The why of COVID-19’s ‘fifth wave’ in the Berkshires – Berkshire Eagle

Updated at 9:51 a.m. on May 20, 2022

Yesterday afternoon, I called the UCLA epidemiologist Anne Rimoin to ask about the European outbreak of monkeypoxa rare but potentially severe viral illness with dozens of confirmed or suspected cases in the United Kingdom, Spain, and Portugal. If we see those clusters, given the amount of travel between the United States and Europe, I wouldnt be surprised to see cases here, Rimoin, who studies the disease, told me. Ten minutes later, she stopped mid-sentence to say that a colleague had just texted her a press release: Massachusetts Public Health Officials Confirm Case of Monkeypox.

The virus behind monkeypox is a close relative of the one that caused smallpox but is less deadly and less transmissible, causing symptoms that include fever and a rash. Endemic to western and central Africa, it was first discovered in laboratory monkeys in 1958hence the namebut the wild animals that harbor the virus are probably rodents. The virus occasionally spills over into humans, and such infections have become more common in recent decades. Rarely, monkeypox makes it to other continents, and when it does, outbreaks are so small, theyre measured in single digits, Thomas Inglesby, the director of the Johns Hopkins Center for Health Security, told me. The only significant American outbreak occurred in 2003, when a shipment of Ghanaian rodents spread the virus to prairie dogs in Illinois, which were sold as pets and infected up to 47 people, none fatally. Just last year, two travelers independently carried the virus to the U.S. from Nigeria but infected no one else.

The current outbreaks in Europe and the U.S. are different and very concerning. The first case, which was identified in the United Kingdom on May 7, fit the traditional pattern: The individual had recently traveled to Nigeria. But several others hadnt recently been to endemic countries, and some had had no obvious contact with people known to be infected. This suggests that the monkeypox virus may be surreptitiously spreading from person to person, with some number of undetected cases. (The incubation period between infection and symptoms is long, ranging from five to 21 days.) Its uncommon to see this number of cases in four countries at the same time, Inglesby said. (The count is now 11: Since we spoke on Wednesday, monkeypox has also been confirmed in Sweden, Italy, Germany, Belgium, France, Canada, and Australia.)

These monkeypox outbreaks are also unique because well theyre occurring in the third year of a pandemic, when the public is primed to be more acutely aware of outbreaks, Boghuma Kabisen Titanji, a physician at Emory University, told me. I dont think thats necessarily a good thing. When it comes to epidemics, people tend to fight the last war. During the West African Ebola outbreak of 2014, American experts had to quell waves of undue paranoia, which likely contributed to the initial downplaying of the coronavirus. Now, because the U.S. catastrophically underestimated COVID, many Americans are panicking about monkeypox and reflexively distrusting any reassuring official statements. I dont think people should be freaking out at this stage, Carl Bergstrom of the University of Washington told me, but I dont trust my own gut feelings anymore, because Im so sick of all this shit that I tend to be optimistic.

Monkeypox, then, is a test of the lessons that the world has (or hasnt) learned from COVID. Can we better thread the needle between panic and laxity, or will we once again eschew uncertainty in a frantic quest for answers that later prove to be wrong?

To be clear, monkeypox isnt COVIDtheyre different diseases caused by different viruses with markedly different properties. COVID was completely unfamiliar when it first appeared, but monkeypox is a known quantity, and experts on the virus actually exist. One of them, Andrea McCollum of the CDC, told me that based on existing studies, monkeypox doesnt spread easily, and not over long distances through the air. It transmits via contaminated surfaces or prolonged proximity with other people, which is why most outbreaks have been small, and why people have mostly transmitted the disease to either household members or health-care workers. This isnt a virus that, as far as were aware, would really take off in a population like COVID, she said. It really requires close contact for human-to-human transmission.

Of course, we have heard that before. In early 2020, many experts claimed that COVID spread only via contaminated surfaces or close-splashing dropletshence the six-feet rules and hygiene theater. Now it is widely accepted that the disease spreads through smaller and farther-reaching aerosol particleshence the importance of ventilation and masks. But that doesnt mean history is repeating with monkeypox. A 2012 study suggested that the virus can persist in aerosols for several daysbut that was under artificial laboratory conditions, and persistence is just one small part of the infection process. Chad Roy, an aerobiologist at Tulane University School of Medicine who led that study, told me that compared to the SARS-CoV-2 coronavirus, monkeypox is "an altogether different virus and the risk of natural transmission by aerosol far less likely. And the fact remains that past monkeypox outbreaks have been inconsistent with a virus that travels as easily as the coronavirus. Monkeypox does not scream airborne at me; COVID-19 did, Linsey Marr, an aerosol expert at Virginia Tech, told me.

Then again, Marr is less certain about monkeypox than she was about COVID. And Titanji notes that our knowledge of monkeypox is based on just 1,500 or so recorded cases, as of 2018. Ive seen a lot of people writing as if everything we know about monkeypox is definitive and finalized, but the reality is that it is still a rare zoonotic infection, she said. For that reason, Im in Team Cautious, she said. We cant use what happened with previous monkeypox outbreaks to make sweeping statements. If weve learned anything from COVID, its to have humility.

For decades, a few scientists have voiced concerns that the monkeypox virus could have become better at infecting peopleironically because we eradicated its relative, smallpox, in the late 1970s. The smallpox vaccine incidentally protected against monkeypox. And when new generations were born into a world without either smallpox or smallpox-vaccination campaigns, they grew up vulnerable to monkeypox. In the Democratic Republic of Congo, this dwindling immunity meant that monkeypox infections increased 20-fold in the three decades after smallpox vanished, as Rimoin showed in 2010. That gives the virus more chances to evolve into a more transmissible pathogen in humans. To date, its R0the average number of people who catch the disease from one infected personhas been less than 1, which means that outbreaks naturally peter out. But it could eventually evolve above that threshold, and cause more protracted epidemics, as Bergstrom simulated in 2003. We saw monkeypox as a ticking time bomb, he told me.

This possibility casts a cloud of uncertainty over the current unusual outbreaks, which everyone I spoke with is concerned about. Are they the work of a new and more transmissible strain of monkeypox? Or are they simply the result of people traveling more after global COVID restrictions were lifted? Or could they be due to something else entirely? So far, the cases are more numerous than a normal monkeypox outbreak, but not so numerous as to suggest a radically different virus, Inglesby told me. But he also doesnt have a clear explanation for the outbreaks unusual patternsnor does anyone else.

Answers should come quickly, though. Within days, scientists should have sequenced the viruses from the current outbreaks, which will show whether they harbor mutations that might have changed their properties. Within weeks, European epidemiologists should have a clearer idea of how the existing cases began, and whether there are connections between them. As for the U.S., McCollum told me that she is standing by for more cases. The day after we spoke, another suspected case was announceda patient being cared for at Bellevue Hospital in New York City.

The U.S. is, of course, in a better position with monkeypox than with COVID. Although the nation hadnt planned for a coronavirus pandemic, it has spent decades thinking about how to handle smallpox bioterrorism. The two cases of monkeypox in 2021 provided handy test runs for those plans, which are now unfolding smoothly. For example, the case in Massachusetts was identified when the patients physician, having reviewed reports from the U.K., called the states public-health department on Tuesday. Within 12 hours, the department had collected and tested the patients samples. The next day, more samples arrived at the CDC, which confirmed monkeypox. All of that worked really well, McCollum said. Were a fairly well-oiled machine.

Also, theres already a vaccine. One smallpox vaccine is 85 percent effective at preventing monkeypox and has already been licensed for use against the virus. And as another bioterrorism precaution, stockpiles of three smallpox vaccines are large enough to vaccinate basically everyone in the U.S. Inglesby said. And though monkeypox patients usually get just supportive care, a possible treatment does exist and has also been stockpiled: Tecovirimat, or TPOXX, was developed to treat smallpox but would likely work for monkeypox too.

Monkeypox may also be less deadly than is frequently claimed. The oft-cited fatality rate of about 10 percent applies to a strain that infected people in the Congo Basin. The West African strain, which several of the current cases have been linked to, has a fatality rate closer to 1 percentand thats in poor, rural populations. We havent seen fatalities in people whove had monkeypox in high-resource settings, Rimoin said.

Still, as COVID has shown, even when a disease doesnt kill you, it can hardly count as mild. Monkeypox might not take off in the way that COVID did, but for those who get it, it remains a substantial illness, McCollum said. If individuals are sick, theyre often sick for two to four weeks. Its urgent to identify people early, get them treatment, and identify contacts. It helps that one common symptom is an obvious rash, which looks like an extreme version of chickenpox. But unlike chickenpox, the monkeypox rash is usually preceded by a fever, the lesions are initially more painful than itchy, and the lymph nodes are often inflamed. The constructive thing to do is to make sure that the public is aware of what monkeypox looks like, Titanji said.

For that reason, she added, its important to avoid stigmatizing infected people. Many of the current cases are in men who identify as gay, bisexual, or men who have sex with menan unusual pattern not seen in previous monkeypox outbreaks. That has raised questions about a new route of transmission, but sex obviously involves prolonged close contact, which is how the virus normally spreads. As COVID showed, early narratives about a disease can rapidly and prematurely harden into accepted lore. And if those narratives turn into stigma, they could stop people from coming forward with symptoms.

