SARS. What’s in a name?

• The name of a viral agent is of great importance.
• Viruses are real: Viral species are man made taxonomic constructs (Van Regenmortel 2003)
• Would a rose by any other name …..? (Shakespeare)
• Words are viruses (William S Burroughs)
• Question everything: Especially the use of words.
• In this seminar there will be open questions, but no closed answers.
• The words of others are the only hard data points. They used them. We can ask why.

WHO press conferences 2020

• January “Of course this is a novel coronavirus, and it’s a new discovery. So identifying the pathogen was done swiftly, and it shows the capacity that China has now. And the sequencing was done quickly. But more importantly, it was shared immediately.”
• February 12 "COVID-19 is not as deadly as other coronaviruses including SARS and MERS. More than 80% of patients have mild disease and will recover. The risk of death increases the older you are. We see relatively few cases among children. More research is needed to understand why.
• February 17 “This virus is not SARS, it’s not MERS and it’s not influenza. It is a unique virus with unique characteristics. COVID-19 does not transmit as efficiently as influenza”
• March 12 "Anyone there at the WHO have comments about the US president Donald Trump’s continued usage of the term, the Chinese virus, as recently as this morning, to refer to COVID?
• April “The SARS-CoV-2 virus is causing COVID-19”

Questions

• Why did the WHO declare the virus to be novel?
• What does novelty mean? – A new born kitten is a novel animal, never before seen. It is still a cat, it has feline characteristics.
• Why did the WHO switch from first calling the virus itself COVID-19 to using SARS-CoV-2 for the infectious agent?
• Why did the name “covid” return as an almost ubiquitous designation for “the virus” (e.g. zero covid, covid test, covid vaccine)?

Viral species and viral sequences

• There are an essentially infinite number of viral sequences. If a virus is a sequence then every one is novel.
• The number of viral species is determined by taxonomists.
• Novelty is a construct which arises when a name is given.
• Very few of the viral sequences found in nature are clearly grouped into species.
• Most “viruses” are “sin nombre.”

Number of viral “species”

• Perhaps “over one million viral species” of vertebrates (Morse, source unclear)
• “Minimum of 320,000 mammalian viral species awaiting discovery” (Anthony et al. 2013)
• But .. how is a “viral species” defined?

Definitions

• A species definition for any organism is very slippery. For viruses its almost impossible.
• In 1982 ICTV tried a phenetic definition “a cluster of strains from a variety of sources, or a population of strains from a particular source, which have in common a set of stable properties that separate the cluster from other clusters of strains.”
• Replaced in 1991 by “A virus species is a polythetic class of viruses that constitutes a replicating lineage and occupies a particular ecological niche.”
• 2013 became “A species is a monophyletic group of viruses whose properties can be distinguished from those of other species by multiple criteria.”
• The current definition essentially defines virus species (clades) based only on a part of their genomic sequence (but it still somehow manages to tack on some other ill defined stuff)

Monophyletic evolution

• A group of taxa (clade) composed of a common ancestor and all of its lineal descendants.
• No crossovers (i.e no recombinants) allowed
• Phylogeny has to be traced to a single root
• Not truly equivalent to geneology within a sexually reproducing organisms
• Tracing deep ancestry to a single point can only use some sequences that are inherited unchanged. So, any recombination in these viral sequences would completely mess up the phylogenies.

Species, strains and variants

• The only (poorly) defined lower taxonomic level is the species.
• Definitions of strains, variants and viral isolates cause more confusion (Alimpiev 2019)
• A single viral isolate is a single sequence. So Wuhan-1 is just one sequence.
• The lab origin theories revolve around a single emergence of infection with one ancestral sequence.
• Theories of zoonotic species origin should never propose any single point emergence.

Coronaviridae Study Group of the International Committee on Taxonomy of Viruses

• March 2020. Looked at all the available sequences at the time (not just one)
• “Based on phylogeny, taxonomy and established practice, the CSG recognizes this virus as forming a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus, and designates it as SARS-CoV-2.”
• This implies, under the current definition, that SARS-CoV-2 is a direct descendent of SARS, or shares a common ancestor. The CSG used the word “individuum” for sequence.

