporting "no scientific evidence" that NSAIDs could worsen COVID-19. The US Food and Drug Administration also opted not to take a stance.

The debate prompted discussion on social media, with various reactions from around the world. It also inspired Craig Wilen, MD, PhD, from Yale University School of Medicine in New Haven, Connecticut, and his team to examine the effect of NSAIDs on COVID-19 infection and immune response. Their findings were published online January 20 in the Journal of Virology.

"It really bothered me that nonevidence-based decisions were driving the conversation," Wilen said. "Millions of people are taking NSAIDs every day and clinical decisions about their care shouldn't be made on a hypothesis."

One theory is that NSAIDs alter susceptibility to infection by modifying angiotensin-converting enzyme 2 (ACE2). The drugs might also change the cell entry receptor for SARS-CoV-2, alter virus replication, or even modify the immune response.

British researchers, also questioning the safety of NSAIDs in patients with COVID-19, delved into National Health Service records to study two large groups of patients, some of whom were taking the pain relievers.

"We were watching the controversy and the lack of evidence and wanted to contribute," lead investigator Angel Wong, PhD, from the London School of Hygiene and Tropical Medicine, told Medscape Medical News.

And with nearly 11 million NSAID prescriptions dispensed in primary care in England alone in the past 12 months, the inconsistency was concerning.

The team compared COVID-19-related deaths in two groups: one group of more than 700,000 people taking NSAIDs, including patients with rheumatoid arthritis and osteoarthritis; and another of almost 3.5 million people not on the medication.

NSAIDs work by inhibiting cyclooxygenase (COX)-1 and COX-2 enzymes in the body, which are crucial for the generation of prostaglandins. These lipid molecules play a role in inflammation and are blocked by NSAIDs.

The investigators found no evidence of a harmful effect of NSAIDs on COVID-19-related deaths; their results were published online January 21 in the Annals of the Rheumatic Diseases.

The results, they point out, are in line with a Danish study that also showed no evidence of a higher risk for severe COVID-19 outcomes with NSAID use.

"It's reassuring," Wong said, "that patients can safely continue treatment."

More New Evidence

Wilen's team found that SARS-CoV-2 infection stimulated COX-2 expression in human and mice cells. However, suppression of COX-2 by two commonly used NSAIDs, ibuprofen and meloxicam, had no effect on ACE2 expression, viral entry, or viral replication.

In their mouse model of SARS-CoV-2 infection, the investigators saw that NSAIDs impaired the production of proinflammatory cytokines and neutralizing antibodies. The findings suggest that NSAIDs influence COVID-19 outcomes by dampening the inflammatory response and production of protective antibodies, rather than modifying susceptibility to infection or viral replication.

Understanding the effect of NSAIDs on cytokine production is critical, Wilen pointed out, because they might be protective early in COVID-19 but pathologic at later stages.

Timing is crucial in the case of other immunomodulatory drugs. For example, dexamethasone lowers mortality in COVID-19 patients on respiratory support but is potentially harmful for those with milder disease.

There is a lot to learn, still, Wilen acknowledged. "We may be seeing something similar going on with NSAIDs, where the timing of treatment is important."

https://www.medscape.com/viewarticle/944956

Employers' Post-Pandemic Playbook

 As the vaccination rate steadily builds toward "herd immunity" to COVID-19, employers will be faced with a "new normal" in terms of workplace safety and employee heath. Will they try to wash their hands of the whole COVID-19 mess or, hopefully, will they realize that improving employee health should be a business priority? Judging from their efforts in 2020, I am betting that some of the largest U.S. employers will opt for the latter. Here are two examples.

Walmart: Like many other large companies, Walmart responded quickly to the pandemic by updating and implementing health safety policies (e.g., daily temperature checks and health screenings), providing personal protective equipment (PPE) for its employees at more than 5,000 locations, assuring paid leave for employees (e.g., quarantine pay, pay while dealing with confirmed case of COVID-19), and offering cash bonuses to help all employees.

