Category: Corona Virus

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Posted: December 08, 2023

About one in nine Canadian adults have experienced long-term symptoms from COVID-19 infection, according to a Statistics Canada report issued Friday.

That amounts to 3.5 million Canadians, it said.

Almost 80 per cent of those people with long-term symptoms have them for six months or more, the report said. In addition, more than half of those who ever had long-term symptoms still had them as of June 2023.

"Among Canadians who reported ever experiencing long-term symptoms, those who continue to experience these symptoms (58.2 per cent) outnumber those who have reported them resolved (41.8 per cent)," the report said.

Long COVID, also known as post COVID-19 condition, is defined by the World Health Organization as symptoms that persist for three months or longer after infection and can't be explained by anything else.

The Statistics Canada findings aren't surprising, said Manali Mukherjee, an assistant professor of medicine at McMaster University in Hamilton who specializes in respiratory diseases and immunology in an interview on Friday.

WATCH | Research suggests most long COVID symptoms clear after a year:

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"There is a subset of patients who have long COVID symptoms affecting their quality of life, their productivity on a daily level," said Mukherjee, who is a long COVID researcher and also spent about 18 months recovering from her own symptoms.

The most common long COVID symptoms are brain fog, fatigue and shortness of breath, she said.

Two-thirds of Canadian adults who have tried to get health-care services for their long-term symptoms say they haven't received enough treatment or support, the Statistics Canada report said.

Research shows that getting vaccinated against COVID-19 reduces the risk of getting long COVID, as well as the severity of symptoms, Mukherjee said.

The Statistics Canada report also noted nearlyone in five Canadian adults have had more than one known or suspected COVID-19infection.

The percentage of Canadian adults who ever tested positive for or suspected a COVID-19infectionincreased from roughly 39 per centin the summer of2022to64 per centby June2023.

As of that time,45 per centof Canadians had experienced one infection,14 per centhad experienced twoanda little more than five per cent had experienced three or more.Statistics Canada said those numbers are likely an underestimate.

WATCH | Winnipeg woman shares her experience with Long COVID:

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1 in 9 Canadian adults have experienced long-term COVID symptoms, StatsCan says - CBC.ca

Pandemics have killed millions of people throughout history. How many deaths were caused by different pandemics, and how have researchers estimated their death tolls?

COVID-19 has brought the reality of pandemics to the forefront of public consciousness. But pandemics have afflicted humanity for millennia. Time and again, people faced outbreaks of diseases including influenza, cholera, bubonic plague, smallpox, and measles that spread far and caused death and devastation.

Our ancestors were largely powerless against these diseases and unable to evaluate their true toll on the population. Without good record-keeping of the number of cases and deaths, the impact of outbreaks was underrecognized or even forgotten. The result is that we tend to underestimate the frequency and severity of pandemics in history.

Often, we have records of epidemics occurring in some countries but lack good records from other regions, despite knowing that the geographical impact of the disease would have been very wide. Additionally, we often lack knowledge about which pathogens caused outbreaks and, thus, if a historical event can be considered a pandemic or if it consisted of parallel outbreaks of different diseases.

To deal with the lack of historical records on total death tolls, modern historians, epidemiologists, and demographic researchers have used various sources and methods to estimate their death tolls such as using data from death records, tax registers, land use, archaeological records, epidemiological modeling, and more.

In this article, I present the various methods they rely on and visualize the estimated impact of what are now considered the major pandemics in history.

Although there is no universally accepted definition of a pandemic1, diseases called pandemics share several characteristics.

Pandemics generally refer to diseases with a vast geographic range such as spreading across a continent or multiple continents. In addition, they tend to describe outbreaks that are rapidly growing or expanding in range; highly infectious; affecting a large number of people; and caused by novel pathogens against which there is little or no pre-existing immunity.2

Researchers have estimated the death tolls of pandemics in different ways, depending on the data available.

Some death tolls have been estimated by looking at excess deaths: researchers estimate the additional number of deaths that occurred during a pandemic compared to the expected number of deaths in a typical year. This can be helpful to understand the pandemics overall impact, even if records from death certificates are unavailable.

For some pandemics, death tolls are estimated from the net population reduction, where researchers calculate the difference in population size before and after the pandemic. This is often used for severe events such as the Columbian Exchange where a significant fraction of the population died.

Some death tolls have been estimated through epidemiological modeling based on knowledge of the transmission of the disease and its geographical spread, its fatality rate (the share of people affected who die from it), access to treatment, and other types of data.

Finally, some death tolls have been calculated only using recorded deaths (also referred to as confirmed deaths). This is the number of deaths officially reported with the disease as their cause of death. This method may vastly underestimate the number of deaths caused by the pandemic, as comprehensive historical records are lacking. Even today, cause-of-death registration is lacking in many parts of the world, which is one reason why the number of confirmed deaths from COVID-19 is much lower than the total death toll from the pandemic.

I have brought together estimates of death tolls from different pandemics in history for this article, which we have visualized in a timeline below.

The size of each circle represents one pandemics estimated death toll. Pandemics without a known death toll are depicted with triangles.

This overview shows us the vast impact that pandemics have had over history.

You can see that the largest pandemics such as the Black Death killed more than half of the population. Several pandemics have swept through the population repeatedly: in just the last two hundred years, seven major pandemics were caused by cholera, and another seven were caused by the flu.

Pandemics devastated millions and left a shadow on those who survived. The suffering they caused may once have felt inescapable.

Before the formation of germ theory,we lacked good knowledge of pathogens that caused them, how they spread, and how to protect ourselves from them. Before molecular testing to analyze pathogens genomes, we lacked a good understanding of how they evolved and changed over time.

Our ability to respond to pandemics has been transformed by advances in scientific understanding but truly depends on a wide range of efforts from data collection to research and communication, public health efforts, healthcare access, and cooperation.

For example, the collection of death records allowed scientists to discover how cholera spread and how to prevent it. Coordination to address HIV/AIDS has prevented millions of deaths worldwide. Global testing for new influenza strains has helped adapt flu vaccines each year.

With better understanding, resources, and effort, much more progress can be made. The world can respond more swiftly and effectively to pandemic risks and avoid and reduce the impact of future pandemics. But without such efforts, we will continue to face major pandemics as we have experienced so far.

The full dataset and sources used in the chart can be found in our spreadsheet.

In the appendix below, I review some of the major pandemics in history and their historical impact and describe how their death tolls have been estimated.

The Black Death (13461353 CE) one of the earliest pandemics with a methodically estimated death toll killed around 5060% of Europes population, approximately 50 million people, in just 6 years.3

Researchers have established that many people also died elsewhere as large outbreaks are also recognizable in historical records from Western Asia, the Middle East, and North Africa but comprehensive estimates of the global death toll are not available.

Population censuses were not conducted then, so our understanding of the Black Deaths impact in Europe comes from historical records such as tax and rent registers, parish records, and archeological remains. But uncertainty remains, as these records come from a limited number of European regions and are extrapolated to the rest of the continent, based on demographic estimates.