Overlaps between SARS-CoV-1 and SARS-CoV-2 cluster of sequences

• Around 86% sequence similarity between SARS-CoV-1 cluster and SARS-CoV-2 cluster
• Considerable sequence diversity within each clade
• “In terms of taxonomy, SARS-CoV-2 is (just) another virus in the species Severe acute respiratory syndrome-related coronavirus” (Gorbalenya et al. 2020)

Non-identical base pairs

• Overlaps in between and within clade sequence differences (Gorbalenya et al. 2020)
• Precise nature of shared sequence elements are not clear.
• The 86% similarity is an average. Both are clusters of sequences.

Next strain SARS-CoV-2

Questions

• Why was one sequence, at the root of the tree, singled out for attention and essentially attached to the name SARS-CoV-2?
• What defines the named clades being called variants?
• What would the tree look like if it were rooted on a SARS1 sequence?

Implications

• The origin of what the WHO called the virus can be traced to Wuhan, at or just before, the date of publication of the sequence.
• The origin of the species that it belongs to (SARS) is unknown, but it is much earlier.
• Why did the WHO not use all the prior information on SARS as a basis for a response to SARS-CoV-2?

Time line of the first recorded SARS outbreak

• Main source CDC archive (2020)
• From November 1, 2002 to July 11, 2003, a total of 8,427 probable SARS cases were reported to the WHO from 29 countries.
• 813 deaths (case fatality rate: 9.6%) with no SARS-related deaths in the United States
• Very pronounced age gradient and strong association with comorbities found everywhere.
• On July 5 2003, WHO announced that all known person-to-person transmission of SARS-CoV had ceased.
• Note that an IFR for SARS was never established. Many cases were never confirmed and many infections never detected.

First reports in China.

• Initially reported as atypical pneumonia in Guangdong November 2002. Given name SARS in January 2003. (What was “atypical” with respect to pneumonia?). No causal agent suggested until end of March 2003 (Drosten et al. 2003)
• The WHO issued a global alert about the outbreak on March 12 2003, cautioning that “a severe respiratory illness may spread to hospital staff. No link has been made between this illness and any known influenza, including the”bird flu" (A[H5N1]) outbreak reported in Hong Kong on February 19."
• April 2003 a physician at an army hospital in Beijing, alleged that the actual number of SARS cases was much higher than the official count.
• First reported in Hong Kong in February 2003 when a 64-year-old medical professor from Guangdong stayed at the Metropole Hotel. The professor died within two weeks.
• The assumption was made that this single individual infected other guests, who then spread SARS to Singapore, Toronto, Hanoi and onwards.

Questions

• How were the health authorities so certain about chains of transmission involving named individuals?
• What was the connection with the Hong Kong bird flu?
• Why was a Chinese army “whistle blower” involved in raising the alarm level?
• If a transmissible virus was circulating in Guangdong, why did it apparently take so long to get to Hong Kong and only arrived once?

CDC April 2003

• “SARS has been associated etiologically with a novel coronavirus, SARS-CoV. Evidence of SARS-CoV infection has been identified in patients with SARS in several countries, including the United States. A PCR test specific for viral RNA has been positive within the first 10 days after onset of fever in specimens from some SARS patients, but the duration of detectable viremia or viral shedding is unknown. No instances of SARS-CoV infection have been detected in persons who are asymptomatic. However, data are insufficient to exclude the possibility of asymptomatic infection with SARS-CoV and the possibility that such persons can transmit the virus. Investigations of close contacts and health-care workers exposed to SARS patients might provide information about the occurrence of asymptomatic infected persons. Similarly, the clinical manifestations of SARS might extend beyond respiratory illness.”

Beijing outbreaks Pang et al. (2003)

• Chinese authorities publicly announced the outbreak in April. 30 thousand persons quarantined.
• Public masking became common
• Closed schools and libraries when the outbreak was peaking.
• 14 million people screened for fever at the airport, train stations, and roadside check- points, only 12 were found to have probable SARS.
• Later claimed that these measures suppressed the outbreak.

Toronto outbreaks

• Assumed to arise from travel to China and/or Hong Kong.
• WHO issued travel advisory in April. It was strongly criticised and lifted in a week.
• Two “waves”
• Almost entirely nosocomial
• Reports of a similar outbreak with a higher CFR in Vancouver were later attributed to a OC43 infection.

