Open Forum Infectious Diseases NOVEL ID CASES Critical Presentation of a Severe Acute responses against SARS-CoV-2. All antibody isotypes tested as well as SARS-CoV-2 neutralizing antibodies increased sharply Respiratory Syndrome Coronavirus 2 after day 8 postsymptoms. A slight increase of T-cell responses Reinfection: A Case Report was observed at day 19 after symptom onset. Conclusions. The reinfection was firmly documented and Marta Massanella,1, Anabel Martin-Urda,2 Lourdes Mateu,3,4 Toni Marín,5 Irene Aldas,5 Eva Riveira-Muñoz,1 Athina Kipelainen,1 Esther Jiménez-Moyano,1 occurred in the absence of robust preexisting humoral and cel- Maria Luisa Rodriguez de la Concepción,1 Carlos Avila-Nieto,1 Benjamin Trinité,1 lular immunity. SARS-CoV-2 immunity in some subjects is Edwards Pradenas,1 Jordi Rodon,6 Silvia Marfil,1 Mariona Parera,1 Jorge Carrillo,1 unprotective and/or short-lived; therefore, SARS-CoV-2 vac- Julià Blanco,1,7 Julia G Prado,1 Ester Ballana,1 Júlia Vergara-Alert,6 Joaquim Segalés,6,8 Marc Noguera-Julian,1,7, Àngels Masabeu,2 cine schedules inducing long-term immunity will be required Bonaventura Clotet,1,3,7 Maria de la Roca Toda,2 and Roger Paredes1,3,7 to bring the pandemic under control. 1 IrsiCaixa-AIDS Research Institute and Germans Trias i Pujol Health Research Institute, Keywords. immune responses; life-threatening COVID- Badalona, Catalonia, Spain, 2Internal Medicine Department, Hospital de Palamós, Palamós, 19; reinfection; SARS-CoV-2; secondary infection. Catalonia, Spain, 3Infectious Diseases Department, Hospital Germans Trias i Pujol, Catalonia, Spain, 4Universitat Autònoma de Barcelona, Catalonia, Spain, 5Pneumology Department, Hospital Germans Trias i Pujol, Catalonia, Spain, 6Institute of Agrifood Research and High levels of population immunity against severe acute respi- Technology Centre de Recerca en Sanitat Animal, Campus de la Universitat Autònoma de ratory syndrome coronavirus 2 (SARS-CoV-2) will be needed Barcelona, Bellaterra, Catalonia, Spain, and 7Universitat de Vic Central de Catalunya, Vic, Catalonia, Spain, and 8Departament de Sanitat i Anatomia Animals, Facultat de Veterinària, to control the coronavirus disease 2019 (COVID-19) pandemic. Universitat Autònoma de Barcelona, Bellaterra, Catalonia, Spain A handful of cases of SARS-CoV-2 reinfection have been re- ported worldwide since September 2020 [1–7], casting doubts Background. Severe acute respiratory syndrome corona- on the durability of immune responses to this virus. Whereas virus 2 (SARS-CoV-2) reinfections have been reported; how- infections by the closely related betacoronaviruses severe acute ever, most cases are milder than the primary infection. We respiratory syndrome coronavirus and Middle East respiratory report the first case of a life-threatening critical presentation of syndrome coronavirus elicit long-lasting protective immunity a SARS-CoV-2 reinfection. [8, 9], immune responses to common-cold coronaviruses are Methods. A 62-year-old man from Palamós (Spain) suf- fered a first mild coronavirus disease 2019 (COVID-19) epi- short-lived [10]. Reinfections may occur after a few months, sode in March 2020, confirmed by 2 independent SARS-CoV-2 but usually with mild symptoms [11]. SARS-CoV-2 reinfection nasopharyngeal polymerase chain reaction (PCR) assays and a cases have generally been mild except in 1 case, and none have normal radiograph. He recovered completely and tested negative been life-threatening. Here we report the first critical presenta- on 2 consecutive PCRs. In August 2020, the patient developed tion of a SARS-CoV-2 reinfection and investigate its virological a second SARS-CoV-2 infection with life-threatening bilateral and immune correlates. pneumonia and Acute respiratory distress syndrome criteria, requiring COVID-19–specific treatment (remdesivir + dexa- CASE REPORT methasone) plus high-flow oxygen therapy. Nasopharyngeal swabs from the second episode were obtained for virus quanti- The patient was a 62-year-old male hospitalist physician from fication by real-time PCR, for virus outgrowth and sequencing. Palamós (Girona) with previous history of mild asthma, hy- In addition, plasma and peripheral blood mononuclear cells pertension, dyslipidemia, liver steatosis, hyperuricemia, and during the hospitalization period were used to determine overweight (body mass index ≥30 kg/m2). He was receiving SARS-CoV-2–specific humoral and T-cell responses. treatment with olmesartan, hydrochlorothiazide, and