Sunday, September 27, 2020

Revisiting the COVID-19 outbreak on the Charles de Gaulle aircraft carrier

Some solid facts about COVID-19 epidemiology.

Recently stumbled upon a report by the "Centre d’épidémiologie et de santé publique des armées" about this outbreak - "Document n°929/ARM/SSA/CESPA du 4 mai 2020" - report in French

Back when it was an ongoing story in the headlines, news reports read like "many infected, most without any symptoms, no dead". Time to look at it again.

Short summary

Out of 1767 people on board, at least 1064 were confirmed as infected (60%) and 29 developed serious disease requiring oxygen.

Of those 1568 participated in a subsequent phone survey (study population), age range 18-60, median age 29 years. 1001 of the study population were confirmed PCR positive, 546 negative and 21 results were unknown.

Out of those merely 13% were asymptomatic. 8.1% reported atypical symptoms (neither loss of smell or taste, no fever nor cough), 78.9% reported typical symptoms, see bellow.

26 of the confirmed cases became seriously ill requiring oxygen - that is 2.4% of the total infected or 1.5% of the total population of a cohort with a median age of 29 years and presumably way above average fitness. Further 3 cases required oxygen but their PCR test was negative or not available at the time the report was written.

The symptoms considered "typical" were: loss of smell 57%, headaches 56,7%, loss of taste 46,4%, weakness 46,3%, muscle pain (myalgia) 45,2%, fever 44,8%.

Those seriously ill reported different prevalence of symptoms: fever 90%, muscle pain 90%, cough 86%, headaches 76%, dyspnoe 72%, weakness 66%.

In univariate analysis those aged 36-46 had a 6fold risk to develop serious disease, those 46-60 14.5 fold. Obesity (defined as BMI>25) carried an approximately 3.5 fold risk.

According to the authors loss of smell and/or taste as symptom had a sensitivity of 67% and a specificity of 80%

Comment and secondary analysis

This numbers leave very little room to speculations that there might be a high percentage of asymptomatic cases and only a very small fraction of those infected become seriously ill. Also this leaves very little room to speculations that some substantial share of the population might be magically immune to COVID-19.
We can safely assume that a little more than just the confirmed 1064 were infected: the PCR tests used had a sensitivity of around 96% under optimal circumstances back than, in reality the testing started a little late so many infections might have cleared before testing for COVID-19 was done. The specificity of the PCR teste otoh was well over 99% even back then so the number of false positives should have been 18 or less.

To illustrate the disaster which an uncontrolled spread could cause in a western society consider this numbers: in the 36-45 age group 5.2% of the infected or 3.4% of the total population would require oxygen. In the 46-60 age group this would be 11.6% resp. 8.7%. Even in the less affected 18-25 and 26-35 age groups still around 1% of all infected require oxygen. Those numbers are certainly extremely optimistic - comparing the top fit sailors with the same age group of the general population, assuming that the epidemy would stop after infecteing 60% of the population and not even considering those over 60.

Did something change since the outbreak? I think there is some progress reducing mortality, however this is at the cost of treating patients earlier with oxygen which would cause even higher demands on the health system to provide optimal treatment.

Saturday, May 23, 2020

Another look a Taiwan, some discomforting numbers

Taiwan was very successful at containing spread of COVID-19. As of May 17th, out of accumulated 440 cases, 349 are imported and 55 are local spread, 36 are naval crew. Airport health checks were imposed as early as December 31th 2019, further restrictions and quarantine for all arrivals from all countries followed soon after that. The early reaction clearly paid off, local spread was minimized and the most "drastic" measure that had to be imposed so far was prolonging school holidays by 2 weeks in February.

Till May 11th there were 7 dead, 4 of those from imported cases. Counting only the imported cases we have exact knowledge of the number of infections and can estimate an IFR mortality of 1.2%  (assuming that the quarantine measures were mostly effective at detecting infection cases) . This is a surprisingly high mortality given that most of the dead were in their 40ies to 60ies and obviously fit to travel long distance flights. Even worse, a large share of the imported cases were people working abroad in their 20s-30s

Press releases from the Taiwan CDC : https://www.cdc.gov.tw/En/Bulletin/List/7tUXjTBf6paRvrhEl-mrPg?page=1

One particularly strange case of protracted course is https://www.cdc.gov.tw/En/Bulletin/Detail/luxJ7okGbOKlEDqtYUgysA?typeid=158


Bellow some details about the deaths:

16.2 : https://focustaiwan.tw/society/202002160012
first dead: a 61-year-old male, had Hepatitis B and diabetes, had not traveled overseas recently and no known contact with COVID-19 patients, was a taxi driver who had many customers that regularly travel to and from China, Hong Kong and Macau.

20.3: https://focustaiwan.tw/society/202003200017
second death: man in his 80s, who had no recent history of overseas travel, diabetes and was on kidney dialysis.