Toronto outbreaks

Low (2006)

Toronto outbreaks

"Provincial emergency on March 26, 2003. All hospitals in the Greater Toronto Area (GTA) suspended nonessential services, limited visitors and created isolation units for potential SARS patients with PPR for exposed staff (i.e., gowns, masks, and goggles). Four days later, provincial officials extended access restrictions to all Ontario hospitals.

• May 14, 2003, WHO removed Toronto from the list of areas with recent local transmission.
• May 17 Emergency lifted. Total 140 probable and 178 suspect infections with 24 deaths.

Toronto outbreaks

• “During the first phase of the outbreak in Toronto, SARS chiefly affected health care workers (HCW), patients, and their visitors at four hospitals”
• “Nosocomial transmission in the hospital began when case A presented to the emergency department on March 7 with severe respiratory symptoms. During this time, SARS was transmitted to two other patients in the emergency department (cases B and C). Case B, who had presented with rapid atrial fibrillation, was in the bed adjacent to case A, about 1.5 meters away and separated by a curtain, and was discharged home after 9 hours in the emergency department. Case C, who had presented with shortness of breath secondary to a pleural effusion, was three beds (about 5 meters) away from case A and was transferred to a hospital ward and later discharged home on March 10. The three patients were cared for by the same nurse.”
• The infection spread to three other members of case B’s family. SARS developed in a number of people who were in contact with case B and his wife on March 16, including the 2 paramedics who brought him to the hospital, a firefighter, 5 emergency department staff, 1 other hospital staff, 2 patients in the emergency department, 1 housekeeper who worked in the emergency department while case B was there, and 7 visitors who were also in the emergency department at the same time as case B (symptom onset March 19 to 26). The 16 hospital staff, visitors, and patients transmitted the infection to 8 household members and 8 other family contacts.

Reactions

• Thousands of Canadians were quarantined. Many voluntarily quarantined themselves in their homes. Airports in Toronto and Vancouver screened travellers for high fever. https://thecanadianencyclopedia.ca/en/article/sars-severe-acute-respiratory-syndrome
• Health departments at all levels of government posted regular updates online. Public health officials became the dominant voice in daily press conferences and news coverage.
• “Academic studies of media coverage during the Canadian SARS outbreak have concluded that it was excessive, sensationalist and sometimes inaccurate.”
• News stories often featured images of Asian people wearing surgical masks taken overseas but paired with local coverage. SARS was described as “fearful,” “mysterious” and “exotic”
• A Toronto legal clinic filed a formal complaint against the Immigration and Refugee Board (IRB) about members wearing surgical masks at hearings for Asian claimants. These claimants were not recent arrivals to Canada. The claimants were also reportedly screened for SARS before their hearings. The IRB stopped these practices as a result of the complaint.

The CDC were quite relaxed in an April 22 2003 press conference

“CDC and the State Department routinely issue various kinds of advice to outbound travelers. One kind of advice is called a health alert, that’s just simply a heads-up. We have issued a health alert to travelers to Toronto, Canada. And that health alert basically says, no reason to stay home, but if you’re going there, be aware that SARS is present in some settings in the community and you may wish to avoid the hospital environment or the health care environment. A different level of advice to outbound passengers is a travel advisory, and we also have travel advisories for SARS. These are now in effect for China, including mainland China as well as the Hong Kong Special Administrative Region, Hanoi, and Singapore. These outbound advisories right now are saying, please avoid non-essential travel to these areas because there is ongoing transmission in the community that is not linked back to the initial cases.”

Official end of the epidemic (July 2003)

Toronto July 2003

• “450,000 people crowded Toronto’s Downsview Park for the show. The city’s tourism industry was suffering after the worldwide SARS outbreak affected Canada, placing a stigma on resources throughout the city. Thousands of hotel and tourism industry workers were laid off, with one local official telling the CBC that hundreds of millions of dollars were lost in just a few short months.The World Health Organization’s travel advisory had been lifted by mid-summer, but the SARS stigma remained, prompting Mick Jagger and the Stones to whip into action.” (Dukes 2015)

Postscript. China 2004

• April 22-29, the Chinese Ministry of Health (MOH) reported a total of nine cases of SARS in China ; seven of the patients were from Beijing , and two were from Anhui Province , located in east-central China . One of the patients died. Two of the nine patients were graduate students who worked at China’s National Institute of Virology Laboratory (NIVL) in Beijing , which is known to conduct research on SARS coronavirus (SARS-CoV).
• Of the seven other SARS cases, two were directly linked to close personal contact with one of the graduate students who worked at NIVL
• No further cases of SARS in China or anywhere else in the world have been reported since April 29.
• May 18, the World Health Organization (WHO) reported on its website external icon that the outbreak in China appears to have been contained, but that biosafety concerns remain and further investigation is under way. WHO and Chinese health officials are still in the process of determining precisely what caused the outbreak. CDC is in close communication with WHO and is working with its public health partners to reinforce the need for strict adherence to applicable biosafety precautions to reduce the risk of laboratory-related exposures to SARS-CoV.