allo- Results. Genomic analysis of SARS-CoV-2 showed that the purinol. Occasionally, he received oral corticosteroids for his virus had probably originated shortly before symptom onset. asthma, and intra-articular slow-release triamcinolone plus hy- When the reinfection occurred, the subject showed a weak aluronic acid to treat recurrent episodes of right knee pain and immune response, with marginal humoral and specific T-cell swelling. Received 10 March 2021; editorial decision 15 June 2021; accepted 21 June 2021. First Episode of SARS-CoV-2 Infection Correspondence: Marta Massanella, PhD, Hospital Germans Trias i Pujol, Ctra de Canyet s/n, 08916 Badalona, Catalonia, Spain (mmassanella@irsicaixa.es). Being previously well, on 23 March 2020, he developed fever Open Forum Infectious Diseases 2021 ® of 38ºC, diarrhea, anosmia, dysgeusia, cough, intense asthenia, © The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases and arthromyalgias. Two consecutive nasopharyngeal PCR Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ tests on 24 and 25 March were positive for SARS-CoV-2. With by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any a normal radiograph (Figure 1A), the subject was confined at medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com home and received treatment with hydroxychloroquine per https://doi.org/10.1093/ofid/ofab329 oral (PO) for 7 days (400 mg twice daily on day 1, followed by NOVEL ID CASES • ofid • 1 200 mg twice daily on days 2–7) plus azithromycin 500 mg PO pressure of oxygen in arterial blood (PaO2) = 80.5 mm Hg, once daily for 3 days. Symptoms improved, but the anosmia, and partial pressure of carbon dioxide (PaCO2) = 31.0 mm Hg dysgeusia, asthenia, and shortness of breath did not completely (PaO2/FiO2: 383 mm Hg). resolve until mid-April. On 2 April, a COVID-19 immunoglob- On 2 September (day 5 postsymptoms), he initiated remdesivir ulin M (IgM)/immunoglobulin G (IgG) rapid test (Leccurate, (200 mg the first day, followed by 100 mg/day for 5 days), dexa- Lepu Medical) was negative, and on 7 and 8 April, 2 nasopha- methasone (6 mg/day PO), and enoxaparin (40 mg/day subcu- ryngeal swab PCRs tested negative for SARS-CoV-2. In prepa- taneously), as well as intravenous (IV) amoxicillin-clavulanate, ration for a trekking excursion, on 30 May he received 1 dose which was eventually withdrawn when urine pneumococcal of intra-articular triamcinolone 40 mg plus hyaluronic acid in and Legionella species antigens and bacterial sputum and blood the right knee. cultures were negative. Initially, he remained with oxygen satu- ration 96%–97% with nasal cannulas 2 L/minute (FiO2 = 24%), Second Episode but showed worsening of his radiologic infiltrates with per- On 28 August, 3 days after returning to work from vacation in sistence of elevated inflammation markers. A lung computed northern Spain, he developed intense arthromyalgias, head- tomography angiogram on 3 September ruled out pulmonary ache, fever, cough, and dyspnea. He prescribed himself treat- thromboembolism and confirmed extensive bilateral lung in- ment with oral azithromycin 500 mg once daily for 3 days, filtrates with areas of pneumonic consolidation (Figure 1C). inhaled salmeterol, and oral prednisone (30 mg PO the first He then received 2 doses of tocilizumab (600 mg IV) on 3 day, followed by 15 mg PO once daily thereafter). Again, he and 4 September, and dexamethasone dosing was increased to underwent 2 consecutive nasopharyngeal SARS-CoV-2 PCR 20 mg/day. Despite progression of the lung infiltrates (Figure tests on 31 August (hospital laboratory) and 1 September (pri- 1D), he remained clinically stable until 7 September (day 10 vate laboratory), both of which were positive. On 2 September, postsymptoms), when his respiratory status deteriorated ab- he was admitted to the emergency room of the Hospital de ruptly, with ABG (FiO2 = 35%) of pH = 7.45, PaO2 = 55 mm Palamós for worsening dyspnea and cough. He reported chills, Hg, and PaCO2 = 38 mm Hg (PaO2/FiO2: 157 mm Hg). He fever 39ºC, myalgias, anosmia, and ageusia. His respiratory rate was transferred to the respiratory intermediate care unit at was 36 breaths/minute, his heart rate was 100 beats/minute, Hospital Germans Trias i Pujol in Badalona for hypoxemic res- and he had bilateral inspiratory crackles. The electrocardio- piratory failure on 8 September. He was started on high-flow gram was normal and the chest radiograph showed bilateral oxygen therapy (HFOT) (50 