Collection of Covid-19 links and research

All-cause mortality in Europe

- https://www.euromomo.eu/

Earliest detections of SARS-CoV-2 outside of Wuhan (all in 2019)

- 12 March 2019 (!) in Barcelona, Spain:

 https://www.medrxiv.org/content/10.1101/2020.06.13.20129627v1.full.pdf

"Most COVID-19 cases show mild influenza-like symptoms and it has been suggested that some uncharacterized influenza cases may have masked COVID-19 cases in the
2019-2020 season. This possibility prompted us to analyze some archival WWTP samples from January 2018 to December 2019 (Figure 2). All samples came out to be negative for the presence of SARS-CoV-2 genomes with the exception of March 12, 2019, in which both IP2 and IP4 target assays were positive. This striking finding indicates circulation of the virus in Barcelona long before the report of any COVID-19 case worldwide. Barcelona is a business and commerce hub, as well as a popular venue for massive events, gathering visitors from many parts of the world. It is nevertheless likely that similar situations may have occurred in several other parts
of the world, with circulation of unnoticed COVID-19 cases in the community."

- 27 November 2019 in Santa Catarina, Brazil: 

https://www.medrxiv.org/content/10.1101/2020.06.26.20140731v1

"Our results show that SARS-CoV-2 has been circulating in Brazil since late November 2019, much earlier than the first reported case in the Americas (21st January 2020, USA)"

- 18 December 2019 in Turin and Milan, Italy:

https://www.iss.it/comunicati-stampa1/-/asset_publisher/Cz8X9Kas2PGp/content/id/5422725

"I risultati, confermati nei due diversi laboratori con due differenti metodiche, hanno evidenziato presenza di RNA di SARS-Cov-2 nei campioni prelevati a Milano e Torino il 18/12/2019"

- 27 December 2019 in Paris, France:

 https://www.sciencedirect.com/science/article/pii/S0924857920301643

"SARS-CoV-2 was already spreading in France in late December 2019, 1 month before the first official cases in the country."

Retrospective CoVid-19 cases (why CoVid-19 can be confused not only with flu/pneumonia but also with heart attacks and strokes)

- https://edition.cnn.com/2020/04/22/us/california-deaths-earliest-in-us/index.html

- https://edition.cnn.com/2020/04/23/us/california-woman-first-coronavirus-death/index.html

- https://www.mercurynews.com/2020/04/25/coronavirus-first-known-victim-in-u-s-died-of-burst-heart-pathologist-says/

Serology and IFR (Infection Fatality Rate)

- https://www.medrxiv.org/content/10.1101/2020.05.03.20089854v4

"Systematically reviewing the literature and meta-analyzing the results shows an IFR of 0.68% (0.5 3-0.82%)"

- https://www.medrxiv.org/content/10.1101/2020.05.13.20101253v3.full.pdf

"Seroprevalence estimates ranged from 0.222% to 47%. Infection fatality rates ranged from 0.00% to 1.63% and corrected values ranged from 0.00% to 1.31%. Across 32 different
locations, the median infection fatality rate was 0.27% (corrected 0.24%). Most studies were done in pandemic epicenters with high death tolls. Median corrected IFR was 0.10% in locations with COVID-19 population mortality rate less than the global average (<73 deaths per million as of July 12, 2020), 0.27% in locations with 73-500 COVID-19 deaths per million, and 0.90% in locations exceeding 500 COVID-19 deaths per million. Among people <70 years old, infection fatality rates ranged from 0.00% to 0.57% with median of 0.05% across the different locations (corrected median of 0.04%). The infection fatality rate of COVID-19 can vary substantially across different locations and this may reflect differences in population age structure and case-mix of infected and deceased patients as well as multiple other factors. Estimates of infection fatality rates inferred from seroprevalence studies tend to be much lower than original speculations made in the early days of the pandemic."

- https://www.medrxiv.org/content/10.1101/2020.05.11.20098442v2

"At the outbreak start, the overall adjusted seroprevalence of SARS-CoV-2 was 2.7%, 95% c.i. 0.3-6% (P<0.0001 vs. 120 historical controls). During the study period characterized by a gradual implementation of social distancing measures, there was a progressive increase in adjusted seroprevalence to 5.2%, 95% c.i. 2.4-9.0"

"Conclusions: SARS-CoV-2 infection was already circulating in Milan at the outbreak start. Social distancing may have been more effective in younger individuals, and by the end of April 2.4-9.0% of healthy adults had evidence of seroconversion."

Prevalence and seriousness of Influenza-Like-Ilnesses, including extra-pulmonary complications and effects on younger patients

- https://www.sciencedirect.com/science/article/pii/S1201971219303285

"• In the winter seasons from 2013/14 to 2016/17, an estimated average of 5,290,000 ILI cases occurred in Italy, corresponding to an incidence of 9%.
• More than 68,000 deaths attributable to flu epidemics were estimated in the study period.
• Italy showed a higher influenza attributable excess mortality compared to other European countries, especially in the elderly."