In terms of post-pandemic employee and consumer health improvement planning, Walmart is ahead of the game -- and making a profit in the process. As COVID-19 made its presence known in the U.S. last January, the company had just expanded its employee benefits through telehealth; the $4 charge for Doctor-on-Demand visits was waived for employees during the pandemic. Over the course of 2020, the company began to pilot a freestanding clinic model aimed at lowering the cost of health services by as much as 40% (e.g., $30 medical checkups, $25 teeth cleanings, $1 per minute mental health counseling) while reducing administrative red tape. A partnership with Quest Diagnostics is helping to expand COVID testing by opening testing locations at about 500 Walmart pharmacies.

Amazon: In addition to a reported $2.5 billion in pandemic related employee bonuses and incentives, Amazon invested approximately $10 billion in COVID-related initiatives in 2020 -- from enhanced cleaning, disinfectant spraying and social distancing measures to distributing PPE and checking employee temperatures across worldwide operations. Employee benefits were adjusted to provide up to 2 weeks of paid time off in addition to other options for those diagnosed with COVID-19.

It is already clear that healthcare will remain an important focus for the company post-pandemic. For instance, the company has forged partnerships with CVS and Thermo Fisher Scientific to promote employer-based COVID-19 testing; Carrier Global Corp. to boost temperature controlled delivery of medicines and vaccines; and Crossover Health (a primary care clinic chain) to provide virtual or in-person visits and develop employee health centers in five cities.

For all employers, COVID-19 and its growing cadre of variants will continue to put the health of all employees at risk in the foreseeable future. In addition to determining that the virus meets the "direct threat" standard under the Americans with Disabilities Act (a move that has enabled employers to ask employees health-related questions and keep those with symptoms from entering the workplace), the Equal Employment Opportunity Commission has made it clear that employers may opt to make vaccination mandatory. As a result, many employers are discussing plans to mandate vaccinations before permitting their employees return to the office.

I suggest that all employers give serious consideration to a mandatory vaccine policy for their workforces, keeping in mind some practical issues such as:

• Does the company need a mandatory vaccine policy? Do employees work remotely, making it feasible for them to make their own decisions? Is close contact required among employees or with the public, making vaccination a "must"?
• If a policy is implemented, how will requests for exemptions be handled -- and what happens to those who refuse?

In a big shift from the previous administration's position (i.e., leaving coronavirus precautions to the discretion of employers), President Biden has tasked the Occupational Safety and Health Administration (OSHA) with ensuring that workers are protected from catching or spreading COVID-19. National standards for employers will be established and OSHA will have the power to enforce them. Because workers are guaranteed the right to refuse employment that will jeopardize their health, workers will be allowed to receive unemployment benefits if they quit jobs that do not follow pandemic protocols.

For employers, it all boils down to this: you can run, but you cannot hide! Like mandatory drug testing for certain jobs and mandatory meningitis vaccinations on college campuses, requiring a COVID-19 vaccination for certain employee populations is totally appropriate. Think of it as a "passport" to work.

I recognize that not every firm has the resources of a Walmart or an Amazon but, in the final analysis, your own employees don't care about that. As your employees, they look to you.

David Nash, MD, MBA, is founding dean emeritus and the Dr. Raymond C. and Doris N. Grandon Professor of Health Policy at the Jefferson College of Population Health. He serves as special assistant to Bruce Meyer, MD, MBA, president of Jefferson Health. He is also editor-in-chief of the American Journal of Medical Quality and of Population Health Management.

https://www.medpagetoday.com/columns/focusonpolicy/90961

Goldman: Hedge fund exposures 'close to records, ongoing sell-off risk'

 

U.S. hedge funds last week bought and sold the most stock in more than 10 years amid wild swings in GameStop Corp shares that many had bet against, but their market exposure to stocks is still near record levels, according to an analysis by Goldman Sachs Inc.

"According to Goldman Sachs Prime Services, this week represented the largest active hedge fund de-grossing since February 2009. Funds in their coverage sold long positions and covered shorts in every sector," the investment bank wrote in a note late Friday.

