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Estimating the True Case-Fatality Rate of COVID-19

For several months, we have been inundated by reports summarizing incidence and mortality data for COVID-19, on both the national and global level. In a previous ProMED post I cautioned that “reported cases” cannot be equated with “total cases” without inclusion of individuals with asymptomatic of sub-clinical infection that do not seek medical care. [1] If a large segment of the population is found to be seropositive, we might conclude that the true case-fatality ratio of COVID-19 is lower than official data might suggest. A seroprevalence study reported this week seems to provide solid evidence that this is the case. [2]

A national survey of individuals identified IgG antibody toward SARS-CoV-2 in 5.0% of the general population of Spain. At the stated specificity of 100% and sensitivity of 98%, the true seropositivity may be estimated at 5.15%. Although factors which determine seroprevalence rates in Spain need not apply to other countries, the following chart extrapolates the potential impact of a 5.15% population seroprevalence on case-fatality data from high-incidence countries in the European Region, United States and China. [3]

The impact of future SARS-CoV-2 seroprevalence surveys will largely depend in the quality of the test itself, the duration of immunity and protective role of the antibody, possible emergence of newer strains of coronavirus, and other factors. In any event, additional seroprevalence data will play a key role in planning our response to this pandemic going forward.

COVID-19 Reported vs. Estimated cases

Country Reported cases % of population Reported Deaths CFR (%)* Estimated cases** Estimated CFR (%)***
Belgium 55,280 0.48% 9,052 16.4 596,548 1.52
China 82,947 0.0058% 4,634 5.6 74,125,174 0.0063
France 179,569 0.28% 28,108 15.7 3,360,686 1.14
Germany 176,651 0.21% 8,049 4.6 4,313,197 0.19
Israel 16,617 0.19% 272 1.6 444,866 0.061
Italy 225,435 0.37% 31,908 14.1 3,114,329 1.02
Spain 277,719 0.59% 27,650 10 2,407,759 1.14
U.K. 243,695 0.35% 34,636 14.3 3,493,878 0.99
U.S.A 1,527,664 0.46% 90,978 6 17,034,349 0.53

* CFR = deaths / cases X 100
** True number of cases based on population seroprevalence of 5.15%
*** Adjusted CFR = deaths / estimated true cases X 100

References

  1. ProMED – What’s the denominator 20200228.7035438
  2. ProMED – Spain: seroprevalence study 20200516.7342334
  3. https://www.worldometers.info/coronavirus/ (status as of May 17)

…But There Are No Cases in Turkmenistan

written by Dr. Stephen A. Berger

If you search the Internet for countries which have reported COVID-19, an endless variety of sources will describe the status of this disease in 207 countries and their dependencies. Few if any of these sites mention countries where this disease does not exist!

As of April 19, GIDEON lists twenty-four countries (10.4% of the global total) that had not yet encountered a single case. Ironically, at this point, these countries enjoy a form of “medical isolation” – thanks to the disease itself! The chance that a traveler – let alone an infected traveler – can arrive in a new country is vanishingly-small because the idea of international travel has been erased by COVID-19.

In most cases, countries that are not reporting COVID-19 cases have instituted travel restrictions, surveillance and preventive measures (masks, social distancing, etc). Several Pacific Island Nations listed below are geographically isolated, lack sufficient medical resources, and enforce similar forms of restriction and enforcement.

The approach of two European countries – Tajikistan and Turkmenistan – is notably different. Although Tajikistan enforces restricted travel and quarantine for arriving travelers, large public gatherings and sporting events are not restricted. Face masks, though not required, are commonly seen in the streets. In contrast, a report by Reporters Without Borders stated that Turkmenistan had banned the use of the word “coronavirus” and that people wearing masks could be arrested. Nonetheless, Turkmenistan does ascribe an absence of COVID-19 cases to strict enforcement of travel restrictions and announced in early April that all citizens will be tested for the virus.