- https://journals.sagepub.com/doi/10.1177/1403494816649833

"The Italian National Institute of Statistics released mortality data for 2015 in February 2016. These data reported a 9.1%  excess mortality compared with 2014, corresponding to 54,000 excess deaths, the highest reported mortality rate (10.7 per 1000 population) since the Second World War."

"These data are in line with patterns elsewhere in Europe. In March 2015, data from 14 European countries showed that the 2014–2015 winter season excess mortality among people aged >65 years was significantly higher than in the four previous winter seasons. These data were poorly covered in the media."

- https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/articles/highestnumberofexcesswinterdeathssince19992000/2015-11-25

"Very high levels of flu were seen in 1999/00, when there were 48,000 excess winter deaths

Winter 2009/10 was exceptionally cold and yet had an average number of excess winter deaths at 26,000

Excess winter deaths spike in 2014/15 at 44,000"

- https://www.rivm.nl/en/news/flu-season-in-winter-of-2014-2015-more-severe-and-longer-than-preceding-years

"The flu epidemic in the winter of 2014 / 2015 lasted 21 weeks and as such was the longest epidemic ever recorded in the Netherlands. Nearly two million people suffered from flu-like symptoms. About 10,000 people were hospitalised for complications from flu, such as pneumonia. During the flu epidemic period, more than 65,000 persons died in the Netherlands; this is approximately 8,600 persons more than the expected number of deaths in this 21-week period. "

- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596521/

"Although influenza is primarily considered a viral infection that results in pathology limited to the respiratory system, clinical reports suggest that influenza infection is frequently associated with a number of clinical syndromes that involve organ systems outside the respiratory tract. A comprehensive MEDLINE literature review of articles pertaining to extra-pulmonary complications of influenza infection, using organ-specific search terms, yielded 218 articles including case reports, epidemiologic investigations, and autopsy studies that were reviewed to determine the clinical involvement of other organs. The most frequently described clinical entities were viral myocarditis and viral encephalitis."

"There have been approximately 44 cases of influenza-associated myocarditis in adult patients described in case reports and case series (Table 2).(..)
Among those reported, 52% (23/44) occurred in men and 68% (30/44) occurred in patients under 40 years of age."

T-Cell and cross-immunity with other coronaviruses, including the common cold

- https://www.nature.com/articles/s41577-020-0389-z

"In conclusion, it is now established that SARS-CoV-2 pre-existing immune reactivity exists to some degree in the general population. It is hypothesized, but not yet proven, that this might be due to immunity to CCCs. This might have implications for COVID-19 disease severity, herd immunity and vaccine development, which still await to be addressed with actual data"

- https://www.cell.com/cell/fulltext/S0092-8674(20)30610-3

"• Epitope pools detect CD4+ and CD8+ T cells in 100% and 70% of convalescent COVID patients
• T-cell reactivity to SARS-CoV-2 epitopes is also detected in non-exposed individuals"

- https://www.sciencedirect.com/science/article/pii/S0092867420310084

- https://science.sciencemag.org/content/early/2020/08/04/science.abd3871

- https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(20)30260-7/fulltext

- https://www.nature.com/articles/s41586-020-2550-z

Measures to mitigate/control pandemics

- https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.556.2672&rep=rep1&type=pdf (by D. A. Henderson, the eradicator of smallpox, et al )

"There are no historical observations or scientific studies that support the confinement by quarantine of groups of possibly infected people for extended periods in order to slow the spread of influenza. A World Health Organization (WHO) Writing Group, after reviewing the literature and considering contemporary international experience, concluded that “forced isolation and quarantine are ineffective and impractical.” Despite this recommendation by experts, mandatory large-scale quarantine continues to be considered as an option by some authorities and government officials.

The interest in quarantine reflects the views and conditions prevalent more than 50 years ago, when much less was known about the epidemiology of infectious diseases and when there was far less international and domestic travel in a less densely populated world. It is difficult to identify circumstances in the past half-century when large-scale quarantine has been effectively used in the control of any disease. The negative consequences of large-scale quarantine are so extreme (forced confinement of sick people with the well; complete restriction of movement of large populations; difficulty in getting critical supplies, medicines, and food to people inside the quarantine zone) that this mitigation measure should be eliminated from serious consideration."

"Travel restrictions, such as closing airports and screening travelers at borders, have historically been ineffective. The World Health Organization Writing Group concluded that “screening and quarantining entering travelers at international borders did not substantially delay virus introduction in past pandemics . . . and will likely be even less effective in the modern era."

"It is reasonable to assume that the economic costs of shutting down air or train travel would be very high, and the societal costs involved in interrupting all air or train travel would be extreme."