"Despite this active deleveraging, hedge fund net and gross exposures on a mark-to-market basis both remain close to the highest levels on record, indicating ongoing risk of positioning-driven sell-offs."

https://www.marketscreener.com/news/latest/Goldman-sees-hedge-fund-exposures-close-to-records-ongoing-sell-off-risk-after-GameStop-swings--32321177/

Don't Bank on Covid-19 Killing off Cash Just Yet

 Peter Coffey, an advertising copywriter, has used cash just once since the Covid-19 pandemic started -- to buy a used car.

When the health crisis began, he set up his smartphone's tap-to-pay function with a credit card. "Some places weren't accepting cash. I just got into the habit of never even thinking about cash," he said.

Mr. Coffey, 28 years old, who is working remotely from Tucson, Ariz., said he expects to continue using touchless payment technologies after the pandemic. "It's great, the amount of times I've gone to the store and realized I don't have my credit card. It's fine -- I just tap with my phone."

He and many other U.S. consumers are shunning cash for a number of reasons, including convenience and a desire to avoid bills and coins as potential sources of coronavirus transmission. In the same way the Covid-19 pandemic has changed the ways we work, shop and socialize, it has also shifted the way many people pay for things.

Digital retail sales were up 37% in the third quarter, seasonally adjusted, from the same period a year earlier, according to the Commerce Department. Cash wasn't an option for those payments: Spending online or using an app like Uber Eats requires an electronic method such as a debit card or PayPal account.

"A central theme of Covid-19 is things that would have taken five years are taking five months, and it's a reinforcing of existing trends. It's the same with cash," said Kenneth Rogoff, a Harvard University economist.

Around the world, fears of infection have driven an increase in contactless payments -- electronic payments like Apple Pay and tap-to-pay offerings that avoid even swiping or inserting cards -- according to credit-card companies. Contactless as a share of in-person transactions grew at least 10% in more than 80 markets for Mastercard Inc. in 2020, driven by demand for increased speed and safety, Chief Executive Michael Miebach said on an earnings call Thursday.

The shift to more electronic payments could spur consumer spending, giving economic growth a boost, once widespread Covid-19 vaccinations enable a fuller economic recovery, analysts say. When shoppers pay with plastic, they tend to spend more.

A Deutsche Bank survey in January 2020 found that 43% of Americans tend to think less about the amount they spend when using a card, and 36% think less about the amount when using a digital wallet.

The pandemic has accelerated the decline in cash payments and the move toward e-commerce by about four or five years, said Marion Laboure, a Deutsche Bank economist.

Americans' use of cash was gradually declining for years before the pandemic as they embraced credit and debit cards, mobile wallets, online transfers and apps. They used cash in 26% of all payments in 2019, down from 40% in 2012, according to the Federal Reserve's annual look at payment habits.

A Fed survey, conducted in May, found that 28% of respondents said they were avoiding using cash, while 70% said they weren't.

"Consumer payments is a habit, like the way you like to drink your coffee in the morning," said Claire Greene, an expert on payments at the Federal Reserve Bank of Atlanta. Adopting new payment habits -- like contactless payments -- due to the pandemic requires effort and learning by both consumers and retailers, she said.

Still, while shoppers' embrace of digital commerce looks likely to last, economists say it is too soon to know if U.S. consumers' shift to cashless payments will as well, for several reasons.

To start, U.S. household spending overall remains below its pre-pandemic level. As spending rebounds, so might cash payments.

Also, much of the shift was forced. Business closures and other restrictions pushed much shopping online. It is unclear whether people will readily reach for bills and coins again once more widespread vaccinations enable them to return to stores.

Some consumers' privacy concerns make them hesitant to have their every swipe or click tracked.

A recent study by Visa Inc. found that 24% of U.S. consumers said they would resume their old payment methods after a vaccine is widely available.

