First Effective, Inexpensive, Widely Available Outpatient Treatment for COVID-19?

 It’s fluvoxamine.

This rarely used antidepressant, long off-patent, has quietly been going through high-quality clinical studies for treatment of COVID-19. It certainly won’t be endorsed or promoted by any deep-pocketed pharmaceutical company, but deserves some attention nonetheless.

Here’s why I think we might finally be onto something with this “repurposed” drug, even after stumbling numerous times with hydroxychloroquine, lopinavir-ritonavir, ivermectin, azithromycin, doxycycline, colchicine, et al.

First, there is a legitimate mechanism of action — actually, multiple mechanisms, as it has anti-inflammatory, anti-platelet, and potentially antiviral activity independent of its psychoactive properties. If you want to get into the weeds, read this nice summary. But of course many drugs have in vitro mechanisms of action that don’t pan out.

Next, Dr. Eric Lenze and colleagues published a small double-blind clinical trial — well-designed and conducted — which showed benefit. Out of 152 participants enrolled, clinical deterioration occurred in 0 patients treated with fluvoxamine vs. 6 (8.3%) patients treated with placebo, a difference that was statistically significant.

But the problem with such small studies is that a tiny shift in outcomes for the treatment group would substantially change the conclusion. In other words, the results were “fragile.” The authors appropriately concluded that further larger studies were necessary.

After this trial, there was an observational study of opt-in versus opt-out fluvoxamine among newly infected workers at a horse racing track. Despite having more symptoms at baseline, the opt-in group receiving fluvoxamine had better outcomes than those who declined treatment — specifically, 0/65 hospitalizations for fluvoxamine, vs. 6/48 who chose observation only.

But the observational nature of this study also couldn’t provide a high enough level of evidence to change practice. What if the people choosing fluvoxamine were just more “health seeking” — and hence healthier — than those who declined, biasing the result? A highly plausible explanation for the results.

Still, these studies got enough attention to warrant further research, and even a spot on 60 Minutes. The research includes the innovative TOGETHER trial, led by a multinational group of investigators primarily in Canada and Brazil.

Here’s the “adaptive” study design, which shows the tested candidate drugs and the novel way the investigators drop unsuccessful treatments:

Eligible participants must have had symptom onset within the previous 7 days, a positive test for SARS-CoV-2, be older than 18, and have at least one risk factor for disease progression. The primary endpoint for these outpatient treatments was a composite of emergency room visits or hospitalizations due to the progression of COVID-19. The participants enrolled in 10 study sites in Brazil.

The group already published the negative results of their first study, showing that neither lopinavir-ritonavir nor hydroxychloroquine prevented progression to hospitalization or death better than placebo — which means those treatments have been appropriately dropped.

Time to move on to the next bracket, which included fluvoxamine, metformin, and ivermectin! Interim results were presented for the first time last week at an NIH meeting. The metformin didn’t do much of anything, and has been dropped; the ivermectin did a bit more, but still nothing practice-changing or statistically significant, with a relative risk of progression of 0.91 (95% confidence interval 0.69-1.19).

But the fluvoxamine treatment was much more promising. Among the 1480 participants randomized, fluvoxamine reduced the risk of disease progression by 29% (thanks to the lead investigator Dr. Edward Mills for this updated slide):

Most of the secondary endpoints also favored fluvoxamine, though the differences were not always statistically significant given the smaller event rate. No data on safety were presented, but Dr. Mills verbally stated that there were no unexpected toxicities.

No, an interim analysis of an ongoing study is not enough to change treatment guidelines — but it’s getting close, especially given the lack of other options and the favorable safety profile. The results are strong enough for the investigators to stop this comparison in this study, and no doubt a pre-print and submitted paper should be coming soon for further review.

Look, we’ve all been burned by promising studies of these repurposed drugs, and it’s quite reasonable to reserve final judgment until we see the complete data, and even other studies. Both the University of Minnesota COVID-OUT study and the NIH’s ACTIV-6 study include fluvoxamine arms.

But this already feels different from hydroxychloroquine and company given the high quality of the research. And it raises many interesting questions, including:

• Would the results be additive to monoclonal antibodies, which we know work well in early disease but remain limited in availability, expensive, and cumbersome to administer?
• How about combined with inhaled budesonide? Or with molnupiravir? (As an ID specialist with a research focus on HIV, you can tell I think combination therapy is a very good thing.)
• Should it be tried in inpatients, especially for those requiring oxygen, for whom anti-inflammatory approaches seem most beneficial?
• Would it work in other countries?
• On a global level, would fluoxetine be just as effective, as this SSRI is far more widely available?
• What should clinicians do now? Should they prescribe fluvoxamine for newly diagnosed patients with COVID-19? If so, for which ones?