Communication might prove to be one of monkeypoxs hardest challenges, as it has been with COVID. We need leaders who are saying, Heres what we know; heres what we dont know; well find out; and well be back tomorrow, Inglesby said. But some leaders have lost credibility during the recent pandemic, while others are being drowned out by armchair experts who have amassed large followings. All of a sudden, everyones an expert in monkeypox, Titanji said.

Alan Guebert| South Bend Tribune

Its no surprise that the nations five largest meatpackers, according to a May 12 government report, engaged in a concerted effort with Trump Administration political officials to insulate themselves from coronavirus-related oversight.

After all, the House Select Subcommittee on the Coronavirus Crisis (the Committee), the body charged with oversight of governments response to the pandemic, released a 23-page Memorandum last October that mapped how meatpackers and the Trump Administration joined forces to keep employees working in coronavirus-rife meat plants.

Those efforts paid off big time for Big Meat but proved deadly for their employees. According to the Committee, tens of thousands became infected with coronavirus and nearly 300 died of it.

Still, Trumps Big Ag supporters were uncharacteristically silent after the May 12 report was released. None rose to declare it fake news or partisan hackery.

They didnt because they couldnt. The 12-member Committee is decidedly bipartisan; its seven Democrats and five Republicans feature James Clyburn, the Dems third highest ranking House member, and Steve Scalise, the Republicans second most powerful member.

As for facts, the Committee has bushels gleaned from 29 public hearings and 151,000 pages of evidence. Twenty-six of the May 12 reports 61 pages are footnotes documenting every detail of the meatpackers actions to influence government, often the U.S. Department of Agriculture (USDA).

The evidence is remarkable for how brazen the meatpackers and their Big Ag allies especially the North American Meat Institute (NAMI) were in pushing their private agenda on public officials and how reflexively responsive government again, especially USDA was to the backdoor lobbying and backroom deals.

For example, meatpackers knew their plants were coronavirus hotbeds even as they lobbied to keep them open. An April 2020 email from a doctor in a hospital near JBS … facility, tells JBS that 100% of all COVID-19 patients we have in the hospital are either direct employees or family member[s] of your employees, and warn[s] that your employees will get sick and may die if this factory continues to be open.

The meatpackers prevailed because, the Committee reports, of a pattern of interference by Trump-appointed USDA officials with state and local health departments … with career [USDA] staff being walled off, and leaving no paper trail of such meetings.

The report names names. One was USDAs Under Secretary for Food Safety Mindy Brashears, whose efforts delighted the packer lobbyists who later crowed how fortunate it was to have USDA as their primary regulator because it was representing [the] industrys interests in every important interagency conversation.

Brashears was more than helpful: A few months later, a meatpacking lobbyist told [another meatpacking] executive that Brashears hasnt lost a battle for us in connection with efforts to block a local health department order to regulate coronavirus measures in a (named) facility.

Theres more. The report details how the meatpackers drafted the federal order to keep their plants open and how the Trump White House requested that they then issue positive statements and social media about the Presidents action …

For example, meatpackers were so sure they could push Trump Administration officials to issue an Executive Order to keep meatpacking plants open that Julie Anna Potts, the CEO of packer lobbyist NAMI, emailed Tyson Foods boss Noel White on April 18, 2020, to note, As of my conversations with USDA, they still think that they are … in better shape with POTUS than other agencies.

But, Potts related, I have said we have to see some results!

On April 28, her meatpacker members got their results: the White House ordered plants to remain open. Big Meats capture of government was complete.

But The results, reports the Committee, …were tragic: during the first year of the pandemic, workforces for the Big Five packers alone saw at least 59,000 worker infections, at least 269 deaths, and countless more cases and deaths among meatpacking-adjacent communities …

And, most likely, the only punishment any of the Big Five packers Tyson Foods, JBS USA, Smithfield, Cargilland National Beef will ever face for all the predicted illness and death is this detailed, shame-filled, soon-to-be-forgotten report.

Alan Guebert is an agricultural journalist. See past columns atfarmandfoodfile.com.

New Jersey on Saturday reported seven more COVID-19 deaths and 4,015 new confirmed positive tests as the seven-day average continues to compared to a month ago.

The average was 3,960 on Saturday, up 10% from a week ago and up 139% from a month ago. Though the statewide rate of transmission dropped slightly Saturday to 1.25 compared to 1.28 the prior day. When the transmission rate is over 1, that means each new case is leading to at least one additional case and the outbreak is expanding.

There were 836 patients with confirmed or suspected coronavirus cases reported across the states 71 hospitals as of Friday night. Hospitalizations still remain significantly lower than when they peaked at 6,089 on Jan. 10 during the Omicron wave.

There were at least 188 people discharged in that same 24-hour period ending Friday, according to state data. Of those hospitalized, 117 were in intensive care and 39 were on ventilators.

The positivity rate for tests conducted on Sunday, the most recent day with available data, was 18.85%.

The state on Saturday also reported 1,378 probable cases from rapid antigen testing at medical sites.

The BA.2 strain of COVID-19 has been spreading in New Jersey for weeks, though at much lower rates than the Omicron surge in December and January. Officials have said the Omicron stealth sub-variant appears to spread more easily but generally does not cause more severe illness.

For the week ending April 30, BA.2 accounted for 91.4% of the positive tests sampled (slightly up from 89.4% the previous week), while the BA2.12.1 omicron subvariant accounted for 6% of positive tests sampled (down from 6.7% the previous week).

The Centers for Disease Control and Prevention now lists 10 New Jersey counties with high transmission rates Atlantic, Burlington, Camden, Cape May, Gloucester, Monmouth, Morris, Ocean, Salem and Sussex. Those in high-risk areas are recommended to wear a mask indoors in public and on public transportation and stay up-to-date on vaccination, according to the U.S. Centers for Disease Control and Prevention.

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

New Jersey has reported 2,021,344 total confirmed COVID-19 cases out of more than 17.7 million PCR tests conducted in the more than two years since the state reported its first known case March 4, 2020.

The Garden State has also recorded 331,306 positive antigen or rapid tests, which are considered probable cases. And there are numerous cases that have likely never been counted, including at-home positive tests that are not included in the states numbers.

The state of 9.2 million residents has reported 33,610 COVID-19 deaths 30,552 confirmed fatalities and 3,058 probable.

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

The latest numbers follow a major study that revealed even a mild case of COVID-19 can significantly affect the brain. Long COVID the term commonly used to describe symptoms stemming from the virus long after a person no longer tests positive has been found to affect between 10% and 30% of those who contract the infection, regardless of whether they have a mild or serious case.

More than 6.89 million of the 8.46 million eligible people who live, work or study in New Jersey have received the initial course of vaccinations and more than 7.8 million have received a first dose since vaccinations began here on Dec. 15, 2020.

More than 3.74 million people in the state eligible for boosters have received one. That number may rise after the FDA on Tuesday approved booster shots for healthy children between the ages of 5 and 11. U.S. regulators authorized the booster for kids hoping an extra vaccine dose will enhance their protection as infections once again creep upward.

For the week ending May 8, with about 59% of schools reporting data, another 8,923 COVID-19 cases were reported among staff (2,461) and students (6,462) across New Jerseys schools.

Since the start of the academic year, there have been 116,771 students and 34,685 school staff members who have contracted COVID-19 in New Jersey, though the state has never had more than two-thirds of the school districts reporting data in any week.

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

New Jersey has reported 807 total in-school outbreaks, including 5,671 cases among students and staff. That includes 82 new outbreaks in the latest weekly report ending May 16. The state reported 72 in-school outbreaks the previous week.

At least 9,049 of the states COVID-19 deaths have been among residents and staff members at nursing homes and other long-term care facilities, according to state data.

There were active outbreaks at 323 facilities, resulting in 3,482 current cases among residents and 3,144 cases among staff, as of the latest data.

As of Saturday, there have been more than 527 million COVID-19 cases reported across the globe, according to Johns Hopkins University, and more than 6.28 million people died due to the virus.

The U.S. has reported the most cases (more than 83.2 million) and deaths (at least 1,002,025) of any nation.

There have been more than 11.44 billion vaccine doses administered globally.

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Matt Arco may be reached at marco@njadvancemedia.com. Follow him on Twitter at @MatthewArco.

ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection  Science

It is difficult to know what COVID is doing to the people of Africa.

The World Health Organization (WHO) says the death toll has been vastly undercounted in much of the world, but poor data collection in most African countries makes it difficult to assess the true impact on the continent.

Evidence on COVID-related deaths in South Africa suggests there are serious grounds for concern. Experts at South Africas Medical Research Council believe hundreds of thousands of deaths have been lost in the paperwork. The real death toll is thought to be three times the official number of 101,000.

Health officials are also grappling with worryingly low rates of vaccination in many African countries. As a whole, only 17% of Africans have been fully vaccinated against COVID, a rate that lags far behind other parts of the world - like Europe (65.7%), Asia (69%), and South America (74.5%).