30.3 : https://focustaiwan.tw/society/202003300004
third death: a patient in his 40s, was confirmed on March 19 to have contracted the coronavirus after he led a group tour to Austria and the Czech Republic March 5-14. Was not listed as in critical condition before his death.

30.3 : https://focustaiwan.tw/society/202003300014 , https://www.taiwannews.com.tw/en/news/3907086
two  deaths : a woman in her 50s (infected locally in hospital cluster), and a man in his 60s with a history of recent travel to Spain

The male patient visited Spain with a tour group March 12-20 and tested positive for the coronavirus on March 23 after he returned to Taiwan with a cough and fever.

10.4 : https://focustaiwan.tw/society/202004100008

one death: a patient in his 70s. The man, who suffered from underlying conditions, was part of a tour group that visited Egypt from March 3-12. He started displaying symptoms on March 17 and was confirmed positive on March 19. The man's condition started to deteriorate on March 20 when he suffered breathing difficulties and was transferred to the intensive care unit, passed away April 9.

11.5. : https://focustaiwan.tw/society/202005110012 https://www.cdc.gov.tw/En/Bulletin/Detail/GBNcOUGOrevC4GT_-pzLrg?typeid=158
one death: a man in his 40s, had been in the United States to visit family, and after he returned to Taiwan he developed symptoms typical of the disease on March 19. He then went to see a doctor on March 21 and tested positive for COVID-19 on March 24. The patient did not have a history of chronic illnesses.


The Spanish COVID-19 prevalence study

Estudio de prevalencia coronavirus - preliminary results

Antibody testing (IgM + IgG) carried out between Apr 27th to May 5th, 60,983 participants with valid test results on mainland Spain and further 3,234 participants on the islands. Two tests were performed, one "quick" immunochromatographic assay and an antibody immunoassay. The authors report problems with the IgM testing, hence the preliminary report is mostly based on the IgG results.

https://www.mscbs.gob.es/ciudadanos/ene-covid/home.htm
https://www.mscbs.gob.es/ciudadanos/ene-covid/docs/ESTUDIO_ENE-COVID19_PRIMERA_RONDA_INFORME_PRELIMINAR.pdf
https://portalcne.isciii.es/enecovid19/indexev.html
https://portalcne.isciii.es/enecovid19/documentos/ene_covid19_sum_pre_rep.pdf

Total prevalence of SARS-Cov2 antibodies was estimated to be 5% of the population. In Spain, approximately 90% of COVID-19 infections went undetected by the health system (not a stellar performance, given that only 33.7% were found to be asymptomatic). The data shows a great geographical variation of prevalence from 1-2% for the least affected places up to almost 15% for the most affected places. No big differences by age or sex were detected - only young children had a markedly lower IgG prevalence. The reason for this is not known, might be less social contacts or biological reasons such different immune system response.

In the general population the most specific (but rare) symptom indicating a COVID-19 infection was anosmia: 3.07% of participants reported anosmia, of those 43.3% had antibodies. The other symptoms were more prevalent in the population but much less specific - having a combination of 5 or more other symptoms was correlated with 14.7% of positive cases. Apparently approximately 33.7% of cases were without any symptoms.

Analysis by Jesús Molina Cabrillana, epidemiologist of the Spanish Preventive Medicine Society (Sociedad Española de Medicina Preventiva) estimates the IFR mortality based on this study and other results to be 1-1.3%  - a preliminary estimate given that the excess mortality in Spain indicates COVID-19 might have had a much higher death toll than known.

https://elpais.com/sociedad/2020-05-13/solo-un-5-de-los-espanoles-se-han-contagiado-de-coronavirus-segun-los-primeros-datos-del-estudio-de-prevalencia.html
https://english.elpais.com/society/2020-05-14/antibody-study-shows-just-5-of-spaniards-have-contracted-the-coronavirus.html

https://www.dw.com/en/covid-19-death-rate-sinking-data-reveals-a-complex-reality/a-53365771

Strong points:
* large size of the sample, allowing meaningful statistical analysis of "positive" cases

Comment:
even severely hit Spain is far away from anything like a herd immunity (if that exists). The health system in some parts of Spain was heavily overloaded so the numbers of hospitalizations are not meaningful and the number of deaths uncertain. Despite those problems this prevalence study offers interesting data regarding symptoms, prevalence of antibodies after PCR tests and mortality.

Stay tuned for the final results of this study.

The Austrian COVID-19 prevalence studies

Austria did two representative COVID-19 prevalence studies that so far gained little international attention despite their unique strong points.

