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Scientists from the Department of Physiology of the University of Granada (UGR) have shown that caffeine (about 3 mg/kg, the equivalent of a strong coffee) ingested half an hour before aerobic exercise significantly increases the rate of fat-burning. They also found that if the exercise is performed in the afternoon, the effects of the caffeine are more marked than in the morning.
In their study, published in the Journal of the International Society of Sports Nutrition, the researchers aimed to determine whether caffeine — one of the most commonly-consumed ergogenic substances in the world to improve sports performance — actually does increase oxidation or “burning” of fat during exercise. Despite the fact that its consumption in the form of supplements is very common, the scientific evidence for its beneficial claims is scarce.
“The recommendation to exercise on an empty stomach in the morning to increase fat oxidation is commonplace. However, this recommendation may be lacking a scientific basis, as it is unknown whether this increase is due to exercising in the morning or due to going without food for a longer period of time,” explains the lead author of this research, Francisco José Amaro-Gahete of the UGR’s Department of Physiology.
A total of 15 men (mean age, 32) participated in the research, completing an exercise test four times at seven-day intervals. Subjects ingested 3 mg/kg of caffeine or a placebo at 8am and 5pm (each subject completed the tests in all four conditions in a random order). The conditions prior to each exercise test (hours elapsed since last meal, physical exercise, or consumption of stimulant substances) were strictly standardized, and fat oxidation during exercise was calculated accordingly.
Maximum fat oxidation
“The results of our study showed that acute caffeine ingestion 30 minutes before performing an aerobic exercise test increased maximum fat oxidation during exercise regardless of the time of day,” explains Francisco J. Amaro. The existence of a diurnal variation in fat oxidation during exercise was confirmed, the values being higher in the afternoon than in the morning for equal hours of fasting.
These results also show that caffeine increases fat oxidation during morning exercise in a similar way to that observed without caffeine intake in the afternoon.
In summary, the findings of this study suggest that the combination of acute caffeine intake and aerobic exercise performed at moderate intensity in the afternoon provides the optimal scenario for people seeking to increase fat-burning during physical exercise.
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Materials provided by University of Granada. Note: Content may be edited for style and length.

Scientists at Sanford Burnham Prebys Medical Discovery Institute have identified a drug candidate that blocks the uptake of glutamine, a key food source for many tumors, and slows the growth of melanoma. The drug is a small molecule that targets a glutamine transporter, SLC1A5, which pumps the nutrient into cancer cells — offering a promising new approach for treating melanoma and other cancers. The study was published in the journal Molecular Cancer Therapeutics.
“While great strides have been made recently in the treatment of melanoma, many patients’ tumors become resistant to therapy, and this has become a major obstacle in the successful treatment of the disease,” says Ze’ev Ronai, Ph.D., director of the National Cancer Institute (NCI)-designated Cancer Center at Sanford Burnham Prebys and senior author of the study. “This study describes a promising compound that selectively targets the uptake of glutamine, an amino acid nutrient that tumors rely on for survival. We are hopeful this drug will fill an unmet medical need for people living with this deadly cancer.”
More than 7,000 people die from melanoma each year in the U.S., according to the American Cancer Society, and cases continue to increase annually. In the past decade, immunotherapy and personalized treatments have extended survival times for many patients. However, because of the high incidence of cancer recurrence, scientists are increasingly focused on therapeutic strategies to prevent relapse and increase overall survival.
“This is a very important study because many targeted drugs for melanoma treatment have been significantly hindered by the rapid development of treatment resistance, sometimes as quickly as within several months. While immunotherapy approaches are promising, they are only effective in a subset of patients, and treatment resistance can also develop in this setting as well,” says M. Celeste Simon, Ph.D., Arthur H. Rubenstein, MBBCh Professor in the department of Cell and Developmental Biology and scientific director of the Abramson Family Cancer Research Institute at the Perelman School of Medicine at the University of Pennsylvania. “The drug candidate identified in Dr. Ronai’s study offers an exciting new therapeutic approach for treating tumors addicted to glutamine, which includes a long list of human cancers, and will hopefully lengthen the amount of time that people with melanoma respond to available treatments.”
Blocking the tumor’s food supply
Researchers know that rapidly growing tumors are able to reprogram their metabolism to generate extra energy to survive and grow. Tumors often achieve this by pumping increasing levels of the amino acid glutamine into their cells, primarily through a pump called SLC1A5. As a result, cancer researchers are working to find drugs that block SLC1A5 and reduce glutamine levels.
In the study, Ronai and his team set out to identify drug(s) that can inhibit glutamine uptake. Working in collaboration with researchers at the Institute’s Conrad Prebys Center for Chemical Genomics, the scientists screened 7,000 diverse compounds for their ability to interfere with SLC1A5. This work identified about 20 hits, or promising options, and one was selected based on its superior ability to prevent SLC1A5 from reaching the cell membrane. This drug candidate, IMD-0354, inhibited tumor growth in both cell culture and in mice with melanoma.
“Our study shows that targeting SLC1A5, which stops glutamine from ever entering the cell in the first place, is an effective way to slow cancer cell growth,” says Yongmei Feng, Ph.D., staff scientist in the Ronai lab at Sanford Burnham Prebys and first author of the study. “Because many tumor types are dependent upon glutamine for survival, this drug may be able to treat many different types of cancers.”
As a next step, Ronai and his team will further refine IMD-0354, with a focus on improving biophysical properties that will help accelerate preclinical evaluation of the drug candidate.

A new research study at the University of Chicago Medicine has found that when it comes to COVID-19, having vitamin D levels above those traditionally considered sufficient may lower the risk of infection, especially for Black people.