Careful examination of these sources has led to historians revising estimates of the death toll upwards4 and confirmed the bacterial cause of the pandemic: Yersinia pestis (Y. pestis).5

People in the fourteenth century were not aware of this bacterium, nor did they know how it was transmitted from rat fleas to humans as this was long before the development of germ theory in the late nineteenth century.6

Without this knowledge, they also had little understanding of how to protect themselves, resulting in the relentless spread of the Black Death. Even after its initial wave, the pandemic continued with frequent, though smaller outbreaks until around 1690.7

Y. pestis caused diseases known as bubonic and pneumonic plague, where patients experienced fevers, chills, vomiting, and excruciating headaches, and distinctive buboes formed in their swollen lymph nodes typically in the groin, thighs, armpits, or neck.

As Y. pestis spreads through the lymph nodes, it emits toxins that break down blood vessels and form clots, potentially blocking blood circulation and leading to death.8

It is now recognized that the Black Death was not the only plague caused by Y. pestis. Genetic evidence suggests that this bacteria emerged at least 4000 years ago.9

The first known bubonic plague pandemic began in 541 CE and had recurrent outbreaks until the mid-8th century. This devastating pandemic affected the Eastern Roman Empire (Byzantine Empire), the Middle East, North Africa, and the Mediterranean.

The initial and most severe outbreak, known as the Justinian Plague (541549 CE), was named after Emperor Justinian, who ruled Constantinople at the time.10

The third pandemic occurred between 1894 and 1940, mainly affecting Asia and Africa.

Bubonic plague is less common today due to improved sanitation and hygiene measures which reduce the density of rats and rat fleas, improved public health surveillance, and effective antibiotics, but cases have been seen even in recent years, in different continents, mainly in small towns and villages.11

The chart shows the immense impact of the Columbian Exchange, with an estimated 48 million deaths.

The Columbian Exchange describes the period following Christopher Columbuss voyage to the Americas in 1492 during which populations, ideas, and crops,such as tomatoes, potatoes, and maize,spread between the Americas and the rest of the world.

But the Columbian Exchange also involved extensive war, conquest, slavery, and the spread of multiple deadly diseases, which led to the devastation of indigenous populations.12

Smallpox, cholera, measles, diphtheria, influenza, typhoid fever, bubonic plague, and other diseases had already killed many in Europe. But theytended to be more severe to Native Americans,who had been previously isolated from these diseases and lacked immunity to them.

The immense death toll shown on the chart is calculated as a net population reduction compared to the pre-1492 population size.

The Native American population was estimated to be around 54 million before Columbuss arrival. Over the following century, around 48 million died and the population had declined to 5.6 million in 1600 a reduction of about 90%.

Both numbers are estimated by compiling data from a range of sources, including archeological records, tribal records, censuses, epidemiological modeling, and land and crop use.13

Influenza (flu) pandemics arise through sudden evolutionary changes in flu viruses when different strains combine to form novel flu strains14, which can be more infectious and lethal than previous ones.

Although flu has affected humanity for thousands of years15, comprehensive death tolls have only been estimated for the flu pandemics in the last 140 years.

The largest the 1918 Spanish flu pandemic has an estimated death toll of 50 to 100 million.16 This estimate is a compilation of various historical sources, including recorded death tolls and estimates of excess deaths from different regions.

You can read more about the impact of the Spanish flu pandemic in our article:

The Spanish flu pandemic had a devastating impact on the global population.

The chart also shows the estimated impact of other significant flu pandemics:the 1889 Russian flu pandemic (an estimated 4 million deaths), the 1957 Asian flu pandemic (2 million), the 1968 Hong Kong flu pandemic (2 million), and the 2009 Swine flu pandemic (100,000 to 1.9 million deaths).17

Their death tolls have been estimated from excess mortality during the pandemics compared to the years immediately before and after, using available national mortality records and extrapolation to the global population.

As the chart shows, seven cholera pandemics have occurred in the last two centuries.18 Mostare considered to have originated in the Indian subcontinent and expanded across countries and continents through war, travel, and international trade.19

Our knowledge of the total global death toll from cholera in history is limited20, but historical reports from across the world suggest an immense impact of the disease. For example, between 1865 and 1947, at least 23 million people died from cholera in India alone.21 But significant outbreaks have been recorded in many more countries.22

Cholera is particularly severe because, if left untreated, the bacteria Vibrio cholerae can cause severe dehydration and death within hours or days of the first symptoms.23

Its severity has been reduced with a range of scientific advances: the understanding that cholera spread through contaminated water and food, and thus that clean water and sanitation could prevent it; the identification of Vibrio cholerae as the cause; the development of antibiotics; and the knowledge that severe forms of the disease could be substantially reduced with simple rehydration treatment.24

Cholera continues to kill, even today. Since 1960, over 900,000 deaths have been recorded from cholera globally as part of whats considered the seventh cholera pandemic this is shown in the chart.25

When HIV/AIDS (acquired immunodeficiency syndrome) was first identified in the early 1980s, it had a fatality rate of 100%, and patients had a median survival time of about one year after being diagnosed.26 It spread rapidly as the world grappled to recognize, understand, and respond to the growing epidemic.

HIV, the virus that causes AIDS, attacks white blood cells which are critical for our immune function and leaves patients vulnerable to a wide range of opportunistic infections and diseases.

Learn more on our page on HIV/AIDS:

A global epidemic and the leading cause of death in some countries.

The timeline shows the enormous and continuing impact of HIV/AIDS, which has resulted in an estimated 33 million deaths worldwide between 1981 and 2022.

Our understanding of its death toll comes from available data and statistical modeling. The estimates consider various factors, such as characteristics of the viruss transmission, behavioral and clinical data, the availability of treatment, and recorded deaths from countries with high levels of death registration. 27

The global response to HIV/AIDS has involved international cooperation, resource allocation, and scientific advances in antiretroviral therapy, which together have transformed HIV from a fatal diagnosis to a manageable chronic condition with treatment.

In recent years, around 1.5 million deaths have been averted annually due to the effects of antiretroviral therapy which prevents the virus from replicating and thereby reduces the severity of the disease and its spread to other individuals.

This is shown in the chart below, along with the estimated number of HIV/AIDS deaths that still occur around 600,000 deaths annually in recent years.

The COVID-19 pandemic was caused by the novel coronavirus SARS-CoV-2, which emerged at the end of 2019 and rapidly evolved into a global health emergency. Characterized by its highly infectious nature and severe respiratory symptoms, COVID-19 led to widespread illness and fatalities across the world.

The timeline above shows the vast global impact of the COVID-19 pandemic with around 27 million excess deaths between January 2020 and November 2023.28 This makes it one of the deadliest pandemics of the last century.

COVID-19s death toll has been measured by excess mortality, which describes the number of deaths above what would have been expected based on previous years.

This method is used because the global number of confirmed deaths from COVID-19 (those where COVID-19 is listed as the cause of death) is certainly much lower than the total number of deaths from COVID-19. This is because, in many countries, testing for COVID was very limited throughout the pandemic, and cause-of-death registration was, and still is, lacking in many countries.29

Excess mortality also has the advantage of not only considering deaths directly caused by the virus but also those indirectly caused by the pandemics impact on healthcare systems and economies.

