Clinical application of SARS-CoV-2 antibody detection and monoclonal antibody therapies against COVID-19

Table 1 Seropositive rates of severe acute respiratory distress syndrome coronavirus-2-specific immunoglobulin G and immunoglobulin M at various time points after symptom onset

Days after symptom onset	IgM positivity rate (%)	IgG positivity rate (%)
0–5	44/118 (37.3)	71/118 (60.2)
6–15	36/55 (65.5)	44/55 (80.0)
16–25	48/70 (68.6)	56/70 (80.0)
26–35	26/56 (46.4)	2/56 (75.0)
36–95	17/95 (17.9)	56/95 (58.9)

IgG: Immunoglobulin G; IgM: Immunoglobulin M.

Table 2 Clinical significance of combined detection of severe acute respiratory distress syndrome coronavirus-2-specific antibodies and RNA

No.	Antibody assay		Nucleic acid detection	Clinical significance
	IgM	IgG
1	+	+	+	During the active infection period, the body has a certain resistance to COVID-19 (persistent IgG has been produced)
2	+	-	+	The patient may be in the middle of the SARS-CoV-2 infection. The body's immune response produces IgM antibodies early in the disease course. IgG has not yet been produced, or the IgG level has not reached the limit of detection
3	-	+	+	The patient may be in the middle or late phase of the disease or may have a recurrent infection of SARS-CoV-2
4	-	-	+	This is the COVID-19 "window period", which usually lasts 2 wk
5	+	+	-	The patient is in the recovery phase of COVID-19. The virus has been cleared from the body, and IgM and IgG are positive. Alternatively, this may indicate that the nucleic acid test result was a false negative, and the patient is in the active phase of infection
6	+	-	-	IgM positivity indicates that the patient may be in the early stage of infection. Suspicious nucleic acid test results require repeated sampling and verification
7	±	-	-	This indicates that the patient is in the early stage of viral infection, and the viral load is very low. The patient is in the acute stage of COVID-19, and the body has not yet produced IgG. Alternatively, the result for IgM may have been an error caused by the presence of rheumatoid factor. One week later, the examination and diagnosis must be repeated based to evaluate for changes in IgM and IgG
8	-	+	-	The patient may have been infected with the virus in the past and has recovered; the virus has been cleared from the body. IgG can last for a long time, possibly even for life
9	-	-	-	The individual is healthy or in the incubation period of infection

IgM: Immunoglobulin M; IgG: Immunoglobulin G; COVID-19: Coronavirus infectious disease 2019; SARS-CoV-2: Severe acute respiratory distress syndrome coronavirus-2.

Table 3 Sensitivity of Omicron variants to therapeutic monoclonal antibodies

mAb (s)	FDA EUA	Target on S	Omicron variant
			BA.1	IC50	BA.2	IC50
Bamla/Etese	Yes	BRD or S	Reduction in activity vs control approximately 1000-fold (highly resistant)	> 10000 ng/mL	Reduction in activity vs control approximately 1000-fold (highly resistant)	> 10000 ng/mL
Casir/Imdev	Yes	BRD	Reduction in activity vs control approximately 1000-fold (highly resistant)	> 10000 ng/mL	Reduction in activity vs control approximately 1000-fold (highly resistant)	> 10000 ng/mL
Sotro	Yes	BRD	Median fold reduction in susceptibility 4.0 (IQR: 2.6 to 6.9)	Median 276 ng/mL (IQR: 163 to 423)	Median fold reduction in susceptibility 17 (IQR: 13 to 30)	Median 1250 ng/mL (IQR: 567 to 1456)
Cilag/Tixag	Yes	BRD	Median fold reduction in susceptibility 86 (IQR:27 to 151). The FDA recommended that the dosage for each mAb in this combination be increased 300 mg and administered intramuscularly	Median 256 ng/mL (IQR: 170 to 750)	Median fold reduction in susceptibility 5.4 (IQR: 3.7 to 6.9). Nearly complete restoration BA.2 susceptibility to cilgavimab	Median 44 ng/mL (IQR: 27 to 73)
Bebte	Yes	BRD	Median fold reduction in susceptibility 1.0 (IQR: 0.7 to 1.4) Bebtelovimab is the only mAb active against the current dominant circulating Omicron variant; in non- hospitalized adults, bebtelovimab may be used as an alternative therapy when no preferred therapy (e.g., nirmatrelvir/ritonavir, remdesivir) available	Median 2.6 ng/mL (IQR: 1.8 to 5.0)	Median fold reduction in susceptibility 1.0 (IQR: 0.7 to 1)	Median 4.0 ng/mL (IQR: 0.8 to 5.0)
Regda	No	BRD	Displayed little residual activity	NA	Displayed little residual activity	NA
Amuba	No	BRD	Displayed little residual activity	NA	Displayed little residual activity	NA
Romlu	No	BRD	Retained partial activity	NA	Displayed little residual activity	NA
Adint	No	BRD	Retained partial activity	NA		NA

Adint: Adintrevimab; Amuba: Amubarvimab; Bamla/Etese: Bamlanivimab/Etesevimab; Bebte: Bebtelovimab; BRD: Spike receptor binding domain; Casir/Imdev: Casirivimab/Imdevimab; Cilag/Tixa: Cilgavimab/Tixagevimab; EUA: Emergency use authorization; FDA: United States Food and Drug Administration; IC₅₀: 50% inhibitory concentration; IQR: Interquartile range; mAbs: Monoclonal antibodies; NA: Not available; Regda: Regdanvimab; Romlu: Romlusevimab; S: Spike protein; Sotro: Sotrovimab.