These dismal numbers are compounded by the fact that the drive to vaccinate the public in dozens of African nations has effectively stalled.

In fact, nearly half the vaccine doses delivered to the continent so far have gone unused.

This time last year, health officials in Africa were trying to find a way to secure supplies after wealthier nations reserved most of the stock.

Now, they need to figure out how to get them into peoples arms. It is absolutely critical that they succeed.

Are 'vaccine convoys' the solution?

Abandoning the global effort to reach the WHOs 70% vaccination target may lead to the emergence of deadly new variants, thereby derailing the world's precarious attempts to live with the virus.

But the task is immense. In South Africa, less than half the adult population is vaccinated. In the Democratic Republic of Congo, just 1.2% is fully immunised.

It has become clear to leading figures like Dr Ian Sanne, who leads the health organisation Right to Care, that governments and institutions need to rethink the way they distribute vaccines.

"At the moment, the politicians and our procurement (systems) are focused on getting vaccines into the country, but the harder part is that we have to deliver them and roll them out," he said.

"And you've seen what it takes to bring these vaccines into remote areas."

Right to Care, with funding from the US government's development agency, USAID, has put together a number of "vaccine convoys" to venture into some of the most remote and impoverished areas of South Africa's Eastern Cape.

We joined a convoy as it bounced its way down a series of near-impassable tracks, before reaching a village called Lundini. Its 800 or so residents have never been offered a COVID vaccine.

It was a time-consuming process, requiring planning and specialist personnel - and plenty of money. Dr Sanne says he can vaccinate someone near Johannesburg for around US $9, but it takes nearly three times that amount to administer a jab in the rural parts of the Eastern Cape.

But this may be the only way to do it.

'We understand the mistrust - the fear'

I asked a teacher called Ethel Numbezi why she had not gone to the city of Durban, on the coast, to get a jab. She burst into laughter.

"It would be too difficult," she said, trying to stifle her laughter, "because it's far way away from us."

While many of these logistical challenges can be fixed with funding, there is another problem proving much harder to solve. We noticed that Right to Care's nurses often struggled to convince people in Lundini to have the jab. Some residents said they were scared - and just about everyone seemed a little nervous.

I asked nurse Vuyelwa Lubando to explain.

"They say sometimes the government want to eliminate, um, because of the, um"

Nurse Lubando pointed her skin.

"You mean, black people?" I asked.

"Yes."

"The government wants to get rid of black people?"

"So we are trying to tell them there is no such (thing)."

Myths surrounding COVID vaccine side effects have become a major headache for health officials, but Heena Brahmbhatt, a senior advisor to USAID, says the vaccine convoys are a good way to get around it.

"We all underestimated the mistrust, the level of fear, the use of social media to spread disinformation, but if you get (vaccines) to the people, they are likely to get vaccinated. You can see people lining up (behind me). You barely get this in urban settings in South Africa any more."

Read more: What's the COVID situation in your local hospital?

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Disturbing data shows scale of problem

The situation in many other African countries is worse, as so-called vaccine hesitancy combines with other factors to suppress vaccination rates.

Data from the WHO dashboard reveals that levels of so-called "vaccine absorption", or the use of available stocks of COVID vaccines, is pitifully low in countries like Cameroon, where only 15% of its supply has been used.

In the Democratic Republic of Congo, just 8% of available vaccines have been administered while in Burundi, that number is a disturbing 2%.

If you take the average number of vaccinations administered in each country since the pandemic began and calculate how long it would take to meet the WHO's 70% target - if that rate continued into the future - the numbers raise troubling questions.

Based on past performance, Cameroon would not reach the 70% target until 2036. The DRC would require an additional 41 years or to 2070 to satisfy the WHO target. The people of Burundi would have to wait until 2194 at which point they would have died.

Read more: Who will get autumn COVID booster jabs?

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This is an academic exercise, a reflection of how some countries have fared up until this point, and it shows how much more work is left to do - a point made by Liya Temeselew, policy associate at the Tony Blair Institute.

"Despite competing priorities and limited resources, governments in Africa continue to use innovative methods for vaccine campaigns," she said.

"For example, in Ghana, vaccine campaigns include intensive social awareness campaigns to combat vaccine hesitancy and health workers going door to door to make vaccines more accessible to people.

"The international community needs to work alongside governments and invest in last mile delivery to ensure the health and economic cost of COVID-19 is minimised."

This is calculated by taking the number of people that need to be vaccinated to cover 70% of each country's population, and dividing this number by the average number of people fully vaccinated each month thus far. This calculation assumes that there will be no significant increase or decrease in vaccine demand and supply in the future.

Background and objective

Since being declared a global pandemic, coronavirus disease 2019 (COVID-19) has led to millions of cases and deathsworldwide. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to wreak havoc on individuals, healthcare systems, and economies, the intensive vaccination strategies adopted by several countries have significantly slowed the progress and the severity of the disease. In this study, we aimed todetermine the COVID-19 vaccination status among healthcare workers (HCWs)and examine the effects of vaccination on disease manifestations.

This cross-sectional study was conducted at a teaching hospital in NortheastIndia from April 2021 to September 2021, during the second phase of the COVID-19 pandemic. HCWs employed in the hospital who were laboratory-confirmed cases of COVID-19 based on semiquantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) or cartridge-based nucleic acid amplification test (CBNAAT) on oropharyngeal samples were included in the study. Data analysis was performed using Microsoft Excel (Microsoft Office Professional Plus 2019, Microsoft Corp., Redmond, WA)

A total of 178 HCWs reported positive for COVID-19 infection during the study period. Of these, 42 (23.59%) were males and 136 were females (76.40%).Among them, 86 (48.32%) HCWs were fully vaccinated, 58 (32.58%) were partially vaccinated, and 34 (19.10%) were not vaccinated.Most of the HCWs experienced mild disease (145, 81.46%), and only four (2.24%) reported moderate to severe disease. Compared with unvaccinated HCWs, individuals who have had either one or twodoses of vaccines were less likely to have moderate to severe disease or seek treatment at the hospital. On symptoms analysis, shortness of breath was found to be more common in unvaccinated individuals than in vaccinated patients, and anosmia and loss of taste were more common in vaccinated than in unvaccinated individuals. No deaths were reported among the participants included in this study.

Following the first and second waves of the COVID-19 pandemic, a substantial proportion of HCWs were infected with SARS-CoV-2, likely as a result of the acquisition of the virus in the community during the early phase of local spread. Fully vaccinated individuals with COVID-19 were more likely to be completely asymptomatic or only mildly symptomatic compared to unvaccinated HCWs.

Coronavirus diseases 2019 (COVID-19) is caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. It was first reported in Wuhan, Hubei Province, China in December 2019 [2]. Since the onset of the COVID-19 pandemic, more than 238 million people have been infected, leading to more than 4.8 million mortalities, as ofOctober 9, 2021 [3]. In the absence of any specific treatment against the COVID-19 virus, vaccination remains the only viable option to combat this pandemic for now. The United States Food and Drug Administration (USFDA) gave its firstapproval for a vaccine against the COVID-19onDecember 11, 2020, on an emergency use authorization basis, for the COVID-19 mRNA vaccine (BNT162b2). As ofOctober 9, 2021, more than 6.47 billion doses of various COVID-19 vaccines have been administeredworldwide [4]. Due to the shortage of vaccines in the immediate aftermath of the initial rollout of vaccines, only those people at high risk of getting an infection or at risk of developing severe disease were vaccinated on a priority basis. Healthcare workers (HCWs) directly involved in the care of COVID-19 patients face a higher risk of getting infected in comparison to the general population [5]. Hence, they were the first group of people to be vaccinated against COVID-19. In India, vaccination against COVID-19 was started on January 16, 2021, and as ofOctober 9, 2021, more than 946 million doses of vaccine have been administered [6]. However, like in the case of any other vaccine, there has been vaccination hesitancy amongthe HCWs regarding the COVID-19 vaccine as well and, as a result, there have been many cases where HCWs diagnosed with COVID-19 were found to be unvaccinated[7].

Individuals diagnosed with COVID-19 may have protean manifestations and different clinical needs [8]. There have been scarce data from NortheastIndia regarding the COVID-19 pandemic[9-11]. Analysis of symptom profiles among individual COVID-19patients following vaccination is valuable in terms of clinical utility, assessment and identification of risk groups (e.g., long COVID) for intervention, and the appropriate use of testing guidelines [12]. Against this background, the present study was conducted during the second wave of COVID-19 in India, which was mostly attributed due to the emergence of the Delta variant of the COVID-19 virus [13]. Our objectives were as follows: (1) to determine the COVID-19 vaccination status among HCWs at the time of COVID-19 diagnosis, and (2) to study the effect of the COVID-19 vaccination ondisease manifestations.

