*1.1. Known Coronaviruses with Fairly Benign Outcomes*

Coronaviruses infecting humans are not new. The wide range of possible hosts includes birds, pets, bats, farm animals and camels. Currently there are seven coronavirus species causing disease in humans. In four of these, called 229E, OC43, NL63 and HKU1, respiratory symptoms predominantly consist of self-limiting common cold symptoms, causing a respiratory or gastrointestinal disease. Infections with the strain 229E can be associated with fever and cough in 10−20% of cases. The illness usually lasts between 2 and 18 days [2]. Patients affected by the strain OC43 have the same symptoms as those affected by the 229E strain. Infections with NL63, a strain known since 2004 and initially described in the Netherlands, cause typically mild symptoms, whereby it primarily is observed in young children, elderly and immunocompromised patients with prior respiratory illnesses. In children it can also cause obstructive laryngitis (croup) [4]. However, a subtype of NL63 has been associated with severe lower respiratory tract infection in hospitalized children in China [5]. The HKU1 strain was discovered in 2005 in Hong Kong, causing relatively mild respiratory symptoms in children, but it is also associated with a high incidence of seizures and has also been found in a patient with meningitis [4,6,7]. In contrast to the benign outcomes in the general population, in lung transplant recipients these viruses can cause acute febrile illnesses, and may even persist for up to several months in some individuals, making concurrent infection with another virus difficult to interpret [8]. In lung transplant recipients, a viral respiratory tract infection (VRTI) is associated with chronic lung allograft dysfunction (CLAD). In the first year after lung transplantation, coronavirus in particular is associated with increased risk of CLAD development [9]. In a study by Magnusson, in a total of 125 lung transplant recipients with VRTI, 19.2% (n = 21) had a coronavirus infection. The coronavirus subspecies were OC43 in 7.2% (n = 9), 229E in 5.6% (n = 7), NL63 in 3.2% (n = 4) and HKU1 in 0.8% (n = 1) [9]. Another study showed that coronaviruses have an important role among patients with underlying conditions and in transplanted patients [10]. In healthy children, human coronaviruses were detected in 3.3% (n = 11), in healthy adults in 12% (n = 6), in health care workers in 12.8% (n = 86), in patients after renal transplantation in 20.3% (n = 30), in children with heart diseases in 24.7% (n = 44) and in patients after stem cell transplantation in 24.3% (n = 44) [10].