L/minute, 87%) with an ABG of alveolar-interstitial infiltrates (Figure 1B). Upon admission, pH = 7.48, PaO2 = 105 mm Hg, and PaCO2 = 37 mm Hg (PaO2/ he had lymphopenia and high C-reactive protein, with normal FiO2: 121 mm Hg); the ratio of oxygen saturation index was D-dimer and procalcitonin. Baseline arterial blood gas (ABG) 5.95 at 6 hours. High-flow respiratory support was maintained (fraction of inspired oxygen [FiO2], 0.21) was pH = 7.45, partial during the following 4 days with progressive improvement, and A B C D Figure 1. Clinical characterization of the reinfected patient. A, First coronavirus disease 2019 (COVID-19) episode, 30 May 2020, with no radiologic infiltrates. Panels B–D correspond to 3 consecutive days of the second COVID-19 episode in September 2020, that is, 2 September (day of hospital admission, showing bilateral lung infiltrates, B), 3 September (lung angiogram that ruled out a lung thromboembolism but showed extensive bilateral lung infiltrates with left pneumonic consolidation, C) and 4 September (with clear radiologic progression in 48 hours, D). 2 • ofid • NOVEL ID CASES was withdrawn after an ABG (0.35% 30 L/minute HFOT) of onset (Figure 2C). Thereafter, all antibody isotypes as well as pH = 7.43, PaO2 = 102 mm Hg, and PaCO2 = 38 mm Hg (PaO2/ SARS-CoV-2 neutralizing antibodies increased sharply after FiO2: 291 mm Hg). Dexamethasone dosing was reduced to day 8 postsymptoms (Figure 2D). Neutralizing antibody levels 6 mg/day and tapered until withdrawal after 14 days. Given his peaked at days 11–13 from symptoms and plateaued afterward. favorable evolution, the patient was transferred to the infectious diseases ward, where conventional oxygen support was gradu- Cellular Immunology ally reduced and completely withdrawn on 17 September. The An interferon gamma (IFN-γ) enzyme-linked immunosorbent patient was finally discharged home on 18 September without spot assay detected a weak response against SARS-CoV-2 NP and further complications. spike recombinant proteins 7 days after symptom onset (Figure 2E). T-cell response levels remained below the limit of detec- METHODS tion up to day 19 after symptom onset, when a slight increase Patient Consent Statement of T-cell responses was observed, particularly against spike. The subject provided written informed consent for using diag- Direct intracellular quantification of IFN-γ, interleukin 2, and nostic images and clinical history, as well as for the prospective tumor necrosis factor–α production against S and NP recombi- collection of nasopharyngeal swabs, saliva, and blood samples nant proteins in CD4+ and CD8+ T cells (Figure 2F) revealed a to characterize the viral and immunological correlates of the consistent peak for all cytokines at day 11 postsymptoms, par- second SARS-CoV-2 episode (Supplementary Methods). No re- ticularly against NP. However, absolute levels of intracellular maining sample materials were available from the first episode. cytokine production remained low. Finally, we identified spike- The study was approved by the Hospital Universitari Germans specific CD4+ T-cell responses marked by CD25+OX40+ expres- Trias i Pujol Ethics Committee Board (reference PI-20-217). sion 18 days after symptom onset. RESULTS DISCUSSION Virology This first report of a SARS-CoV-2 reinfection with a life- High levels of SARS-CoV-2 particles (12.0 log10 copies of RNA/ threatening presentation has important clinical and public mL) were detected by quantitative real-time PCR in nasopha- health implications. Five months after a mild SARS-CoV-2 in- ryngeal swab and saliva samples at day 3 postsymptoms (31 fection confirmed by 2 independent SARS-CoV-2 PCRs, and August), decreasing progressively thereafter in both compart- following clinical and PCR resolution, this physician hospi- ments (Figure 2A). An infective SARS-CoV-2 isolate was re- talist suffered from a second SARS-CoV-2 infection with life- covered in Vero E6 cells from the 31 August nasopharyngeal threatening, severe respiratory failure, which required intensive swab sample. The full SARS-CoV-2 genome sequence was clas- respiratory support and COVID-19–specific treatment and, sified as genotype B.1.79 (G). According to Nextclade analysis fortunately, evolved well. The SARS-CoV-2 reinfection was [12], it contains 7 known amino acid substitutions (S:L18F, firmly documented through (1) quantitative real-time PCR S:A222V, S:D614G, nsp12:P323L, N:A220V, ORF14:L67F, showing repeatedly high