Coronaviruses: old and new

Dieter Stürchler

 

Conventional coronaviruses have circulated in humans since the mid-1960s. Infections range from inapparent to the common cold, flu-like illnesses and pneumonia. Worldwide, they may account for about 4% of all airway illness. Conventional coronaviruses must be differentiated from the new coronavirus COVID-19.

Coronavirus is a genus of enveloped RNA viruses (Nidovirales: Coronaviridae). Species in humans include 229E (1967), OC43 (1967), SARS (severe acute respiratory syndrome, 2002-03), NL63 (2004), HKU1 (2005), MERS (Middle East respiratory syndrome, 2012), and COVID (December 2019) [1–34].

Related species circulate in wildlife, livestock and pets. Coronaviruses fall into three groups: α infecting humans (229E, NL63), bats, camels and rats; β infecting humans (OC43, HKU1, SARS, MERS, COVID-19), bats, pigs, horses, cattle and dogs; and γ in birds and marine mammals.

Of conventional coronavirus infections (229E, OC43, NL63, HKU1), SARS or MERS, about 25−90% are inapparent. The main manifestations are the common cold (rhinitis, sore throat), acute upper (bronchitis) and lower (pneumonia) airway infections, and flu-like illnesses (fever, myalgia). Ongoing or past infection is detected from clinical materials (swabs, sputum, blood) by molecular methods (reverse transcription polymerase chain reaction [RT-PCR] sequencing) or serology (immunoglobulin [Ig] M and/or IgG). Tests need to differentiate conventional coronaviruses from COVID and other viruses such as human adenovirus, enterovirus-rhinovirus, influenzavirus, parainfluenza viruses and respiratory syncytial virus.

Here, I summarise the circulation of conventional coronaviruses in people and their significance in airway or febrile diseases. I searched the literature of the mid-1960s to early 2020s for coronavirus infections in people. Non-exhaustive crude prevalences in groups of ill or apparently healthy individuals were aggregated by continent.

Conventional coronaviruses were recorded in 69 countries on 5 continents (table 1).

 

Table 1: Conventional coronaviruses (229E, NL63, OC43, HKU1) in people, 1960s to early 2020s.

Parameter	Africa	America	Asia	Oceania	Europe
Countries, number (= n)	16 (of 56)	11 (of 45)	33 (of 48)	2 (of 23)	28 (of 41)
Prevalence: median (range), %	7 (0−22)	4 (0−48)	4 (0−67)	2 (0.3−3)	3 (0−58)

 

 

 

 

This compares with 62 countries for COVID (as of 1 March 2020), 27 countries for MERS (2012−19) and 27 for SARS (2002−03). Combining healthy and ill people and recent (viraemia, nucleic acid tests) and past (anti-coronavirus  IgG) infections gave median prevalences (and ranges) by continent of: 7% (0−22%) in Africa (15 studies), 4% (0−48%) in America (17 studies), 4% (0−67%) in Asia (48 studies), 2% (0.3−3%) in Oceania (3 studies) and 3% (0−58% in Europe (31 studies) (tables 2 to 6). The surprisingly homogenous medians gave an overall global prevalence of 4%, which compares with the above respiratory viruses in humans.

 

Table 2: Conventional coronaviruses (CoV) in people: prevalence (%, rounded) – Africa.

