Relapse of COVID-19 and Viral Evolution in a Patient With Good Syndrome: A Case Report

Abstract

Delays in clearance and rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in immunocompromised patients. We encountered a case of recurrent, multi-mutational SARS-CoV-2 infection in a 40-year-old man with severe immunodeficiency due to Good syndrome. The patient had not received the SARS-CoV-2 vaccination. In August 2021, he was first admitted to the hospital owing to coronavirus disease 2019 (COVID-19) pneumonia and was administered dexamethasone, remdesivir, and baricitinib. Although his fever and respiratory condition improved once, chest computed tomography (CT) revealed extensive diffuse consolidation and ground-glass opacities (GGOs), and both methylprednisolone pulse therapy and tocilizumab yielded a limited effect. After a third course of remdesivir without immunosuppressants or steroids, the patient recovered, and he tested negative for SARS-CoV-2. On day 272 since the clinical onset, he was readmitted with dyspnea and mild fever due to a COVID-19 recurrence. He was infected with the Delta variant (AY.29), despite the Omicron (BA.2) variant being predominant at that time. During this admission, additional remdesivir and casirivimab/imdevimab yielded marked effects, and the SARS-CoV-2 quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) tests rapidly returned negative. Phylogenetic analysis demonstrated the accumulation of mutations, including those yielding remdesivir resistance, throughout the SARS-CoV-2 genome. Appropriate use of antivirals and monoclonal antibodies may aid in the recovery of patients with COVID-19 and immunodeficiency and in preventing the emergence of multi-mutational SARS-CoV-2 variants.

Keywords: covid-19; good syndrome; relapse; sars-cov-2; viral evolution.

Figure 1. A series of chest computed tomography (CT) images of the patient with Good syndrome with recurrent COVID-19.

Denotes the number of days after symptom onset. A. On day 42, extensive ground-glass opacities (GGOs) and consolidation were observed in both lungs. B. On day 61, the GGOs and consolidation improved after the administration of remdesivir, corticosteroids, and tocilizumab. C. On day 65, new GGOs emerged bilaterally. D. On day 79, only a few patchy GGOs remained at the time of discharge. E. On day 272, various abnormal shadows, such as reticulonodular shadows and bronchiectasis, were observed. Moreover, new consolidations and GGOs emerged. F. On day 300, the patient’s respiratory condition improved, and most GGOs had turned into reticular shadows.

Figure 2. The clinical course of the 40-year-old male patient with recurrent SARS-CoV-2 infection.

A. The upper panel shows the clinical course of the patient. Black squares, red circles, and blue stars indicate Cq values, IgG-S, and CT scans, respectively. SARS-CoV-2 positivity (qRT-PCR) is indicated in the upper part of the graph by a + (positive) or – (negative) sign. Each treatment regimen is indicated in the upper part of the graph by horizontal lines. The bottom panel represents the number of daily new cases of SARS-CoV-2 infections in Japan. B. Phylogenetic analysis was performed using patient-derived sequences (blue circle, n = 4) and sequences derived from the GISAID database (yellow circle, n = 778). The branch length corresponds to nucleotide divergence. A cluster of patient-derived sequences is enlarged in the lower right frame. Cq: quantification of cycle; GISAID: Global Initiative on Sharing All Influenza Data

Figure 3. Whole genome sequencing of patient-derived SARS-CoV-2

Schematic representation of the locations of amino acid mutations in the patient at two sampling time points, P1 (upper) and P4 (lower), as compared with Wuhan-Hu-1 (NC_045512.2). The images were generated by the Stanford SARS-CoV-2 Sequence Analysis tool (https://covdb.stanford.edu/sierra/sars2/by-sequences/). Red-shaded areas are positions that were not sequenced or aligned.