viral loads and expected kinetics in ORF10:V30L) and 14 nucleotide mutations, 11 of which were independent compartments; (2) the ability to obtain a pro- private. To infer the origin of the virus, we aligned the viral ge- ductively infective SARS-CoV-2 in Vero E6 cells; and (3) the nome against the full GISAID database (16 October 2020) and genomic analysis of SARS-CoV-2 showed that the virus had selected the 100 best Spanish and the 100 best global hits for probably originated shortly before symptom onset. phylogenetic reconstruction (Figure 2B and Supplementary When the reinfection occurred, the subject had no evidence Data). All best BLAST hits corresponded to sequences anno- of preexisting humoral or cellular immune protection: either tated on 11 August or later, which were clearly divergent from the first SARS-CoV-2 infection did not generate a protective March and April sequences, strongly suggesting a recent origin immune response, or such response was lost between the 2 epi- of the reinfection virus. sodes. A rapid serology test performed between the 2 COVID- 19 episodes was negative for both IgM and IgG. However, 6 days Humoral Immunology after the reinitiation of symptoms, a more sensitive in-house se- Plasma and serum IgG, immunoglobulin A, and IgM anti- rological assay detected traces of anti-NP SARS-CoV-2 IgG. At bodies against SARS-CoV-2 receptor-binding domain (RBD), that time, there was no neutralizing activity at all, and T-cell nucleoprotein (NP), and spike antigens were determined using responses against spike and NP were very weak. The subsequent an in-house sandwich enzyme-linked immunosorbent assay. increase in humoral and cellular responses on days 11 and 18 Antigen-free conditions were used for background subtraction. postsymptoms, respectively, suggests that findings at day 6 were IgG antibodies against SARS-CoV-2 NP (but not against RBD residual adaptative responses from the first COVID-19 episode, or spike) were detectable at very low levels 6 days after symptom which did not protect him from a second infection. NOVEL ID CASES • ofid • 3 A B 1012 1010 (Log10 copies/mL) 108 Viral load Reinfection virus 106 104 Nasopharyngeal swab 102 March 2020 Saliva April 2020 100 August 2020 0 5 10 15 20 25 September 2020 Days postsymptoms 0.00040 0.00030 0.00020 0.00010 0.00000 Serum Plasma C RBD D NP Spike IgG IgA IgM Neutralization 1.5 1.5 0.5 10 000 Plasma (reciprocal dilution) Neutralization titer 0.4 OD Ag-OD BSA OD Ag-OD BSA OD Ag-OD BSA Serum 1.0 1.0 1000 0.3 0.2 0.5 0.5 100 0.1 0.0 0.0 0.0 10 0 5 10 15 20 0 5 10 15 20 0 5 10 15 20 0 5 10 15 20 25 Days postsymptoms Days postsymptoms Days postsymptoms Days postsymptoms E Days post Spike NP PHA symptoms 11 300 IFN-γ ELISPOT (SFC/106 PBMCs) NP 250 13 Spike 200 16 150 19 100 50 21 0 0 5 10 15 20 25 Days postsymptoms CD4 CD8 F Spike % TNF CoV-2 specific T cells % IL-2 CoV-2 specific T cells NP % IFN CoV-2 specific T cells 2.0 2.0 2.0 2.0 %CD25+OX40+ T cells 1.5 1.5 1.5 1.5 1.0 1.0 1.0 1.0 0.5 0.5 0.5 0.5 0.0 0.0 0.0 0.0 0 5 10 15 20 25 0 5 10 15 20 25 0 5 10 15 20 25 0 5 10 15 20 25 Days postsymptoms Days postsymptoms Days postsymptoms Days postsymptoms Figure 2. Virological and immunological characterization of the second episode of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection. A, Viral load of SARS-CoV-2 was determined in nasopharyngeal swabs (green circles) and saliva (orange squares) by Real-Time Quantitative Reverse Transcription polymerase chain reaction up to 21 days post–symptom onset. Viral load values were log10 transformed. B, Phylogenetic tree reconstruction of SARS-CoV-2 including European samples from April–May (blue squares) and August–September 2020 (red circles). The sample obtained from our patient from 31 August 2020 is indicated in green. C, The presence of anti–SARS-CoV-2 anti- bodies, including immunoglobulin G (IgG, left panel), immunoglobulin A (IgA, middle panel), and immunoglobulin M (IgM, right panel), against receptor-binding domain (RBD, blue squares), nucleocapsid (NP, orange triangles), and spike (green circles) antigens (Ag) was quantified by enzyme-linked immunosorbent assay in serum or plasma samples up to 16 days postsymptoms. The signal was analyzed as the optical density (OD) with noise correction. The specific signal for each Ag was calculated after subtracting the background signal obtained for each sample in Ag-free wells. Dotted lines indicate the limit of positivity. D, The presence of neutralizing