Questions

• Why were the Chinese (+ Hong Kong, Taiwan and Singapore) NPI actions credited with ending the outbreak?
• Why did SARS get the reputation of having widespread community transmission when the evidence was purely nosocomial or from lab leaks?
• Why are the lab leak cases from the NIVL (and in Singapore) rarely mentioned?
• Almost all the fatalities had other commorbities. Were there mild and “asymptomatic” infections with the virus?
• If so, what was the true IFR of SARS?
• If not, how could the Chinese NPI measures (school closures etc) have had any possible benefit?
• What happened to the SARS class of viral sequences in humans?

The PCR test

• PCR test developed by (Drosten et al. 2003)
• Found other potential pathogens in the samples but concentrated on coronavirus. “By testing for a broad range of known pathogens, we also obtained evidence for infection with paramyxoviruses and C. pneumoniae. Paramyxoviruses — in particular, human metapneumovirus, which was previously implicated in SARS”
• “The involvement of a coronavirus in a respiratory disease would not be without precedent: the two human coronaviruses are known to cause mild respiratory illness. One should bear in mind, however, that in the past, viruses have been initially isolated from patients with a specific disease but subsequent investigations revealed no actual association at all. Thus, larger studies with appropriate control groups are needed to verify or eliminate our hypothesis about the cause of SARS.”
• Suggested that PCR was a promising research tool.

Hamburg 1 (Muth et al. 2018)

• Drosten thought he may have found some answers to question regarding the fate of SARS in humans.
• Fully sequenced a sample from the German traveller to China and experimented in cell cultures.
• “A 29 nucleotide deletion in open reading frame 8 (ORF8) is the most obvious genetic change in severe acute respiratory syndrome coronavirus (SARS-CoV) during its emergence in humans. It remains unclear whether the deletion actually reflects adaptation to humans. Here we engineered full, partially deleted (−29 nt), and fully deleted ORF8 into a SARS-CoV infectious cDNA clone, strain Frankfurt-1. Replication of the resulting viruses was compared in primate cell cultures as well as Rhinolophus bat cells made permissive for SARS-CoV replication by lentiviral transduction of the human angiotensin-converting enzyme 2 receptor.The 29 nt deletion in SARS-CoV is a deleterious mutation acquired along the initial human-to-human transmission chain.”

Could deletions actually increase fitness?

(Muth et al. 2018) “As pointed out in Marzi et al. for Ebola virus Makona, a prolonged survival time as seen with late epidemic strains could have increased the duration of infectious virus shedding in humans and may thus have increased the long-term fitness of those viruses. We cannot, at present, exclude whether similar effects may have provided a fitness advantage to SARS-CoV on host population level, such as by keeping infected individuals socially interactive for prolonged times while infected with a slightly attenuated virus.”

Endemic coronavirus prevalence often drops to unoticeable levels (Killerby et al. 2018)

Could a mild version of SARS have become endemic in humans?

• Only suspected respiratory viruses are tested for using PCR.
• Most people infected with SARS with the 29nt deletion showed few if any symptoms.
• Was there any PCR testing for SARS related sequences in humans after 2004?
• L. F. Wang and Eaton (2007) reported “(Zheng et al. 2004), found that 17 of 938 (or 1.7%) adults recruited in 2001 had antibodies to SARS-CoV detected by immunofluorescence and virus neutralisation assays. These findings suggest that a small proportion of healthy individuals in Hong Kong had been exposed to SARS-CoV related viruses at least 2 years before the SARS outbreak reached Hong Kong in mid-February 2003.”