A seeming absence of COVID-19 in North Korea has led to considerable speculation and even conspiracy theories. The fact that this country shares a border with China would suggest that infected individuals are likely to have entered the country; however, North Korea did impose closure of the border at an early stage of the Chinese outbreak, and imposes strict control, surveillance, and quarantine over potential cases.

Countries Which Have Not Reported COVID-19 (as of April 19)

  – Travel bans enforced including restrictions on incoming aircraft

  – Has physically refused entry to approaching cruise ships

    – State of Emergency declared

    – No additional information available

American Samoa

Christmas Island

Cook Islands

Kiribati

Lesotho

Marshall Islands

Micronesia

Nauru

Niue

Norfolk Island

North Korea

Palau

Pitcairn Island

Saint Helena

Samoa

Solomon Islands

Tajikistan

Tokelau

Tonga

Turkmenistan

Tuvalu  

Vanuatu

Wallis and Futuna Islands

Wake Island

 

Update: Posted in ProMED

COVID-19: What is the Denominator

Since the 1st cases of infection by SARS-CoV-2 were reported in China, we have all been confronted by death and case-fatality statistics, which are both misleading and inaccurate. As of this morning, 2837 from a total of 83 774 reported cases of COVID-19 were fatal. Public Health professionals, the lay public, and politicians will conclude that this disease carries a “mortality rate” of 3.4%. Relatively few realize that “only” 1.4% of patients treated outside of Mainland China have died of COVID-19: 0.7% of passengers on the Diamond Princess cruise ship, 0.5% of patients in South Korea, etc.

One explanation for these discrepant case-fatality statistics is related to demography. Patients reported by official sources have a higher mean age and prevalence of underlying chronic disease than the general Chinese population (or international travelers). Case-definition, variation in quality of care, genetic and nutritional factors might also explain higher fatality rates among Chinese patients. Indeed, several of the patients who died of COVID-19 outside of Mainland China have also been Chinese Nationals.

A fundamental error in all of this could be related to the term, “reported cases.” How many infections in China are asymptomatic or sub-clinical? If, for example, only one-in-10 individuals who acquire infection by SARS-CoV-2 are sufficiently ill to visit a clinic or hospital, the true case-fatality rate decreases from 3.4% to 0.34% A seroprevalence survey in the general population could easily determine the true impact of this disease.

This week, details of an antibody assay for SARS-CoV-2 infection were reported in Journal of Medical Virology. [1] The authors state that the procedure detects both IgM and IgG antibodies within 15 minutes, with a test sensitivity and specificity of 88.86% and 90.63%, respectively.

Beyond the search for vaccines and effective anti-viral agents, an immediate remedy for much of the uncertainty regarding COVID-19 will be a comprehensive serological survey of populations in affected areas. Tested individuals should be questioned regarding recent travel, occupational contact, and relevant symptoms which may have occurred during the preceding 2 months.

If a high background sero-prevalence rate exists among people in Wuhan (or China as a whole) COVID-19 becomes little more threatening than other “new strains of flu” that we deal with each year.

References:
1. Li S, Yi Y, Lou X, et al. 2020. Development and Clinical Application of a Rapid IgM‐IgG Combined Antibody Test for SARS‐CoV‐2 Infection Diagnosis. J Med Virol (ahead of print) PMID: 32104917 DOI: 10.1002/jmv.25727.

 

Note featured on ProMED

Cryptosporidiosis in Sweden

The incidence of cryptosporidiosis in Scandinavia has increased dramatically in recent years.  As shown in the following chart, rates in Sweden per 100,000 population are approximately twice those reported in the United States – and almost four-fold those reported in the European Region as a whole.  [1-3]

References:

  1. Gideon e-Gideon multi-graph tool,   https://www.gideononline.com/cases/multi-graphs/
  2. Berger S. Infectious Diseases of Sweden, 2019. 416 pages , 143 graphs , 1,146 references. Gideon e-books,  https://www.gideononline.com/ebooks/country/infectious-diseases-of-sweden/
  3. Berger S. Cryptosporidiosis: Global Status, 2019.  147 pages , 53 graphs , 2,041 references.  https://www.gideononline.com/ebooks/disease/cryptosporidiosis-global-status/