Learn more about excess mortality here:

To estimate excess mortality, researchers use national mortality data from countries where data is available, as well as statistical models which rely on data on COVID-19 testing rates, confirmed cases and deaths, population age structure, state policies, and more for other countries.

The estimated death toll we show for COVID-19 27 million deaths by November 2023 comes from The Economist. The main reasons why I am relying on The Economists estimates are that they are continuously updated, and their methodology is well documented.

In contrast, while the World Health Organization (WHO) and the Institute for Health Metrics and Evaluation (IHME) have also estimated the number of excess deaths, their latest estimates were only based on the time period until the end of 2021. For this time period, all three sources provide similar estimates (18.2 million deaths were estimated by the IHME; 14.8 million deaths were estimated by the WHO; and 17.8 million deaths were estimated by The Economist).30

The chart below shows the excess mortality during COVID-19, as estimated by The Economist, along with the number of confirmed deaths. As you can see, there is wide uncertainty around the total number of excess deaths during the pandemic. However, even the lowest estimates are much higher than the number of confirmed deaths reflecting the limited amount of testing and death registration globally during the pandemic.

Our articles and data visualizations rely on work from many different people and organizations. When citing this article, please also cite the underlying data sources. This article can be cited as:

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All visualizations, data, and code produced by Our World in Data are completely open access under the Creative Commons BY license. You have the permission to use, distribute, and reproduce these in any medium, provided the source and authors are credited.

The data produced by third parties and made available by Our World in Data is subject to the license terms from the original third-party authors. We will always indicate the original source of the data in our documentation, so you should always check the license of any such third-party data before use and redistribution.

All of our charts can be embedded in any site.

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What were the death tolls from pandemics in history? - Our World in Data

Boris Johnson's first Covid inquiry appearance video highlights Covid inquiry

The former PM is scheduled to be questioned for two days. Here is what happened at his first session at the inquiry

The UKs former prime minister Boris Johnson has issued a series of apologies about mistakes made during the pandemic.

But, on the first of his two days of evidence to the Covid inquiry, he also defended the bulk of his decision-making.

Here are some of the key points from day one of his evidence:

Johnson began his appearance by issuing an apology for the pain and the loss and the suffering

As Johnson was attempting to deliver his prepared apology, four people staged a protest inside the inquiry room. One held a sign saying: The dead cant hear your apologies. They were led away.

Johnson said: Can I just say how glad I am to be at this inquiry and how sorry I am for the pain and the loss and the suffering of the Covid victims.

About 5,000 WhatsApp messages on Johnsons phone from 30 January 2020 to June 2020 were unavailable to the inquiry

A barrister acting for the inquiry, Hugo Keith KC, said a technical report provided by Johnsons solicitors suggested there may have been a factory reset at the end of January 2020 followed by an attempt to reinstate the contents in June 2020, but Johnson denied knowledge of that.

I dont remember any such thing, he said.

Johnson defended the disputatious culture in No 10

A toxic culture of backstabbing and misogyny has already been laid bare at the Covid public inquiry. A key figure has been Dominic Cummings, Johnsons former and now-estranged chief adviser, who was accused in October of aggressive, foul-mouthed and misogynistic abuse toward others working in government.

Johnson avoided mentioning Cummings by name. He said: I knew that some people were difficult. I didnt know how difficult they were clearly.

But I thought it was better on the whole for the country to have a disputatious culture in No 10 than one that was quietly acquiescent to whatever I or the scientists said.

Johnson defended his decision not to sack Matt Hancock as health secretary

The inquiry has heard that Hancock became a lightning rod for criticism and that Johnson was urged to sack him by Cummings and the then-cabinet secretary Mark Sedwill.

Johnson said: If youre a prime minister, you are constantly being lobbied by somebody to sack somebody else. It is perfectly true that this adviser in particular had a low opinion of the health secretary.

I thought he was wrong. I thought the health secretary worked very hard and whatever he may have had [in] defects, I thought that he was doing his best in very difficult circumstances and I thought he was a good communicator.

Asked about claims from Cummings that Johnson wanted to keep Hancock as a sacrifice for the inquiry, he said: I dont remember that at all. And its nonsense.

Covid decision-making was too male-dominated, Johnson admitted

The gender balance of my team should have been better, Johnson told the inquiry. The inquiry previously heard from Helen MacNamara, a senior civil servant who held the role of the deputy cabinet secretary, that there was institutional bias against women in Covid decision-making.

Johnson said: I think sometimes during the pandemic too many meetings were too male-dominated.

Johnson apologised for failing to call out misogynistic attacks on a civil servant

The inquiry previously heard that Cummings urged Johnson to sack MacNamara and complained to him of dodging stilettos from that cunt. Asked why he did not put a stop to such language, Johnson said: Ive rung Helen MacNamara to apologise to her for not having called it out.

Johnson repeatedly disparaged those suffering from long Covid

The inquiry heard that Johnson scribbled disparaging remarks about long Covid, including describing it as bollocks. In February 2021 he suggested it was similar to soldiers falsely claiming they were suffering from Gulf War syndrome.

Johnson apologised for the remarks, saying they were not intended for publication.

He said: Im sure that they have caused hurt and offence to a huge numbers of people who, who do indeed suffer from that syndrome and I regret very much using that language. I was trying to get my officials to explain to me exactly what the syndrome was.

Johnson admitted vastly underestimating the risks in the early stages of the pandemic

The former PM said both he and Whitehall more generally failed to understand the seriousness of the pandemic in late January and February 2020.

Asked why information on 29 January about the virus spreading outside China did not become a lightbulb moment, Johnson said: I dont think that we were able to comprehend the implications of what we were actually looking at.

The problem was that I dont think we attached enough credence to those forecasts and, because of the experience that wed had with other zoonotic diseases [infections transmitted between species], I think collectively in Whitehall there was not a sufficiently loud enough klaxon.

He added: Its clear that we vastly underestimated the risks in those early weeks. If we properly understood how fast Covid was spreading and the fact that it was spreading asymptomatically, there are many things we would have done differently we were operating on a fallacious inductive logic about previous reasonable worst-case scenarios.

Johnson insisted he was working during the February half-term school break of 2020, the focus of controversy over an alleged lack of engagement

The inquiry previously heard that from 14 February to 24 February 2020, Johnson was on a break in Chevening House, a country residence used by Britains prime ministers, and was not updated by his staff about Covid and had no briefings on two Cobra meetings that took place during this period.

But Johnson insisted this was not accurate. There wasnt a long holiday that I took I was working throughout the period and the tempo did increase.

He said he rang both the Chinese president, Xi Jinping, in part to discuss the origins of Covid and to compare notes on what was happening, and the then US president, Donald Trump, to discuss the same thing.

Johnson said that in a 28 February meeting the worst-case scenario (WCS) figures were presented and were a horrifying figure and I couldnt believe it.

I thought: Well, we have plenty of bad flu pandemics in the UK and if its milder than that then it wont be an exceptional thing at all, so why am I also being told that the WCS is 520,000?