No, I don’t have the answers. But this looks like progress, which during a pandemic is always great to see.

https://blogs.jwatch.org/hiv-id-observations/index.php/could-this-be-our-first-effective-inexpensive-widely-available-outpatient-treatment-for-covid-19/2021/08/12/

US to offer boosters to all Americans in aggressive plan to counter delta's spread

 The Biden administration, faced with resurgent coronavirus infections across much of the U.S., is calling for all Americans to receive a booster shot eight months after their initial vaccination against COVID-19. 

The plan, announced by senior health officials Wednesday morning, is a significant step in an immunization campaign that began last December and by early summer had allowed for a halting relaxation of public health measures in many states. 

But the fast spread of the more infectious delta variant of the coronavirus has imperiled those gains, and officials have grown concerned that protection from vaccination may wane over time, particularly among at-risk groups like older adults. Cases of COVID-19 have surged since mid-July and now regularly top 150,000 per day, overwhelming hospitals in regional hot spots like Louisiana, Mississippi and Florida.

"Having reviewed the most current data, it is now our clinical judgment that the time to lay out a plan for COVID-19 boosters is now," said Vivek Murthy, the U.S. surgeon general, in the Wednesday briefing. "Recent data makes clear that the protection against mild and moderate disease has decreased over time."

Other officials from the Health and Human Services department, including Centers for Disease Control and Prevention Director Rochelle Walensky and Food and Drug Administration head Janet Woodcock, joined Murthy in a separate statement announcing the plan.

People who previously got two doses of either Pfizer's or Moderna's vaccine would eventually receive a third, ideally of the same make as their first, the officials said. Just over 155 million people have been fully vaccinated with the two messenger RNA shots, according to the latest data from the CDC. 

The officials are not yet calling for people who received Johnson & Johnson's one-dose vaccine to get a booster. Data from a large trial run by the drugmaker of two doses is expected in the next few weeks and could inform similar advice for the nearly 14 million Americans vaccinated to date with J&J's shot.

In their statement Wednesday, the officials said they "anticipate booster shots will likely be needed" for people who received J&J's vaccine.

In presenting a plan for booster shots to the public, the Biden administration is getting ahead of regulators and the official CDC process for setting vaccine recommendations. The FDA has not yet authorized a third dose of either Pfizer or Moderna's vaccine, although the former company officially applied this week for broad clearance of a booster dose.

A CDC advisory panel on vaccines, meanwhile, is next scheduled to meet on August 24. 

In Wednesday's briefing, Murthy was adamant the administration isn't skipping over FDA or CDC authorization. Rather, officials wanted to outline the plan ahead of time to ensure states and counties can plan ahead. "You have to lay the groundwork," he said.

Experts are also still debating whether boosters are needed for healthy adults. While drugmaker studies have shown antibody levels against the coronavirus fall over time and data from real-world use suggest reduced efficacy against infections, it's not yet certain whether protection against hospitalization and death will eventually be compromised as well. Recent evidence, for example, has shown vaccine efficacy against those outcomes remains high, albeit somewhat lower than initially reported in Pfizer's and Moderna's studies. 

"We are concerned that this pattern of decline we're seeing will continue in the months ahead, which could lead to reduced protection against severe disease, hospitalization and death," said Murthy on Wednesday.

Administration officials said they expected people could receive boosters beginning the week of September 20, following an FDA authorization and CDC recommendation. Nursing home residents and healthcare workers would be the focus first, similar to the initial roll-out of vaccines last December.

Already, however, people are seeking out booster doses on their own, a decision that could be encouraged by the Biden administration's announcement Wednesday. According to the CDC, about 1.1 million people have received an additional vaccine dose beyond their initial vaccination. 

Booster doses will also be free to U.S. residents regardless of immigration or health insurance status, per White House officials.

The drive to administer additional doses to Americans while hundreds of millions of people in many countries around the world have yet to receive their first is likely to fuel further criticism the U.S., along with other wealthy nations, is hoarding vaccine supplies at the expense of poorer ones. 

While the U.S. has begun donating vaccine doses abroad and to the World Health Organization's COVAX initiative, many more are still needed. The latter effort is falling well short of its initial goals and some of the doses it's secured are still going to rich countries like the U.K. that had originally signed up as members, the Associated Press recently reported. 