The study was conducted at a tertiary care medical teaching institute in the state of Meghalaya in Northeast India. The study included cases diagnosed during the period from April 2021 to September 2021, which coincided with the second wave of the COVID-19 in the state of Meghalaya. Only those HCWs who are working in the institute where the study was conducted were included, and they were followed up for at least three weeks from the date of diagnosis. The study included 178laboratory-confirmed cases of COVID-19 based on either semiquantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) or cartridge-based nucleic acid amplification test (CBNAAT) on oropharyngeal samples. All patients were under the direct supervision of the treating institute. Patients who were treated outside the institute were excluded from the study. For the purpose of comparison, the cases were classified into three groups based on the vaccination status:

Category-A: Nonvaccinated - Patients who were either not vaccinated or received their first dose of vaccine within seven days of the diagnosis of COVID-19.

Category-B: Partially vaccinated - Patients who either received the first dose of vaccineeight or more days prior to the COVID-19 diagnosis or received the second dose of vaccine within seven days of the diagnosis of COVID-19.

Category-C: Fully vaccinated - Patients who received the second dose of vaccine eight or more days prior to the diagnosis of COVID-19.

Data related todemographic details, vaccination status, clinical manifestations, and disease outcomes were collected. Ethical approval was obtained from the Institution Ethics Committee, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences vide letter No. NEIGR/IEC/M15/F20/2021 dated August 28, 2021, and informed written consent was obtained from allstudy participants.

A totalof 178 cases were included in the present study. Of them, 42 (23.59%) were males and 136 (76.40%) were females, with a male-to-female ratio of 0.31:1. Most of the study patients were nursing officers (n=102, 57.30%) followed by resident doctors (n=37, 16.29%), technicians (n=17, 7.86%), housekeeping staff(n=12, 6.74%), and faculty members (n=10, 5.62%). The number of cases in Category-A, Category-B, and Category-C was 58 (32.58%), 34 (19.10%), and 86 (48.32%) respectively. All those who were vaccinated had received only Covishield [ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant)] manufactured by the Serum Institute of India Pvt Ltd. The vaccination status among the different categories of the staff at the time of COVID-19 diagnosis is shown in Table 1. Characteristics such as the mean age, gender distribution, and severity of disease in the different categories are shown in Table 2.

Figure 1 illustrates symptoms in various categories of HCWs who were diagnosed with COVID-19.

In the absence of an effective and sustainable infection control strategy and the non-availability of a specific treatment against the COVID-19, effective vaccination remains the only viable option to fight against the COVID-19 pandemic. The sense of urgency to have an effective vaccine against COVID-19 coupled with great human effort has led to the development of multiple vaccines against COVID-19within a year of the first reported case of the ongoing COVID-19 pandemic. As of February 2022, India has authorized three vaccines against SARS-CoV-2: Covishield (AstraZeneca's vaccine manufactured by the Serum Institute of India), Covaxin (manufactured by Bharat Biotech Limited), and Sputnik V [14]. But coronaviruses are known to undergo genetic mutation as they propagate, and it has happened in the case of SARS-CoV-2 as well,resulting in the appearance of multiple variants of the virus leading to multiple waves of increased cases and reinfections [15-18]. The appearance of multiple variants also has the potential to render the existing vaccines ineffective [19].

Even though vaccines against COVID-19 were made available within the shortest possible period, many people including HCWs remained hesitant to get vaccinated due to doubts regarding the efficacy and safety of the available vaccines. In the present study, 32.59% of HCWs had not received any dose of vaccine at the time of COVID-19 diagnosis, 19.10% were partially vaccinated, and only 48.31% were completely vaccinated. Among the categories of HCWs, the housekeeping staff was the most unvaccinated group followed by the nursing staff. Doctors including faculty members and residents were predominantly vaccinated at the time of COVID-19 diagnosis. Vaccine hesitancy was found to be higher among the nursing staff and housekeeping staff in the present study, which is similar to the findings reported in other studies [20,21].

All HCWs in the fully vaccinated category had either mild disease or were asymptomatic. Among the partially vaccinated or completely unvaccinated, 4.34% of cases developed moderate to severe disease. No mortality was reported in the present study in any of thecategories. Similar findings were reported by other studies where most of the HCWs with breakthrough infections after receiving the Oxford-Astra Zeneca vaccinewere either asymptomatic or had mild disease [22,23].

In a study by Teranet al. involving 75 skilled nursing care facilities in Chicago, among 627 persons with SARS-CoV-2 infection since vaccination began, 22 (4%) were identified as residents and staff members of skilled nursing facilities. On further analysis, nearly two-thirds (14/22, 64%) of the patients were found asymptomatic with two COVID-19-related hospitalizations and one death [24]. Similar results were also reported by different studies across India; however, none of these studies reported any deaths related to COVID-19 among HCWs who received two doses of the vaccine (Table 3) [25-28]. The possible hypothesis for this post-vaccination COVID-19 infection could be ascribed to the emergence of new COVID-19 variants, which may bypass vaccine-induced immunity [29]. It is reassuring that the majority of infections seen in our facility were either asymptomatic or mild.

Based on our findings, COVID-19 vaccination acceptance is not uniform among the different categories of the HCWs. Vaccination acceptance is almost universal among doctors but less among the nursingand housekeeping staff. Those who were completely vaccinated were found to have negligible levels of serious disease when compared to those who were either unvaccinated or incompletely vaccinated.These findings suggest that widespread and effective vaccination among HCWs provides a safe environment, even in the setting of a high rate of SARS-CoV-2 infection in the community.

Abstract

Objective To estimate associations between covid-19 vaccination and long covid symptoms in adults with SARS-CoV-2 infection before vaccination.

Design Observational cohort study.

Setting Community dwelling population, UK.

Participants 28356 participants in the Office for National Statistics COVID-19 Infection Survey aged 18-69 years who received at least one dose of an adenovirus vector or mRNA covid-19 vaccine after testing positive for SARS-CoV-2 infection.

Main outcome measure Presence of long covid symptoms at least 12 weeks after infection over the follow-up period 3 February to 5 September 2021.

Results Mean age of participants was 46 years, 55.6% (n=15760) were women, and 88.7% (n=25141) were of white ethnicity. Median follow-up was 141 days from first vaccination (among all participants) and 67 days from second vaccination (83.8% of participants). 6729 participants (23.7%) reported long covid symptoms of any severity at least once during follow-up. A first vaccine dose was associated with an initial 12.8% decrease (95% confidence interval 18.6% to 6.6%, P<0.001) in the odds of long covid, with subsequent data compatible with both increases and decreases in the trajectory (0.3% per week, 95% confidence interval 0.6% to 1.2% per week, P=0.51). A second dose was associated with an initial 8.8% decrease (95% confidence interval 14.1% to 3.1%, P=0.003) in the odds of long covid, with a subsequent decrease by 0.8% per week (1.2% to 0.4% per week, P<0.001). Heterogeneity was not found in associations between vaccination and long covid by sociodemographic characteristics, health status, hospital admission with acute covid-19, vaccine type (adenovirus vector or mRNA), or duration from SARS-CoV-2 infection to vaccination.

Conclusions The likelihood of long covid symptoms was observed to decrease after covid-19 vaccination and evidence suggested sustained improvement after a second dose, at least over the median follow-up of 67 days. Vaccination may contribute to a reduction in the population health burden of long covid, although longer follow-up is needed.

By the end of 2021 in the UK, when 90% of the population had received at least one dose of a covid-19 vaccine, nearly 14 million cases of SARS-CoV-2 had been confirmed, 640000 patients had been admitted to hospital, and 158000 had died with covid-19.1 Symptoms of infection may persist for months, defined in UK clinical guidelines as ongoing symptomatic covid-19 (signs and symptoms 4-12 weeks after onset) or post-covid-19 syndrome (>12 weeks after onset).2 These symptoms are collectively and commonly referred to as long covid. Long covid is characterised by a range of manifestations across organ systems, including fatigue, shortness of breath, and cognitive impairment,3 often with fluctuating periods of wellness followed by relapse.456 By 8 February 2021, nearly 6% of adults in England might have experienced prolonged symptoms after SARS-CoV-2 infection since the pandemic began,7 and in October 2021 an estimated 1.2 million people in private households in the UK (1.9%) had reported experiencing long covid, with symptoms in two thirds of these individuals having a detrimental impact on day-to-day activities.3

Population level immunisation against covid-19 began in the UK on 8 December 2020, and both adenovirus vector and mRNA vaccines administered to the population have shown safety and efficacy in trials891011 and real world effectiveness at reducing rates of SARS-CoV-2 infection,1213 transmission,14 admission to hospital,15 and death.1516 Preliminary research suggests that long covid symptoms are less common in breakthrough infections,17 but the effectiveness of vaccination on pre-existing long covid is less clear. Anecdotal evidence suggests variations in the lived experience of long covid after vaccination, with patients describing improvement, deterioration, and no change in their symptoms. In an online survey of members of a long covid patient advocacy group in the US, about 40% of respondents reported full or partial symptom resolution after vaccination and 14% reported deterioration.18 In a similar survey conducted by a UK based patient group, more than a half of participants experienced an improvement in long covid symptoms and a fifth experienced a worsening of symptoms.19 Although such studies are informative, they included self-selected groups of participants who might not be representative of the population of interest and lacked control groups and long term follow-up, and other studies have included small sample sizes.2021 A quarter of the UK population aged 12 years and older were yet to receive two doses of a covid-19 vaccine by 5 September 2021, and 16% had not received their first dose.1 Possible vaccine hesitancy among people with long covid symptoms has been identified through social media discourse.22

Greater evidence is therefore needed on the symptomology of SARS-CoV-2 infection after vaccination, which may facilitate informed decision making among individuals with long covid. To estimate associations between covid-19 vaccination and long covid symptoms in adults infected with SARS-CoV-2 before vaccination, we used data from the Office for National Statistics COVID-19 Infection Survey, a large, community based population survey.

