SARS-CoV-2 evolution in a patient with secondary B-cell immunodeficiency: A clinical case

Figures & data

Table 1. Dynamics of PCR results and serum levels of IgM and IgG to SARS-CoV-2.

Date	PCR for SARS-CoV-2 RNA*	IgM to SARS-CoV-2, IU/mL**	IgG to SARS-CoV-2, IU/mL***	Additional Information
Oct 23, 2020	Negative	0.13	0.00	The last injection of 700 mg of Rituximab Oct 26, 2020
Nov 7, 2020	Positive	Not performed	Not performed	Febrile body temperature; Outpatient treatment: Umiferovir + Azithromycin
Nov 17, 2020	Negative	Not performed	Not performed	Bilateral polysegmental pneumonia – CT class 1
Dec 23, 2020	Positive	0.11	0.14	Bilateral polysegmental pneumonia – CT class 2
Jan 3, 2021	Negative	0.11	0.19	Worsening of clinical symptoms, hospitalization to January 12
Jan 23, 2021	Negative	Not performed	Not performed	Re-hospitalization, change of therapy to February 5
Mar 15, 2021	Positive	Not performed	Not performed	Bilateral polysegmental pneumonia – CT class 2. Outpatient treatment: Areprivir+Methylprednisolone+ Levofloxacin, human intravenous immunoglobulin (IVIG) replacement therapy (50 mg/mL, 2.5 g protein once every 3 days, 3 transfusions)
Mar 31, 2021	Negative	Not performed	Not performed
Apr 7, 2021	Positive	0.09	0.0	Negative trend on CT scan. Outpatient treatment: Triazaverine 250 mg (1 tablet 3 times daily) + Acetylcysteine (600 mg daily)
Apr 18, 2021	Positive	Not performed	Not performed
May 24, 2021	Negative	Not performed	Not performed	Therapy with 150 mL of COVID globulin (Nacimbio), May 20 2021
May 27, 2021	Notperformed	0.12	33.21	Improvement of clinical manifestations
Jun 11, 2021	Negative	0.1	17.29	Increased tolerance to physical activity. Positive dynamics on chest CT

*Analytical sensitivity of the method: 25 copies per PCR sample, corresponding to 1 × 10³ copies/ml of the original sample. The response format for PCR testing was qualitative: positive/negative.

**Negative IgM test for SARS-CoV-2 < 2 IU/mL.

***Negative IgG test for SARS-CoV-2 < 10 IU/mL; CT- chest computed tomography with a 32-slice CT scanner.

Table 2. BR scores of mutated sites in ancestral and derived states for HLA alleles of the patient.

Mutation	Class of HLA	Allele	BR in ancestral state	BR in derived state
S:G75A	HLA I	HLA-A *25:01	1.28	0.85
S:G75A	HLA I	HLA-A *32:01	No binding	No binding
S:G75A	HLA I	HLA-B × 40:02	No binding	No binding
S:G75A	HLA I	HLA-B × 44:02	No binding	No binding
S:G75A	HLA I	HLA-C × 02:02	No binding	No binding
S:G75A	HLA I	HLA-C × 07:04	No binding	No binding
ORF3a:L37I	HLA I	HLA-A *25:01	0.35	0.18
ORF3a:L37I	HLA I	HLA-A *32:01	0.09	0.05
ORF3a:L37I	HLA I	HLA-B × 40:02	No binding	No binding
ORF3a:L37I	HLA I	HLA-B × 44:02	1.18	1.02
ORF3a:L37I	HLA I	HLA-C × 02:02	0.24	0.13
ORF3a:L37I	HLA I	HLA-C × 07:04	0.50	0.55
S:G75A	HLA II	HLA-DRB1 × 11:01	2.63	2.88
S:G75A	HLA II	HLA-DRB3 × 02:02	4.00	2.37
S:G75A	HLA II	HLA-DQB1 × 03:01	5.76	2.40
ORF3a:L37I	HLA II	HLA-DRB1 × 11:01	9.02	7.66
ORF3a:L37I	HLA II	HLA-DRB3 × 02:02	2.70	2.24
ORF3a:L37I	HLA II	HLA-DQB1 × 03:01	2.38	1.11

BR – Best Rank_EL score.¹¹ Ancestral – the nearest known SARS-CoV-2 ancestor. Derived – SARS-CoV-2 isolated from the patient.

Table 3. PHBR scores of mutated sites in ancestral and derived states for two classes of HLA alleles.

Mutation	PHBR before mutations	PHBR after mutation	Class of HLA
S:G75A	3.53	2.68	HLA I
ORF3a:L73I	0.27	0.17	HLA I
S:G75A	3.73	2.52	HLA II
ORF3a:L73I	3.33	2.03	HLA II

PHBR – Patient Harmonic-mean Best Rank.¹¹ Ancestral – the nearest known SARS-CoV-2 ancestor. Derived – SARS-CoV-2 isolated from the patient.

Reynisson B, Alvarez B, Paul S, Peters B, Nielsen M. NetMhcpan-4.1 and NetMhciipan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data. Nucleic Acids Res. 2020;48(W1):W449–W454. doi:10.1093/nar/gkaa379.

 PubMed Web of Science ®Google Scholar