The first was the SORA study, carried out on behalf of the Austrian ministry of science by the SORA Institute with the intention to investigate the number of unrecognized cases slipping through official surveillance, testing and contact tracking

https://www.sora.at/nc/news-presse/news/news-einzelansicht/news/covid-19-praevalenz-1006.html

English Summary: https://www.sora.at/fileadmin/downloads/projekte/Austria_Spread_of_SARS-CoV-2_Study_Report.pdf

 In the SORA study 1544 PCR tests (cobas SARS-CoV-2) were carried out in a representative sample of the Austrian population in the period April 1-6 with 6 "positive" results. The authors concluded that 0.33% (or 28500 individuals) of the Austrian population was COVID-19 positive by that time - with a fairly wide 95% CI of 0.12-0.77% .

Compared to that on April 5th the "official" number of "active" cases was 8849 (JHU CSSE https://github.com/CSSEGISandData/COVID-19/ ) so it appears the "real" number of cases was approximately 3 fold of the "known" cases.

The authors did not attempt to calculate the mortality from this data but a very adhoc calculation shows that the IFR (mortality) could be somewhere around 1%. 

The strengths of this study:

* prevalence was tested using "gold standard" PCR test

* it was carried out near (probably shortly after) the first (and hopefully last) peak of the pandemics in Austria when PCR tests allow good estimate of prevalence

* relatively homogeneous population in a small country, meaning fairly representative results.

Conclusion: the study shows that only a very small part of Austrian population (probably in the order of 0.44%) was ever infected with the SARS-CoV-2 virus until April 2020.


The second was performed by "Statistik Austria" between April 21th to 24th. 

This time not only representative PCR testing was done, but a special focus was put on several known hotspots where SARS-CoV-2-Antibody tests were performed.

https://www.statistik.at/web_de/frageboegen/private_haushalte/covid19/index.html
http://www.statistik.at/web_de/presse/123051.html

 The results in summary:

* in the time of April 21th to 24th less than 0.15% of Austrian residents were acutely infected with SARS-CoV-2, iow less than 10823 individuals.

* higher prevalence of active infections of up to 0.75% was found in known hotspots

* in the 27 most severely affected places approximately 4.71% of the population tested positive for SARS-CoV-2antibodies


Comment:

The results of the second study seem the confirm the data from the first study. Overall Austria is very far away from achieving "herd immunity" (if it exists).

Mortality (IFR) judged by the data from Austria seems to be around 1%.

For every known case there were at least 2 undetected cases which may seem like a huge problem for epidemic control. Despite that Austria is currently very successful at limiting the epidemic.

The Czech COVID-19 prevalence studies

SARS-CoV-2-CZ-Preval

Czech republic closed down its borders early and was fairly successful limiting the COVID-19 pandemic. While demographic and risk factors (over 50K skiing vacations in Italy and Austria) were comparable to neighboring Bavaria and Austria the per million the death count is only about half that of Austria and almost 8 times lower than in Bavaria, not to mention Belgium, Sweden or Italy.

The first results of the Czech COVID-19 prevalence testing results were published on May 6th. Out of 27,011 tests 26549 passed the quality control and were evaluated. 8 cohorts were tested, 2 fully randomized representative of the general population, 1 representative of chronically ill patients and 5 for the known hotspot regions of the Czech republic which were non-representative.

The study was carried  out on behalf of the Czech ministry of health by multiple institutions under coordination of the  "Institute of Health Information and Statistics of the Czech Republic" : https://www.uzis.cz/index.php?pg=aktuality&aid=8398

Overal 107 tested positive for antibodies (IgM & IgG) out of 26549. From the representative cohorts an overall prevalence (past and acute cases) in the general population of 90.5/100,000 inhabitants was calculated for the day of 16. April 2020. This is approximately 2.25 times  of the known cases to that date - meaning that regular symptom based testing and contact tracing have detected approximately 44.5% of total cases.

Southern Moravia had the least cases with 38/100,000 while the known hotspot Litovel had 786/100,000 cases.

Out of the 107 cases detected 51% reported no noticeable symptoms, the other 49% have (retrospectively) reported this symptoms(multiple possible):
* cough: 65%
* temp >37.5: 54%
* pain in the throat: 40%
* loss of smell or taste:  35% ( https://smelltracker.org/ )
* breathing difficulties: 21%
* other - 42%

Summary: only a very small part of the Czech population (probably in the order of 0.1%) was ever infected by SARS-CoV-2. The elderly were advised to protect themselves and test results suggest that this worked - at least outside of institutional care..

Comment: Testing and contact tracing was successful at detecting cases - only about half of the total cases went undetected which seems comparable or only moderately worse than in "best performers" like Taiwan or South Korea.

The prevalence was much lower than anticipated by the authors of the study resulting in statistically somewhat underpowered data, especially the size of the fully randomized sample.

Mortality (IFR) calculated from that data seems to be around 2% which appears rather high.

Strong points:

* large sample

* (fairly) homogenous population without no-go areas

* good validation

More reading:

https://www.radio.cz/en/section/curraffrs/czech-study-shows-extremely-low-level-of-collective-immunity-to-covid-19-virus

https://en.m.wikipedia.org/wiki/COVID-19_pandemic_in_the_Czech_Republic