Data were obtained from the COVID-19 Infection Survey,23 a longitudinal survey of people aged 2 years or older in randomly sampled UK households (excluding communal establishments such as hospitals, care homes, halls of residence, and prisons).

Enrolment rates were as high as 51% in the initial pilot phase of the survey from April 2020, when eligible households comprised previous respondents to ONS surveys who had consented to participate in future research. As the sample was expanded and transitioned to random selection from address lists in August 2020, however, the enrolment rate dropped to 12% (see supplementary table 1 for details). Once participants are enrolled into the study, the attrition rate is generally low; using a definition of either formally withdrawing from the study or having not attended the three most recently scheduled follow-up visits, the attrition rate among enrolled survey participants was less than 1% in 2021.

A study worker visited each selected household, after verbal agreement to participate had been obtained, to provide written confirmed consent (from parents or carers for those aged 2-15 years; those aged 10-15 years also provided written assent). At the first visit, participants could consent for (optional) follow-up visits every week for the next month and then monthly for 12 months or longer.

All participants provided a self-collected nose and throat swab sample for reverse transcription polymerase chain reaction testing at each follow-up visit. Those aged 16 years or older in a random subsample of households (initially 10% but expanded from April 2021), and those in households where another household member previously tested positive for SARS-CoV-2, were invited to provide monthly blood samples for S antibody testing. Participants also reported whether they had tested positive either for SARS-CoV-2 or for antibodies to SARS-CoV-2 outside of the study (for example, through national testing programmes).

At every monthly visit from 3 February 2021, survey participants were asked whether they would describe themselves as currently experiencing long coviddefined as symptoms persisting for at least four weeks from confirmed or suspected SARS-CoV-2 infection that could not be explained by another health condition. This definition uses self-classification of long covid rather than a prespecified symptoms list or clinical diagnosis, and thus reflects participants perception of whether their lived experience is consistent with what they understand of the condition. Participants who responded positively to the long covid question were further asked about the extent to which their day-to-day activities were limited as a result and the presence of 21 individual symptoms as part of their experience of long covid (selected on the basis of being among the most commonly reported when the survey question was developed5624; see full list in supplementary table 2).

For participants in England, information on vaccination (number of doses, dates, manufacturer) was obtained from self-reported responses to the COVID-19 Infection Survey and linked National Immunisation Management System records, with the latter being prioritised when data conflicted. Concordance between self-reported and National Immunisation Management System data was previously found to be high for vaccination type (98%) and date (95% within 7 days).12 As administrative records were not available for participants in Wales, Scotland, and Northern Ireland, vaccination data for these individuals were taken from the survey alone.

The analysis included survey participants aged 18 to 69 years on 3 February 2021. Participants were included if they responded to the survey question on long covid at least once by 5 September 2021 (end of follow-up), received at least one dose of a covid-19 vaccine before or during the follow-up period, and received a positive swab or blood test result for SARS-CoV-2, either through the survey or reported outside of the study, before vaccination. We excluded survey participants who remained unvaccinated by 5 September 2021 because they were likely to differ from those who were vaccinated according to unmeasured characteristics (for example, personal considerations related to vaccine hesitancy).

We defined the time of infection as the date of a first positive swab or antibody test result (ignoring blood test results after first vaccination), or the date when participants first thought they had covid-19 that was later confirmed by a positive test result, whichever was earlier. Although the survey question asks about long covid symptoms persisting for at least four weeks from infection, for this analysis we used a longer 12 week threshold, consistent with the UK clinical case definition of post-covid-19 syndrome2 and the World Health Organizations definition of post-covid-19 condition.25 We therefore excluded any follow-up visits within 12 weeks of the infection date.

Participants were observed from their first survey follow-up visit that took place after their first SARS-CoV-2 infection and after the long covid question was added to the COVID-19 Infection Survey on 3 February 2021. Follow-up ended on the date of the participants final follow-up visit that took place by 5 September 2021.

The explanatory variables of interest were first and second doses of an adenovirus vector (ChAdOx1 nCoV-19 (AZD1222), Oxford-AstraZeneca) or mRNA (BNT162b2, Pfizer-BioNTech; mRNA-1273, Moderna) covid-19 vaccine. The recommended interval between the first and second vaccine doses was 11 to 12 weeks for most participants in the study sample (having been increased from four weeks on 30 December 2020), with a reduction to eight weeks in May 2021 for people in the top nine vaccination priority groups.26 For each vaccine dose, we estimated the associated change in outcomes using a binary variable to indicate whether participants had received each dose at each follow-up visit; and a variable equal to the number of days since receiving each dose at each follow-up visit to estimate post-vaccination changes in the outcome trajectory (set to 0 for visits before receiving each dose). This specification implies that any change in the odds of long covid occurs instantly after vaccination, although in reality this may take place over several days or weeks.

The primary outcome at each visit was long covid of any severity, with a secondary outcome of long covid resulting in limitation of day-to-day activities (a little or a lot versus not at all or no long covid); this definition of functional impairment is standardised across data collections by the UK Government Statistical Service and is designed to measure disability as defined in the Equality Act 2010. We also evaluated the 10 individual symptoms that were most commonly reported over the follow-up period and whether participants were experiencing more than three or more than five of the 21 symptoms included on the survey.

As well as time from infection and the vaccination variables to modify the time trajectory of long covid, we adjusted for covariates hypothesised to be related to vaccine type and timing27 and the probability of experiencing long covid symptoms3: age, sex, white or non-white ethnicity, region or country, area deprivation fifth group, health status, patient-facing health or social care worker, and hospital admission with acute covid-19. We also adjusted for calendar time of infection to control for temporal effects that might be related to the risk of developing prolonged symptoms, such as viral variant (the alpha and delta variants were both dominant at different periods during follow-up) and changes in healthcare practice. Supplementary table 3 provides details of the covariates.

We compared covariates between participants who received an adenovirus vector vaccine and mRNA vaccine using means and proportions for continuous and categorical variables, respectively. Standardised differences >10% indicated large differences.28

An individual level interrupted time series approach was used to estimate associations between vaccination variables and outcomes.29 For each outcome, we included all vaccination variables and covariates in a binary logistic regression model and estimated robust (clustered) standard errors to account for correlation within participants from having repeated measures. We opted for a linear fit for time since infection as this specification minimised the bayesian information criterion compared with higher order polynomial or spline fits, thus providing a better balance between goodness of fit and parsimony (see supplementary figure 1).

We explored heterogeneity in associations between vaccination and long covid by interacting all four vaccination variables (change in level and slope after each dose) with each of age group (18-29 years, 30-39 years, 40-49 years, 50-59 years, 60 years), sex, white or non-white ethnicity, area deprivation fifth group, health status, hospital admission with acute covid-19, vaccine type (adenovirus vector or mRNA), and duration from infection to first vaccination (modelled as a restricted cubic spline). For each outcome, statistically significant interactions were identified at the 5% level after performing Holm-Bonferroni and Benjamini-Yekutieli corrections to P values to account for multiple comparisons across vaccination variables and modifiers. All statistical analyses were performed using R version 3.6.

We restricted the sample firstly to participants with at least one observation before and after each vaccination and secondly to those with at least three observations after each vaccination. We omitted follow-up visits within the first week after each vaccination, which may have been influenced by post-vaccine side effects. Survey participants were added who remained unvaccinated by their last follow-up visit during the study period (who were excluded from the main analysis). Because mass testing for SARS-CoV-2 was largely unavailable during the first wave of the pandemic, we excluded participants who were infected before the start of the second wave on 11 September 2020,30 and therefore these infections were likely to have been more severe than the majority included in the analysis. For 2.5% of participants where this was determined we reset the infection date by when the participant first thought they had covid-19 (later confirmed by a positive test result) that was >14 days before a positive swab result (the estimated maximum incubation period31); these participants may have been reinfected but only their second infection was validated by means of a positive test result, so the infection date was moved forward to the date of this test. Finally, we excluded participants whose infection date was determined by a positive blood test result for SARS-CoV-2 antibodies that was obtained before or on the date of their first survey follow-up visit; the precise timing of infection was unknown for these participants.

NAA contributed to this paper both as someone with lived experience of long covid and as a public health researcher. She has previously strongly advocated against the separation of identities of people with long covid who are also scientists, researchers, or health professionals. She has also written on patient involvement in long covid research and the lessons learnt that could apply to other conditions.3233 She contributed to informing this analysiss concept, design, and interpretation.