The study, published March 19 in JAMA Open Network, retrospectively examined the relationship between vitamin D levels and likelihood of testing positive for COVID-19. While levels of 30 ng/ml or more are usually considered “sufficient,” the authors found that Black individuals who had levels of 30 to 40 ng/ml had a 2.64 times higher risk of testing positive for COVID-19 than people with levels of 40 ng/ml or greater. Statistically significant associations of vitamin D levels with COVID-19 risk were not found in white people. The study looked at data from over 3,000 patients at UChicago Medicine who had had their vitamin D levels tested within 14 days before a COVID-19 test.
The research team is now recruiting participants for two separate clinical trials testing the efficacy of vitamin D supplements for preventing COVID-19.
This research is an expansion of an earlier study showing that a vitamin D deficiency (less than 20 ng/ml) may raise the risk of testing positive for COVID-19. In the current study, those results were further supported, finding that individuals with a vitamin D deficiency had a 7.2% chance of testing positive for the virus. A separate study recently found that over 80% of patients diagnosed with COVID-19 were vitamin D deficient.
“These new results tell us that having vitamin D levels above those normally considered sufficient is associated with decreased risk of testing positive for COVID-19, at least in Black individuals,” said David Meltzer, MD, PhD, Chief of Hospital Medicine at UChicago Medicine and lead author of the study. “This supports arguments for designing clinical trials that can test whether or not vitamin D may be a viable intervention to lower the risk of the disease, especially in persons of color.”
Meltzer was inspired to investigate this topic after seeing an article in early 2020 that found people with vitamin D deficiency who had randomly been assigned to receive vitamin D supplementation had much lower rates of viral respiratory infections compared to those who did not receive supplementation. He decided to examine data being collected at UChicago Medicine on COVID-19 to determine the role that vitamin D levels might be playing.
“There’s a lot of literature on vitamin D. Most of it has been focused on bone health, which is where the current standards for sufficient vitamin D levels come from,” Meltzer explained. “But there’s also some evidence that vitamin D might improve immune function and decrease inflammation. So far, the data has been relatively inconclusive. Based on these results, we think that earlier studies may have given doses that were too low to have much of an effect on the immune system, even if they were sufficient for bone health. It may be that different levels of vitamin D are adequate for different functions.”
Vitamin D can be obtained through diet or supplements, or produced by the body in response to exposure of the skin to sunlight. Meltzer noted that most individuals, especially people with darker skin, have lower levels of vitamin D; roughly half of the world’s population has levels below 30ng/ml. “Lifeguards, surfers, those are the kinds of folks who tend to have more than sufficient vitamin D levels,” he said. “Most folks living in Chicago in the winter are going to have levels that are well below that.”
While vitamin D supplements are relatively safe to take, excessive consumption of vitamin D supplements is associated with hypercalcemia, a condition in which calcium builds up in the blood stream and causes nausea, vomiting, weakness, and frequent urination. If left unchecked, it can further lead to bone pain and kidney stones.
“Currently, the adult recommended dietary allowance for vitamin D is 600 to 800 international units (IUs) per day,” said Meltzer. “The National Academy of Medicine has said that taking up to 4,000 IUs per day is safe for the vast majority of people, and risk of hypercalcemia increases at levels over 10,000 IUs per day.”
One of the challenges of this study is that it is currently difficult to determine exactly how vitamin D may be supporting immune function. “This is an observational study,” said Meltzer. “We can see that there’s an association between vitamin D levels and likelihood of a COVID-19 diagnosis, but we don’t know exactly why that is, or whether these results are due to the vitamin D directly or other related biological factors.”
Prompted by the evidence that people with vitamin D deficiency are more likely to test positive for COVID-19 and experience significant symptoms, a team at the University of Chicago and Rush University is conducting two studies to learn whether taking a daily vitamin D supplement can help prevent COVID-19 or decrease the severity of its symptoms.

The first year of the COVID-19 pandemic has taken the lives of millions of people around the world but has also left hundreds with lingering symptoms or completely new symptoms weeks after recovery.
Much is unknown about what causes these symptoms and how long they last. But with nearly 740,000 cases of COVID reported in New York City since last March — and 28 million in the United States — physicians are increasingly seeing these “long-haulers” in their practices.
“Over the course of the summer, we started getting a sense of what issues these people were having,” says Ani Nalbandian, MD, a cardiology fellow at Columbia University Vagelos College of Physicians and Surgeons and first author of a new review of post-acute COVID-19.
“We felt that a review of all these possible issues would be important not only for health care providers but also for patients. It’s important for patients to know that what they’re experiencing may be a consequence of COVID-19 infection and that they are not alone in experiencing lingering effects of COVID-19 infection.”
Nalbandian, along with co-first author Kartik Sehgal, MD, medical oncologist at Harvard Medical School and Dana Farber Cancer Institute, spearheaded the review effort, bringing together more than 30 experts from Columbia and other medical centers hit by the initial wave. The review summarizes what the physicians were seeing in their own patients and what others had reported in the literature. The experts represented a wide range of fields, including neurology, cardiology, and nephrology.
Nalbandian and Elaine Y. Wan, MD, the Esther Aboodi Assistant Professor of Medicine in Cardiology and Cardiac Electrophysiology at Columbia University, the review’s senior author, discuss the symptoms that patients and providers should know about COVID-19 long haulers.

An unfortunate biological “feed-forward” loop drives cartilage cells in an arthritic joint to actually contribute to progression of the disease, say researchers at Duke University and Washington University in Saint Louis.
Pain researcher and mechanobiologist Wolfgang Liedtke, a professor of neurology at Duke, partnered with former Duke colleague and cartilage expert Farshid Guilak, now at the Washington University School of Medicine, to examine the activity of pressure-sensitive ion channels in cartilage. Their study appears the week of March 22 in the Proceedings of the National Academy of Sciences.
Cartilage is the highly lubricated, low-friction, elastic tissue that lines joint surfaces, cushioning movements and absorbing millions of cycles of mechanical compression. As cartilage breaks down in painful osteoarthritis, the ends of bones can come together bone-on-bone, increasing pain even more.
