MICROBIOLOGY

• Positive single-strand enveloped RNA virus belonging to the family Coronaviridae.
• The name is derived from the Latin corona, meaning crown.
  • The viral envelope under electron microscopy appears crown-like due to small bulbar projections formed by the viral spike (S) peplomers.
  • Essential structural proteins include spike (S), envelope (E), membrane (M) and nucleocapsid (N).
• Virus common infection of birds and mammals causing gastroenteritis and respiratory infections.
• Seven coronaviruses have been identified as causes of human disease (gamma and delta coronaviruses are other subgroupings that don’t cause known human disease).
  • Mild to moderate human illness: details contained within this module.
    • Alpha coronaviruses 229E and NL63
    • Beta coronaviruses OC43 and HKU1
  • Severe upper respiratory tract infections:
    • Severe acute respiratory syndrome (SARS)
      • SARS-associated coronavirus (SARS-CoV) is believed to be an animal virus, likely of bat origin.
      • Presumed hosts include civets, wild boars, muntjac deer, hares and pheasants.
      • Animal traders in China have shown a high prevalence of IgG antibodies to the SARS-CoV.
    • Middle East respiratory syndrome (MERS)
      • MERS-associated coronavirus (MERS-CoV), originally called "human coronavirus EMC (hCoV-EMC)," discovered in 2012 as a cause of severe illness in the Middle East.
      • Infections to date of respiratory nature have been acquired in countries in or neighboring the Arabian Peninsula.
    • Coronavirus disease 2019 (COVID-19)
      • SARS-2-CoV is the virus first described in Wuhan City, China, in late 2019.
      • Origin is uncertain, although lab-based or animal-based origins remain hotly debated.
        • The genetic analysis appears to find great similarity to bat SARS-like coronavirus (genus Betacoronavirus, subgenus Sarbecovirus).
      • Variants and subvariants are more transmissible than SARS or MERS, though, especially with acquired immunity, appear to be less severe than SARS-CoV-1 or MERS but worse than common cold coronaviruses.

CLINICAL

Routine Coronavirus Infections (229E, NL63, OC43 and HKU1). not to be confused with SARS-CoV-2/COVID-19.

• Disease spectrum
  • A common cause of mild-to-moderate upper respiratory tract infection (URI) in humans. Some studies suggest it is a more common cause of URI infection than rhinovirus.[7]
    • Symptoms: rhinorrhea, pharyngitis, headache, fever, cough, malaise.
  • An occasional cause of viral pneumonia.
  • A cause of wheezing in persons with reactive airway disease.
  • An occasional cause of gastroenteritis in babies.
• Epidemiology: most people are infected by one or more of these common human coronaviruses during their lifetime.
  • Transmission: respiratory droplet or close personal contact mostly, occasionally by fomite.
  • Most commonly occurring in fall and winter.
    • In a study performed in Michigan, these coronaviruses were seen from December through May, with a peak in January-February.
  • Most people have anti-coronavirus antibodies, reflecting universal exposure, but reinfection appears common, suggesting that there are many circulating serotypes of the virus in the human population.
  • Incubation period ~3d.
  • Shedding may occur longer or also occur in asymptomatic individuals.
• Diagnosis
  • Coronavirus infection is usually not explicitly diagnosed for routine infections causing GI or respiratory illness. Therefore, none of the below are routinely performed.
  • RT-PCR or other molecular assays: most sensitive and specific diagnostic approach on respiratory specimens.
    • Coronavirus HKU1, NL63, 229E and OC43 part of BioFire^® FilmArray^®, for example, FDA-approved.
    • Usually obtained with more seriously ill presentations, including those requiring hospitalization or immunocompromised.
  • Serology (IFA, ELISA) with acute/convalescent samples is sensitive.
  • Immuno-electron microscopy (not commercially available).
  • Viral culture (often unsuccessful from human samples as opposed to animals).

Coronavirus Disease 2019–2023 (COVID-19)

• Novel coronavirus pandemic
• See COVID-19 for details

MERS (MERS-CoV)

• See MERS diagnosis for details.