Note featured on ProMED

 

 

Viral Agents of Childhood Respiratory Tract Infection in the United States

As of October, 2019 Gideon www.GideonOnline.com and the Gideon e-book series contain details of 69,204 epidemiological surveys – of which 1,107 (1.6%) are related to the prevalence of specific viral species in patients with respiratory tract infection.  [1-3]

The following chronology of published studies summarizes the relative proportion of viral agents associated with non-influenza childhood respiratory infection in the United States.  Additional details and primary references are available on request.

1976 – 2001 Tennessee
hMPV accounted for 20% of acute respiratory illness among children ages 0 to 5 years having no other identifiable etiology. 78% of infections in this group occurred during the months December to April.

1977 – 2001 Tennessee
Coronaviruses were found in 5.0% of nasal wash specimens from children below age 5 years with URI or LRI – 9% of these 229 E, 59% OC43 and 33% NL63

1982 – 2001 Tennessee – Nashville
hMPV accounted for 5% of upper respiratory tract infections among children, when other viruses are not identified

2000 – 2001 New York
hMPV was found in 3.9% of children ages 0 to 5 years, hospitalized for respiratory
illness

2001 – 2002 Ohio
HcoV-HKU1 was found in 1% of children below age 5 years with suspected viral infection in whom other viruses were not found

2001 – 2003 Multiple locations
Coronaviruses were found in 2.2% of children below age 2 years hospitalized for acute respiratory symptoms or fever

2001 – 2003 Multiple locations
hMPV was found in 3.8% of children below age <5 years old hospitalized with acute respiratory infection (rate 120 per 100,000 per year)

2001 – 2002 Connecticut
hMPV accounted for 6.4% of lower respiratory tract infections in children below the age of 5 years

2003 – 2004 Multiple locations
Rhinoviruses were found in 8.1% of children below age 5 years hospitalized with acute respiratory infection vs. 2.2% of a control group

2003 – 2009 Multiple locations
hMPV accounted for 6% of acute respiratory illness or fever among inpatient and outpatient children less than 5 years of age in three counties

2003 Washington – Seattle
hMPV was found in 11% of children with bronchiolitis, Coronavirus 8%, RSV 77%, Adenovirus 15%, Parainfluenza virus 6%

2003 – 2004 Missouri – St. Louis
WU polyomavirus (WUPyV) was found in 2.7% of children with respiratory infection

2004 Connecticut
Rhinoviruses were found in 26.3% of children below age 2 years with wheezing and 3% of asymptomatic children

2004 Connecticut
HBoV was present in 5.2% of respiratory specimens submitted from children below age 2 years, and negative for other detectable viruses

2004 – 2005 Colorado
Coronaviruses were found in 5% samples from children with respiratory infections which were negative for common viral etiologies

2004 New York
HBoV was found in 5.5% of tonsil samples from children undergoing elective tonsillectomy/adenoidectomy

2005 – 2006 Multiple locations
hMPV was found in 9% of children below age 2 years with acute bronchiolitis, and Rhinoviruses in 16%

2005 – 2007 Alaska
Rhinoviruses were found in 44% of Alaskan children below age 3 years hospitalized with respiratory infection, Adenovirus 30%, RSV 23%, Parainfluenza virus 18%, hMPV 15% and Coronavirus 6%

2005* Connecticut – New Haven
New Haven Coronavirus infection was identified in 8.8% of children below age 5 with respiratory disease

2006* California
Human Bocavirus (HBoV) was present in 5.6% of children with lower respiratory tract infection

2007 – 2011 na
Non-influenza respiratory viruses accounted for 41% of unexplained respiratory disease outbreaks investigated by CDC

2007 – 2010 Multiple locations
RSV was found in 51% of hospitalized children age <2 years with bronchiolitis, and Rhinovirus in 21%