The cells that build and maintain cartilage are called chondrocytes, and on their surface can be found ion channels that are sensitive to force, called Piezo1 and Piezo2. In response to mechanical loads on the joint, Piezo channels send signals into the cell that can change gene activity in that cell.
Normally, chondrocytes produce extracellular matrix, the structural proteins and other biomolecules that give cartilage its mechanical stiffness, elasticity and low friction. But in osteoarthritis, degeneration and malfunction of these cells — which are incapable of repair by cell division — contribute to the progressive breakdown of cartilage.
One of the other hallmarks of osteoarthritis is chronic, low-grade inflammation, driven by a signaling molecule called interleukin-1 alpha. Using cartilage cells from pigs and from human joints removed for replacement surgeries, the researchers wanted to see how inflammation affects chondrocytes.

A University of New Mexico research team conducted a data analysis that has found that as a larger portion of the population gets vaccinated against COVID-19, it becomes economically advantageous to start relaxing social distancing measures and open businesses.
Francesco Sorrentino, associate professor of mechanical engineering, is lead author of “Data-driven Optimized Control of the COVID-19 Epidemics,” published March 22 in Scientific Reports.
Co-authors of the study are Afroza Shirin of the Department of Mechanical Engineering and the Department of Electrical and Computer Engineering, and Yen Ting Lin, a staff scientist of the Information Science Group in the Computer, Computational and Statistical Sciences Division at Los Alamos National Laboratory.
The study looked at data from four metropolitan statistical areas (MSAs) within the United States: Seattle, New York City, Los Angeles and Houston from January 21 to July 8, 2020. The four cities were chosen because they have had divergent trends with the virus (Seattle and New York City were early hotspots, while Los Angeles and Houston peaked in the summer).
Sorrentino said that while the findings perhaps may seem obvious, they are significant because the model is inferred and parametrized by regional new case reports and could potentially help guide policy decisions as more businesses, schools and other organizations ponder when and how to reopen during the pandemic.
“Our work is quantitative, so it can hopefully offer some evidence that shows the vaccines are going to allow us to loosen social distancing measures, including opening businesses,” he said. “It provides a measure of hope as we go forward and increase the percentage of citizens who are vaccinated.”
He points out that the study was looking at just the numbers, what he calls an “optimization problem,” to determine the economic cost of keeping many businesses closed or at reduced capacity. Sorrentino said the study defined economic impact by the extent that a city’s economy was closed — businesses like restaurants, gyms, salons and airports that would lose business without people’s physical presence. The study took into account both the costs associated with quarantining (which requires supervision costs as well as costs due to lowered productivity) as well as social distancing (which incurs costs only due to productivity).

SharecloseShare pageCopy linkAbout sharingimage copyrightReutersThe European Union has warned it could ban exports of vaccines produced there, as it struggles to speed up its vaccination rollout.European Commission President Ursula von der Leyen told AstraZeneca: “You fulfil your part of the deal towards Europe, before you start to deliver to other countries.”Why is the EU having vaccine problems?Where is the AstraZeneca vaccine made?The Oxford-AstraZeneca vaccine is made in the UK at two sites: in Oxford and Keele. A third plant in Wrexham puts the vaccine into vials and packages it up for distribution. The UK has ordered 100 million doses. Almost all will come from within the UK, but 10 million doses are being made by the Serum Institute in India.Half of these have already been received, with half held up by delays.Why is India struggling to meet global vaccine demand?The EU has ordered 400 million doses of the Oxford-AstraZeneca vaccine. The company says supplies are coming mainly from the US and a site in Seneffe in Belgium. AstraZeneca is working with suppliers in 15 countries to make the vaccine.A site in Leiden in the Netherlands is also producing some vaccine, although the pharmaceutical company said it was not significant. AstraZeneca confirmed that the UK has not received any vaccines or components from the EU – apart from one “tiny” batch from the Leiden plant.Who funded the AstraZeneca vaccine? The Oxford-AstraZeneca vaccine was, as the name implies, chiefly funded by the university and the pharmaceutical company. The research also received £65.5m in funding from the UK government.There was some other investment, but a University of Oxford spokesperson said it was difficult to untangle, because of the way research is funded. Why is the EU unhappy with AstraZeneca? In January, AstraZeneca said it would have to cut the number of doses it could deliver to the EU. It blamed production delays in Belgium and the Netherlands. This prompted criticism from the EU. AstraZeneca said its agreement with the EU allowed the option of supplying Europe from UK sites, but only once the UK had sufficient supplies.image copyrightReutersThe full details of the company’s deals with the UK and the EU have not been made public. But analysis by the Politico website points to a clause in the UK’s contract which says the government “may terminate the deal and invoke what appear to be punishment clauses” if there is a delay in supply. According to Politico, the EU waived its right to sue the company in the event of delivery delays. The European Commission says it is now involved in a “dispute mechanism” with the company.Is the EU running out of AstraZeneca doses?No – in fact, EU countries have been reporting hundreds of thousands of unused doses because of a drop in public confidence in the jab. Fact-checking President Macron’s vaccine claimWhy is the EU warning the UK over vaccines?France and Germany have used only about half of the AstraZeneca jabs they have received, according to the European Centre for Disease Prevention and Control (ECDC). As of 22 March, France has distributed 1.4 million out of 2.7 million doses available, while Germany received 3.4 million but has used only 1.8 million. The Netherlands has used only 38% of its supply. In most other EU countries, the proportion of the unused AstraZeneca vaccines is much higher than the proportion of unused Pfizer jabs. What about other vaccines?The Pfizer jab is mostly made in Puurs in Belgium, and a manufacturing site has also been set up in the German town of Marburg.The UK has ordered 40 million doses. The company says these deliveries are on track, but did not comment on whether they could be affected by an EU export ban. In Europe, the Moderna vaccine is produced in Switzerland and put into vials in Spain – the UK has ordered 17 million doses. The Janssen jab is made in the Netherlands – the UK has ordered 30 million doses.Vaccines may be produced in one place but “filled and finished” – put into vials and prepared for export – in another. And some components used in making the vaccine may be made at yet another location. For example, a UK company called Croda is supplying a component to Pfizer to make its vaccine. The lipid components – fat molecules used to encase the virus’s fragile genetic material and transport it into the body – are in relatively short supply, according to science data company Airfinity.Can the EU ban vaccine exports? The EU imposed export controls on coronavirus vaccines at the end of January. The measures will be in place until the end of June. They were used for the first time in March, to stop a shipment of 250,000 doses of AstraZeneca vaccine, from Italy to Australia.Ms von der Leyen has pointed out that more than 10 million doses of vaccine (Pfizer) produced in the EU have been exported to the UK. The UK government has not been able to confirm whether any vaccines have gone the other way but insists a ban is not in place.Prime Minister Boris Johnson has said: “I am reassured by talking to EU partners over the last few months that they don’t want to see blockades.”

