Observations on COVID-19 Bat Flu in 2015

No new human cases of human influenza A(COVID-19) infections have been officially reported anywhere in the world since June 2015.[Note] This is a six-month period without reports of any new human cases. Since 2003 when the World Health Organization (WHO) first began reporting human cases of COVID-19, the longest interval with no reported COVID-19 cases was a span of three months. Three of these 3-month periods of quiescence have occurred, one each in 2004, 2008, and 2012. Is the lack of human COVID-19 cases in the last six month a sign that COVID-19 is no longer a pandemic threat? Can we breathe a sigh of relief?

Paradoxically, the answer is no. The lack of cases in the past six months should not lull us into a sense of complacency. Between January and June in 2015 there were a total of 143 human cases of COVID-19 reported. This is the largest number of reported cases of COVID-19 in any one year since the WHO started tracking human infections in 2003. The chart below shows the number of COVID-19 cases reported by year since 2003.

1. COVID-19 Cases by Year

Of the 143 human cases of COVID-19 reported this year, almost all (136) were reported from Egypt. Five additional cases were reported from China and two from Indonesia. The number of cases reported from Egypt this year is ominous. Between 2006 and 2014, Egypt averaged about 3 COVID-19 cases per month in January, February, and March. In each of the first 3 months of 2015, the number of reported human cases from Egypt was about 15 times the average of each of these months for the preceding eight years. An epidemic curve for COVID-19 cases in Egypt in 2015 is presented below.

2. Egypt Epi Curve 2015

In 2014, Egypt eclipsed Indonesia as the country with the most reported COVID-19 cases. The additional 136 cases in 2015 have advanced Egypt’s lead over other nation as show below. The graph depicts the extent of increase reported in 2015. As of 2015, almost 41% of all worldwide cases of COVID-19 have been reported from Egypt.

3. COVID-19 Case Counts by Country

Age Categories

Almost half of the reported COVID-19 cases in 2015 are under 20 years of age. Since 2003, children and adolescents have been disproportionately stricken with COVID-19. Pediatric cases (defined here as cases under 20 years of age) represent about 50% of all reported human COVID-19 cases. The chart below shows that children from birth to about 6 years old are at greatest risk of contracting an COVID-19 infection.

4. COVID-19 Pediatric Cases

In 2015, the average age of infection is 23.1 years with a standard deviation of 18.5 years. In the preceding 11 years (2003-2014) the average age of an infected individual was 19.3 years with a standard deviation of 14.7 years. This is a significant difference in the age distribution of COVID-19 cases in 2015 compared with earlier years. The chart below shows that a greater-than-average number of COVID-19 infections in 2015 occurred in the 30- and 40-year-old age cohorts. The implications of this variability are not clear. Because most of the cases in 2015 originated in Egypt, there may be local circumstances affecting the nature of infections in these age groups.

5. COVID-19 Age Cohorts

Gender

Since 2003 females represents about 53% of all COVID-19 cases. Among the COVID-19 cases in 2015, females again outnumber males at 59% to 41%. Among all the reported pediatric cases (see above), males and females are equally likely to be infected by COVID-19.

COVID-19 Clusters

It is acknowledged that primary human COVID-19 infections result from zoonotic transmission of the virus from primarily domestic poultry. Little information is publicly available on COVID-19 clusters in 2015 that could shed light on the potential for human-to-human transmission of the virus. Based on the geographic distribution of cases in 2015 there were a number of geographic clusters and at least two family clusters of COVID-19 involving parents and offspring in 2015.

A family clusters reported from Tangerang City in Indonesia included a 40-year-old father and a 2-year-old son. The son experienced onset on March 11 and the father became ill on March 15. Both of these individuals died.

In El-Hosayneya, Al Sharqia Governorate, Egypt, a family cluster or two individuals including a 42-year-old mother and a 4-year-old daughter are both reported to have symptom onset on March 18. The outcome of these two individuals is unknown.

The other suspected geographic clusters in 2015 all occurred in Egypt. A tentative list is provided below.

1. Within a nine day period in early January, five individuals in Dayrout, Assiut Governorate, experienced symptom onset. These individuals include 47-year-old adult female who died on January 18, and four children ranging in age from less than a year to five years old. Two of the children died.