Although we did not directly involve patients and members of the public more broadly, the study design was informed by views expressed by patient representatives in monthly meetings attended by DA (the Department of Health and Social Cares long covid ministerial roundtable, NHS Englands long covid national taskforce). These meetings were attended by the founders of three major long covid patient support groups in the UK, whose insights on aspects such as the range of long covid symptoms experienced and their relapsing and remitting nature informed the data collected and definitions used in this study.

Of 323685 participants in the COVID-19 Infection Survey aged 18 to 69 years with at least one visit between 3 February and 5 September 2021, 28356 had test confirmed SARS-CoV-2 at least 12 weeks before their final visit and had been vaccinated post-infection and were therefore included in analysis (fig 1).

Study participant flow diagram. CIS=Office for National Statistics COVID-19 Infection Survey

Median time to the final follow-up visit was 169 (interquartile range 141-185) days from the first visit and 267 (219-431) days from first SARS-CoV-2 infection. By design, all study participants received their first vaccination by 5 September 2021, 12971 (45.7%) after the start of the study period on 3 February. Overall, 23753 (83.8%) participants were double vaccinated by 5 September 2021, with 20335 (71.7%) receiving their second dose after 3 February, with a median time between doses of 72 (interquartile range 61-77) days (see supplementary figure 2). Supplementary table 4 shows vaccination status during follow-up by age and health status (two of the main vaccination prioritisation determinants). Participants had a median of 4 (interquartile range 2-5) visits over a median of 141 (interquartile range 86-173) days after their first dose and, among those double vaccinated, 2 (1-3) visits over 67 (20-99) days after their second dose.

At the last visit, the mean age of participants was 46 years (standard deviation 14 years), 55.6% (n=15760) were women, and 88.7% (n=25141) were of white ethnicity (table 1). Compared with participants who received an adenovirus vector vaccine, those who received an mRNA vaccine were on average younger (mean 40 v 51 years) and more likely to be of non-white ethnicity (13.7% v 9.4%), resident in London (27.0% v 22.4%) or Northern Ireland (3.3% v 1.5%), and a patient-facing health or social care worker (17.1% v 6.4%).

Characteristics of study participants at their final follow-up visit, stratified by covid-19 vaccine type

Long covid symptoms of any severity were reported by 6729 participants (23.7%) at least once during follow-up. Before vaccination, the odds of experiencing long covid changed little over time (0.3% per week, 95% confidence interval 0.9% to 0.2%, P=0.25; table 2). A first vaccine dose was associated with an initial 12.8% decrease (95% confidence interval 18.6% to 6.6%, P<0.001) in the odds, with the data being compatible with both increases and decreases in the trajectory (0.3% per week, 95% confidence interval 0.6% to 1.2% per week, P=0.51) between the first and second doses. A second vaccine dose was associated with an initial 8.8% decrease (14.1% to 3.1%, P=0.003) in the odds, followed by a decrease of 0.8% (1.2% to 0.4%, P<0.001) per week (fig 2).

Estimated time trajectories of long covid from SARS-CoV-2 infection, and changes in trajectories after covid-19 vaccination

Modelled probabilities of long covid for a hypothetical study participant who received a first covid-19 vaccine dose 24 weeks after SARS-CoV-2 infection and a second dose 12 weeks later. Probabilities are shown for participants of mean age (50 years) and in the modal group for other covariates (woman, white ethnicity, resident in London, resident in an area in the least deprived fifth group, not a patient-facing health or social care worker, no pre-existing health conditions, not admitted to hospital during the acute phase of infection, infected on 7 September 2020). Although estimated probabilities are specific to this profile, proportional changes in probabilities after vaccination do not vary across characteristics and can therefore be generalised to other profiles. Dashed lines represent timing of vaccination. Shaded areas are 95% confidence intervals

Long covid resulting in limitation of activities was reported by 4747 participants (16.7%) at least once during follow-up. A first vaccine dose was associated with an initial 12.3% decrease (19.5% to 4.5%, P=0.003) in the odds of activity-limiting long covid, followed by an uncertain trajectory (0.9% per week, 95% confidence interval 0.2% to 1.9%, P=0.11) until the second dose was administered. A second vaccine dose was associated with an initial 9.1% decrease (95% confidence interval 15.6% to 2.1%, P=0.01) in the odds of activity-limiting long covid, followed by 0.5% per week (95% confidence interval 1.0% to 0.05%, P=0.08) until the end of follow-up.

To illustrate the impact of each vaccine dose, figure 2 shows the estimated probability of reporting long covid for study participants receiving their first vaccine dose 24 weeks after infection and their second dose 12 weeks later. Sensitivity analyses (see supplementary figures 3a-i) were generally consistent with the main results. Evidence of a change to an increasing trend in long covid between first and second vaccine doses was, however, stronger when the sample was restricted to participants who received their first dose during the follow-up period 3 February to 5 September 2021 (P<0.001 for long covid of any severity, P=0.01 for activity-limiting long covid).

We found no statistical evidence of differences in post-vaccination long covid trajectories between participants who received an adenovirus vector vaccine and those who received an mRNA vaccine (table 3, fig 3) for changes in either levels (P=0.31 for dose 1, P=0.97 for dose 2) or slopes (P=0.33 for change between dose 1 and dose 2, and P=0.33 for change after dose 2). Vaccination was associated with an initial 14.9% decrease (95% confidence interval 21.8% to 7.5%, P<0.001) in the odds of long covid after a first dose of an adenovirus vector vaccine, and a numerical 8.9% decrease (95% confidence interval 18.2% to 1.4%, P=0.09) after a first dose of an mRNA vaccine, although the data were also compatible with increased odds for the latter. Decreases in the odds after a second vaccine dose were numerically similar between vaccine types, at 8.7% (95% confidence interval 15.4% to 1.4%, P=0.02) for an adenovirus vector vaccine and 8.9% (17.6% to 0.7%, P=0.07) for a mRNA vaccine.

Estimated time trajectories of long covid from SARS-CoV-2 infection, and changes in trajectories after covid-19 vaccination, moderated by vaccine type

Modelled probabilities of long covid for a hypothetical study participant who received a first dose of an adenovirus vector or mRNA vaccine 24 weeks after SARS-CoV-2 infection and a second dose 12 weeks later. Probabilities are shown for participants of mean age (50 years) and in the modal group for other covariates (woman, white ethnicity, resident in London, resident in an area in the least deprived fifth group, not a patient-facing health or social care worker, no pre-existing health conditions, not admitted to hospital during the acute phase of infection, infected on 7 September 2020). Although estimated probabilities are specific to this profile, proportional changes in probabilities after vaccination do not vary across characteristics and can therefore be generalised to other profiles. Dashed lines represent timing of vaccination. Shaded areas are 95% confidence intervals

The odds of long covid after a first dose of a covid-19 vaccine numerically decreased with duration from SARS-CoV-2 infection, with estimated numerical decreases of 24.8%, 16.5%, and 4.8% for participants who received a first vaccine dose 9, 12, and 15 months after infection (see supplementary figures 4a-b). Duration from infection to first vaccine dose, however, was not a statistically significant moderator of the vaccination-long covid relationship (see supplementary tables 5a-d).

We found no statistical evidence of differences in post-vaccination long covid trends according to sociodemographic characteristics (age, sex, ethnic group, area deprivation) or health related factors (self-reported health status not related to covid-19, whether admitted to hospital with acute covid-19) (see supplementary tables 5a-d).

The odds of experiencing most symptoms, as well as more than three or more than five symptoms together, initially numerically decreased after each vaccination (fig 4). After a first vaccine dose, the largest numerical decreases were observed for loss of smell (12.5%, 95% confidence interval 21.5% to 2.5%, P=0.02), loss of taste (9.2%, 19.8% to 2.7%, P=0.13), and trouble sleeping (8.8%, 19.4% to 3.3%, P=0.15). After a second vaccine dose, the largest numerical decreases were observed for fatigue (9.7%, 16.5% to 2.4%, P=0.01), headache (9.0%, 18.1% to 1.0%, P=0.08), and trouble sleeping (9.0%, 18.2% to 1.2%, P=0.08).

Modelled probabilities of individual long covid symptoms for a hypothetical study participant who received a first dose of a covid-19 vaccine 24 weeks after SARS-CoV-2 infection and a second dose 12 weeks later. Top 10 most frequently reported symptoms ordered by modelled probability at 12 weeks post-infection. Probabilities are shown for a participant of mean age (50 years) and in the modal group for other covariates (woman, white ethnicity, resident in London, resident in an area in the least deprived fifth group, not a patient-facing health or social care worker, no pre-existing health conditions, not admitted to hospital during the acute phase of infection, infected on 7 September 2020). Although the estimated probabilities are specific to this profile, proportional changes in probabilities after vaccination do not vary across characteristics and can therefore be generalised to other profiles. Dashed lines represent timing of vaccination. Shaded areas are 95% confidence intervals

Similar to long covid overall, the odds of experiencing most individual symptoms and more than three or more than five symptoms together, numerically decreased after the first vaccine dose. Trends were generally upwards between the first and second vaccine doses, with most returning to a declining or flat trend after the second dose. However, owing to lack of statistical power, the data for most symptoms were compatible with both initial increases and decreases and both upward and downward trends in the likelihood of experiencing symptoms after each vaccine dose (see supplementary table 6).