Indoor fitness classes, which often result in heavy breathing in poorly ventilated rooms, can be risky. Here’s a guide to help you decide if your gym is doing enough to prevent the spread of Covid-19.Last summer, a 37-year-old fitness instructor in Hawaii taught a spin class to 10 people. He was perched on a bike in the front of the room, facing his students as he shouted instructions and encouragement. The doors and windows were closed, but three large floor fans created a breeze to keep everyone cool. As a precaution against Covid-19, all the bikes were spaced at least six feet apart. (At the time, the gym didn’t require people to wear masks.)But just four hours after class, the instructor began feeling fatigued. By the morning he had chills, body aches, a cough and other respiratory symptoms. Soon, he tested positive for Covid-19, and eventually, everyone who attended his class that day tested positive, too.The outbreak didn’t stop there, though. A 46-year-old fitness instructor who attended the spin class went on to infect another 11 people during personal training sessions and kickboxing classes over the next few days, before falling ill himself and landing in intensive care.The case of the Hawaii spin instructor was alarming because of the efficiency with which the virus left his respiratory tract and swirled around the enclosed classroom, reaching every person in the room. Among epidemiologists, that’s known as a 100 percent attack rate, and it’s a lesson in why group fitness classes, which often encourage high-energy huffing and puffing in poorly ventilated classrooms present such a daunting challenge to infection control.At the same time, most public health experts agree that the drop in physical activity and weight gain that many people experienced during a year of pandemic living presents another set of risks to human health, and that communities need to find a balance between infection control and allowing people to return to their favorite fitness activities.In the United States, gyms and fitness programs have reopened in some capacity in every state, allowing an estimated 73 million eager members to return to exercise. For the first time in more than a year, indoor group fitness classes were allowed to resume in New York City as of Monday, albeit at 33 percent capacity, and face coverings will be required.The good news is that it’s possible to lower the risk of group fitness classes by improving ventilation, limiting class size, wearing a mask and increasing physical distance between participants.Linsey Marr, an engineering professor at Virginia Tech and one of the world’s leading experts on viral transmission, is an avid exerciser herself and longed to return to her CrossFit sessions as the pandemic wore on. She worked with the owner of the gym, examining building plans and calculating potential class size and ventilation patterns in the facility.Dr. Marr said the challenge with group fitness classes is that the participants often are breathing heavily. During a workout, people exhale and inhale at far higher volumes than when at rest.“If someone is there who happens to be infected, they are releasing more virus into the air,” Dr. Marr said. “And the people around them are breathing heavily too, so they’re taking more in. You get this multiplicative factor. You’re breathing four times as hard, and the person who is sick is breathing four times as hard, so you’re breathing in 16 times more than you would under nonexercise conditions.”Because of the potential for heavy breathing, Dr. Marr suggested increasing the physical distance between participants at the workout space to 10 feet rather than the standard recommendation of six feet. To achieve that level of spacing, it required limiting the class size at Dr. Marr’s workouts to just 10 people.The facility took additional measures to minimize the chances of infection.The solution was to open multiple garage-style doors, even in the middle of the Virginia winter. To make sure the ventilation was adequate, the gym acquired a carbon dioxide monitor to measure the buildup of carbon dioxide in a room. Because humans exhale carbon dioxide, its level can be an indicator of how well a room is ventilated.Under everyday conditions, such as while shopping at a supermarket, an indoor carbon dioxide reading of 800 parts per million suggests that ventilation levels are adequate to reduce the risk of breathing in other people’s exhaled germs. But given the heavy breathing that occurs during a workout, Dr. Marr advised trying to keep indoor carbon dioxide levels even lower, to around 500 parts per million, and to increase ventilation if the number begins to creep toward 600.Wearing a mask during exercise is recommended by the Centers for Disease Control and Prevention, but Dr. Marr noted that with heavy breathing, mask material can quickly get moist and lose its effectiveness. “The level of protection provided by masks is so variable that we cannot rely on them alone,” she said.So far, the strategy seems to be working. Dr. Marr said her gym hasn’t experienced any coronavirus outbreaks, even though her state doesn’t require gym goers to wear masks while exercising. “We figured out if we kept all the doors open it should be pretty low risk,” she said. “But it was cold!”There was one instructor who contracted the virus from somewhere outside the facility, but the well-ventilated room and rules about physical distancing appear to have protected 50 people who were exposed to him during several different classes.While Dr. Marr’s gym is just a single case study, it shows that group fitness classes can continue safely during the pandemic, provided the facility focuses on ventilation and enforces distancing precautions and capacity limits. (Dr. Marr notes that CrossFit Inc. invited her to join its medical advisory board in December, and she helped craft a set of safety recommendations.)We asked Dr. Marr and other experts to answer questions about how participants can decide whether their fitness class is safe to attend. Here’s what they had to say.Does the type of exercise in the classroom make a difference?Yes. While Covid can spread in any type of indoor class, risk is likely to go up as exercise intensity increases because breathing rates increase.The volume of air someone breathes in and out every minute is called the “minute ventilation rate,” said Dr. Michael Koehle, the director of the Environmental Physiology Laboratory at the University of British Columbia and an expert on respiration during exercise. It naturally rises more during strenuous workouts, such as spin or dance classes, than in lighter workouts, such as yoga or Pilates.