Country	%	n	Group, test, place, time, reference
Cameroon	5	561	Flu-like (0−75 y), NAT, 14 centres 2009 [35]
Côte d’Ivoire	11	470	Flu-like (0−5 y), NAT, 2009−10 [32]
Egypt	0	179	Abattoir work, anti-CoV 2013 [3]
Gabon	6.5	1041	Flu-like (0−82 y), NAT, 4 sites 2010−11 [36]
Kenya	0.2	1222	Livestock work, anti-CoV 2013–14 [3]
Kenya	0	760	Camel contact, anti-CoV 2012–13 [3]
Kenya	7–7	96–759	Mild pneumonia (<12 y), NAT, coast 2007 [37]
Madagascar	10–10	60–80	Controls–pneumonia (≤5 y), NAT, 2010–14 [7]
Mali	9–9	93–118	Controls–pneumonia (≤5 y), NAT, 2011–12 [7]
Niger	13	160	Ill airway (<5 y), NAT, 5 regions 2010–12 [38]
Nigeria	0	261	Abattoir work (camels), anti-CoV (NT) 2016 [3]
RSA	4	627	Ill airway (<5 y), NAT, Pretoria 2006–07 [39]
Tanzania	14–8	166–207	Healthy–febrile (<5 y), NAT, Zanzibar 2011 [40]
Tunisia	22	372	Ill airway (0–5 y), NAT Sousse 2013–14 [41]
Zambia	0.5	199	Ill airway (≤5 y), NAT throat, 2011–12 [42]
MERS = Middle East respiratory syndrome; NAT = nucleic acid tests; y = year(s)

 

Table 3: Conventional coronaviruses (CoV) in people: prevalence (%, rounded) – Americas.

Country	%	n	Group, test, place, time, reference
Argentina	10.5	315	Ill (<6 y), NAT, Buenos Aires 2008–10 [40]
Bolivia	5	564	Flu-like (0–60+ y), NAT, 2010–12 [43]
Brazil	1	260	Ill (<3 y), NAT, Porto Alegre 2007 [44]
Canada	0.5(0.3–0.9)	4903	Ill airway, country 2014–19 (www.canada.ca/en/public-health.html)
Canada	4.5	177	Common cold, travel to MERS-areas 2012–14 [45]
Canada	1.8	3847	Child airway specimens, NAT, Montreal 2009–10 [44]
Chile	4.5	268	Pneumonia (>18 y), NAT 2005–07 [46]
Haiti	8–5	101–122	Pneumonia–controls (≤5 y), NAT, 2010–14 [7]
Mexico	7	1’051	Flu-like (0–96 y), 2010–11 [14]
Paraguay	8–7	99–100	Pneumonia–controls (≤5 y), NAT 2010–14 [7]
Trinidad	1–1	70–80	Children acute wheeze–stable, NAT 2004–05 [23]
USA	2	2259	Pneumonia (18–80+ y), NAT, IL/TN 2010–12 [10]
USA	6–4	440–425	Ill airway (<3 y), NAT 2005–07 [22]
USA	3	515	Ill (<1 y), NAT, 4 inner cities, 2005–08 [17]
USA	2.7–45	1990	Ill (<45 y), rise–CF ≥1:4, Michigan 1966–67 [29]
USA	0–7	222–317	Ill infant–adult, paired sera 229E, 1965–67 [30]
USA	2–48	222–317	Ill infant–adult, low titre to 229E, 1965–67 [30]
MERS = Middle East respiratory syndrome; NAT = nucleic acid tests; y = year(s)

 

Table 4: Conventional coronaviruses (CoV) in people: prevalence (%, rounded) – Asia.

