Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Reinfection by a Phylogenetically Distinct Strain

Abstract

To the Editor—To and colleagues reported the first documented case of an asymptomatic reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after 4.5 months [1]. As the patient experienced only mild symptoms during the first episode, the question remains whether a weak immune response after the first episode might explain the reinfection. It has been suggested that patients with an asymptomatic or mild SARS-CoV-2 infection have a weaker immune response because their antibody titers are significantly lower than in patients with pneumonia [2]. An estimated 20% do not seroconvert [3]. It also remains unclear whether patients can have a symptomatic reinfection. A recent Italian study reported no clinical reinfections within 3 months after hospital discharge [4]. We here report a symptomatic reinfection 93 days after a moderate SARS-CoV-2 infection. In March 2020, a 51-year-old women presented to the general practitioner symptoms of headache, fever, myalgia, coughing, chest pain, and dyspnea. She also mentioned anosmia and a change in taste. She was not immunocompromised but took a daily dose of inhaled corticosteroids for asthma. A nasopharyngeal swab tested positive with SARS-CoV-2 polymerase chain reaction (PCR). Routine biochemistry and complete blood count did not show any abnormalities besides mildly elevated liver enzymes. Oxygen saturation by capillary oximeter was 94%. Hospitalization was not deemed necessary at the time, and the patient was asked to self-quarantine for 2 weeks. Because of persisting symptoms of tiredness, muscle pain, and dyspnoe, she stayed at home for 5 weeks before returning to work. Three months after initial onset of symptoms, she experienced a relapse of symptoms with headache, cough, and fatigue. Rhinitis was also present. There was no travel history. The patient told the general practitioner that the symptoms felt similar to the first episode in March, although milder. The nasopharyngeal swab was again positive for SARS-CoV-2, suggesting a reinfection (Table 1). The symptoms resolved after 1 week. At that time, the patient tested positive for anti-SARS-CoV-2 nucleocapsid antibodies (Roche total immunoglobulin [Ig] signal/cutoff 134). Reverse-Transcription Polymerase Chain Reaction (RT-PCR) and Full-length Genome-sequencing Results Abbreviations: Ct, cycle threshold; GISAID, Global Initiative on Sharing All Influenza Data; NS, nonsynonymous mutation; qPCR, quantitative polymerase chain reaction; S, synonymous mutation; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. a2019-nCoV CDC EUA kit. bNomenclature based on reference [5]. Full-length genome sequencing with ONT MinION revealed that the initial infection was caused by a lineage B.1.1 SARS-CoV-2 virus and the relapsing infection by a lineage A [5]. Eleven mutations were identified across the genome of the 2 strains (11/29 903 differences, 99.7% identity; Table 1). This difference is in line with other circulating strains in Belgium [6]. Documenting reinfection requires full-length genome sequencing or viral culture as PCR can remain positive for up to 104 days [7]. Usually asymptomatic and mild cases exhibit longer RNA shedding than severe cases [2]. The fact that a symptomatic reinfection with SARS-CoV-2 can occur already 3 months after the first infection is not unexpected. Symptomatic reinfections with human non-SARS coronaviruses are common and not atypical within 1 year after initial infection, despite the presence of antibodies. Reinfections with human non-SARS coronaviruses are, however, typically milder as was the case in our patient [8–10]. The fact that clinical reinfection can occur shortly after the first infection further underlines the fact that both healthcare workers and patients who had a prior SARS-CoV-2 infection are not always protected against reinfection. Acknowledgments. P. V. is a senior clinical investigator of the FWO-Vlaanderen. Author contributions. P. M., K. L., and P. V. conceived the study. J. V. E., P. V., T. W. B., B. V. M., E. W., and P. M. conducted experiments and drafted the manuscript. All other authors aided in collecting data and critically reviewed the manuscript. Potential conflicts of interest. P. V. reports personal fees from Roche, outside the submitted work. K. L. reports personal fees and nonfinancial support from Pfizer, MSD, personal fees from SMB Laboratoires, Gilead, and FUJIFILM Wako outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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