“At low intensities — yoga, Pilates and some strength work — you can breathe more through your nose, which is a natural filter,” said Dr. Koehle. “Another very important factor is that it is more comfortable to wear a mask during strength training and lower-intensity exercise than high-intensity exercise. People should still be wearing masks indoors.”This past August, an outbreak occurred among high-intensity exercisers at a fitness facility in Chicago. Everyone brought their own weights and mats, but not everyone wore masks. In that case, 55 out of 81 people (68 percent) who attended classes over an eight-day period at one facility came down with Covid-19. Early in the pandemic, 112 people in South Korea who took part in Zumba classes, or spent time with someone who did, were infected.How will I know if the room has adequate ventilation?While gyms and fitness classes are advised to meet certain ventilation standards, it’s tough for the average person to know whether a building ventilation system is adequate for infection control. “High ceilings are good,” said Dr. Marr. “If you can smell someone else, that’s a bad sign.”Ideally, a group class should be held in a room with open windows and doors on opposite sides of the room to allow for cross ventilation. A classroom with only one entrance and no windows — a common situation in many gyms — probably does not have adequate ventilation to keep you safe. Adding several portable air cleaners to a space that lacks more doors or windows could help. “It would be much better if you can get cross ventilation — opening doors or windows on opposite sides,” said Dr. Marr. “That’s what we specified in my gym, at least two open on opposite sides.”Do fans help?Overhead exhaust fans or window fans that pull air out of the room are fine. But avoid any class that uses fans to recirculate air and cool down the room. Fans that recirculate air in the room just increase the risk of viral spread.How far apart should I stand?While six feet of distancing is recommended by public health officials for most situations, Dr. Marr advises extending it to at least 10 feet — in front of you, to either side, and behind you — during exercise.The rules vary by state. In Massachusetts, for instance, indoor classes must have enough room for people to stand 14 feet apart. If barriers between participants are installed, then six feet is considered adequate. South Carolina requires a 10-foot by 10-foot area (100 square feet) per person; New Jersey requires twice that. Montana has required fitness classes to take place outdoors, while South Dakota has no guidance. (You can find more details about different state requirements here.)How many people should be in the class?States have different rules for class size, with some limiting attendance to 25 percent to 40 percent of capacity, and others allowing no more than nine or 10 people per class. Dr. Marr notes that class size is best determined by how far apart people can stand. When people keep 10 feet of distance from one another on all sides, that often limits the class size to 10 people or fewer. If you can’t achieve that much space between you and other participants, including the instructor, it’s time to find a new class.Do I need to wear a mask?It’s a good idea to wear a mask, and many states require them, but you can’t rely on your mask to protect you entirely. Mask quality varies, and during exercise, masks get moist, reducing their filtering efficiency. And while many gyms require masks to enter, mask wearing often is not enforced or even required during exercise classes.In the Chicago and Hawaii outbreaks, most people were not wearing masks. At the Hawaii gym, two participants wore masks during kickboxing sessions, but their infected instructor did not, and both became ill. The C.D.C. advises that “to reduce SARS-CoV-2 transmission in exercise facilities, employees and patrons should wear a mask, even during high-intensity activities.”Is there a way to monitor the air in my fitness class?Not every facility will have a carbon dioxide monitor, but it’s worth asking your facility if they have one in the group fitness room and whether you can check it. If the carbon dioxide levels are below 600 parts per million (the closer to 500 the better), it’s a sign that the room ventilation is adequate for exercise. If the numbers start to increase, ask to open a window or door — or leave the class. When Dr. Marr was attending an indoor swimming pool, she noticed ventilation levels in the room were poor, so she left.Is there a way to know if my gym has made a commitment to Covid safety precautions?The International Health, Racquet and Sportsclub Association, an industry group, has an initiative called the IHRSA Active & Safe Commitment to follow industry best practices to provide a safe environment. Facilities that sign the pledge promise to adhere to physical distancing and mitigation measures, safety protocols and contact tracing.The IHRSA urges the gym to have a list of protocols on its website and at the facility. At the bare minimum, protocols should include ventilation and fresh air exchange, capacity limits, distancing protocols and a clear mask policy. “I would specifically ask about ventilation practices, if mask wearing at all times is mandatory, and if classes and equipment were to be spaced out to allow for appropriate social distancing,” said Cedric Bryant, president and chief science officer for the American Council on Exercise.What if I’ve been vaccinated?Your risk for contracting coronavirus or developing serious illness drops dramatically if you’ve been vaccinated, but people who are vaccinated are still advised to take the same precautions as everyone else in public settings. And in most states, the people most likely to go to gyms or instruct a fitness class are younger and healthier, and therefore less likely to be among the first groups to be vaccinated. According to the IHRSA, 73 percent of gym and fitness class participants are 55 and younger.Does cleaning and disinfection make a difference?While everyone should wash their hands and wipe down gym equipment, patrons should not judge a gym solely on how often it promises to clean and sanitize an area. “We should still do what we did before, which is wipe down your machine when you’re done,” said Dr. Marr. “Maintaining a normal level of cleaning is appropriate. But any extra time and effort a gym has, put it toward cleaning the air.”Dr. Marr notes that proper ventilation, physical distancing and class size limits will have the biggest impact on your safety. She recently posted on Twitter that ventilation is so important, she even had a nightmare about it.