In this community based study of adults aged 18 to 69 years infected with SARS-CoV-2 before vaccination against covid-19, we found that the odds of experiencing long covid symptoms that persisted for at least 12 weeks decreased by an average of 13% after a first covid-19 vaccine dose. It is, however, unclear from the data whether the improvement was sustained until a second vaccine dose was administered. Receiving a second vaccine dose was associated with a further 9% decrease in the odds of long covid, and statistical evidence suggested a sustained improvement after this, at least over the median follow-up of 67 days. Similar findings were obtained when the focus was on long covid severe enough to result in functional impairment.

We found no statistical evidence of heterogeneity in the associations between vaccination and long covid symptoms according to vaccine type; duration from infection to first vaccination; sociodemographic characteristics, such as age, sex, ethnicity, and area deprivation; self-reported health status; and hospital admission with acute covid-19. This observational study was unlikely to have been sufficiently powered to detect these associations, however, particularly given the multiplicity of testing, and absence of evidence does not necessarily imply evidence of absence.

Our results add to existing evidence on the trajectory of long covid after vaccination. A non-controlled study of 900 social media users found that more than half had experienced an improvement in symptoms after vaccination compared with 7% who reported a deterioration.19 A study of 44 vaccinated patients and 22 unvaccinated controls previously admitted to hospital with covid-19 in the UK, which inevitably had limited power to detect clinically relevant effects, found no evidence for vaccination being associated with worsening of long covid symptoms or quality of life.20 A French study of 455 self-selected participants found reduced symptom burden and double the rate of remission at 120 days in vaccinated participants compared with unvaccinated controls.21

Vaccination against covid-19 effectively reduces rates of infection1213 and transmission.14 Evidence also suggests that the incidence of long covid is reduced in those infected after vaccination; in a study of 906 mobile phone app users, the odds of having symptoms 28 days post-infection was approximately halved in fully vaccinated participants compared with unvaccinated controls.17 Together with our results, these findings suggest that vaccination against covid-19 might reduce the population prevalence of long covid by reducing the risk of continuing to experience persistent symptoms in those who already have symptoms when vaccinated; developing persistent symptoms after breakthrough infections; being infected in the first place; and transmitting the virus after infection.

Our principal finding, of a decrease in the likelihood of experiencing long covid symptoms after a second covid-19 vaccine dose, supports hypothesised biological mechanisms. People with long covid who experience dysregulation of the immune system may benefit from autoimmune processes being reset by vaccination (although whether this is long lasting remains to be established), while any residual viral reservoir may also be destroyed by the antibody response.34 Immunological phenotyping suggests differences in those who experience persistent symptoms after SARS-CoV-2 infection compared with healthy controls.35 The presence of autoantibodies against interferon type I or autoimmune processes triggered by SARS-CoV-2 through molecular mimicry has been proposed as a manifestation of immune dysregulation in long covid, possibly similar to autoimmune rheumatic diseases.36 Another proposed mechanism is the persistence of viral antigen modifying the immune response months after infection.37 In this scenario, it is reasonable to hypothesise that covid-19 vaccination may be beneficial.

The symptom trajectory following the initial decrease after a first vaccine dose was unclear, being compatible with both increasing and decreasing odds of long covid over time. Evidence was, however, found of an increasing trend when the sample was restricted to participants vaccinated during the follow-up period. Relapsing symptoms are common in long covid,456 and persistent symptoms are associated with a weak antibody response,38 so it is possible that receiving a first vaccine dose alone is insufficient for sustained improvement in some people.

UK Government guidelines recommend that people should delay vaccination for four weeks after a positive test result for SARS-CoV-2. Given that we only considered follow-up visits beyond 12 weeks of participants first positive test result (as our outcome of interest was long covid symptoms at least 12 weeks after infection), it seems unlikely that this guidance would have affected our analysis. The National Health Service advises patients with ongoing complications of covid-19 to consult their doctor about vaccination, so it is possible that some people with long covid symptoms may choose to delay vaccination until their symptoms resolve, which would induce an association. However, this is unlikely to have affected our analysis, as we found no evidence that study participants with long covid deferred their covid-19 vaccination compared with those without long covid (see supplementary figure 5). Because our study was observational, we cannot rule out the possibility of a change in reported symptoms after vaccination being due to a placebo effect. Although we might expect to observe a post-vaccination relapse in some participants whose symptoms initially improved, our ability to do this was limited by the follow-up available to us (a median of 67 days from the second vaccine dose).

The main strength of the study is its use of the ONS COVID-19 Infection Survey, a large survey of about half a million people from the community dwelling population of the UK with longitudinal follow-up. Random sampling from address lists mitigates against selection bias, whereas the prospective design means that survey responses are not subject to outcome recall bias (such as participants overestimating the duration of previously experienced symptoms). All of the surveys participants are swabbed for SARS-CoV-2 at every follow-up visit, irrespective of symptoms, so our study includes asymptomatic as well symptomatic infections.

The study also has limitations. Its observational design means that causality cannot be inferred, and placebo and side effects of vaccination may have contributed to our findings; however, estimates were robust to excluding follow-up visits within the first week of each vaccination, suggesting that the impact of these effects is likely to be small. Although we adjusted for a wide range of potential confounders, unmeasured factors, such as those related to take-up of a second vaccine dose, may remain. The observed changes after vaccination could be related to the relapsing and remitting symptoms experienced by many people living with long covid456 rather than to a causal effect of the vaccine. Future analysis should consider differing patterns of illness, including quantification of the frequency and duration of symptom-free periods after vaccination.

By definition, symptoms are self-reported with no other way to assess them. Together with the impact of symptoms on daily life, the presence of symptoms is how WHO defines long covid.25 However, attributing symptoms to a previous SARS-CoV-2 infection is likely to be more difficult in the absence of a diagnostic test for long covid and probably results in under-recording in electronic health records.39 Although all infections in this study were confirmed by testing, long covid status was self-reported and we did not have data on related healthcare use, so we cannot exclude some participants symptoms being caused by a medical condition other than covid-19. Although clinical case definitions for long covid exist in the UK2 and internationally,25 consensus over a suitable working definition for research purposes is lacking; thus there is potential for inconsistencies in outcome measurement between our study and other studies on long covid. Based on the same data source as that used in this study, ONS previously estimated 12 week prevalence rates from 3% (based on tracking 12 specific symptoms) to 12% (based on self-classification of long covid),40 showing the sensitivity of estimates as to how long covid prevalence is measured. Nonetheless, we investigated changes in the illness trajectory after vaccination rather than estimate the prevalence of long covid at a particular time point, and our outcome definition was consistent over the study period.

Given the staged roll-out of the vaccination programme in the UK, the main determinant of vaccination timing is age, and thus older study participants tended to have longer post-vaccination follow-up time than younger participants; this may have influenced our analysis of effect modification, whereby we found no evidence of heterogeneity in the post-vaccination trajectory of long covid according to age group. The measure of functional impairment recorded on the COVID-19 Infection Survey (day-to-day activities: not limited, limited a little, or limited a lot) did not give a detailed indication of the specific ways that participants lives have been affected by long covid or the resulting impact on quality of life. It is possible that the average improvement in long covid symptoms and functional impact may wane with time, and longer term follow-up is required to establish whether the estimated changes after second vaccination are sustained. Follow-up after a booster dosenow widely available in the UK adult populationis also required. The study sample was restricted to participants aged 18 to 69 years, so our findings may not generalise to children or older adults, nor may they apply to people who had not received a vaccine by 5 September 2021, in particular those with vaccine hesitancy because of their long covid symptoms. Furthermore, symptom data were collected prospectively rather than retrospectively, so variable estimates relating to changes in the odds of long covid may not be generalisable to participants who were vaccinated before the long covid question was added to the COVID-19 Infection Survey on 3 February 2021. However, our results were insensitive to inclusion of participants who remained unvaccinated by the end of the study period or to exclusion of those who were vaccinated before the start of the study period.

We found that vaccination against covid-19 is associated with a decrease in the likelihood of continuing to experience long covid symptoms in adults aged 18 to 69 years, and this appeared to be sustained after a second vaccine dose. Our results suggest that vaccination of people previously infected may be associated with a reduction in the burden of long covid on population health, at least in the first few months after vaccination. Further research is required to evaluate the long term relationship between vaccination and long covid, in particular the impact of the omicron variant, which has become dominant in the UK, booster doses, now widely available to adults in the population, and reinfections. Studies are also needed to understand the biological mechanisms underpinning any improvements in symptoms after vaccination, which may contribute to the development of therapeutics for long covid.