The U.S. is unlikely to allow most businesses to abandon cash payments because of concerns about consumers lacking access to or familiarity with digital payment methods. These include senior citizens, undocumented immigrants, people who can't qualify for credit cards or afford smartphones, and the millions of households that lack bank accounts. New York City, Philadelphia, New Jersey and San Francisco have passed legislation requiring most stores and restaurants to accept cash.

Meanwhile, people still like to have physical dollars and cents. Although people in the U.S. were using cash less in transactions, they were holding more of it as a store of value, the May Fed survey found.

The demand for U.S. currency has boomed globally since the pandemic began. U.S. currency in circulation -- paper bills and coins in the hands of the public -- had jumped to $2.07 trillion in December from $1.80 trillion in January 2020. In the same period of 2019, the amount of cash in circulation rose far less, to $1.79 trillion from $1.71 trillion.

https://www.marketscreener.com/news/latest/Don-t-Bank-on-Covid-19-Killing-off-Cash-Just-Yet--32316066/

China's New Covid-19 Outbreaks Trip Up Economic Momentum

 China's economy started the new year on a weaker footing as new coronavirus outbreaks and pandemic-containment measures sapped factory production and weighed on the country's services recovery, official data showed Sunday.

Official gauges of industrial and services activities eased more than expected in January, with demand taking a particular hit as authorities discouraged travel ahead of February's Lunar New Year festival, according to data from Beijing's National Bureau of Statistics.

China's official manufacturing purchasing managers index softened to 51.3 in January, lower than December's 51.9 reading and the 51.5 median forecast among economists polled by The Wall Street Journal.

The nonmanufacturing PMI, which includes services and construction activity, weakened even more to 52.4, from 55.7 in December, according to the statistics bureau.

Though both indexes showed activity remaining above the 50 mark that separates expansion from contraction, the new-orders subindex for the nonmanufacturing sector, a key measure of demand, dropped below the 50 line--to 48.7 from 51.9 the previous month--marking the lowest level since February last year, when the Chinese economy was absorbing the very worst of the coronavirus shock.

Sunday's PMI readings provided the first look at the economic damage wrought by fresh outbreaks of the coronavirus in northern China--the worst since the initial outbreak that began in Wuhan about a year ago. The latest wave has sickened hundreds and put restrictions on the movements of millions of people.

To keep the number of cases from rising further, government authorities nationwide are dissuading residents from traveling during the most important holiday of the year, Lunar New Year, which runs for a week beginning February 12.

The stricter quarantine and testing requirements imposed during this frantic season--when hundreds of millions of people typically travel to see family and splash out on gifts and dining--are likely to restrain economic activity.

Services requiring close human contact have borne the biggest brunt. Subindexes tracking business activity in catering, accommodations, logistics, transportation and entertainment fell sharply into contractionary territory in January, official data showed.

Hunter Chan, an economist at Standard Chartered Bank, expects the damage to persist through the end of the festival in late February, though he is optimistic that the economy will rebound.

"The economy will normalize quickly as effective control measures limit the prolonged impact," he said.

As coronavirus restrictions threaten a second straight year of Lunar New Year festivities, local governments have in recent weeks rolled out shopping vouchers in hopes of enticing people to stay in place over the holiday and to keep spending.

China's services and consumption sectors have lagged behind its broader economic recovery over the past year amid lingering concerns over infections and worker incomes that have been squeezed by the pandemic.

China's 2.3% expansion in gross domestic product in 2020, which made it the only major economy to post growth last year, was powered largely by industrial production, exports and government-backed investment. Retail sales, by contrast, was one of the few closely watched economic indicators to finish 2020 lower than the prior year.

In addition to the weakness in the services sector, Sunday's PMI reading also showed emerging signs of slowing momentum in the industrial sector, with both demand and production easing.

The subindex measuring manufacturing production fell to 53.5 in January, from 54.2 in December, while total new orders dropped to 52.3 from December's 53.6 reading. The subindex tracking new export orders also eased to 50.2 from 51.3 in December, but remained above the 50 mark for a fifth straight month.