Concerned many countries will remain unable to access vaccines this year, the WHO recently called for a global moratorium on administering booster doses until later this year. Several countries, including Israel, France and the U.K., have moved ahead with their own plans, however. 

"We're planning to hand the extra life jackets to people who already have life jackets, while we're leaving other people to drown without a single life jacket," said Mike Ryan, head of WHO's health emergencies program, in a separate press conference Wednesday. "That's the reality. Science is not certain on this."

On Wednesday, Jeffrey Zients, the White House's COVID-19 response coordinator, pushed back against the criticism, emphasizing that the U.S. can support both efforts.

"I do not accept the idea that we have to choose between America and the world. We clearly see our responsibility to do both," Zients said, adding that they expect to administer 100 million boosters over the coming months while donating 200 million over the same time period.

The White House decision to endorse boosters, despite the risk of backlash abroad, was driven by worrying data compiled by CDC researchers over several months that indicated vaccine efficacy appeared to drop over time, POLITICO reported Tuesday.

For example, CDC director Walensky cited data from a study in New York that showed declining protection from vaccines against coronavirus infection. Protection against hospitalization, however, remained high. Another, of nursing home residents, showed a similarly concerning drop in efficacy versus infection. 

Despite limited evidence of lower protection from COVID-19 hospitalization, White House officials on Wednesday emphasized the chance of further erosion in efficacy.

"We are concerned that the current strong protection against severe infection hospitalization and death could decrease in the months ahead, especially among those who are at higher risk, or who were vaccinated earlier during the phases of our vaccination rollout," Walenksy said.

Officials believe that boosting levels of neutralizing antibodies with a third shot will avoid those consequences. National Institute of Allergy and Infectious Diseases Director Anthony Fauci said that higher levels of neutralizing antibodies are "very likely" predictive of immunity, and preliminary evidence has shown a third shot boosts levels of those antibodies many times.

The White House's conclusions also drew from recent information from Israel, which moved more quickly than the U.S. to vaccinate a greater share of its population, that showed breakthrough infections were occurring more often in individuals vaccinated early on, in January and February.

The decision to forge ahead with boosters more broadly follows last week's authorization by the FDA of a third dose for people who previously received organ transplants, or whose immune systems were similarly compromised.

https://www.biopharmadive.com/news/coronavirus-vaccine-booster-us-biden-pfizer-moderna/605152/

Study boosts hopes for broad vaccine to combat COVID variants, future virus outbreaks

 Scientists from Duke-NUS Medical School and National Centre for Infectious Diseases (NCID) found that 2003 SARS survivors who have been vaccinated with the Pfizer-BioNTech mRNA vaccine produced highly potent functional antibodies that are capable of neutralizing not only all known SARS-CoV-2 variants of concerns (VOCs) but also other animal coronaviruses that have the potential to cause human infection. This finding, published in The New England Journal of Medicine, is the first time that such cross-neutralizing reactivity has been demonstrated in humans, and further boosts hopes of developing an effective and broad-spectrum next-generation vaccine against different coronaviruses.

Among the coronavirus family, one sub-group relies on the ACE2 molecule to enter human cells. Both SARS-CoV-1 and SARS-CoV-2 belong to this group as well as a number of coronaviruses circulating in animals such as bats, pangolins and civets. While the exact route of transmission remains unknown, these viruses have the potential to jump from animals to humans and could start the next pandemic. Collectively, this group of viruses is called sarbecovirus. 

"We explored the possibility of inducing pan-sarbecovirus neutralizing antibodies that can block the common human ACE2-virus interaction, which will be protective not only against all known and unknown SARS-CoV-2 VOCs, but also future sarbecoviruses," said Dr Chee Wah Tan, Senior Research Fellow with Duke-NUS' Emerging Infectious Diseases (EID) program and co-first author of this study. 

To test their hypothesis, researchers recruited eight people who recovered from SARS-CoV-1, which was responsible for the 2003 SARS epidemic, as well as ten healthy people and ten COVID-19 survivors. They then compared the immune response of the three groups before and after they were vaccinated with the SARS-CoV-2 vaccine. In particular, they wanted to understand whether the neutralizing antibodies developed in SARS-Vaccinated group could wipe out both SARS-CoV-1 and SARS-CoV-2 viruses as well as other sarbecoviruses, including potentially zoonotic sarbecoviruses that have been identified in bats and pangolins.