Country	%	n	Group, test, place, time, reference
Cambodia	10	1904	Ill (≥5 y), NAT 2007–09 [47]
Cambodia	3–7	176–95	Pneumonia–controls (≤5 y), NAT 2010–14 [7]
China	0.9	3978	Fever (0–96 y), NAT, Beijing 2011–14 [48]
China	3	3181	Ill (≤16 y), NAT, Chongqing 2009–13 [12]
China	5–8	39–138	Pneumonia–controls (≤5 y), NAT 2010–14 [7]
China	5	279	Ill (0–12 y), NAT, Gansu Province 2011 [49]
China	3.7	4755	Ill (0–91 y), NAT, Guangzhou 2009–11 [16]
China	11	490	Flu-like, NAT, Nanjing 2010–11 [18]
Georgia	5	1624	Ill, NAT 2015–17 [50]
India	8–14	96–96	Pneumonia–controls (≤5 y), NAT, 2010–14 [7]
India	1–3	71–70	Pneumonia–controls (≤5 y), NAT, 2010–14 [7]
Indonesia	5	148	Pneumonia (>13 y), NAT Semarang 2007–09 [51]
Iran	2.5	455	Ill (0–80 y), NAT, Isfahan 2009–10 [51]
Israel	10	1910	Flu-like, NAT, 2015–16 [4]
Japan	5	1380	Ill (0–15+ y), NAT, 2014–16 [6]
Jordan	7	124	MERS contacts, anti-CoV, 2012–13 [3]
Korea, South	4	36,915	Ill (<1–65+ y), NAT, country 2013–15 [5]
Korea, South	8	207	Ill soldiers, NAT, 2011–12 [13]
Korea, South	5	675	MERS contacts, NAT 2015 [3]
Korea, South	1	1169	Health care work, anti-MERS-CoV, 2015 [3]
Kuwait	0	1014	Ill (0–76 y), NAT <2010 [52]
Laos	2	292	Admitted ill airway (0–86 y), NAT 2009–10 [53]
Malaysia	3	2060	Ill adults, NAT, 2012–13 [8]
Mongolia	8–4	108–93	Pneumonia–controls (≤5 y), NAT 2010–14 [7]
Nepal	0.8	3693	Flu-like, pregnant, NAT, 2011–14 [53]
Oman	0.4	259	Ill (<5 y), NAT, 2007–08 [54]
Pakistan	13	91	Near camels (8–76 y), anti-MERS-CoV, 2017–18 [55]
Pakistan	0	840	Camel herders, anti-CoV, 2016 [3]
Qatar	3	294	Work (camels), anti-CoV 2013–14 [3]
Saudi Arabia	67	30	Work (camels), anti-CoV/T cell response 2018 [3]
Saudi Arabia	2–8	879–107	Health care work, NAT, 2 studies 2017 [3]
Saudi Arabia	1	57,363	MERS suspects, NAT, 2015–16 [3]
Saudi Arabia	2-20	1206–1162	Pilgrims (18–88 y) arrive–depart, NAT, 2013 [56]
Saudi Arabia	0–0	191–226	Abattoir work, anti-CoV, 2013/4–2012 [3]
Saudi Arabia	1	1695	Health care work, NAT, 2012–13 [3]
Saudi Arabia	14–10	79	MERS contacts, NAT–anti-CoV 2014 [3]
Saudi Arabia	4	280	MERS contacts, anti-CoV, 2013 [3]
Saudi Arabia	0.1	10,009	Residents, anti-CoV, 13 provinces 2012–13 [3]
Saudi Arabia	0.2–1	519–2699	Pilgrims, arrive-depart, NAT, 2009 [57]
Singapore	0.6	500	Ill (0–12 y), NAT, 2005–07 [58]
Sri Lanka	1.5	571	Flu-like (1–75 y), NAT 2013–15 [59]
Taiwan	5	113	Bronchiolitis (<2 y), 2009–11 [60]
Thailand	0	48	MERS contacts, NAT, 2015 [3]
Thailand	0.8	5833	Flu-like, NAT, 2012–13 [61]
Turkey	6	624	Sore throat (3–85 y), NAT, Kayseri 2013 [62]
UAE	54–0	124	Patients–contacts, anti-CoV, 2013–18 [3]
UAE	4	1586	MERS suspects, NAT, 2013–14 [3]
Vietnam	8	309	Ill (<15 y), NAT, Ho Chi Minh City 2004–08 [63]
MERS = Middle East respiratory syndrome; NAT = nucleic acid tests; y = year(s)

 

Table 5: Conventional coronaviruses (CoV) in people: prevalence (%, rounded) – Oceania

Country	%	n	Group, test, place, time, reference
Australia	3	543	Ill (<5 y), NAT, Melbourne 2003–04 [64]
Australia	0.3	23,177	Submitted stools, any test, 1991–2000 [65]
New Zealand	2	304	Pneumonia (>18 y), NAT, 1999–2000 [26]
MERS = Middle East respiratory syndrome; NAT = nucleic acid tests; y = year(s)

 

Table 6: Conventional coronaviruses (CoV) in people: prevalence (%, rounded) – Europe.