China's statistics bureau said some workers had returned to their hometowns in anticipation of the tightening control measures, leading to a labor shortage at some factories.

https://www.marketscreener.com/quote/stock/STANDARD-CHARTERED-PLC-4003394/news/China-s-New-Covid-19-Outbreaks-Trip-Up-Economic-Momentum-32315268/

How Not to Waste COVID Vaccines

 

What do you do when your COVID-19 vaccine clinic is 20 minutes from closing, only six people showed up for the day's last appointment, and you just opened a 10-dose Moderna vial?

Reports suggest that many clinics dump their leftover doses in the trash.

But some facilities have found solutions to minimize vaccine waste. Relying on constant communication, flexible planning, and a focused workforce including diligent volunteers, they said they have found takers for nearly all the thousands of doses they have prepared since vaccinations began last month.

"So far this has been not a hard problem to solve," said Dora Anne Mills, MD, who is coordinating the 11-hospital MaineHealth system's vaccination sites. "It's really about planning and keeping an eye on things."

Once a vial's seal is punctured, workers have only a few hours to administer them. Some fortunate bystanders have gotten vaccinated merely by being at the right grocery store at the right time. But that can be chancy, and can also draw criticism for giving precious doses to people not on the current priority list.

"There are vaccines that are being wasted and that is a travesty," Terry Fulmer, president of the John A. Hartford Foundation, told ABC News. "Even one dose wasted is too many."

Some facilities told MedPage Today they establish plans every morning and then adjust throughout the day. At Northern Light in Maine, for example, staff remove enough vaccine to cover the first three hours' worth of booked patients; then they prepare smaller batches every hour to ensure they do not take too much out, said James Jarvis, MD, a family medicine and obstetrics specialist who oversees the 11-site system's COVID response.

Ascension St Vincent's four sites in the Indianapolis area keep the vials they think they will need for the day in a fridge -- usually enough for 1,000-1,500 doses of the Moderna and Pfizer vaccines, said Cindy Adams, PhD, the system's chief nursing officer and COVID vaccine coordinator.

In New Jersey, Rowan School of Osteopathic Medicine staff assemble 100 doses to cover the first couple hours, then draw about 50, then 20. To cover the last two hours before the site shuts to the public at 4 p.m., they bring out one vial at a time as needed. Sometimes they don't know if the last 10 patients will all show up, said site coordinator Joshua Coren, DO, but they know they at least will not waste all 10 shots. "You're never going to be exactly right, but I'd rather open up only one vial as we need it," said Coren, chair of the family medicine program. The site gives 300-500 Moderna doses daily.

These sites also maintain lists of healthcare workers, first responders, and others currently prioritized by their states. When they find they have doses unaccounted for, they methodically call these people, working their way down the list until enough of them agree to come in. Sometimes they settle on whoever is willing and available -- including nonclinical staff and volunteer workers, even when they don't qualify under the current priority scheme.

MaineHealth's Mills said the system has vaccinated unbooked spouses who come with patients to appointments when extra doses are available.

"We always have somebody waiting in the wings," said Jarvis at Northern Light, where staff at one location with leftover doses called a nearby dental office to offer them.

Rowan assembles a list late in the day of who is around and unvaccinated, then offers them leftover doses.

"The vaccines are going to go bad anyway. You might as well give [such] individuals the vaccine," Erik Hefti, executive director and assistant professor of pharmaceutical sciences at Harrisburg University of Science and Technology in Pennsylvania, told a local TV station.

"We don't want any vaccine wasted, so if they're going to vaccinate someone in [group] 1B as opposed to wasting it that's absolutely fine," Pennsylvania Secretary of Health Rachel Levine said earlier this month when dosing was nominally restricted to group 1A.

Ascension St. Vincent's pharmacists have drawn on the first few weeks of vaccination to predict no-shows and expected patient flow, Adams said.

That is no cinch: "It is very hard to predict exactly how many vaccines you're going to use in a day," Julie Willems Van Dijk, acting secretary of Wisconsin's Department of Health Services, told the Racine Journal Times newspaper.

https://www.medpagetoday.com/special-reports/exclusives/90935

80% of COVID-19 Patients May Have Lingering Symptoms, Signs

 Eight of 10 COVID-19 patients had lingering symptoms or signs 14 or more days after acute infection, a systematic review and meta-analysis showed.