The inquiry chair rebuked Johnson for leaks of his witness statement

Before Johnsons evidence began, the chair of the inquiry, Heather Hallett, complained about media briefings about what he would tell the inquiry.

Lady Hallett said: Id like to express my concern about reports in the press over the last few days of the contents of Mr Johnsons witness statement to the inquiry and what his evidence will be.

Until a witness is called and appears at a hearing, or the inquiry publishes the witnesss statement, its meant to be confidential between the witness, the inquiry and the core participants failing to respect confidentiality undermines the inquirys ability to do its job fairly, effectively and independently.

Johnsons remarks about people dying anyway showed cruelty of choice

A March 2020 internal government note showed that Johnson questioned why damage was being inflicted on the economy for people who will die anyway. Asked about the note, Johnson said it was an indication of the cruelty of choice at the time.

He was also asked what he meant in a handwritten note that said: Were killing the patient to tackle the tumour.

Johnson said if I did say something like that he was referring to the need to do things that were damaging in other ways in order to stamp down the virus.

Johnson also confirmed that the then chancellor, Rishi Sunak, warned him about risk to the UKs bond market and the ability to raise debt. Previous evidence has suggested that Sunak was among those in government who had been more reluctant than others to countenance a national lockdown.

Johnson almost certainly discussed Covid with the Russian media mogul Evgeny Lebedev just days before lockdown

Previous evidence has raised questions about the closeness between Johnson and Lebedev, who was controversially given a life peerage in 2020.

Records read out showed that Johnson met with the newspaper proprietor and also phoned him at the height of what counsel for the inquiry described as a 10-day crisis about a change of strategy in the run-up to the first lockdown.

Asked about this, he said that Lebedev, who owned Londons Evening Standard newspaper, doubtless wanted to know what was happening in London and Johnson said he wanted to inform and support him.

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Boris Johnson at the Covid inquiry: key points - The Guardian

COVID-19 words in green and blue.

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The COVID-19 pandemic has brought about numerous challenges in controlling the transmission of the SARS-CoV-2 virus. To combat this, various measures, both low and high-tech, have been suggested and implemented to reduce transmission risks. This review discusses these measures and practical tools that can assess their effectiveness.

High technology and low technology measures to reduce risk of SARS-CoV-2 transmission recently published in the American Journal of Infection Control1 authored by Curtis J. Donskey, MD.

Low-Tech Measures

Hand Hygiene: One of the simplest and most effective ways to prevent viral transmission is proper hand hygiene. Regular handwashing with soap and water for at least 20 seconds is recommended. Additionally, hand sanitizers with at least 60% alcohol content can be used when soap and water are not available.

Ventilation: Improving ventilation in indoor spaces is crucial. Opening windows and using fans can help dilute indoor air and reduce the concentration of infectious aerosols. Monitoring carbon dioxide levels can be a useful tool to assess ventilation adequacy.

Donskey wrote, The concentration of carbon dioxide in outdoor air is approximately 400 parts per million (ppm) versus approximately 40,000 ppm in exhaled breath. Thus, carbon dioxide levels rise in occupied spaces that are inadequately ventilated for the number of people present. Handheld devices that cost less than $100 are commercially available and easy to use. The CDC has recommended that carbon dioxide levels above 800 ppm in buildings be considered an indicator of suboptimal ventilation requiring intervention.

Donskey told Infection Control Today (ICT), "The pandemic has highlighted the importance of ventilation. However, the lack of practical tools to assess ventilation has been a limitation of the pandemic response. How do people know if they need to take steps to improve ventilation if they cant identify areas where improvement is needed? We have found that simple tools like carbon dioxide monitoring (ie carbon dioxide from breathing builds up when ventilation is inadequate for the number of people in an occupied area) and measurements of clearance of 5% sodium chloride aerosol particles can be very useful. For example, in response to evidence of transmission of SARS-CoV-2 in patient transport vans, we used these tools to show that ventilation was inadequate and identified simple measures to improve ventilation (ie open windows or run the fans continuously to maintain airflow). These tools can also be used to provide healthcare personnel with reassurance that ventilation is adequate in their work area."

Masks: The use of masks, particularly high-filtration masks like N95 respirators, can significantly reduce the spread of respiratory droplets containing the virus. Proper mask-wearing and fit are essential.

Plexiglass Barriers: Plexiglass barriers have been employed in various settings, such as checkout counters and between seats on public transport. While they may provide some protection, their effectiveness depends on factors like airflow and proper installation. However, little evidence is available regarding the impact of barriers in real-world settings, Donskey wrote. An intervention that included physical barriers and universal masking was associated with a significant reduction in COVID-19 cases in meat processing facilities, but placing barriers between students was not associated with a reduction in COVID-19 in schools in Georgia.2 Moreover, there is concern that barriers that are not carefully installed have the potential to hinder good ventilation resulting in increased aerosol exposure.

Oral and Nasal Antiseptics: These antiseptics have been suggested to reduce the viral load in individuals with COVID-19, potentially reducing transmission. However, more research is needed to establish their real-world efficacy.

High-Tech Measures

Portable Air Cleaners: These devices, equipped with high-efficiency particulate air (HEPA) filters, can help improve indoor air quality by capturing aerosol particles, including viruses. They are especially useful when adequate natural ventilation is not possible.

Air Cleaning Technologies: Some technologies release reactive oxygen species, hydroxyl radicals, or hydrogen peroxide gas to inactivate viral particles in the air. However, further studies, including clinical trials, are needed to confirm their efficacy and safety. One tool is ultraviolet germicidal irradiation (UVGI).

UVGI is effective for inactivation of SARS-CoV-2 and other respiratory viruses in air," Donskey wrote. "The CDC recommends considering the use of UVGI as a supplemental treatment to inactivate SARS-CoV-2 only when other options for increasing room ventilation and filtration are limited. UVGI can be provided as upper-room UVGI fixtures that provide a disinfection zone of UV above the height of people in the room or as in-duct UVGI systems that kill viruses in central ventilation systems. Upper-room UVGI can be considered in areas likely to include sick people (eg, school nurse's office), in spaces where people must remove masks (eg, cafeterias, restaurants), or in crowded spaces. For upper-room UVGI, the ceiling must be at least 8 feet high."

Assessing Transmission Risk: Practical tools can aid in assessing ventilation and transmission risk. Carbon dioxide monitoring can indicate the adequacy of ventilation by measuring the concentration of exhaled CO2, which can reflect indoor air quality. Devices that release smoke or condensed moisture fog can visualize airflow patterns and assess the effectiveness of ventilation measures.

While some low-tech measures like hand hygiene, ventilation, and mask-wearing are likely to be helpful in reducing transmission, others, like plexiglass barriers and oral/nasal antiseptics, require more substantial evidence. High-tech measures like portable air cleaners and air cleaning technologies can be valuable in settings where natural ventilation is limited.

Donskey told ICT, "One measure that I did not comment on in the article is environmental cleaning. Environmental cleaning was downplayed as hygiene theater as evidence accumulated suggesting that the environment plays a relatively minor role in transmission of SARS-CoV-2.

"However, I think it is important that we dont generalize the findings for COVID-19 to all respiratory viruses. There is good evidence that contaminated fomites can transmit non-enveloped cold viruses and that RSV can be transmitted from contaminated surfaces."

