Epidemic Alert Management of Patients with COVID (Coronavirus Disease 19 – State of Knowledge

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1- Virology:

• Wrapped RNA virus belonging to the Coronaviridae family, genus betacoronavirus
• In humans: six known coronavirus species

1. seasonal hCoV: 220E, OC43, NL63, HKU1
2. Emerging coVs with increased pathogenicity

• SARS -CoV: 10% lethality
• MERS-CoV: 37% lethality

• SARS-CoV-2 shares

1. 80% genetic identity with SARS-CoV
2. 96% identity with a bat virus (Rhinolophusaffinis)

2- Epidemiology:

• Reproductive rate (R0)

• 2.2 to 3.28

• Patient ages (years)

• Medium: 55 (up/-13)
• Median: 59[15-89]

• Doubling time

• 6.4 to 7.5 days

• Permanent update of epidemic dynamics

• ECDC COVID-19 dedicated webpage
• John Hopkins University Mapping

3- Transmission:

• Human-to-human transmission
• Average incubation: 5.2 days

Contaminated health professionals:

• No. 1716; 247 severe/critical, 5 deaths
• No.40; medical services (31), emergencies (7), resuscitation (2)
• Proportions increasing over time from 3% (1st to 11/01) to 7% (12 to 22/01)
• Cluster six members, same family in Wuhan:

• Two members, visit to the hospital of a relative for pneumonia; contamination of 4 other members:
• including a child (7 years old) asymptomatic, radiological abnormalities;
• and another child (10 years old), untaminated (wearing a mask)

4- Protection:

• Standard and additional precautions such as "air" and "contact" – enhanced precautions REB:

• Sha
• FFP2 mask
• On single-use blouse (waterproof if dirty care)
• Non-sterile single-use gloves
• Protective goggles

• Suspicious patient or possible case – single room, closed door
• Confirmed case – single room, closed door, ideally in negative pressure

ELIMINATION EPI in DASRI before leaving the room, except for glasses and APR that will be removed after leaving the room

5- Clinical, Biological and Imaging Table:

Demographics:

• Median age (years): 56
• Woman: 63 (46%)
• Comorbidities: 64 (46%)

• Cardiovascular: 27 (20%)
• Diabetes: 14 (10%)
• Cancer: 10 (7%)

Biology:

• Leukocytes (/mm3): 4500
• Lymphocytes (/mm3): 800
• LDH (U/L): 261
• Procalcitonin (ng/mL): 49

Clinical:

• Fever: 136 (99%)
• Cough: 82 (59%)
• Dyspnea: 43 (31%)
• Myalgias: 48 (35%)
• Odynophagia: 24 (11%)
• Diarrhea: 14 (10%)

Evolution:

• USI admission: 36 (26%)
• SDRA: 27 (20%)
• Acute kidney failure: 5 (4%)
• Septic shock: 12 (9%)
• Healing: 47 (34%)
• Deaths: 14 (14%); 6 (4%)

Clinic, imaging:

Evolution:

Treatment:

Antiviral treatments:

• Patients treated:

• Oseltamivir: 124 (90%)

• Treated patients: 75 (76%)

• Oseltamivir
• Ganciclovir
• Lopinavir/ritonavir

Antibiotic treatments:

• Patients treated:

• Moxifloxacin: 89 (64%)
• Ceftriaxone: 34 (25%)

• Treated patients: 70 (71%)

Support treatments:

• Oxygen therapy: 106 (77%)
• Mechanical ventilation

• Non-invasive: 15 (11%)
• Invasive: 17 (12%)

• Dialysis: 2 (1%)
• ECMO: 4 (3%)

Evolution:

CHINESE CDC, No. 72672

• Confirmed by PCR: 44672 (62%)
• Asymptomatic: 889 (1%)

Demographics:

• Age: (No. 44672)