"Prior to vaccination, SARS-CoV-1 survivors had detectable neutralizing antibodies against SARS-CoV-1 but no or low-level anti-SARS-CoV-2 neutralizing antibodies. After receiving two doses of the mRNA vaccine, all displayed high levels of neutralizing antibodies against both SARS-CoV-1 and SARS-CoV-2," said Dr Wanni Chia, Research Fellow at the Duke-NUS EID' program and co-first author of this study. "Most importantly, they are the only group with a broad spectrum of neutralizing antibodies against ten sarbecoviruses that were chosen to be examined."

 "Our study points to a novel strategy for the development of next-generation vaccines, which will not only help us control the current COVID-19 pandemic, but may also prevent or reduce the risk of future pandemics caused by related viruses," said Professor Wang Linfa from Duke-NUS EID program, who is the senior corresponding author of this study.

"Professor Wang's team made an astute serendipitous observation in an ongoing national multicentre immune monitoring study of COVID-19 vaccination called the Singapore COVID-19 Vaccine Immune Response and Protection Study (SCOPE), which is coordinated by NCID. As emerging variants of concern have already demonstrated some degree of immune evasion against the first-generation vaccines, this discovery has the potential to address that problem as the world continues COVID-19 vaccination to exit the pandemic. In addition, this can potentially act as a highly promising preventive vaccine against future coronavirus pandemics," said Associate Professor David Lye, Director, Infectious Disease Research and Training Office, NCID and joint corresponding author of the study.

The team conducted their investigation using an improved version of the surrogate virus neutralization test (sVNT) developed by Duke-NUS in early 2020. Prof Wang and his team invented the sVNT assay, trade named cPass[1], which has been granted Emergency Use Authorisation by the US FDA to determine SARS-CoV-2-specific neutralizing antibodies in human sera following infection or vaccination. Dr Tan and Dr Chia are part of Prof Wang's team and co-inventors of the sVNT. The improved multiplex sVNT allows simultaneous detection of neutralizing antibodies against different sarbecoviruses in a single tube, thus playing a pivotal role in studies like this that require accurate side-by-side comparison of neutralizing antibody levels against different viruses.

The team is currently conducting a proof-of-concept study to develop a third-generation vaccine against different coronaviruses (3GCoVax) as well as broad neutralizing antibodies for therapy and is looking to recruit individuals who recovered from SARS infection in 2003.

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Explore further

Bats and pangolins in Southeast Asia harbor SARS-CoV-2-related coronaviruses, reveals new study

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More information: Chee-Wah Tan et al, Pan-Sarbecovirus Neutralizing Antibodies in BNT162b2-Immunized SARS-CoV-1 Survivors, New England Journal of Medicine (2021). DOI: 10.1056/NEJMoa2108453

For those who would like to take part in ongoing studies, please contact scrn@ncid.sg.

https://medicalxpress.com/news/2021-08-boosts-broad-vaccine-combat-covid-.html

Fears of 'violent' delta offshoot arise in Israel with 10 new cases of AY.3 reported

 Delta plus variant potentially better at escaping immune system, research shows

The Israeli Health Ministry is investigating 10 new cases in the country of a "violent" offshoot of the COVID-19 delta variant, Channel 13 news reports.

The 10 cases of the AY.3 strain were detected on Thursday with eight infected people returning from abroad and two infected in Israel.

Delta plus variants have a mutation in the spike protein also found in the beta and gamma variants that may help to evade antibodies. A report by the Indian Council of Medical Research found that AY.3 in particular is potentially better at escaping the immune system.

According to the US Centers for Disease Control and Prevention, the delta variant is about twice as infectious as the original coronavirus strain and 60 percent more contagious than the alpha variant.

The AY.3 sublineage of the delta variant accounts for approximately 15 percent of COVID-19 cases in the United States and has been detected in at least 61 countries.

As of August 10, 17,792 sequences of the AY.3 strain had been detected.

Of more concern is the lambda variant, also known as C.37, which is wreaking havoc in South America and has been identified in the US. 

“If it reaches Israel, we will get to the lockdown that we so desperately want to avoid,” Dr Asher Salmon, director of the Health Ministry’s Department of International Relations, told the Knesset (Israel Parliament) Law and Constitution Committee recently.