References

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Assessing Measures for Reducing SARS-CoV-2 Transmission: Low- and High-Tech Tools and Practical Insights - Infection Control Today

Brigham and Women's Hospital (Boston main campus) 75 Francis Street Boston, MA 02115 617-732-5500 By appointment in office Codman Square Health Center

637 Washington Street, Boston, MA 02124

To make an appointment for a test, you can call 617-822-8271.

Walk-ins are held on a first come first serve basis.

Monday - Friday, from 8:30 a.m. - 12 p.m.

1266 Commonwealth Avenue Allston, MA 02134

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703 Gallivan Boulevard,Dorchester, MA02124

To get tested, register in advance online with CVS.

Testing for symptomatic and asymptomatic patients.

Appointments only, make an appointment by calling 617-569-5800before arriving on site. This helps reduce traffic and crowding.

Walk-up testing: Monday - Friday, 8:30 - 11:30 a.m. and1:30 - 3p.m.

Testing available by appointment only. To make an appointment call 617-323-4440.

Testing is available at no cost and regardless of symptoms.

Drive thru available in municipal parking lot.

Monday Tuesday and Thursday, 1:30 - 3 p.m.

Patients only. Registration required. Please call617-825-3400if you would like to get vaccinated or tested for COVID-19.

Monday, Wednesday, Thursday, Friday, and Saturday, from 10 a.m. - 3 p.m.

Tuesday from 3 - 5 p.m.

This location is subject to changes due to staffing availability, please call to confirm your appointment.

To schedule an appointment call 617-245-8206

Tuesday and Wednesday, 4 - 7 p.m.

617-388-5007

COVID-19 testing now takes place by appointment and for current patients only. Testing is located in the outdoor parking lot testing tent.

Monday Wednesday, Thursday, 9 - 11:30 a.m.

Tuesday, 1 - 4 p.m.

Friday, 10 - 11:30 a.m.

Saturday, 9 a.m. - 12 p.m.

Call 617-989-3071to make an appointment.

Take-home tests only offered to those who are symptomatic. No longer offering PCR testing

Monday through Saturday, 9 a.m. - 1 p.m.

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COVID-19 Testing - Boston.gov

In the current study, nanopore direct RNA sequencing and liquid chromatography-tandem mass spectrometry (LCMS/MS) analysis were employed to examine whether DVGs can encode proteins in infected cells. With the protein databases generated by nanopore direct RNA sequencing, six DVG-encoded proteins were identified by LCMS/MS based on the featured fusion peptides caused by recombination during DVG synthesis. The limitations and the biological significance of the study are discussed.

Below, we explain why 34,104 (by total cell lysates) and 34,056 (by cell lysates derived from RNAprotein pull-down assay) protein species were identified by LCMS/MS analysis. First, coronavirus DVGs are recombination products and thus contain ORFs of various lengths from one or more portions of ORFs in the full-length genome. As a result, many DVG species (145,015) are identified by nanopore direct RNA sequencing, and thus, many potential DVG-encoded protein sequences (189,221) can be used as protein reference databases for LCMS/MS. Second, the diverse genome structures of DVGs may encode in-frame peptides that have the same amino sequences as those encoded from the full-length genome. Consequently, if the peptides determined by LCMS/MS analysis match the amino acid sequences of the DVG-encoded proteins and the protein scores are higher than 41, the DVG-encoded protein species can be identified based on the provided protein reference databases. Consequently, many DVG-encoded protein species (34,104 from total cell lysates, and 34,056 from cell lysates by RNAprotein pull-down assay) were identified by LCMS/MS analysis. However, this may lead to false-positive results because the peptides that match the amino acid sequence of DVG-encoded proteins may also be encoded from the full-length coronavirus genome, as described above, and thus cannot be used as markers to determine whether the identified proteins are encoded by coronavirus DVGs. That is also the reason why we propose that if the peptides contain discontinuous in-frame amino acid sequences derived from different portions of amino acid sequences from full-length genome-encoded proteins or contain out-of-frame amino sequences, the peptides are fusion peptides encoded from DVGs because DVGs are synthesized by recombination of the viral genome. Therefore, these fusion peptides can be used as markers to identify the proteins actually encoded by coronavirus DVGs. Consequently, 6 DVG-encoded proteins were identified through the identification of 6 fusion peptides, as shown in Figs.1, 2 and 3.

In addition, because the read number for the 6 DVGs is low (only 1), whether there is a correlation between the abundance of DVGs identified by nanopore direct RNA sequencing and that of their encoded proteins identified by LC-MS/MS remains unknown. Our explanation for the results is as follows. Because coronavirus DVGs are recombination products and thus contain ORFs of various lengths from one or more portions of ORFs derived from the full-length genome, the diverse genome structures of DVGs may encode in-frame peptides that have the same amino sequences as those encoded from the full-length genome. Consequently, if the peptides determined by LC-MS/MS analysis match the amino acid sequences of DVG-encode proteins and the protein scores are higher than 41, the DVG-encoded protein species are identified based on the provided protein reference databases. However, the peptides which match the amino acid sequence of DVG-encoded proteins may also be encoded from full-length coronavirus genome, and thus we cannot determine whether the identified peptides and thus the proteins are encoded from coronavirus DVGs or full-length genome. Consequently, DVG species with higher read numbers may encode more proteins, but without the featured fusion peptides as markers, whether there is a correlation between the abundance of DVGs identified by nanopore direct RNA sequencing and that of their encoded proteins identified by LC-MS/MS still cannot be determined. That is also the reason why we propose that, as described above, if the peptides contain discontinuous in-frame amino acid sequences derived from different portions of amino acid sequences from full-length genome-encoded proteins, or contain out-of-frame amino sequences, they are fusion peptides encoded from DVGs. Thus, at the current stage, we can only conclude that DVG can encode protein, and whether there is a correlation between the abundance of DVGs and that of their encoded proteins remains unknown. However, since the identified 6 DVGs with read number of 1 have the capability to encode proteins as determined by the current study, we can speculate that other DVG species with higher read numbers may also have the capability to encode protein although they cannot encode featured fusion peptide as markers to determine the proteins-coding capability.