• 80 years: 1408 (3%)
• 30-79 years: 38680 (87%)
• 20-29 years: 3619 (8%)
• 10-19 years: 549 (1%)
• <10 ans: 416 (1%) ans:="" 416=""></10 ans: 416 (1%)>

• Male: 22,981 (51%)

Clinical:

• Clinical Form: (No. 44415)

• Moderate: 36160 (81%)
• Grave: 6168 (14%)
• Review: 2087 (5%)

Evolution

• Death

• Total: 2.3% (1023/44672)
• Age 80: 14.8% (208/1408)
• Age 70-79: 8.0% (312/3918)
• Critical clinical form: 49.0% (1023/2087)

• Health Professionals No.1716 (3.8%)

• Wuhan: 63% (No.1080)
• Serious or critical forms: 14% (No.247)
• Deaths: 0.3% (No.5)

Critical:

Monocentric study, retrospective, intensive care unit, No. 52

Demographics:

Average age (years): 59.7 (up 13.3)

Male: 35 (67%)

• Comorbidities: 21 (40%)

• heart disease: 5 (10%)
• respiratory: 4 (8%)
• cerebrovascular: 7 (13.5%)
• diabetes: 9 (17%)
• cancer: 2 (4%)

Clinical:

• Fever: 51 (98%)
• Cough: 40 (77%)
• Dyspnea: 33 (64%)
• Discomfort: 18 (35%)
• Myalgias: 6 (12%)
• Rhinorrhea: 3 (6%)

Imaging:

• Bilateral pneumonia: 52 (100%)
• Median delays between the onset of clinical signs and:

• diagnosis of lung disease: 5 (IQR 3-7)
• ICU admission: 9.5 (IQR 7-12.5)

Gravity:

• APACHE II score: 17 (IQR14-19)
• SDRA: 35 (67%)
• Acute kidney failure: 15 (29%)
• Heart failure: 12 (23%)
• Liver insufficiency: 15 (29%)
• Septic shock: 12 (9%)

Treatment:

• NAV: 29 (56%)
• Intubation: 22 (42%)
• Ventral decubitus: 6 (12%)
• ECMO: 6 (12%)
• Antivirals (anti-COVID -19): 23 (44%)
• Antibiotics: 49 (94%)
• Corticosteroids: 30 (58%)
• Immunoglobulins: 28 (54%)

Evolution:

• Death: 32 (62%)
• Healing: 8 (15%)

Synthesis:

• Patients with COVID-19
• Most common clinical signs: fever, cough, dyspnea
• Radiological signs: condensation outbreaks and extensive infiltrats
• Most common benign forms; serious or critical: 15 to 20%
• Possible secondary aggravation, to J8-J9 (dyspnea -SDRA)
• Fatal outcome: death 2% to 14% (according to studies)

6- Support:

"Information for UAS and other 1st line carers – COREB" regularly updated on the COREB website to be consulted here

From the patient suspect REB to the confirmed case… or excluded

From the patient suspect REB to the confirmed case… or excluded

7- Samples:

Professionals in the events performing the samples: personal protective equipment (EPI)

Type of respiratory samples	Collectibles
Nasopharyngeal and oropharyngeal swab	Flaky swabs in dacron or polyester
Washing Broncho alveolar	Sterile container
Tracheal aspiration, nasopharyngeal suction or nasal wash	Sterile container
Sputum	Sterile container

 

Transport temperature: 4C – Storage time until test completion: If 5 days: 4 C, if 5 days: 70 C

SARS-CoV-2: Group 2 biological agent, requiring triple packaging:

• One or more watertight primary containers
• Waterproof secondary packaging
• Rigid exterior packaging

Note the virus may be present in stool, urine…

PCR SARS-CoV-2 negative, depending on condition, may require verification

8- SARS-CoV treatments, MERS-CoV:

• Lopinavir-ritonavir-Ribavirine:

• SARS-CoV: 41 infected patients treated for 21 days, clinical improvement of treated subjects
• MERS-CoV: 76 infected patients, ongoing study (MIRACLE), Saudi Arabia

• Remdesivir (RDV): Antiviral broad spectrum

1. Model of the mouse hepatitis virus: inhibition of viral replication in vitro
2. MERS-CoV: higher re-ctivity than LPVrin vitro

9- References:

1. Na Zhu et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. NEJM – Jan 24, 2020 https://www.nejm.org/doi/10.1056/NEJMoa2001017
2. Wu Z et al. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases From the Chinese Center for Disease Control and Prevention. JAMA – 24 Feb 2020
3. Liu Y et al. The reproductive number of COVID-19 is higher compared to SARS coronavirus. J Travel Med – 13 Feb2020
4. Imperial College London. Report 3: Estimating the potential total number of novel coronavirus cases in Wuhan City, China. 22 Jan2020 https://www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gida-fellowships/Imperial-2019-nCoV-transmissibility.pdf
5. Wu JT et al. Nowcastingand forecasting the potential domestic and international spread of the 2019-nCoV outbreak outbreaking in Wuhan, China: a modelling study. Lancet. 2020 Jan 31 https://www.sciencedirect.com/science/article/pii/S0140673620302609?via%3Dihub
6. QunLi et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. NEJM – Jan 29, https://www.nejm.org/doi/full/10.1056/NEJMoa2001316?query=featured_home
7. Nanshan Chen et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet – Jan 29, 2020 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30211-7/fulltext
8. Jasper Fuk-Woo Chan et al. A family cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet – Jan 24, 2020 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30154-9/fulltext
9. Wang D et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. Jama. 2020Feb https://jamanetwork.com/journals/jama/fullarticle/2761044
10. French Hygiene Society hospitalièrehttps://www.sf2h.net/avis-sf2h-2019-ncov-publication-de-28-janvier-2020
11. Xiaoboet al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Lancet RespirMed 2020 -21 fev2020 https://www.thelancet.com/journals/lanres/article/PIIS2213-2600 (20)30079-5/fulltext
12. ChaolinHuanget al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet – Jan 24, 2020 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30183-5/fulltext
13. French Society of Microbiology https://www.sfm-microbiologie.org/wp-content/uploads/2020/02/Fiche-nCOV-NL-14022020.pdf
14. https://www.pasteur.fr/fr/sante-publique/centres-nationaux-reference/materiel-biologique/comment-expedier-ses-echantillons
15. https://www.legifrance.gouv.fr/affichCodeArticle.do?idArticle=LEGIARTI000018530508&cidTexte=LEGITEXT000006072050&dateTexte=20080501
16. https://apps.who.int/iris/bitstream/handle/10665/330374/WHO-2019-nCoV-laboratory-2020.1-eng.pdf
17. Chu CM et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virologicaland clinical findings. Thorax Mar 2004 https://thorax.bmj.com/content/59/3/252
18. Arabi YM et al. Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-1b (MIRACLE trial): study protocol for a randomized controlled trial. Trials Jan 2018 https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-017-2427-0
19. Maria L. Agostini et al. Coronavirus Susceptibility to the Antiviral Remdesivir (GS5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. mBio -Mar 2018 https://mbio.asm.org/content/9/2/e00221-18.long
20. Sheahan TP et al. Comparative therapeutic efficacy of remdesivirand combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun-10 Jan 2020 https://www.nature.com/articles/s41467-019-13940-6
21. Public Health France, documentation https://partage.santepubliquefrance.fr/public/folder/1COECj7hj0K9Y0jGNeT0sQ/Novel%20Coronavirus_Daily%20Article%20List_February%202020

Contributions: JM Chapplain-G Mellon (Mission COREB), S van der Werf (CNR coronavirus), B Grandbastien (SF2H), B Hoen (SPILF Emergences),D Malvy -D Nguyen (ESR Bordeaux) and infectious scientists ref. Esr