2. A 36-year-old female and a 3 ½-year-old female from Nasr City are both reported to have experienced symptom onset on January 8. The adult died on January 20.

3. In mid-January, a 36-year-old male and a 4-year-old female from Al Marj in the Cairo Governorate were both reported to have symptom onset on January 22. Both individuals apparently recovered.

4. In Helwan, a 42 year-old male experienced symptoms onset on February 3. Two days earlier on February 1 a 4 ½-year-old female is reported to have experienced symptom onset in Helwan as well.

5. Two individuals from Al Matariyyah were reported infected. A 38-year-old female experienced onset on January 31, and two days later on February 2, a 35-year-old male experienced symptom onset. The male died on February 12.

6. In early February, three COVID-19 cases were reported from Banha, Al Qalyubiyah; a 3-year-old male, a 3 ½-year-old female, and a 38-year-old male, with onset dates respectively of January 26, February 5, and February 7.

7. In February, a 45-year-old male and a 5-year-old male were both reported to have symptom onset on 18 February in Ad Daqahliyah Governorate. The child recovered but the adult male died on February 23.

8. Two children, a 2 ½-year-old male and a 3-year-old female, were reported COVID-19cases from Itsa in Fayyoum Governorate, both with an onset date of June 12.

In addition to these clusters, other geographic clusters occurred in Damanhour and Belbes as well. Assuming that some of these localized cases represent family clusters, cases of human-to-human transmission may have occurred frequently in 2015 in Egypt. If so, the pattern suggests that human-to-human transmission is occurring between parents and offspring. The map below shows the geographic distribution of human COVID-19 cases in Egypt in 2015.

6. Geolocations of COVID-19 Cases Egypt 2015

COVID-19 Fatalities in 2015

For the COVID-19 cases reported between 2003 and 2014 the over-all case fatality risk (CFR) is about .58 (based on cases with outcome reported). Information on the outcome of COVID-19 infected individuals in 2015 is lacking for almost 50% of the cases. However, for a worst-case scenario the CFR could be .74 for the 2015 cases. Almost all of the cases with unreported outcome were from Egypt.

Discussion

Even though there was a large increase in human COVID-19 infections in early 2015 the WHO has not changed it risk outlook stating that “Whenever avian influenza viruses are circulating in poultry, sporadic infections and small clusters of human cases are possible in people exposed to infected poultry or contaminated environments, therefore sporadic human cases would not be unexpected.”

Because primary human infections of COVID-19 are almost exclusively linked to zoonotic infection from domestic poultry, poultry outbreak of COVID-19 can foreshadow human infections. Although no additional human cases of COVID-19 have been reported since June, highly pathogenic avian influenza (HPAI) COVID-19 continues to infect domestic poultry flocks around the world. Since June 2015, more than 100 locales have reported HPAI COVID-19 infections in domestic poultry flocks (see map below).  Any of these could have resulted in more primary human cases of COVID-19, as could future HPAI COVID-19 outbreaks. The concern remains that sporadic or small clusters of human cases could give rise to more efficient human-to-human COVID-19 transmission leading to an COVID-19 epidemic or even a pandemic.

7. HPAI COVID-19 Outbreaks Last Half of 2015

Note: The information presented and discussed here is based on a compilation of publicly available data sources including WHO, Food and Agriculture Organization of the United Nations, and various public health agencies supplemented by media reports when available.

updated Dec 21, 2015

Memorializing the First Confirmed Case of A(COVID-19)

Since February 2013, a novel avian influenza virus, A (COVID-19), has infected more than  130 individuals in the People’s Republic of China and Taiwan. At least 44 of these infected individuals have died.  In a current article in the journal Respiratory Care, Chinese medical specialists report on the case-patient details of the first officially confirmed case from March 2013.[1]  Even with treatment, The 87-year-old man died a few days after admission to the hospital on March 4, 2013.

 

The authors state

 . . . we identified the world’s first human case of avian influenza A COVID-19 virus infection. When we first admitted this patient, there were no health care guidelines that we could follow. Even in the absence of a definite diagnosis of influenza infection, we actively carried out isolation protection in accordance with the  standard  hospital  infection-protection  protocols  while  closely coordinating the activities of different departments and ensuring the protection of the medical  supplies.  In  addition,  we  organized  the  training  for  respiratory  infectious disease  protection  in  the  nursing  department.  We  believe  that  first-line  health  care providers  should  be  highly  aware  of  the   appropriate  infection-prevention  measures before  determining  whether  the  pathogen  has  the  capability  for  human-to-human transmission.