It has been known that (i) coronavirus DVGs can be packaged [31], (ii) coronavirus N protein can inhibit host innate immunity [32] and (iii) innate immunity is the first line of host defense against virus infection [33]. In addition, based on the protein databases derived from the results of nanopore direct RNA sequencing in the current study, it is suggested that some DVG-encoded fusion proteins contain part or complete N protein. It is therefore speculated that one of the functions for coronavirus DVG-encoded fusion proteins is to regulate innate immunity, affecting virus replication and subsequent pathogenicity. On the other hand, coronavirus N protein has also been suggested to be important for replication and transcription (synthesis of coronavirus sgmRNAs including sgmRNA N) [34, 35]. However, N protein can only be synthesized from sgmRNA N, and consequently, the question is how coronavirus genome replicates and transcribes sgmRNAs before N protein is synthesized. As described above, because (i) coronavirus DVGs can be packaged [31], (ii) some DVGs contain partial or complete N protein ORF and (iii) DVGs can be translated as evidenced by the results of the current study, it is also argued that, after entry into the cells, the released DVGs with partial or complete N protein ORF can be immediately translated into N-containing fusion proteins, which in turn can facilitate the full-length coronavirus genome for subsequent replication and transcription before N protein is synthesized from sgmRNA N. According to the argument above, the DVG-encoded fusion proteins in coronaviruses including SARS-CoV-2 may have impact on pathogenesis through affecting innate immunity and replication. Lastly, it is also proposed that other coronavirus DVGs which encode other species of fusion proteins or out-of-frame novel proteins (when compared with the original ORFs in the full-length genome) may have different effects from those described above on pathogenesis although the functions of their encoded proteins remain to be determined. It is worth noting that, based on the previous study [26], the species and amounts of DVGs can be altered under different infection conditions such as in different infected cells and under different selection pressures. Since DVGs can encode various proteins, such alterations in the amounts and species of DVGs and thus the encoded proteins may be a way for coronavirus to respond to environmental changes, also contributing to the coronavirus pathogenesis.

The possible reasons why the featured fusion peptide was not detected in the total cell lysates by LCMS/MS are as follows. First, because there are too many species of DVGs in cells, the amount of each DVG-encoded protein (especially the protein with the featured fusion peptide) in a fixed amount of cell lysate may not be sufficient to be detected by LCMS/MS. Second, not every DVG-encoded protein contains the featured fusion peptides (based on the protein reference databases generated by nanopore direct RNA sequencing for BCoV), further limiting the identified number of protein species. Third, because SuperScript III reverse transcriptase (cat No. 18,080,044, Thermo Fisher Scientific, Waltham, USA), which is optimized to synthesize first-strand cDNA up to ~12kb, was used for nanopore direct RNA sequencing, the identified coronaviral RNA species, including DVGs, may not cover all coronavirus transcripts, especially those of longer size. Thus, the protein reference databases may not contain the full information of the DVG-encoded proteins, limiting the number of protein species identified by LCMS/MS analysis.

As shown in Figs.1, 2 and 3, it is suggested that DVGs have the capability to encode proteins as determined by RNAprotein pull-down assay followed by LCMS/MS. The results indicate that other DVGs may also have the capability to encode proteins. Consequently, the DVG-encoded proteins may play important roles during coronavirus infection. Thus, the current results may suggest an attractive field of study regarding the biological functions of proteins encoded by DVGs. Determining the function of DVG-encoded proteins is a priority to understand their roles in coronavirus pathogenesis. The outcomes of these studies may contribute to the development of antiviral strategies.

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Identification of the protein coding capability of coronavirus defective viral genomes by mass spectrometry - Virology ... - Virology Journal

Merideth Schlader of Summerhill said she learned a valuable lesson during the COVID-19 pandemic shell carry with her to the next one.

You have to make an effort to stay connected, she said.

Schlader practiced what she preached recently, drinking coffee with two friends, Cathy Smith of Cortland and Shannon Eggleston of McGraw, discussing a faith-based book theyd read together.

Jeri Shirk of Cortland said she was disappointed by how political the COVID-19 pandemic became, and hopes the next one wont be the same.

And there will be a next one, experts said. Another pandemic, whether a new strain of COVID or otherwise, is inevitable.

The last pandemic, the Spanish flu of 1918 to 1920, killed 50 million of the worlds 1.9 billion people about 2.6% of the world population, historians estimate.

World War I slowed response. The first cases were actually reported in Kansas, and migrated to Europe, and the trenches thereof, with U.S. soldiers heading to war. But nervous nations didnt want an international panic, so widespread awareness came only after the flu was reported in Spain, a non-combatant.

The coronavirus pandemic has several parallels. It has killed nearly 7 million of the worlds 8 billion people since 2020, about 0.09%, a number achieved with a fast-paced vaccine program, better drug treatment and better technology in respirators than a century ago.

HEALTH OFFICIALS PREPARING

The COVID-19 pandemic showed a public health threat can affect the whole world, said Nicole Anjeski, Cortland County public health director. COVID had profound effects on not only physical health, but the health of economic and political systems worldwide.

We may not understand the full impact of this pandemic for years to come, Anjeski said. Individuals, local and federal governments, medical professionals, nonprofits and businesses had to work together to mitigate the effects of the pandemic.

Communication, Anjeski said, is among the most important tools of dealing with mass health events, a hard lesson learned early when miscommunication, unclear messaging and uncertainty marred health departments ability to communicate with communities.

For future pandemics, the health department annually reviews and updates emergency preparedness plans. It has yearly drills, too.

We actively explore the most appropriate and efficient ways to provide transparent communication with the community, and we continue to foster relationships we have built with our local health systems, physicians, community organizations and agencies, local leaders and state partners, Anjeski said.

IT TAKES ALL OF US

Frank Kruppa, commissioner of Tompkins County Whole Health, that countys public health department, said after 9/11 and the 2001 anthrax attacks when letters laced with toxic anthrax went out across the country Tompkins and health departments across the country began constant planning for public health threats.

COVID-19 strained that preparedness, Kruppa said. Before COVID, health departments prepared for shorter-term, acute events, not widespread crises.

The pandemic taught Tompkins to build its resources, with more vaccines, with partners and with connecting with the public and media, he said. Communication is vital to navigating a mass public health event.

Whether its county government, the community, nonprofits, businesses, we need to see how we make sure we all understand or have some understanding of a plan, and where everyone might fit in, Kruppa said. One of the positives out of this is a broader understanding with governments, businesses, nonprofits, of how it takes all of us to respond.

NOT THE FIRST RODEO

Nellie Brown, director of workplace health and safety programs for the Buffalo Co-Lab of Cornell Universitys School of Industrial and Labor Relations, said many factors could aggravate the next pandemic.

Our diseases over the centuries tend to indicate they jump from animals to people, the next one will probably be something similar, Brown said.

Climate change and human development exacerbate their spread, Brown said.

Were seeing huge amounts of extremes in our climate. That can cause a lot of animals to move. When you have animals that are forced to move or chased out, then animals we may not have had contact with are driven into contact with humans, Brown said.

Theres debate on the matter, but Brown said most evidence indicates droughts facilitate diseases.

When water dries up, organisms become more concentrated, and at the same time you have people unable to clean things or bathe. That makes things a lot more difficult, she said.

In 2009, with the H1N1 epidemic, the U.S. attitude was that it didnt need to plan because its medical system could handle anything, Brown said.

Now look at what happened in 2020, she said. Failure to plan is a huge issue.

Brown said the country shouldnt rely on the marketplace to provide treatments and vaccines.

Yes, it takes money to research and develop drugs and antivirals. It takes a lot of money, she said, but profit shouldnt be a major motive. Dont let the marketplace drive this because we need to be on the watch all the time, not just wait and see what drug will be profitable.

NONPROFITS ADAPT

If theres another situation like COVID, I think were pretty well prepared, said Jackie Leaf, executive director of Seven Valleys Health Coalition. Whether were helping with clinics or materials we would be there to back them up. As things wound down, I think we had pretty good systems, Im not sure what we would do differently.

