Coronavirus

MICROBIOLOGY

• Positive single-strand enveloped RNA virus belonging to the family Coronaviridae.
• Name derived from the Latin corona, meaning crown.
  • Viral envelope under electron microscopy appears crown-like due to small bulbar projections formed by the viral spike (S) peplomers.
  • Important 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 shown to have 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 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 bats and pangolins currently implicated.
        • The genetic analysis appears to find great similarity to bat SARS-like coronavirus (genus Betacoronavirus, subgenus Sarbecovirus).[6]
      • Appears to be spread more easily than SARS or MERS though appears to be less severe.

CLINICAL

Routine Coronavirus Infections (229E, NL63, OC43 and HKU1)

• 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.[13]
  • 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 commonly occurring in winter and early spring.
    • In a study performed in Michigan, these coronaviruses were seen during December through May with a peak in January-February.
  • Most people have anti-coronavirus antibodies, reflecting universal exposure, but reinfection appears common, suggestive 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 usually not diagnosed specifically 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.
  • 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 2019–2020 (COVID-19)

• • Novel coronavirus outbreak of 2019-2020
  • 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 thought to account for 5-10% of URTIs.
• Lung: in children especially, may cause pneumonia
  • May travel with other viruses, causing co-infections, e.g., influenza, hMPV.
• Gastrointestinal tract: gastroenteritis 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.
• 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 diagnosis 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 difficult 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 available for the prevention of 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 specific treatment guidelines exist for non-SARS or non-COVID-19 coronavirus infections.
   

References

2. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020.  [PMID:31978945]

   Comment: An early report includes electron microscopy photomicrographs as well as sequence analysis of what is now termed COVID-19 disease and SARS-2-CoV virus.
   

3. Bajema KL, Oster AM, McGovern OL, et al. Persons Evaluated for 2019 Novel Coronavirus - United States, January 2020. MMWR Morb Mortal Wkly Rep. 2020;69(6):166-170.  [PMID:32053579]

   Comment: People evaluated as per this report in the US mostly were those with a history of travel/contacts from Wuhan City, China which is the apparent epicenter of this epidemic. Of 210 people, 148 (70%) had travel-related risk only, 42 (20%) had close contact with an ill laboratory-confirmed 2019-nCoV patient or PUI, and 18 (9%) had both travel- and contact-related risks. Eleven of these persons had a laboratory-confirmed 2019-nCoV infection. Given reports now around the globe, it is unclear if testing only those with potential links to China is prudent, but current availability of test kits from the CDC likely precludes wider testing until either FDA-approved or EUA approval is given to current commercially available respiratory panels to include COVID-19.
   

4. Benvenuto D, Giovanetti M, Salemi M, et al. The global spread of 2019-nCoV: a molecular evolutionary analysis. Pathog Glob Health. 2020.  [PMID:32048560]

   Comment: Strain analysis to date of COVID-19 suggests that they are very similar to bat SAR-like coronavirus.
   

5. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020.  [PMID:32031570]

   Comment: One of the initial major reports of the Wuhan COVID-19 epidemic. In this series, the median age was 56 and slightly more men (54%) affected. Predominant symptoms include fever, fatigue and dry cough. Leukopenia was seen in ~70%. Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]).
   

6. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020.  [PMID:32015507]

   Comment: Authors have sequenced what is now termed SARS-2-CoV. Its genome 79.5% sequence identify to SARS-CoV. Furthermore, it was found that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus.
   

7. Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020.  [PMID:32074550]

   Comment: An early report that suggests the antimalarial chloroquine has shown efficacy against COVID-19 infection in Chinese trials. Of note, this drug has been tried for CHKV and others without good virological effect.
   

8. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020.  [PMID:32020029]

   Comment: Summary of earlier in vitro studies suggesting drugs that may work against COVID-19. Remdesivir is currently under investigation in the Wuhan epidemic. This drug also has had activity for both prevention and treatment in a rhesus macaque module of MERS-CoV,
   

9. Ai T, Yang Z, Hou H, et al. Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases. Radiology. 2020.  [PMID:32101510]

   Comment: Chest CT shows early ground-glass infiltrates which may offer speedier "diagnosis" than PCR studies in an epidemic setting as a first finding if molecular assays not readily available.
   

10. Monto AS, DeJonge P, Callear AP, et al. Coronavirus occurrence and transmission over 8 years in the HIVE cohort of households in Michigan. J Infect Dis. 2020.  [PMID:32246136]

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

11. 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 was found in 10% of hospitalized patients, with high viral loads correlating with the presence of respiratory tract infection.
    

12. 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 was usually occurring in patients with co-morbidities or older age.
    

13. 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.  [PMID:29660826]

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

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

15. 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.
    

16. 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, develop encephalitis with biopsy-proven etiology of OC43 in this letter to the NEJM.
    

17. 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 in 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 of them 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).
    

18. 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.
    

19. 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.
    

20. 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. Both the coronavirus and hMPV infections were identified in 3.3% and 6.1% of specimens respectively. These viruses were also associated with children attending daycare.
    

21. 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.
    

22. 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].
    

23. Woo PC, Lau SK, Tsoi HW, et al. Relative rates of non-pneumonic SARS coronavirus infection and SARS coronavirus pneumonia. Lancet. 2004;363(9412):841-5.  [PMID:15031027]

    Comment: Findings indicate that non-pneumonic cases of SARS co-V infection do occur and were found in 0.48% of the population studied. Such infections may account for cases of SARS in patients with no obvious clinical exposure to symptomatic patients.
    Rating: Important
    

24. 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 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 on-going asthma in these children.
    Rating: Important
    

25. 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