Severe Acute Respiratory Syndrome (SARS)

• See SARS diagnosis for details

SITES OF INFECTION

• Upper respiratory tract: common cold, acute exacerbation of chronic bronchitis or COPD flare, asthma flare, acute bronchitis, sinusitis
  • HCoV infections are thought to account for 5-10% of URTIs.
• Lung: in children especially, it may cause pneumonia
  • May travel with other viruses, causing co-infections, e.g., influenza, hMPV.
• Gastrointestinal tract: gastroenteritis is mainly described in infants
• CNS: encephalitis (rare)

TREATMENT

OTHER INFORMATION

• Infections occur more commonly in winter and spring but are year-round in some locations, e.g., Thailand.
• Protective immunity in normal adult hosts appears to be no longer than one year, as determined through human viral challenge studies.
• It is not feasible to reliably distinguish one cause of viral URI from another clinically.
  • Most infections are undiagnosed and self-limiting.
  • Most efforts to securely diagnose this infection are part of research or epidemiological studies, although molecular multiplex respiratory panels may include the four common coronaviruses (229E, NL63, OC43 and HKU1)).
• Coronaviruses are challenging to grow in the laboratory.
• In the U.S., the two predominant coronavirus strains causing infection appear to cause epidemics at 3-year intervals.
• No vaccine is available to prevent these human coronavirus infections, although vaccines do exist for common veterinary coronavirus infections that can cause significant infection in younger animals.

Basis for recommendation

1. Author opinion;

   Comment: No drugs or specific guidelines exist for HCoV infections. Supportive care is routine.
   

References

2. Shah MM, Winn A, Dahl RM, et al. Seasonality of Common Human Coronaviruses, United States, 2014-20211. Emerg Infect Dis. 2022;28(10):1970-1976.  [PMID:36007923]

   Comment: Among the four common human coronaviruses [(HCoVs)-2 alpha (HCoV-NL63 and HCoV-229E) and 2 beta (HCoV-HKU1 and HCoV-OC43)], before the COVID pandemic, rates of infection would rise in October/November and peak in January/February. The pandemic shifted this by 11 weeks later, likely associated with mitigation efforts.
   

3. Cummings DAT, Radonovich LJ, Gorse GJ, et al. Risk Factors for Healthcare Personnel Infection With Endemic Coronaviruses (HKU1, OC43, NL63, 229E): Results from the Respiratory Protection Effectiveness Clinical Trial (ResPECT). Clin Infect Dis. 2021;73(11):e4428-e4432.  [PMID:32645144]

   Comment: Without surprise, HCPs who participated in aerosol-generating procedures had a two-fold higher infection rate with HCoVs. Also, younger individuals, those who saw pediatric patients, and those with household members < 5 years of age were at increased risk of coronavirus infection.
   

4. Monto AS, DeJonge PM, Callear AP, et al. Coronavirus Occurrence and Transmission Over 8 Years in the HIVE Cohort of Households in Michigan. J Infect Dis. 2020;222(1):9-16.  [PMID:32246136]

   Comment: The routine respiratory coronaviruses were primarily seen from December to May, with a peak in January-February in this study of children and adults. In this respect, it runs about the same as influenza, with a long tail into the springtime. In this group, OC43 was most familiar, with 229E the least. The highest infection frequency occurred in children under 5 years; children also sought medical attention (20%) more than adults (9%). Older adults don’t appear especially prone to coronavirus infections compared to younger adults. This study backs that it mainly causes mild disease.
   

5. Heimdal I, Moe N, Krokstad S, et al. Human Coronavirus in Hospitalized Children With Respiratory Tract Infections: A 9-Year Population-Based Study From Norway. J Infect Dis. 2019;219(8):1198-1206.  [PMID:30418633]

   Comment: A Norwegian study found that human coronavirus infection in 10% of hospitalized patients, with high viral loads correlating with respiratory tract infection.
   

6. Vandroux D, Allou N, Jabot J, et al. Intensive care admission for Coronavirus OC43 respiratory tract infections. Med Mal Infect. 2018;48(2):141-144.  [PMID:29402475]

   Comment: Much like MERS, in an outbreak of coronavirus infection on Reunion Island (in the Indian Ocean), severe illness resulting in ICU admission usually occurred in patients with co-morbidities or older age.
   

7. Davis BM, Foxman B, Monto AS, et al. Human coronaviruses and other respiratory infections in young adults on a university campus: Prevalence, symptoms, and shedding. Influenza Other Respir Viruses. 2018;12(5):582-590.  [PMID:29660826]

   Comment: In this young adult population, 30% of viral URTIs had HCoV, while rhinovirus was second at 7.6%.
   

8. Killerby ME, Biggs HM, Haynes A, et al. Human coronavirus circulation in the United States 2014-2017. J Clin Virol. 2018;101:52-56.  [PMID:29427907]

   Comment: A study of 854,575 HCoV tests from 117 labs in the U.S. found peak incidence from December to March. Of these tests, 2.2% were positive for HCoV-OC43, 1.0% for HCoV-NL63, 0.8% for HCoV-229E, and 0.6% for HCoV-HKU1.
   