Severe pneumonia in normal times is not easily attributable

• 2320 adults with radiographic evidence of pneumonia (93%), median age 57 years (Jain et al. 2015) (annual incidence of severe pneumonia ~3 per thousand people)
• 498 required intensive care, and 52 (2%) died.
• A pathogen was detected in 853 (38%):
• One or more viruses in 530 (23%),
• Bacteria in 247 (11%),
• Bacterial and viral pathogens in 59 (3%).
• Fungal or mycobacterial pathogen in 17 (1%).
• The most common pathogens were human rhinovirus (in 9% of patients), influenza virus (in 6%), and Streptococcus pneumoniae (in 5%).

Zoonotic origins. Civets?

• Early SARS cases in Guangdong guessed to be related to restaurant workers handling wild mammals. Very weak evidence based on public health methodologies (markets attract PH officialdom)
• From Yip et al. (2009) "Guan et al. (2003) surveyed the wild animals in a local market and isolated CoVs from Himalayan (masked) palm civets (Paguma lavata), which share 99.8% genome sequence identity to the SCoVs in human.
• Initial phylogenetic analyses suggested SCoVs from human and civets formed two distinct clades (Guan et al., 2003), but the SCoVs from civets are phylogenetically closer to the SCoVs of the early-phase epidemic than to those in the late-phase epidemic (Kan et al., 2005).
• Phylogenetic analyses demonstrated that the SCoVs from the 2002–2003 epidemic and the 2003–2004 re-emergence are phylogenetically distinct, suggesting the inter-species transmission events from civets to human in the two outbreaks might be independent (Song et al., 2005; Wang et al.,2005a).However, a large-scale survey of SCoVs of civets in market in China suggested the lack of widespread infections in civets (Kanet al., 2005) (Song et al., 2005; Lam et al., 2008a). These findings suggested civets might not be the natural reservoir of SCoV and civets only acquired SCoVs shortly before the emergence of SCoV in humans or later.

Guan et al. (2003)

• Guan et al reported that market traders also tested positive but had no symptoms.
• “When the full genome of the animal(n=2) and human (n=5, see above) virus groups were compared, the most striking difference was that these human viruses have a 29-nt deletion”

Questions

• The civets never became ill with SARS (there is little evidence that any wild animals become seriously ill with any coronavirus infections). Were they passive bystanders?
• Why was the presence of “asymptomatic” SARS in the traders not emphasised?
• Were the civets infected from humans?
• Why were no other infections in civets ever found?
• Was this connection being used opportunistically to halt the widely unpopular trade in civets (banned in March, but reinstated in August)?

Were do bats come in to the story?

• As the civets seemed to be a dead end the assumption was made that they were intermediate hosts.
• The zoonotic paradigm involves intermediate hosts and “spillovers.”
• This is because humans do not come into direct contact with very much wildlife.
• Bat viral diversity is extremely high (Wu et al. 2016)
• Around 20% of all mammalian species are bats
• Nipah, Marburg, Hendra, Ebola all traced to bats.

Bat viral diversity

Spillovers

• Humans + livestock ~ 15 times the total wildlife biomass (correlated with cells in which viruses can replicate)
• Livestock accounts for 1.5 times more biomass (cells) than humans
• Even so, most viral genomic diversity must be found in wildlife (~ 5k mammal 10K bird species).

Spillovers

(Cui, Li, and Shi 2019)

Studies of bat coronavirus diversity

• Similar sequences to SARS found throughout the world (Drexler, Corman, and Drosten 2014a)

Illustrative studies in bats

• Multiple examples of coronavirus diversity in bats throughout the world (see reference section for the article titles and links)

• Balboni et al. (2011) Monchatre-Leroy et al. (2017) Hu et al. (2017) Rizzo et al. (2017) Hayman et al. (2013) Plowright et al. (2014) Mendenhall et al. (2019) Lacroix et al. (2020) Wong et al. (2019)Anthony et al. (2013) Tao and Tong (2019) Drexler, Corman, and Drosten (2014b) P. C. Y. Woo et al. (2012) Smith et al. (2016) Patrick C. Y. Woo et al. (2006) Lau et al. (2015) V. M. Corman et al. (2015) Drexler et al. (2011) De Sabato et al. (2019) Kivistö et al. (2020) Musso et al. (2020) Pauly et al. (2017)

Example from Luxembourg

(Pauly et al. 2017)

• Severe acute respiratory syndrome (SARS)-related Betacoronavirus strains were shed by Rhinolophus ferrumequinum
• “The high similarity of the spike gene sequences of these viruses with mammalian Betacoronavirus 1 strains may be of concern. Both the SARS-related and Betacoronavirus 1 strains detected in bats in Luxembourg may cross the species barrier after a host adaptation process.”