“I had my first Covid-19 related nightmare (that I remember),” Dr. Marr’s tweet read. “I finished a hard, group workout in a gym. I looked around and panicked because I saw that all the doors were closed.”Do you have a health question? 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Bobby Stuckey flipped through receipts this month, surprised to see a huge increase in cocktail sales, the highest in the 17-year history of his restaurant, even though the bar section has been closed. The septuagenarians are back.“Every night we are seeing another couple or a pair of couples in the dining room, and they feel so much relief,” said Mr. Stuckey, the owner of Frasca Food and Wine in Boulder, Colo. “Covid was hard on everybody, but you can’t even think of the emotional toll in this group. They haven’t gone out. They want to have the complete experience. It is just joyful to see them again.”Older people, who represent the vast majority of Americans who are fully vaccinated against the coronavirus, are emerging this spring with the daffodils, tilting their faces to the sunlight outdoors. They are filling restaurants, hugging grandchildren and booking flights.Marcia Bosseler is back to playing Ping-Pong — and beating all the men, she says — at her apartment complex in Coral Gables, Fla.Randy and Rochelle Forester went out to eat with another couple for the first time in a year, and Ms. Forester celebrated the pleasure of being “out of sweats, to put on some pretty earrings and lipstick and be back in the world a little bit.” Fully vaccinated, Louis Manus Jr., an 82-year-old Navy veteran in Rapid City, S.D., is getting ready for his first vintage car club meeting in a year.Diners at Frasca Food and Wine in Boulder, Colo. “Every night we are seeing another couple or a pair of couples in the dining room, and they feel so much relief,” said Bobby Stuckey, the owner.Eliza Earle for The New York TimesRandy and Rochelle Forester, right, out to eat with longtime friends Phyllis and Sheldon Schwartz in Detroit. Ms. Forester celebrated being “out of sweats, to put on some pretty earrings and lipstick and be back in the world a little bit.”Cydni Elledge for The New York TimesThe upside-down world in which older Americans are drinking more martinis inside restaurants at a far greater rate than millennials will be short-lived.It’s a fleeting Covid-era interregnum in which the elders celebrate while their younger counterparts lurk in grocery stores in search of leftover shots or rage on social media, envious of those who have received a vaccine. In a few months, all that will most likely be over, and vaccines will be available to all who want them.For now, about two-thirds of Americans over 65 have started the vaccination process and nearly 38 percent are fully vaccinated, compared with 12 percent of the overall population, giving the rest of the nation a glimpse into the after times.“I am just enjoying my life,” said Robbie Bell, 75, who recently went out with two friends for a birthday celebration in Miami — one of whom was hospitalized last year with a dangerous case of Covid — and even hit the dance floor.“This is my just due,” Ms. Bell said. “Seniors gave up more than anybody else.”From left, Loretta McNeir, 68, Robbie Bell, 75, and Anita McGruder, 72, dance to the restaurant’s music as they left after dinner in Miami.Scott McIntyre for The New York TimesMs. Bell, left, and Ms. McNeir, surprised by a friend while out to dinner. “This is my just due,” Ms. Bell said. “Seniors gave up more than anybody else.”Scott McIntyre for The New York TimesMrs. Bosseler, who is 85, is thrilled to go back to live games of Ping-Pong and mahjong at The Palace in Coral Gables.“This is very exciting for me,” she said in a telephone interview.She is happiest to get back to “relationship with friends,” she said.“What was difficult was losing that intimacy of walking together and talking face-to-face. I missed not shaking a hand, or putting a hand on a shoulder.”Her neighbor Modesto Maidique, who is 80, has tiptoed out into the world, grabbing his sandwich indoors. But his central goal, like many older people, is to see his grandchildren.“I am about ready to jump in a plane and fly, and the sooner the better,” Mr. Maidique said. He also teaches a course on “lessons in life, love and leadership” at Florida International University in Miami and “dreaded the thought of people being online and my not having the ability to interact with others,” he said.His tentative plan is to hold a normal class in September.Other older Americans still in the work force are finding their way back into that world before many of the rest of us, too. Ms. Bell, a real estate broker, spent the last year driving around Miami in a car separate from clients, once giving a tour by speakerphone and pointing out landmarks. The clients would then go inside houses by themselves. “That is how I had to function,” she said. “For the first time last week, someone came who had her shots, too. I picked her up and I did my showings.”Modesto Maidique, 80, is excited to see his grandchildren. “I am about ready to jump in a plane and fly, and the sooner the better,” Mr. Maidique said.Scott McIntyre for The New York TimesMs. Bosseler, back at the Ping-Pong table, is eager to reestablish friendships. “I missed not shaking a hand, or putting a hand on a shoulder,” she said.Scott McIntyre for The New York TimesMs. Bell also dared to go out with two girlfriends for a birthday celebration. She and one of the friends are members of a ski club that suffered three Covid deaths related to a trip to Sun Valley, Idaho, early in the pandemic, and one of her two dinner companions also became sick enough to be hospitalized. Their first dinner out was so jubilant that Ms. Bell made her way to the dance floor, where an older gentleman tried to grab her hand and dance. (For that, she was not ready, and she said she swatted him away.) She and her pals “were talking about how great we felt and how nice it was even to be in each other’s company and talk and laugh,” she said.Ms. Bell said she tries not to dwell on the losses and the pain of the last year. “I am not going there,” she said, preferring to focus on the cheerful now. But when she talked about her grandchildren, she began to weep. “Do you know how bad it was not to hug your grandchild?” she asked. “I try not to think about it, it’s so hurtful.”Marsha Henderson, a former commissioner for women’s health with the Food and Drug Administration, also got inoculated and then began helping her friends and neighbors find vaccine appointments in Washington, D.C. As she and her friends crawl out, she said, they are beginning to look at shaking up some of their routes.