2007 – 2008 Washington
HBoV was found in 2% of children ages 2 to 11 years with respiratory illness, and 3% of asymptomatic controls

2008* na
WU polyomavirus was found in 7.1% of symptomatic children and 6.3% of asymptomatic children

2008* na
KI polyomavirus (KIPyV) in 2.2% of symptomatic children and 0% of asymptomatic children

2008* California – San Diego
HBoV was found in 5.6% and hMPV in 5.2% of children presenting to an Emergency Department

2009 Missouri
Human parechovirus (HPeV) was found in respiratory specimens from 3% of children

2009 – 2013 Colorado
Viruses were identified in the nasopharynx of 41.9% of children hospitalized for Kawasaki disease

2010* Washington
HBoV was found in 59% of children attending daycare

2010 – 2011 Tennessee – Memphis
Rhinoviruses were found in 62% to 65% of children with cancer and respiratory tract infection

2011* na
Rhinovirus was the most commonly-detected virus (23.1% of viruses) in children ages 6 to 18 with cystic fibrosis

2012* na
Viruses were identified during 52% of febrile episodes among neutropenic children without bacterial infection

2012* Multiple locations
RSV and / or Human Rhinovirus was found in 84.5% of children below age 2 years hospitalized with severe bronchiolitis

2012* Multiple locations
hMPV was found in 9.0% of high-risk children with severe lower respiratory tract infection, and RSV in 45%

2012 – 2013 Georgia
RSV infection was identified in 6.4% of children admitted to Intensive Care, and respiratory Picornaviruses in 22.6%

2013* Tennessee
Rhinovirus was identified in 62% of children with sickle cell disease and acute respiratory illness

2015* Washington, DC
hMPV was found in 11% of children ages <=5 years with viral respiratory infection

2015* Multiple locations
Viruses were identified in 66% of children hospitalized for community-acquired pneumonia

2017* na
Human bocavirus DNA was identified in 10.4% of children with community-acquired pneumonia

*     Year of publication

na   Location of study not available

 

References:

  1. Berger SA. Gideon Guide to Surveys. 2019. 4,441 pages, 10,603 tables, 59,327 references. Gideon e-books, https://www.gideononline.com/ebooks/surveys/
  2. Berger SA. Miscellaneous Respiratory Viruses: Global Status, 2019. 94 pages, 1,395 references. Gideon e-books, https://www.gideononline.com/ebooks/disease/miscellaneous-respiratory-viruses-global-status/
  3. Berger SA. Infectious Diseases of the United States, 2019. 1,422 pages, 513 graphs, 18,048 references. Gideon e-books, https://www.gideononline.com/ebooks/country/infectious-diseases-of-the-united-states/

Coccidioidomycosis in the United States

Although largely limited to the western and southwestern states, Coccidioidomycosis is more commonly reported than legionellosis. More Americans die from Coccidioidomycosis than from the other two regional mycoses, Blastomycosis and Histoplasmosis. [1,2]

 

While Coccidioidomycosis is best known as a disease of California (“Valley Fever”) , highest incidence is reported from Arizona.  These data are even more striking when adjusted for relative population size (cases per 100,000 population).

 

References:

  1. Berger S. Infectious Diseases of the United States, 2019. 1,422 pages , 513 graphs , 18,048 references.  Gideon e-books,  https://www.gideononline.com/ebooks/country/infectious-diseases-of-the-united-states/
  2. Gideon e-Gideon multi-graph tool,   https://www.gideononline.com/cases/multi-graphs/

India: Diphtheria, Pertussis and Tetanus

Although global incidences of Diphtheria, Pertussis and Tetanus declined dramatically during the second half of the twentieth century, relatively high rates for these diseases continue to be reported from India.  India accounted for 17.7% of the total World’s population in 2018, but reported 46% of global Tetanus, 53% of global Diphtheria (and only 10.2% of global Pertussis) that year.  Similarly, 68% of the population of Southeast Asia (SEA) live in India, while that country accounted for 85% of Diphtheria, 75% of Pertussis and 90% of tetanus for SEA in 2018. [1-4]   Trends for these data are charted in the following three graphs. [5]