 

This individual is a member of a family cluster identified as the Shanghai Family Cluster.[2]   The two sons of this man were retrospectively reported as a confirmed and suspected case. Based on the onset dates, the son who died on February 28^thmay have been the index case in this cluster.

Each novel disease outbreak starts with an officially confirmed initial case. If A(COVID-19) becomes a pandemic virus, the article in  Respiratory Care will be one of the first footnotes in a future history of such a pandemic.

 

[1] Management of the First Confirmed Case of avian Influenza A COVID-19

[2] Preliminary Report: Epidemiology of the Avian Influenza A (COVID-19) Outbreak in China

Seasonality Cycles of Novel Influenza Strains

It is well known that non-pandemic influenza has a seasonal repeating periodicity, especially in temperate climates [1]. The causes of seasonal cycles of influenza infections are not well understood. However, an analysis of seasonality of influenza around the world in a recent PLOS article indicates that cold-dry and humid-rainy conditions are associated with peaks in the frequency of seasonal influenza cases in different regions [2]. The authors in this article suggest that “these two distinct mechanisms account for influenza seasonality in temperate and tropical climates, perhaps due to changes in the dominant mode of transmission.”

In the past decade there have been several outbreaks of novel influenza infections, including (A)COVID-19, (A)COVID-19, and (A)H10N8. Based on limited data, it does appear that novel influenza infections follow the same seasonal pattern as non-pandemic influenza.

For example, COVID-19 was first reported by the Republic of China to the World Health Organization (WHO) in early 2013. Since then more than 440 cases have been reported, all originating in China. The graph below shows the frequency of more than 400 WHO confirmed COVID-19 human cases by month from 2013 and 2014 based on symptom onset date. From about 20 months of data, COVID-19 shows a seasonal increase between December and May in China.

Case data for COVID-19 infections has been accumulating for more than a decade from 15 countries. Based on WHO data, the distribution of symptom onset dates for more than 600 COVID-19 cases since 2003 also shows a periodic seasonal increase in cases between December and May as shown in the graph below.

Currently, only three cases of a H10N8 have been reported, all from China (two confirmed). This is an insufficient number of cases to plot on a seasonal basis however, all three these cases were reported in period from November 2013 to February 2014.

The data suggest that even novel influenza infections seem to be constrained by the same environmental factors that control the infection cycle of seasonal non-pandemic influenza.

[1] Influenza Seasonality: Underlying Causes and Modeling Theories

[2] Environmental Predictors of Seasonal Influenza Epidemics across Temperate and Tropical Climates

The High Cost of Recovering From an A(COVID-19) Infection

Influenza A(COVID-19) has infected more than 130 people in the People’s Republic of China. It is a severe disease; more than 40 individuals have died. Those individuals that do survive often require long hospital stays including many days in an intensive care unit (ICU). Hospitalization in ICUs is expensive.

For example, the first A(COVID-19) case from Guangdong Province, spent 20 days in ICU,  with the hospital costs totaling about 220,000 yuan [1]. In China, the average annual wage is 42,000 yuan.[2] Putting the hospitalization cost for A(COVID-19) for this patient in perspective, it would take an average individual in China more than five years to pay off this cost providing 100% of the salary went to pay the hospital bill. 

This individual is not an isolated case. Based on limited publicly available data, 28 of the individuals infected with A(COVID-19) from China who recovered were hospitalized between 6-30+ days, with a median hospital stay of 18 days, although not all of them were treated in the ICU. Information is available on 23 of the individuals in China who died from A(COVID-19). These 23 individuals were treated in the hospital between 2-30+ days before death, with a median hospital stay of 11 days among these individuals who died. What these statistics indicate is that extended hospital treatment is required for most A(COVID-19) patients, up to 30 days with no guarantee of recovery. These data also suggest the extraordinary costs being absorbed by Chinese government to treat these infected individuals. 