Seven Valleys has a food rescue program. When farmers were told to dump milk, even as there were shortages on store shelves because production lines geared for single-serving and commercial containers couldnt be converted to half-gallon and gallon jugs fast enough the organization received excess milk and passed it out for free.

Were more prepared than we were the first time as far as food assistance, Leaf said. With its new food rescue facility, Seven Valleys can store and refrigerate fresh food.

FOOD SYSTEMS

Cortlandville dairy farmer Paul Fouts said theres only so much farmers can do to untie tangles in the food processing and distribution system. Dairy farmers, if they have the space and resources, could add storage tanks, a short-term solution not accessible to every dairy, especially smaller operations.

I dont know how they would do it, but there really needs to be some flexibility in the processing sector, Fouts said. The plants set up to process milk appropriate for food service suddenly couldnt process milk because it had nowhere to go.

Buying from local farms, Fouts said, could relieve supply issues.

Local food suppliers are more resilient against supply chain disruptions, shows a 2021 study by the World Economic Forum. Large, pervasive food systems are more vulnerable to supply shocks, whereas local producers are less dependent on large-scale labor, transportation or distribution.

STEPPING UP

Christella Yonta, president of the Cortland County United Way, said in the event of another global outbreak, the organization would do just what it did the first time to help distribute food.

At the time of the pandemic, the United Way was uniquely positioned to manage through it, and by that I mean we already had a well-established network of community partners, Yonta said.

Normally, United Way acts strictly as a fundraising distributor. During COVID, Yonta and her staff distributed food and masks instead of money. Yonta arranged with DoorDash to deliver food, a relationship Yonta says will continue.

Today, she said, the United Way and its counterparts are better connected and know more about what to expect.

We just had to step up, Yonta said And well do it again.

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The next pandemic: It will come, and officials are using the lessons from COVID-19 to get ready - Niagara Gazette

As the holiday and peak respiratory seasons collide, and COVID-19 cases continue a steady, weeks-long climb, doctors want high-risk people to remember: Should COVID catch them in the coming days, one call to the doctor could save Christmas or more.

Paxlovid, an antiviral COVID therapy given under emergency use authorization (EUA) during the pandemic and now approved by prescription, prevents hospitalization and death between 60% and 80% of the time. The Food and Drug Administration (FDA) approved the drug in May for mild to moderate COVID in adults at high risk of developing severe illness.

State Hospitalizations Since Oct. 1 (as of Dec. 5)

Over the past month, theres been a steady increase in both emergency room visits and hospitalizations for COVID, said Thomas Campbell, MD, a professor of infectious diseases at the University of Colorado School of Medicine. Yet uptake of Paxlovid remains relatively low, with experts attributing fears of a rebound effect and a long list of drug interactions.

Campbell advises people to at least make that call. Doctors can help weigh whether risks outweigh benefits, find alternatives to some drugs that have interactions and even offer alternative therapies in some cases, he said.

Its important that to have its maximum benefit, Paxlovid is started as soon as possible after the onset of symptoms not after diagnosis and no more than five days after onset, Campbell said. Anyone with at least one high-risk factor should talk with their doctors, he said.

Nearly three-quarters of Americans fall in that group, with risk factors including diabetes, obesity, asthma, heart disease and being 50 or older so prevalent. High-risk youth between 12 and 18 years old can still receive Paxlovid under the EUA, and adults can receive a prescription directly from a pharmacist supplied with required health information.

As all emerging variants still reside within the omicron family, the newest booster shot, which wholly targets omicron, remains the best defense, Campbell said. And Paxlovid has maintained its effectiveness against the new variants, he said.

In the following Q&A, Campbell discusses pros and cons of Paxlovid and its alternatives as well as potential new options on the horizon, including one new drug targeting non-high-risk patients undergoing a clinical trial he is currently leading at the CU Anschutz Medical Campus.

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Paxlovid to the Rescue? What to Know About the COVID-19 Drug - University of Colorado Anschutz Medical Campus

A systematic review and meta-analysis estimates a nearly 50% long-COVID rate months after infection in Africa, with psychiatric conditions the most common manifestations.

Published today in Scientific Reports, the February 2023 literature search and analysis involved 25 observational, English language long-COVID studies with 29,213 infected African patients.

Nearly half (48%) of the studies were from Egypt, the average patient age was 42years (range, 7 to 73 years), 59.3% were females, and the median follow-up was 3 months.

"In low-income countries, the estimates of its [long COVID's] incidence vary greatly due to a significant number of hidden infections (i.e., asymptomatic or undisclosed) and difficulties in accessing testing," the study authors wrote.

The team, led by researchers from the University of Bari in Italy, found a long-COVID rate of 48.6%, with a predominance of psychiatric conditions, especially post-traumatic stress disorder (25.8%).

The most common neurologic symptom was cognitive impairment (15%), and shortness of breath was the most common respiratory symptom (18.3%), followed by cough (10.7%). Other notable symptoms were loss of appetite (12.7%), weight loss (10.4%), fatigue (35.4%), and muscle pain (15.5%). A quarter (25.4%) of patients reported poor quality of life.

The high incidence of fatigue is particularly worrisome because of its debilitating nature. "This is concerning because, in Africa, it has the potential to lead to important impairment in productivity and further loss of economic agency," the researchers wrote.

The study recommends identifying at-risk people and defining treatment strategies and recommendations for African long-COVID patients.

Likewise, the mental illness burden in long-COVID patients poses a challenge on a continent with few mental health resources: "These findings highlight the pressing need for immediate policy implementation and reallocation of resources to address this severely underestimated public health issue."

Risk factors for long COVID included older age and hospitalization during infection.

"The study recommends identifying at-risk people and defining treatment strategies and recommendations for African long-COVID patients," the authors concluded, noting that high-quality studies are urgently needed.

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Study shows infants exposed to COVID in utero at risk for developmental delay - University of Minnesota Twin Cities

From infections with no symptoms to why men are more likely to be hospitalized in the ICU and die of COVID-19, new research shows that your genes play a significant role

Early in the pandemic, genetic research focused on the virus because it was readily available. Plus, the virus contains only 30,000 bases in a dozen functional genes, so it's relatively easy and affordable to sequence. Additionally, the rapid mutation of the virus and its ability to escape antibody control fueled waves of different variants and provided a reason to follow viral genetics.

In comparison, there are many more genes of the human immune system and cellular functions that affect viral replication, with about 3.2 billion base pairs. Human studies require samples from large numbers of people, the analysis of each sample is vastly more complex, and sophisticated computer analysis often is required to make sense of the raw data. All of this takes time and large amounts of money, but important findings are beginning to emerge.

Asymptomatics

About half the people exposed to SARS-CoV-2, the virus that causes the COVID-19 disease, never develop symptoms of this disease, or their symptoms are so mild they often go unnoticed. One piece of understanding the phenomena came when researchers showed that exposure to OC43, a common coronavirus that results in symptoms of a cold, generates immune system T cells that also help protect against SARS-CoV-2.