“The Book Club Sisters will meet in April for the first time since Covid,” she said. “The pandemic has encouraged us to look to a new genre, not our usual biographies or politics. We are trying to look to the future, Afro Futuristic short stories. No more Zoom. It will be a hoot!”Marsha Henderson looks forward to her book club meeting in person. “We are trying to look to the future, Afro Futuristic short stories,” she said. “No more Zoom. It will be a hoot!”Michael A. McCoy for The New York TimesMany of those fully vaccinated — older and younger — are still as cautious , more like those crocuses that bloom in the day only to fold quietly back into their stems at night. “I would say that we are less afraid, but not fear-free,” said John Barkin, 76, who lives with his wife, Chris, 70, in Chestertown, Md. “There are so many stories about mutations, etc., and so many yet-to-be-vaccinated people seem to be acting more and more irresponsibly. Both of us feel that we have invested a year of being careful, so to continue on conservatively seems the way to go.”Their vigilance stems from the spread of some more contagious variants of the virus and from uncertainty over whether those who are vaccinated can still spread it. Lindsey J. Leininger, a health policy researcher and a clinical professor at the Tuck School of Business at Dartmouth in Hanover, N.H., said that the public health messaging has been “overcautious” at times.“But I suspect there’s something much deeper at play,” she said.“We’re biologically wired to avoid viral threats and abhor uncertainty,” Dr. Leininger continued. “Sadly, the variants inject some serious uncertainty, although we’re hopeful about emerging data suggesting our vaccines remain protective and that effective boosters can be produced. Some people cope with uncertainty by saying ‘To heck with it!’ and avoid all precaution, while others become super-cautious.”Paul Einbund, owner of The Morris, a restaurant in San Francisco, is seeing the adventurers out again. “We are getting more of our older clientele coming back,” he said. “Normally these are people who if I hadn’t seen in a year it would be so weird I would call them to see if they were OK.” One man who told him before the pandemic that he had a terminal illness came in the other night, to his great shock. “He was dining with three businessmen, and they went big and ordered this incredible chartreuse,” Mr. Einbund said. “That table gave me so much energy that night.”Cocktail sales this month at Frasca Food and Wine in Boulder were the highest in the restaurant’s 17-year history, thanks to older patrons. “It is just joyful to see them again,” said Mr. Stuckey, the owner.Eliza Earle for The New York TimesThe Foresters, right, and their friends, the Schwartzes, toasted the 80th birthday of Phyllis, left, and retirement for Sheldon, right.Cydni Elledge for The New York TimesNancy Arcadipone, 71, who splits time between Chicago and Kalamazoo, Mich., is planning her first trip to the Southwest in 45 years, and plotting when she can next enjoy eggplant parmigiana at La Scarola and a margarita next to a couple of tacos at Frontera Grill, both in Chicago, and live music performances. All within tantalizing reach.Still, her elation is tempered by the generational reversal of vaccine fortunes.“I feel the worst for the younger generation,” Ms. Arcadipone said. “My generation really got to live, experience and experiment. I feel sad for younger people. I find it kind of strange that our generation gets to be socially free first after a year of isolation.”Andrea Westberg, 73, sees it through all lenses, having missed out on a customized tour of Italy last summer with her teenage grandchildren. She and her husband, Gary, 74, moved to an active adult community in Roseville, Calif., two months before the world locked down and immediately longed for the incipient community pickleball, wine club get-togethers, potlucks and seeing new neighbors.“We were so disappointed,” Ms. Westberg said. “We kept busy decorating a new home, but not being able to share it with guests, including our sons and families, was very sad and lonely.”At last, she is together with family again.“I am hopeful for the future but cautious,” she said. “I grieve for those lives lost and hope that science and truth prevail in the years to come.”

Millions of older Americans, chronically ill and trapped at home, pose a big challenge to inoculation efforts. Doctors are on it.One vial of vaccine. Five elderly homebound patients. Six hours to get to them before the vaccine spoiled.Doctors at Northwell Health, the largest heath care provider in New York State, set out last week to solve one of the most vexing medical and logistical challenges of the campaign to get Americans vaccinated against the coronavirus: how to inoculate millions of seniors who live at home and are too frail or disabled to go to a clinic or queue up at a vaccination site.Members of the network’s house calls program had prepared for their first run. A supply of the new Johnson & Johnson coronavirus vaccine made the operation easier, because one visit would do the trick.A medical team mapped out a route that would include a cluster of homes not too far from one another, starting with older patients in underserved communities hard hit by the virus. The doctors contacted the patients well ahead of the visits, knowing they’d need plenty of time to consult with their families about whether to get vaccinated. Only a few turned them down; most were enthusiastic.Before the doctors hit the road, they screened patients on the phone to make sure they were relatively healthy. Any unexpected problems had to be avoided. The doctors were racing against the clock: Once they punctured the seal on the vial and drew the first dose, they had only six hours to use the remaining vaccine, or they would have to throw it out.“We’ll be running a tight ship, I think, but very compassionately,” said Dr. Karen Abrashkin, the program’s medical director, as a bulky, high-tech cooler — actually, a car refrigerator — was loaded onto the back seat of her car last Wednesday and plugged in to a cigarette lighter.Inside was a vial the size of a thimble, containing five doses of vaccine. “It’s a historic moment,” she said.Her first stop was a twofer, the home of a married couple in Hempstead, N.Y. Hector Hernandez, 81, a retired window cleaner who used to scrub high-rise buildings in Manhattan, and his wife, Irma, 80, a retired seamstress, had decided to get vaccinated, after sorting through a potpourri of conflicting advice from friends and family.