References:

  1. Berger S. Infectious Diseases of India, 2019. 620 pages , 109 graphs , 6,807 references. Gideon e-books, https://www.gideononline.com/ebooks/country/infectious-diseases-of-india/
  2. Berger S. Diphtheria: Global Status, 2019. 389 pages , 451 graphs , 699 references. Gideon e-books, https://www.gideononline.com/ebooks/disease/diphtheria-global-status/
  3. Berger S. Tetanus: Global Status, 2019. 561 pages , 816 graphs , 390 references. Gideon e-books, https://www.gideononline.com/ebooks/disease/tetanus-global-status/
  4. Berger S. Pertussis: Global Status, 2019. 417 pages , 514 graphs , 1,028 references. Gideon e-books, https://www.gideononline.com/ebooks/disease/pertussis-global-status/
  5. Gideon e-Gideon multi-graph tool,   https://www.gideononline.com/cases/multi-graphs/

Campylobacteriosis in Scandinavia

For more than twenty years, rates of campylobacteriosis in Scandinavia have been 50% above those of Europe as a whole. [1]. During 1995 to 2000, approximately 20-to-60 cases per 100,000 were reported in Denmark, Finland, Norway and Sweden; increasing to 60-to-100 cases per 100,000 during 2010 to 2018. [2]  Similar regional trends have been reported for EHEC (enterohemorrhagic E. coli) infection; while rates of yersiniosis have been decreasing.

Sweden = Laboratory reports     other countries = Cases

References:

1. Berger S. Campylobacteriosis: Global Status, 2019. 157 pages , 102 graphs , 1,584 references. Gideon e-books,  https://www.gideononline.com/ebooks/disease/campylobacteriosis-global-status/
2. Gideon e-Gideon multi-graph tool,   https://www.gideononline.com/cases/multi-graphs/

Note featured on ProMED

 

 

Venereal Diseases in Europe

As of 2017, the reported incidence of syphilis in the European Union is higher that that of HIV infection.   In the following chart, I’ve contrasted trends of venereal diseases for the region. [1]  Data are derived from GIDEON www.GideonOnline.com and the Gideon e-book series. [2]  Note that gonorrhea is most common, followed by syphilis, HIV / AIDS and lymphogranuloma venereum (LGV).  In fact, if current trends continue, LGV infection may become more common than AIDS in the near future.  As depicted in the second chart,  reported cases of chlamydial infection are higher than the combined total for all other venereal diseases, and continue to be rise at an alarming rate.

References:
1. Gideon e-Gideon multi-graph tool,   https://www.gideononline.com/cases/multi-graphs/

2. Berger S. Infectious Diseases of the World, 2019. 1,750 pages , 456 graphs , 42,302 references. Gideon e-book series,  https://www.gideononline.com/ebooks/country/infectious-diseases-of-the-world/

Japanese Encephalitis in India

Outbreaks in Japanese encephalitis (JE) / Acute encephalitis syndrome (AES) have been reported from Assam and Uttar Pradesh in recent weeks.  Since 2008, official reports from India do distinguish between these two entities.  The following chart [1] indicates that although India has experienced increasing rates for both JE and AES on a national level,  incidence has not increased in these two states. [2,3]

 

References:
1. Gideon e-Gideon multi-graph tool,   https://www.gideononline.com/cases/multi-graphs/
2. Berger S. Infectious Diseases of India, 2019. 620 pages , 109 graphs , 6,807 references. Gideon e-books, https://www.gideononline.com/ebooks/country/infectious-diseases-of-india/
3. Berger S. Japanese Encephalitis: Global Status, 2019. 100 pages , 66 graphs , 1,208 references.  Gideon e-books, https://www.gideononline.com/ebooks/disease/japanese-encephalitis-global-status/

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