More than 50 symptoms tied to SARS-CoV-2 infection persisted, most commonly fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), dyspnea (24%), and anosmia (24%) were identified, according to Sonia Villapol, PhD, of Houston Methodist Research Institute in Texas, and colleagues. The findings were reported in a medRxiv preprint and have not undergone peer review.

"We estimated that a total 80% of the patients infected with SARS-CoV-2 developed one or more long-term symptoms," Villapol said. "Preventive measures, rehabilitation techniques, and clinical management strategies designed to address prevalent long-term effects of COVID-19 are urgently needed," she told MedPage Today.

To date, there's no established diagnosis for the slow, persistent condition that people with lasting effects of COVID-19 experience; terms like "long COVID," "long haulers," and "post-acute COVID-19" have been used, Villapol and colleagues noted. In their review, they referred to lingering symptoms and signs as "long-term effects of COVID-19."

Last year, a widely-cited CDC survey showed 35% of COVID-19 patients had not returned to usual health 2 to 3 weeks after testing positive, but those were mild, outpatient cases. Early in 2021, a study in the Lancet showed that 6 months after illness onset, 76% of hospitalized COVID-19 patients in Wuhan, China, reported at least one symptom that persisted, mostly fatigue or muscle weakness.

In their meta-analysis, Villapol and colleagues included 47,910 people with a confirmed COVID-19 diagnosis in 15 studies that had evaluated symptoms, signs, or laboratory parameters 2 weeks or more week post-viral infection. Each study had a minimum of 100 patients. Nine studies were from Great Britain or Europe, three were from the U.S.

Six studies focused only people hospitalized for COVID-19; the others included mild, moderate, and severe cases. Patients ranged from ages 17 to 87 years, and follow-up time ranged from 14 to 110 days.

Fatigue was the most common symptom of both long and acute COVID-19, Villapol and colleagues noted: "It is present even after 100 days of the first symptom of acute COVID-19."

During follow-up, 34% of patients had an abnormal chest x-ray or CT. Elevated markers also were seen, including D-dimer (20%), NT-proBNP (11%), C-reactive protein (8%), serum ferritin (8%), procalcitonin (4%), and IL-6 (3%).

Other lingering symptoms were pulmonary (cough, chest discomfort, reduced pulmonary diffusing capacity, sleep apnea, pulmonary fibrosis), cardiovascular (arrhythmias, myocarditis), or neurologic or psychiatric (memory loss, depression, anxiety, sleep disorders).

All meta-analyses showed medium to high heterogeneity. "Future studies need to stratify by sex, age, previous comorbidities, severity of COVID-19 (ranging from asymptomatic to severe), and duration of each symptom," the researchers wrote. From the clinical perspective, multi-disciplinary teams with whole-patient perspectives are needed to address long COVID-19 care, they added.

Limitations include possible selection or reporting bias, small sample sizes for some outcomes, and variation in how outcomes and markers were defined. "Another limitation is that, given that COVID-19 is a new disease, it is not possible to determine how long these effects will last," Villapol and colleagues said.

"To determine whether these long-term effects either complicate previous diseases or are a continuation of COVID-19, there is a need for prospective cohort studies." they added. Measures like blood markers of genetic, inflammatory, immune, and metabolic function need to be standardized to compare studies, and open questions should be included.

Disclosures

The research was supported by the National Institute for Neurological Disorders and Stroke and the Houston Methodist Research Institute.

Villapol disclosed no relevant relationships with industry. A co-author is an employee of Novartis.

Primary Source

medRxiv

Source Reference: Lopez-Leon S, et al "More than 50 Long-term effects of COVID-19: a systematic review and meta-analysis" medRxiv 2021; DOI: 10.1101/2021.01.27.21250617.

https://www.medpagetoday.com/infectiousdisease/covid19/90966