Vaccines against covid-19 are effective at reducing rates of SARS-CoV-2 infection, transmission, hospital admission, and death

The incidence of long covid may be reduced in those who are infected after vaccination, but the relationship between vaccination and pre-existing long covid symptoms is unclear, as published studies are generally small and with self-selected participants

A first dose of covid-19 vaccine was associated with a reduction in long covid symptoms, and evidence suggested a sustained improvement after a second dose, at least over the median follow-up of 67 days in this study

No evidence was found of differences in this relationship by sociodemographic characteristics, health related factors, vaccine type, or duration from infection to vaccination

Although causality cannot be inferred from this observational evidence, vaccination may contribute to a reduction in the population health burden of long covid

WEDNESDAY 5/18/2022 2:12 p.m.

The Wisconsin Department of Health Services has reported 1,450,536 total positive coronavirus test results in the state and 12,959 total COVID-19 deaths.

The number of known cases per variant is no longer tracked as The Wisconsin Department of Health Services has updated its website, deleting that section.

Unable to view the tables below?Click here.

The DHS announced an attempt to verify and ensure statistics are accurate, some numbers may be subject to change. The DHS is combing through current and past data to ensure accuracy.

Wisconsins hospitals are reporting, that the 7-day moving average of COVID-19 patients hospitalized was 319 patients. Of those,39 are in an ICU. ICU patients made up 11.3%of hospitalized COVID-19 patients.

The Wisconsin Department of Health Services reports that 9,500,442 vaccine doses and 2,026,466 booster doses have been administered in Wisconsin as of May 18.

Unable to view the tables below?Click here.

The Wisconsin Department of Health Services is using a new module to measure COVID-19 activity levels. They are now using the Center for Disease Control and Preventions (CDC) COVID-19 Community Levels. The map is measured by the impact of COVID-19 illness on health and health care systems in the communities.

The Center for Disease Control and Prevention (CDC) reports seven counties in Wisconsin are experiencing high COVID-19 community levels. None of them are in northeast Wisconsin.

38 counties in Wisconsin are experiencing medium COVID-19 community levels, including Brown, Fond du Lac, Forest, Green Lake, Menominee, Shawano, and Winnebago County in northeast Wisconsin.

Every other county in Wisconsin is experiencing low COVID-19 community levels.

For more information on how the data is collected, visit the CDCs COVID-19 Community Levels data page.

Transparency and clear guidance about COVID boosters are critical to maintaining public support and trust.

"Moving to a regular vaccine schedule will increase clarity and confidence about what actions to take and when, compared to the current piecemeal, wait-and-see approach," said Marcus Schabacker, MD, PhD, president and CEO of ECRI. "Transparency and clear guidance are critical to maintaining public support and trust."

ECRI experts say mental fatigue and a desire for normalcy are likely driving increasing COVID apathy. They say unclear guidance and near-constant changes regarding who, when, and how often individuals need boosters can magnify this apathy and cause the public to completely disengage.

"For mRNA vaccines, boosters can be safely administered at regular intervals to address emerging variants, similar to the flu vaccine," said Marcus Lynch, PhD, MBA, senior manager of clinical excellence and safety at ECRI. "A regular booster schedule may help promote uptake, further decreasing COVID's prevalence."

According to ECRI, one of the main goals of vaccination boosters in an endemic is to reduce the prevalence of a virus to levels that make it possible for society to live with it. The best way to do so, experts say, is with a regular booster schedule guided by evidence and data.

ECRI's position statement, From Pandemic to Endemic: The Role of COVID-19 Vaccine Boosters and the Need for a Recurring Vaccination Schedule, is available for public download on ECRI's website.

For additional information, visit www.ecri.orgor contact ECRI at [emailprotected].

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About ECRIECRI is an independent, nonprofit organization improving the safety, quality, and cost-effectiveness of care across all healthcare settings. With a focus on technology evaluation and safety solutions, ECRI is respected and trusted by healthcare leaders and agencies worldwide. For more than fifty years, ECRI has built its reputation on integrity and disciplined rigor, with an unwavering commitment to independence and strict conflict-of-interest rules.

ECRI is the only organization worldwide to conduct independent medical device evaluations, with labs located in North America and Asia Pacific. ECRI is designated an Evidence-based Practice Center by the U.S. Agency for Healthcare Research and Quality. ECRI and the Institute for Safe Medication Practices PSO is a federally certified Patient Safety Organization as designated by the U.S. Department of Health and Human Services. The Institute for Safe Medication Practices (ISMP) formally became an ECRI Affiliate in 2020. Marcus Schabacker, MD, PhD, President and CEO of ECRI, was recognized by the Philadelphia Business Journal as a Healthcare Leader in 2021. Visit www.ecri.org and follow @ECRI_Org.

SOURCE ECRI

Transcript:

John F. DiPersio, MD, PhD: The last question I had is not related to chronic GVHD [graft-versus-host disease] but involves these patients. What are you doing for patients who are out a year or 2 and grafted but develop chronic GVHD on low levels of immunosuppression, maybe a JAK [janus kinase] inhibitor, etcetera, for COVID-19? Are you just vaccinating them and watching them? Are you vaccinating them and watching their anti-COVID-19 spike protein antibody titers or are you actually giving them EVUSHELD even though they're far out and they may only be on a JAK inhibitor? Pashna?

Pashna N. Munshi, MD: In our program, with our ID [infectious disease] colleagues, we decided that all our immune-compromised patients, whether they're within 100 days or out 1 year or 2 years, all of them are getting the EVUSHELD protection. Obviously, if they're chronic GVHD patients by now, we hope that they've already been vaccinated and had their booster and then we are checking the spike protein level in their body for antibody response. And then, what I'm seeing is happening is that our ID colleagues are recommending that they have to alternate between their shield and then another booster down the road to keep their levels up. And thus, we're trying to do that for our patients.

John F. DiPersio, MD, PhD: It sounds like your ID people are as confused as ours. What are you doing in MGH [Massachusetts General Hospital]?

Yi-Bin Chen, MD: We don't have an organized algorithm partly because it's such a rapidly changing environment. When certain antibodies we had now don't work based on strain and then access to these things has been somewhat restricted and centrally managed and not at the discretion of, say, me. I think that in general, I worry about our long-term chronic GVHD patients more than any other transplant population because most of our fresh transplant patients now are receiving grafts from vaccinated donors. And there's some adaptive immunity that's transferred, whereas these chronic GVHD patients who are transplanted years ago never had any immunity against COVID-19. And if they're on immunosuppression like the drugs we listed, they certainly have an impaired ability to respond.

Thus, I worry about them the most. Thankfully, that the strains present right now seem to have become less severe and that's been helpful. But from an immunity perspective, we obviously recommend vaccination but there is what we've experienced and I'm sure you've seen what has been reported as well as the flares of chronic GVHD that can happen with any vaccine. Not just COVID-19 but vaccines certainly seem to trigger a severe inflammatory response. That for some of our patients they've experienced severe flares of chronic GVHD. We do give EVUSHELD, certainly, and then we do measure the spike antibodies and then we have trials coming up using other monoclonal antibody products as well. It's unfortunate because we don't have an organized treatment algorithm but that's also because of how fast this is changing.

John F. DiPersio, MD, PhD: Hannah, maybe you can answer this last response for the panel today. What are you doing at [The] Ohio State University?

Hannah Choe, MD: For the COVID-19?

John F. DiPersio, MD, PhD: Yes.

Hannah Choe, MD: It's a mix of the same thing. We certainly hinge everything on vaccination as much as possible so regardless of the immunosuppression and understanding that ruxolitinib and other immunosuppressants we were using limit the patient's ability to mount a response; we're still giving the 3 full doses plus a booster. And then, probably shortly here, we are going to be giving another booster once the FDA [Food and Drug Administration] approves that. And then, in certain cases, depending on patient history, considering EVUSHELD. We are not broadly using EVUSHELD and for the same reason that Yi-Ben just mentioned is that we are not sure about the efficacy with the current strain and future strain, etcetera.

John F. DiPersio, MD, PhD: I think it's also that the EVUSHELD studies were done in immunocompetent patients and so there's no extension. You can't make an obvious extension into our patients, but it's well tolerated, and I do agree with you, Yi-Bin. Even with regular vaccinations as well as with the COVID-19 vaccinations, there can be significant flares in chronic GVHD, and it's always been one of my pet peeves about the regular vaccinations. Really, how much benefit are we doing especially if you have a one in 10 out of patients that have a real flare in their chronic GVHD? In any event, we do it obviously and we see the same thing with the covert vaccinations and so I do use EVUSHELD on these patients because I do think that they're immunocompromised for a long time, years and years after transplant, especially if they're on immunosuppression. But I have no evidence that this is protective, especially in this population of patients.

I've really enjoyed listening to the panel's responses to these questions and teaching me about chronic GVHD and acute GVHD. It's been a great hour and I really want to first and foremost thank Pashna, Yi-Bin, and Hannah for their participation in this panel. You guys were great, and I really learned a lot and I want to thank the viewing audience for sticking with us for the last hour. And I hope that you've been provided with some helpful insights and some hints about how to manage this very difficult disease to both diagnose and treat. And with that, I'll bid you all adieu. Thank you very much.

Transcript edited for clarity.