21.04.2020

Antibody Detection and Dynamic Characteristics in Patients with COVID-19

Others InfectiologyVirology
Xiang F et al
Clin Infect Dis

Main result

- IgG and IgM are positive on day 4 after the onset of symptoms (Day 7 for one patient).
- IgM crescent and progressive increase from the beginning
- Clear IgG increase from day 12 and decreased at day 28 (but analysis of only 7 patients and 7 serums)
- IgG and IgM still positive after 30 days of follow-up

=> Group of patients with confirmed diagnosis (therefore all having PCR +) n = 66 (out of 85)
- IgM: sensitivity : 77.3% (51/66), specificity 100% (60/60), PPV 100% [51 / (51 + 0)], NPV 80.0% [60 / (15 + 60)], consistency rate 88.1% [(51 + 60) / (51 + 15 + 0 + 60)],
- IgG: sensitivity: 83.3.3% (55/66), specificity 95.0% (57/60), PPV 94.8% [55 / (55 + 3)], NPV 83.8% [57 / (11 + 57)], consistency rate 88.9% [(55 + 57) / (55 + 11 + 3 + 57)],

=> Group with suspected diagnosis (therefore with all PCR - twice) n = 24/24
- IgM: sensitivity 87.5% (21/24), specificity 100% (60/60), VPP 100% [21 / (21 + 0)], VPN 95.2% [60 / (3 + 60)], and rate of agreement 96.4% [(21 + 60) / (21 + 3 + 0 + 60)]
- IgG: sensitivity 70.8% (17/24), specificity 96.6% (57/60), PPV 85.0% [17 / (17 + 3)], NPV 89.1% [57 / (7 + 57)], and rate of agreement 88.1% [(17 + 57) / (17 + 7 + 3 + 57)]

=> Control group:
- No positive IgM
- 3 cases of positive IgG (1 at very low rates) including 1 possibly considered as asymptomatic & cured
 

Takeaways

The IgM and IgG antibodies are synchronized and detected approximately after 4 days and remain detectable until day 30 minimum (with an IgG decrease on day 28)

IgM antibodies have:
- Good specificity and PPV, which are conserved after day 13 so positive IgM could be good diagnosis tools.
- Lower sensitivity, NPV and agreement rate: therefore, negative IgM can lead to errors and risk of missing an infection, especially in the acute interval
IgG antibodies have:
- Good specificity, NPV, and a good match rate. Diagnosis can be made on a positive IgG result.
The IgM and IgG antibodies have a high specificity = strong argument for diagnostic tests (especially for an advanced stage of the disease).
In the case of negativity and doubt, the article advises repeating the serology after 10 days.
A complementary approach to PCR for the diagnosis of COVID patients

 

Strength of evidence Moderate

"Moderate
Prospective study to assess diagnostic properties versus accepted gold standard (RT-PCR)
A moderate number of patients (65 maximum)
Good methodology
"

Objectives

Study the dynamic characteristics and the magnitude of the specific antibody response of COVID+ patients as well as the serodiagnostic value of IgM and IgG.
 

Method

Prospective, multicentric study
Daily serological tests from day 0 to day 29
Comparison to the gold standard (RT-PCR)
3 groups:
- Control patient (n = 60) healthy patients or patients hospitalized for another reason (5 cases of pneumonia, 3 lung cancers, 2 COPD exacerbations, 2 PID, 1 empyema, and 1 pleurisy).
- Patients with confirmed diagnosis (n = 85): Positive PCR test. With two subcategories
o Normal cases if no severity criteria
o Severe cases if RR> 30%, if saturation <93%, FiO2 <300 and radiographic progression of> 50%
- Patient with suspected diagnosis (n = 24):
o Two negative PCR test
o But anamnesis in favor
 * Travel or residential history in Wuhan or in endemic areas
 * Contact with COVID-19 + pneumonia patients or individuals with fever or respiratory symptoms in these areas within 14 days
 * Group of patients with the same suggestive symptoms and living in a group
o AND minimum 2 out of 3 of the following clinical features :
 * Fever and/or respiratory symptoms.
 * Pulmonary CT results in favor of the diagnosis.
 * Decrease of lymphocytes and the number of WBC at the early stage
 

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