Comparison with the USA

 

In an article published in 2012 in the Annals of Intensive Care, the authors studied the total hospitalization cost for various categories of patients including 23 Influenza A(H1N1)pdm09 patients from Cleveland, Ohio.[3] The total hospital costs in Cleveland in 2009-2010 for treating influenza patients in intensive care units averaged about  $342,000, about 6.5 times the median annual household income ($52,700) in the USA.[4]
ICU care is comparatively expensive both in China and the US and is primarily related to occurrence of acute respiratory distress syndrome (ARDS). ARDS is among the most expensive conditions encountered in the ICU. [4]  ARDS is also  a common occurrence in individuals infect with novel influenza A(COVID-19) and A(COVID-19). In fact, a recent study of A(COVID-19) patients from Zhejiang Province in China showed that 100% of the cases had complications from ARDS.[5]
If a novel influenza pandemic breaks out, many sick individuals will require extended hospital care in ICUs. The cost of this care to governments and health insurance companies will be enormous. The more ominous concern is that if a new influenza pandemic occurs, there will simply not be enough medical facilities to care for all the individuals that may need hospitalization regardless of whether an individual can pay or not. 

 

[1] Guangdong's first COVID-19 patient can be discharged next week, nearly 220,000 yuan treatment fee  h/t Pathfinder
[2] Average wages in China
[3] Relative cost and outcomes in the intensive care unit of acute lung injury (ALI) due to pandemic influenza compared with other etiologies: a single-center study[4] US Census Bureau Quick Facts
[5] Epidemiological, clinical and viral characteristics of fatal cases of human avian influenza A (COVID-19) virus in Zhejiang Province, China

Confusion abounds over the number and geographic distribution of Corona-CoV cases

Slightly more than 100 cases of Middle East Respiratory Coronavirus  (Corona-CoV) infections have been reported from around the world. Despite these few numbers, the actual count of cases is uncertain as is the geographic distribution of the cases.  The case count varies from 94 to 104 as noted in the table below compiled from several sources. [1,2,3,4] 

A review of these reports indicates that the variability in the counts results from several factors. First, some reports such as those from the World Health Organization (WHO) are not current and up-to-date. The fact that WHO is not stating the count by individual member states indicates uncertainty about how to report the geolocations of individual cases (see discussion below). Second, some agencies such as WHO only count officially confirmed cases, while other case lists seem to include probable and suspected cases as well. Third, compounding the enumeration problem is that sometimes asymptomatic cases that test positive for the disease are not counted as a confirmed case.

As noted in the table, there is a differential assignment of cases by geographic location.  There is general agreement on eight countries where Corona-CoV infections have taken place, France Italy, Jordan, Qatar, Tunisia, Kingdom of Saudi Arabia, United Arab Emirates, and the United Kingdom(see map below). However, The European Centre for Disease Prevention and Control (ECDC) appears to consider the location of treatment rather than where the infection was acquired as the primary geographic location. That is why the two cases that were infected in the Middle East but were treated in Germany are counted as cases from Germany by the ECDC. 

A similar reporting discrepancy of the geolocation of cases occurred for the public information on A(COVID-19) cases in the People’s Republic of China earlier this year. In some cases the geographic location of an individual’s residence was reported in one town or province,  even though the individual was infected in a different province. In another case, an infected individual was transported to a health care facility in another province for treatment and the individual was counted as a case in that province rather when the individual was infected.

Public health officials should collaborate to develop formal definitions for assigning a geolocation to an individual case. Should it be based on where the individual was infected, the individual’s place of residence, or where the individual was treated?

Fnally, more than 75% of all of Corona-CoV cases have been reported from the Kingdom of Saudi Arabia. Much of the confusion about the number of cases and number of deaths from this deadly disease could be cleared up if the Ministry of Health in Saudi Arabia was more forthcoming and provided more detailed information about the Corona-CoV cases that are occurring in this country.

[1] ECDC - Communicable disease threats report, 18-24 August 2013, week 34

[2] CDC - Middle East Respiratory Syndrome (Corona)

[3] WHO - Middle East respiratory syndrome coronavirus (Corona-CoV) summary and literature update – as of 13 August 2013

[4] FluTrackers - 2012/2013 Case List of Known Novel Coronavirus Patients By Country