Country	%	n	Group, test, place, time, reference
Multicenter	0–2.5	2 501	Healthy, routine test–NAT, 51 studies 1965–2007 [66]
Croatia	2	182	Ill (>18 y), NAT, 2016–18 [67]
Cyprus	5	424	Ill (0–12 y), NAT, Nicosia 2010–13 [9]
Finland	3	194	Cold (<5 y), Turku (60°N) 1996–98 [24]
France	1	162	MERS contacts, NAT 2013 [3]
France	1	85	Pneumonia (<17 y), NAT St-Etienne 2012–13 [68]
France	9	1021	Children (<2 y), NAT, Caen 2009–10 [69]
GBR	0–6	59–33	Health care work, NAT, 2 studies 2013 [3]
GBR	0	4821	Submitted samples, NAT, 2009–10 [70]
GBR	1.6	12,830	Submitted samples, NAT, Edinburgh 2006–09 [19]
Germany	9	75	Colds, adults, NAT self/staff sampling, 2011 [71]
Germany	3	18,999	Ill (0–16 y), NAT 1996–2006 (CoV >2003) [69]
Germany	58–7	3016–331	Healthy, anti-CoV, past–new 1974–76 [70]
Greece	4	1272	Flu-like (0–18 y), NAT, Athens 2005–08 [21]
Italy	2	237	Ill children NAT, Siena 2006–07 [72]
Italy	9	322	Ill (<2 y), NAT, Milan 2004–06 [25]
Netherlands	2	339	Ill (≥18 y), NAT 2007–10 [73]
Netherlands	6	107	Ill adults, NAT, Utrecht 2002–04 [74]
Netherlands	2	1172	Ill, NAT, 1997–99 [75]
Norway	15	452	Ill (0–16 y), NAT, Trondheim 2006–07 [20]
Poland	15	399	Flu-like, military/families, NAT 2011–12 [76]
Portugal	0	249	Bronchiolitis (0–2 y), NAT, 2007–08 [73]
Romania	0.4	241	Ill (0–8 y), NAT, 2010–11 [77]
Russia	0.8	1560	Ill (0–15 y), NAT, Siberia 2013–17 [78]
Slovenia	5	278	Ill (<5 y), NAT, 2012–13 [79]
Spain	1.3	884	Pneumonia (<14 y), NAT, Madrid 2004–10 [80],
Sweden	16–5.5	1843–403	Adults (25–63 y), NAT self-clinical, 2011–12 [11]
Sweden	3	502	Flu-like (0–17 y), NAT, Stockholm 2009 [81]
Sweden	10	79	Flu-like, travel to MEX/USA, NAT, Gotaland 2009 [82]
Sweden	1	232	Healthy (10–15 y), NAT Malmö (56°N) 2005 [83]
Switzerland	3	117	Ill (1–83 y), Geneva 2001–02 [27]
MERS = Middle East respiratory syndrome; NAT =nucleic acid tests; y =year(s)

In conclusion, as SARS (eliminated by a concerted global effort by 2003) and MERS (virtually not sustained by human-to-human spread) have demonstrated, coronaviruses can be contained or even eliminated. However, information about conventional coronaviruses suggests that COVID could become part of the airway illnesses that, according to host, season and infective dose, may range from inapparent to mild, severe or critical illness. In this latter scenario, COVID must be distinguished from conventional coronaviruses and other respiratory viruses, preferentially by multiple genomic assays.

 

Dieter Stürchler, Emeritus professor of Basel University, Switzerland

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