Drexler et al. (2010)

• Rhinolophids carried severe acute respiratory syndrome (SARS)-related CoV at high frequencies and concentrations (26% of animals are positive; up to 2.4 copies per gram of feces), as well as two Alphacoronavirus clades, one novel and one related to the HKU2 clade.
• All three clades present in Miniopterus bats in China (HKU7, HKU8, and 1A related) were also present in European Miniopterus bats.

Muth et al. (2018)

• “We have previously described the detection of SARS-related CoV in Rhinolophus in Bulgaria”"
• To further investigate the presence of ORF8 in SARS-related CoV in Europe, we analyzed fecal samples from rhinolophid bats in Spain, Bulgaria, Italy, as well as Slovenia
• All five Rhinolophus species commonly encountered in Europe were tested positive for coronavirus RNA
• The variant termed rSCV8 contained a complete ORF8 as encountered in bats, civet cats, as well as in early human cases of SARS i.e. Without the famous 29nt deletion!

V. Corman et al. (2020)

• The SARS-CoV-2 PCR test uses some sequences derived from European bats!

Rhinolophus distribution

Cats as intermediate hosts?

• Civet cats are farmed in China, but comparatively rare in the wild. Omnivorous and don’t generally hunt bats.
• Domestic cats are ubiquitous and they do consume large numbers of bats in their breeding roosts.
• Feline ACE2 reacts with SARS-Cov as well as human ACE2 (Guo et al. 2008) (Jo et al. 2020)

Carnivore hosts

Cats in China

• Thousands of cats were rounded up and killed in China prior to 2008 Olympic games in Beijing
• Suspected of carrying SARS

Cats and SARS-Cov-2

(Zhang et al. 2020)

Bat to human direct transmission?

N. Wang et al. (2018) claimed to have found recent (pre covid19) antibodies to SARS in rural China.

“During questioning, none of the 6 seropositive subjects could recall any clinical symptoms in the past 12 months, suggesting that their bat SARSr-CoV infection either occurred before the time of sampling, or that infections were subclinical or caused only mild symptoms. Our previous work based on cellular and humanized mouse infection studies suggest that these viruses are less virulent than SARS-CoV (Ge et al. 2013; Menachery et al. 2016; Yang et al. 2016). Masked palm civets appeared to play a role as intermediate hosts of SARS-CoV in the 2002–2003 outbreak (Guan et al. 2003). However, considering that these individuals have a high chance of direct exposure to bat secretion in their villages, this study further supports the notion that some bat SARSr-CoVs are able to directly infect humans without intermediate hosts, as suggested by receptor entry and animal infection studies (Menachery et al. 2016).”

Italy 2019

Lecis et al. (2019)

“The detected virus (SarBatCoV1) belonged to clade 2b, including most of the SARS-like CoVs found in bats, as well as human SARS Coronavirus”

Questions

• Are intermediate hosts really necessary?
• If the same clade of viral sequences are found worldwide why do they only pass to humans in China?
• If most previous SARS related infections in humans cause “omicron” like symptoms, would we ever have noticed?
• How solid is the evidence used to produce the spillover diagrams?
• Chinese whispers in an echo chamber?

Suggestions for future research

• Accept that SARS one and two are essentially the same phenomena (viral species)
• Look at all the literature from 2002 onwards
• Study the pathogenesis of SARS related viruses in humans using past case records.
• Keep an open mind and restrain from being influenced by any consensual narrative.

Postscript

• Respiratory illnesses are always common.
• Throughout the years prior to SARS age adjusted mortality was much higher than in 2020
• Severe Acute Respiratory Syndrome associated deaths could have gone unnoticed unless clustered.
• Around 200 per 100 thousand age adjusted deaths per year are recorded as respiratory.
• Approximately one fifth of all adults aged between 75 and 79 years in England are living with a diagnosed respiratory disease.

Age adjusted all cause mortality

(Office for National Statistics 2022)

Deaths from pneumonia England and Wales

• Deaths from pneumonia were around three times more common in 2003 than 2019.

Statista web site (2021)