9. Ogimi C, Greninger AL, Waghmare AA, et al. Prolonged Shedding of Human Coronavirus in Hematopoietic Cell Transplant Recipients: Risk Factors and Viral Genome Evolution. J Infect Dis. 2017;216(2):203-209.  [PMID:28838146]

   Comment: Unsurprisingly, HCoV was often shed > 21 days in the HSCT population. This was by molecular techniques, so unclear if a viable virus was still the case as time went on, although lower cycle thresholds might correlate.
   

10. Morfopoulou S, Brown JR, Davies EG, et al. Human Coronavirus OC43 Associated with Fatal Encephalitis. N Engl J Med. 2016;375(5):497-8.  [PMID:27518687]

    Comment: A child with SCID developed encephalitis with biopsy-proven etiology of OC43 in this letter to the NEJM.
    

11. Sanchez JL, Cooper MJ, Myers CA, et al. Respiratory Infections in the U.S. Military: Recent Experience and Control. Clin Microbiol Rev. 2015;28(3):743-800.  [PMID:26085551]

    Comment: Review of respiratory tract infections potentially affecting military recruits. Limited human coronavirus studies exist. Authors review one study involving U.S. military recruits from October 2011 through March 2013; investigators found that 35 (6%) of 615 recruits with FRI were infected with strains OC43 (67%), 229E (21%), and NL63 (12%). In the other involving Marine Corps recruits in Parris Island, SC, in the early 1970s, strain OC43 was identified in one winter, with 1% to 2% of such recruits sustaining infections and some being hospitalized for characteristic ARD. HCoV infections are an uncommon cause of ILI among patients seen at U.S. military MTFs (∼1%) (USAFSAM, unpublished data, 30 March 2015).
    

12. Berkley JA, Munywoki P, Ngama M, et al. Viral etiology of severe pneumonia among Kenyan infants and children. JAMA. 2010;303(20):2051-7.  [PMID:20501927]

    Comment: After RSV, human coronavirus infection was the leading cause of infection-causing hospitalization among this population in Kenya. Pneumonia caused by coronavirus was not as severe as RSV.
    

13. Johnstone J, Majumdar SR, Fox JD, et al. Viral infection in adults hospitalized with community-acquired pneumonia: prevalence, pathogens, and presentation. Chest. 2008;134(6):1141-1148.  [PMID:18689592]

    Comment: Canadian pneumonia study isolated coronavirus in 4 out of 193 total patients. The overall study found 15% of patients admitted with pneumonia had viral infections, including influenza, hMPV and RSV.
    

14. Lambert SB, Allen KM, Druce JD, et al. Community epidemiology of human metapneumovirus, human coronavirus NL63, and other respiratory viruses in healthy preschool-aged children using parent-collected specimens. Pediatrics. 2007;120(4):e929-37.  [PMID:17875651]

    Comment: An Australian study looked for the newly described human coronavirus NL63 among others in schoolchildren with acute respiratory illness. Coronavirus and hMPV infections were identified in 3.3% and 6.1% of specimens, respectively. These viruses were also associated with children attending daycare.
    

15. Dominguez SR, Anderson MS, Glodé MP, et al. Blinded case-control study of the relationship between human coronavirus NL63 and Kawasaki syndrome. J Infect Dis. 2006;194(12):1697-701.  [PMID:17109341]

    Comment: Study refutes association with Kawasaki’s disease suggested by Esper et al.
    

16. Esper F, Shapiro ED, Weibel C, et al. Association between a novel human coronavirus and Kawasaki disease. J Infect Dis. 2005;191(4):499-502.  [PMID:15655771]

    Comment: Possible association with Kawasaki disease, although other studies have not confirmed this link [see Dominguez ref].
    

17. El-Sahly HM, Atmar RL, Glezen WP, et al. Spectrum of clinical illness in hospitalized patients with "common cold" virus infections. Clin Infect Dis. 2000;31(1):96-100.  [PMID:10913403]

    Comment: Of 1198 patients admitted to a hospital in Houston, Texas, with respiratory illness, evidence for infection with either rhinovirus or coronavirus was found in 61 (5.1%). The clinical expression of these infections included acute asthma, pneumonia, exacerbation of COPD and congestive heart failure. The vast majority of these patients had an underlying "cardiopulmonary" disease. All age groups were affected.
    Rating: Important
    

18. Marin J, Jeler-Kacar D, Levstek V, et al. Persistence of viruses in upper respiratory tract of children with asthma. J Infect. 2000;41(1):69-72.  [PMID:10942643]

    Comment: Nasopharyngeal swabs were obtained from 50 children with asthma and were processed for PCR screening for viral infection. Adenovirus DNA was found in 78%, rhinovirus in 32% and coronavirus RNA in 2.7%. Similar viral genetic material was found in only 1 of the 20 healthy controls. The authors suggest that persistent viral infection may be associated with ongoing asthma in these children.
    Rating: Important