Israel's Prime Minister Naftali Bennett urged Israelis to get vaccinated at a Tuesday press conference, saying that another lockdown would "destroy the future of the country."

https://www.i24news.tv/en/news/coronavirus/1629384853-fears-of-violent-delta-offshoot-arise-in-israel-with-10-new-cases-of-ay-3-reported

Hidden SARS-CoV-2 'gate' found that opens to allow COVID infection

 Since the early days of the COVID pandemic, scientists have aggressively pursued the secrets of the mechanisms that allow severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter and infect healthy human cells.

Early in the pandemic, University of California San Diego's Rommie Amaro, a computational biophysical chemist, helped develop a detailed visualization of the SARS-CoV-2 spike protein that efficiently latches onto our cell receptors.

Now, Amaro and her research colleagues from UC San Diego, University of Pittsburgh, University of Texas at Austin, Columbia University and University of Wisconsin-Milwaukee have discovered how glycans—molecules that make up a sugary residue around the edges of the spike protein—act as infection gateways.

Published August 19 in the journal Nature Chemistry, a research study led by Amaro, co-senior author Lillian Chong at the University of Pittsburgh, first author and UC San Diego graduate student Terra Sztain and co-first author and UC San Diego postdoctoral scholar Surl-Hee Ahn, describes the discovery of glycan "gates" that open to allow SARS-CoV-2 entry.

"We essentially figured out how the spike actually opens and infects," said Amaro, a professor of chemistry and biochemistry and a senior author of the new study. "We've unlocked an important secret of the spike in how it infects cells. Without this gate the virus basically is rendered incapable of infection."

Amaro believes the research team's gate discovery opens potential avenues for new therapeutics to counter SARS-CoV-2 infection. If glycan gates could be pharmacologically locked in the closed position, then the virus is effectively prevented from opening to entry and infection.

The spike's coating of glycans helps deceive the human immune system since it comes across as nothing more than a sugary residue. Previous technologies that imaged these structures depicted glycans in static open or closed positions, which initially didn't draw much interest from scientists. Supercomputing simulations then allowed the researchers to develop dynamic movies that revealed glycan gates activating from one position to another, offering an unprecedented piece of the infection story.

"We were actually able to watch the opening and closing," said Amaro. "That's one of the really cool things these simulations give you—the ability to see really detailed movies. When you watch them you realize you're seeing something that we otherwise would have ignored. You look at just the closed structure, and then you look at the open structure, and it doesn't look like anything special. It's only because we captured the movie of the whole process that you actually see it doing its thing."

"Standard techniques would have required years to simulate this opening process, but with my lab's 'weighted ensemble' advanced simulation tools, we were able to capture the process in only 45 days," said Chong.

The computationally intensive simulations were first run on Comet at the San Diego Supercomputer Center at UC San Diego and later on Longhorn at the Texas Advanced Computing Center at UT Austin. Such computing power provided the researchers with atomic-level views of the spike protein receptor binding domain, or RBD, from more than 300 perspectives. The investigations revealed glycan "N343" as the linchpin that pries the RBD from the "down" to "up" position to allow access to the host cell's ACE2 receptor. The researchers describe N343 glycan activation as similar to a "molecular crowbar" mechanism.

Jason McLellan, an associate professor of molecular biosciences at UT Austin and his team created variants of the spike protein and tested to see how a lack of the glycan gate affected the RBD's ability to open.

"We showed that without this gate, the RBD of the spike protein can't take the conformation it needs to infect cells," McLellan said.

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Explore further

How SARS-CoV-2's sugar-coated shield helps activate the virus

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More information: A glycan gate controls opening of the SARS-CoV-2 spike protein, Nature Chemistry (2021). DOI: 10.1038/s41557-021-00758-3 , www.nature.com/articles/s41557-021-00758-3

https://phys.org/news/2021-08-hidden-sars-cov-gate-covid-infection.html

Where’s data on delta? Lack of testing, info makes it hard to see virus’s full scope

 In the earliest and darkest days of the pandemic last year, health experts were plagued by a lack of coronavirus testing, long wait times for results and an incomplete picture of what was driving outbreaks.

Now, more than a year and a half later, many public health professionals are confronting the same issues.

The delta variant is fueling a devastating new surge of infections, but experts say declines in testing and a lack of granular data about hospitalizations make it difficult to know just how much the virus is circulating in communities — and who remains most vulnerable.

That makes it harder to control new outbreaks, including those in schools as students return. It also hampers scientists’ ability to catch other, potentially more worrisome strains that may emerge.

“Without adequate data, policymakers are just swinging in the dark,” said Dr. Jeffrey Klausner, a clinical professor of population and public health sciences at the University of Southern California. “What you get is a discordant response and somewhat chaotic policies that frequently change, and people are left worse off.”