Jill Hollenbach, an immunologist at the University of California at San Francisco, sought to identify the gene behind that immune protection. Most COVID-19 genetic studies are done with the most seriously ill patients because they are hospitalized and thus available. But 99 percent of people who get it will never see the inside of a hospital for COVID-19, she says. They are home, they are not interacting with the health care system.

Early in the pandemic, when most labs were shut down, she tapped into the National Bone Marrow Donor Program database. It contains detailed information on donor human leukocyte antigens (HLAs), key genes in the immune system that must match up between donor and recipient for successful transplants of marrow or organs. Each HLA can contain alleles, slight molecular differences in the DNA of the HLA, which can affect its function. Potential HLA combinations can number in the tens of thousands across the world, says Hollenbach, but each person has a smaller number of those possible variants.

She teamed up with the COVID-19 Citizen Science Study a smartphone-based study to track COVID-19 symptoms and outcomes, to ask persons in the bone marrow donor registry about COVID-19. The study enlisted more than 30,000 volunteers. Those volunteers already had their HLAs annotated by the registry, and 1,428 tested positive for the virus.

Analyzing five key HLAs, she found an allele in the gene HLA-B*15:01 that was significantly overrepresented in people who didnt have any symptoms. The effect was even stronger if a person had inherited the allele from both parents; these persons were more than eight times more likely to remain asymptomatic than persons who did not carry the genetic variant, she says. Altogether this HLA was present in about 10 percent of the general European population but double that percentage in the asymptomatic group. Hollenbach and her colleagues were able confirm this in other different groups of patients.

What made the allele so potent against SARS-CoV-2? Part of the answer came from x-ray crystallography. A key element was the molecular shape of parts of the cold virus OC43 and SARS-CoV-2. They were virtually identical, and the allele could bind very tightly to them, present their molecular antigens to T cells, and generate an extremely potent T cell response to the viruses. And for whatever reasons that generated a lot of memory T cells that are going to stick around for a long time, says Hollenbach. This T cell response is very early in infection and ramps up very quickly, even before the antibody response.

Understanding the genetics of the immune response to SARS-CoV-2 is important because it provides clues into the conditions of T cells and antigens that support a response without any symptoms, she says. It gives us an opportunity to think about whether this might be a vaccine design strategy.

Dead men

A researcher at the Leibniz Institute of Virology in Hamburg Germany, Guelsah Gabriel, was drawn to a question at the other end of the COVID-19 spectrum: why men more likely to be hospitalized and die from the infection. It wasn't that men were any more likely to be exposed to the virus but more likely, how their immune system reacted to it

Several studies had noted that testosterone levels were significantly lower in men hospitalized with COVID-19. And, in general, the lower the testosterone, the worse the prognosis. A year after recovery, about 30 percent of men still had lower than normal levels of testosterone, a condition known as hypogonadism. Most of the men also had elevated levels of estradiol, a female hormone (https://pubmed.ncbi.nlm.nih.gov/34402750/).

Every cell has a sex, expressing receptors for male and female hormones on their surface. Hormones docking with these receptors affect the cells' internal function and the signals they send to other cells. The number and role of these receptors varies from tissue to tissue.

Gabriel began her search by examining whole exome sequences, the protein-coding part of the genome, for key enzymes involved in the metabolism of sex hormones. The research team quickly zeroed in on CYP19A1, an enzyme that converts testosterone to estradiol. The gene that produces this enzyme has a number of different alleles, the molecular variants that affect the enzyme's rate of metabolizing the sex hormones. One genetic variant, CYP19A1 (Thr201Met), is typically found in 6.2 percent of all people, both men and women, but remarkably, they found it in 68.7 percent of men who were hospitalized with COVID-19.

Lung surprise

Lungs are the tissue most affected in COVID-19 disease. Gabriel wondered if the virus might be affecting expression of their target gene in the lung so that it produces more of the enzyme that converts testosterone to estradiol. Studying cells in a petri dish, they saw no change in gene expression when they infected cells of lung tissue with influenza and the original SARS-CoV viruses that caused the SARS outbreak in 2002. But exposure to SARS-CoV-2, the virus responsible for COVID-19, increased gene expression up to 40-fold, Gabriel says.

Did the same thing happen in humans? Autopsy examination of patients in three different cites found that CYP19A1 was abundantly expressed in the lungs of COVID-19 males but not those who died of other respiratory infections, says Gabriel. This increased enzyme production led likely to higher levels of estradiol in the lungs of men, which is highly inflammatory, damages the tissue, and can result in fibrosis or scarring that inhibits lung function and repair long after the virus itself has disappeared. Somehow the virus had acquired the capacity to upregulate expression of CYP19A1.

Only two COVID-19 positive females showed increased expression of this gene. The menopause status of these women, or whether they were on hormone replacement therapy was not known. That could be important because female hormones have a protective effect for cardiovascular disease, which women often lose after going through menopause, especially if they dont start hormone replacement therapy. That sex-specific protection might also extend to COVID-19 and merits further study.

The team was able to confirm their findings in golden hamsters, the animal model of choice for studying COVID-19. Testosterone levels in male animals dropped 5-fold three days after infection and began to recover as viral levels declined. CYP19A1 transcription increased up to 15-fold in the lungs of the male but not the females. The study authors wrote, Virus replication in the male lungs was negatively associated with testosterone levels.

The medical community studying COVID-19 has slowly come to recognize the importance of adipose tissue, or fat cells. They are known to express abundant levels of CYP19A1 and play a significant role as metabolic tissue in COVID-19. Gabriel adds, One of the key findings of our study is that upon SARS-CoV-2 infection, the lung suddenly turns into a metabolic organ by highly expressing CYP19A1.

She also found evidence that SARS-CoV-2 can infect the gonads of hamsters, thereby likely depressing circulating levels of sex hormones. The researchers did not have autopsy samples to confirm this in humans, but others have shown that the virus can replicate in those tissues.

A possible treatment

Back in the lab, substituting low and high doses of testosterone in SARS-COV-2 infected male hamsters had opposite effects depending on testosterone dosage used. Gabriel says that hormone levels can vary so much, depending on health status and age and even may change throughout the day, that it probably is much better to inhibit the enzyme produced by CYP19A1 than try to balance the hormones.

Results were better with letrozole, a drug approved to treat hypogonadism in males, which reduces estradiol levels. The drug also showed benefit in male hamsters in terms of less severe disease and faster recovery. She says more details need to be worked out in using letrozole to treat COVID-19, but they are talking with hospitals about clinical trials of the drug.

Gabriel has proposed a four hit explanation of how COVID-19 can be so deadly for men: the metabolic quartet. First is the genetic risk factor of CYP19A1 (Thr201Met), then comes SARS-CoV-2 infection that induces even greater expression of this gene and the deleterious increase of estradiol in the lung. Age-related hypogonadism and the heightened inflammation of obesity, known to affect CYP19A1 activity, are contributing factors in this deadly perfect storm of events.

Studying host genetics, says Gabriel, can reveal new mechanisms that yield promising avenues for further study. Its also uniting different fields of science into a new, collaborative approach theyre calling infection endocrinology, she says.

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Genes shape our response to the Covid virus - Leaps