“First I was skeptical — is it safe?” Mr. Hernandez said. Two friends had warned him to be careful because the vaccine was new. But Mrs. Hernandez’s cardiologist assured the couple it was safe, and another friend seemed confident that getting the vaccine was better than not getting it.The couple’s granddaughters, including one who was laid up with Covid-19 for two weeks, advised waiting to see if the vaccine had long-term side effects. In the end, Mr. Hernandez said, their daughter persuaded them to get vaccinated.Dr. Abrashkin prepared the dose for Mr. Hernandez. “First I was skeptical,” he said. “Is it safe?”Checking Mr. Hernandez’s vitals before giving the vaccine.Following reassurances from a friend, a doctor and the couple’s daughter, Mrs. Hernandez got her shot. “She called and said, ‘You have to get it done, because if you ever get Covid, it can be really bad — you can’t breathe,’” Mr. Hernandez said.As Dr. Abrashkin punctured the vial’s seal with a syringe, Lorraine Richardson, a social worker accompanying her, jotted down the time: 10:11 a.m. The two would monitor the Hernandezes for side effects for 15 minutes, and then hit the road. They had until 4:11 p.m. to reach three more patients.At least two million Americans like the Hernandezes are homebound, a population all but invisible. Most suffer from multiple chronic conditions, but cannot get primary care services in their home. They frequently wind up in hospitals, and their ailments leave them vulnerable to the coronavirus. When public health officials drew up plans for distributing vaccines, priority was given to the roughly five million residents and employees of congregate settings like nursing homes, where the coronavirus spread like wildfire during the early days of the pandemic. The virus killed at least 172,000 residents and employees, accounting for about one-third of all Covid-19 deaths in the United States.A vast majority of Americans over 65, however, do not live in nursing homes or assisted living facilities, but in the community, where it’s more challenging to reach them. There is no central registry of the homebound elderly. Geographically dispersed and isolated, they are often difficult to find.“This could be the next big hurdle for the older population,” said Tricia Neuman, a senior vice president at the Kaiser Family Foundation. “So much of the vaccination rollout has been a patchwork at the state or local level, but this presents a whole different set of challenges.”Celebrating teamwork at Northwell Health. “We’ll be running a tight ship, I think, but very compassionately,” Dr. Abrashkin said.Dr. Abrashkin, center, picking up two vials of vaccine from a refrigerator at Northwell Health’s vaccine “pod” for homebound elderly patients.With Dr. Konstantinos Deligiannidis, right, a portable refrigerator with vaccine doses left Northwell Health for home-visit vaccinations.Vaccination rates among seniors have risen quickly, with at least 60 percent inoculated so far. But there is no system in place for reaching the homebound, Dr. Neuman noted: “Some people simply cannot get themselves to a vaccination site, so the challenge is getting the vaccine to them, where they live.”In the absence of a centrally coordinated campaign targeting the homebound, local initiatives have sprung up around the country. Fire Department paramedics are administering vaccines to homebound seniors in Miami Beach, Fla., and in Chicago. A visiting nurse service vaccinates older adults located through the Meals on Wheels program in East St. Louis, Ill.Several health systems, like Geisinger Health in Pennsylvania and Boston Medical Center, have identified hundreds of homebound Americans and sent vaccines to them. In Minnesota, nonprofits have started pop-up vaccination clinics at senior apartment buildings and adult day care centers.On Monday, New York City announced that it was expanding efforts to go door-to-door to vaccinate homebound seniors, with plans to reach at least 23,000 residents. The visiting doctors program at Mount Sinai in New York, which cares for 1,200 homebound residents, has vaccinated 185 patients and has been given the greenlight to vaccinate the seniors’ caregivers as well, according to Dr. Linda DeCherrie, the clinical director of the Mount Sinai at Home program.Northwell’s house calls program, which cares for patients in Queens, Manhattan and Long Island, plans to vaccinate 100 patients a week over the next 10 weeks, a timetable that could be accelerated if nurses are allowed to carry rescue medications in case patients develop adverse reactions like anaphylactic shock.While Dr. Abrashkin was administering vaccines on Long Island last week, Dr. Konstantinos Deligiannidis, a colleague, was vaccinating five elderly women in the Brentwood, N.Y., area over the course of four hours.“They were so relieved,” he said. “They had all been worried — how could they get the vaccine since they couldn’t get out of the house?”Arriving with a vaccine at Juanita Midgette’s home in Roosevelt, N.Y.Ms. Midgette had heard mixed reviews about the vaccine, but she was hopeful the shot would give her the freedom to visit relatives in North Carolina.Ms. Midgette celebrated after receiving her dose. “My research tells me they are doing the best with the data they have collected so far to save lives,” she said.Dr. Abrashkin and Ms. Richardson visited — and vaccinated — two more elderly women on Wednesday before making their last stop at the sunny, plant-filled kitchen of Juanita Midgette, 73, a retired computer science and business teacher living with arthritis who counts Eddie Murphy among her past students. (Spoiler alert: He was a respectful student, she said, and she recommended his new movie, “Coming 2 America.”)It was 12:31 p.m. when they knocked on the door. Ms. Midgette had heard mixed reviews about the coronavirus vaccine, and had been squabbling with her sister about it. But she had been unable to travel to her native North Carolina and visit with relatives since the pandemic hit, and she was hopeful the vaccine would give her the freedom to do so.She believed in God, and in science. Ms. Midgette said her research into the vaccine led her to conclude that “the positivity greatly outweighs the negativity.”“My research tells me they are doing the best with the data they have collected so far to save lives,” Ms. Midgette said.“It reminds me of when we had the first computers, and they were so large, but we started teaching with them,” she said. “Now they fit in the palm of your hand. Had they waited until they got something smaller, the world would look different than it does today.”After getting the shot, she asked Dr. Abrashkin: “Is it all over?”“It’s hard to be isolated,” Ms. Midgette said. “I’m looking forward to being able to mingle again, in some way, somehow.”