Most experts agree that official case numbers probably undercount the true number of Covid infections in the country. Those falling through the cracks are likely to be asymptomatic cases and people who experience only minor symptoms, said Dr. Benjamin Lee, a pediatric infectious disease physician at the University of Vermont.

What that means is that communities are left with a murky picture of where and how the virus is spreading, at least until hospitalization rates, which lag behind infections, start to creep up. That is particularly true with potential breakthrough infections in fully vaccinated people, Lee said.

“There’s sort of the assumption that if I’m vaccinated, I’m protected, so very mild symptoms that may have prompted testing over the winter just aren’t being picked up right now,” he said.

And because the vast majority of breakthrough cases are mild or asymptomatic, people with breakthrough infections may not even know to get tested and could thus transmit the virus unknowingly. Evidence that vaccinated people could readily spread the virus was what caused the Centers for Disease Control and Prevention to declare in internal documents last month that “the war has changed” with the delta variant.

But even that was based on limited data.

“Probably our biggest deficit now is knowing how many of those mild and asymptomatic cases are contributing to ongoing transmission that could subsequently lead to more hospitalizations,” Lee said.

Criticism of the overall lack of data has gained steam in recent weeks. Dr. Scott Gottlieb, a former commissioner of the Food and Drug Administration, tweeted Sunday that the U.S. still has major gaps in its understanding of the current wave of infections.

“In the U.S. we have no firm idea how many kids have already been infected with COVID,” Gottlieb wrote. “We have no idea if hospitalizations in south are tip of a huge iceberg of dire infection — or a sign that COVID has become more pathogenic in children. The CDC should gather this data. It isn’t.”

Emily Oster, an economics professor at Brown University, echoed Gottlieb’s sentiment, arguing that the U.S. needs a “data force” that could be mobilized to gather information about, among other things, breakthrough infections in fully vaccinated people and Covid cases in children.

“The fact is that 18 months into the pandemic, we are still not in the position we should be, in terms of our ability to move quickly to collect and analyze data that is needed for public health decisions,” Oster wrote Monday in her online newsletter.

That may change soon. The CDC announced the creation of a disease forecasting center Wednesday to assess emerging health threats and help guide public health decisions by governments, businesses and communities.

The initiative will probably focus much-needed national attention on addressing infectious disease risks. Klausner, who previously worked for more than a decade at the San Francisco Public Health Department, points to the country’s fractured public health system, which leaves decisions about what to monitor and report up to counties and states, as a major reason for the lack of cohesive data. But declines in coronavirus testing nationwide also play a role.

Testing slowed significantly across the country over the spring and summer, largely in response to vaccinations that helped flatten case counts and offered a brief respite from widespread community transmission. The number of tests administered daily in the U.S. peaked in January, according to data from Johns Hopkins University, and it fell precipitously over the following months.

Without more detailed information about who is getting infected, it’s difficult for public health officials to craft specific policies to protect those at risk, said Dr. William Raszka, a pediatric infectious disease specialist at the University of Vermont. The problem is all the more urgent as millions of children, including young children who aren’t yet eligible for the Covid-19 vaccines, are returning to classrooms for the new school year.

“The whole start of this school year has been anxiety-provoking for me,” Raszka said. “Last year was very straightforward. The governor had emergency powers and said everyone has to mask. That was easy and straightforward. Now it’s ridiculously confusing.”

https://www.nbcnews.com/science/science-news/delta-variant-response-hindered-covid-test-limitations-lack-data-rcna1692

CDC asks travelers at high risk of severe COVID-19 to avoid cruises

 The U.S. Centers for Disease Control and Prevention (CDC) said on Friday people at an increased risk for severe illness from COVID-19 should avoid travel on cruise ships, including river cruises, irrespective of their vaccination status.

Older adults and people with medical conditions are more likely to get severely ill from the disease and should take professional advise before cruise ship travel, the agency said.

Cruise operators have been sailing from U.S. ports again in recent weeks with mostly vaccinated guests and crew after lengthy talks with the CDC.

But a few on-board coronavirus cases and a Delta variant-driven increase in U.S. infections have raised worries about the cruise industry's recovery from the lows seen last year.

The health agency in May began approving some cruise operations and in June eased its warnings and recommended only fully vaccinated people take trips.

https://www.yahoo.com/lifestyle/u-cdc-asks-travelers-high-205737013.html