capacity was determined incubating a serial dilution of serum (light blue squares) or plasma (dark blue circles) with HIV reporter pseudoviruses expressing SARS-CoV-2 S protein and then infecting ACE2-overexpressing HEK293T cells up to 21 days postsymptoms. Neutralization titer was calculated. E, T-cell responses were evaluated using the interferon gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT) assay against NP and spike recombinant proteins in peripheral blood mononuclear cells (PBMCs) up to 21 days postsymptoms. Triplicate wells at each time point are depicted as well as the phytohemagglutinin (PHA)–stimulated positive control (left panel). Longitudinal evolution of spot-forming cells (SFCs) per million PBMCs are shown (right panel). F, Intracellular cytokine production (IFN-γ, interleukin 2 [IL-2], and tumor necrosis factor alpha [TNF-α]) was evaluated in CD4 and CD8 T cells by flow cytometry after stimulation of PBMCs with NP and spike recombinant proteins. Activation-induced markers (CD25 and OX40) after stimulation were also evaluated. Samples below the limit of the detection of the assay are indicated as open symbols. 4 • ofid • NOVEL ID CASES Subjects with asymptomatic or mild COVID-19 often develop the durability of SARS-CoV-2 immune responses are urgently weaker humoral and cellular immune responses than those with needed. They will be key to understand the true frequency and more severe forms of the disease [13–16]. Up to 20% of individuals the clinical, virological, and immunological determinants of do not seroconvert after first infection [17]. Neutralizing SARS- SARS-CoV-2 reinfections, including life-threatening presenta- CoV-2 antibody levels may also decrease rapidly during the first tions. Long-term follow-up of SARS-CoV-2 vaccine-induced 2 months after infection [13, 18]. Defective Bcl-6+ follicular helper immune responses [28] will be required to assess their efficacy T-cell generation and dysregulated humoral immune induction and durability, and thus the potential need for revaccinations. early in COVID-19 disease, including loss of lymph node germinal centers, have been postulated as a mechanistic explanation for the Supplementary Data limited durability of antibody responses in coronavirus infections Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, [19]. SARS-CoV-2–specific T cells often develop in the absence of the posted materials are not copyedited and are the sole responsibility specific antibodies [20], but the adaptive immune correlates fol- of the authors, so questions or comments should be addressed to the lowing mild infections are still poorly understood. corresponding author. In this subject, additional factors such as chronic intermit- tent exposure to corticosteroids and exposure to immune- Notes modulating effects of hydroxychloroquine might have interfered Acknowledgments. We are deeply grateful to all participants and to the technical staff of IrsiCaixa for sample processing (L. Ruiz, E. Grau, R. Ayen, with his ability to mount protective B- and T-cell adaptive im- L. Gomez, C. Ramirez, M. Martinez, T. Puig) and staff from the Fight mune responses following the first SARS-CoV-2 infection. In AIDS Foundation (A. Chamorro, J. Puig). We thank CERCA Programme/ addition to being ineffective to treat SARS-CoV-2 infection, in Generalitat de Catalunya for institutional support and the Foundation Dormeur. We would like to thank everyone who submitted sequences and randomized clinical trials hydroxychloroquine reduced CD4+ metadata to GISAID. T-cell counts and increased HIV-1 replication [21], and led to Author contributions. E. B. and E. R.-M. performed and analyzed clinical deterioration of chikungunya viral infections, due to de- real-time quantitative polymerase chain reaction tests from all samples. M. N.-J. and M. P. performed and analyzed virus sequencing. J. R., J. V.-A., lays on adaptive immunity [22]. and J. S. grew the virus in vitro. J. C., M. R. C., and C. A.-N. determined and Several factors might explain why this patient developed a analyzed anti–SARS-CoV-2 antibodies. J. B., B. T., E. P., and S. M. deter- life-threatening reinfection in contrast with previous cases [1–3, mined and analyzed neutralization activity. J. G.-P., E. J.-M., and A. K. per- 6]. First, he was exposed to a high viral inoculum, as evidenced formed and analyzed specific T-cell responses (ELISPOT and intracellular staining). R. P., L. M., A. M.-U., A. M., I. A., M. T., and B. C. contributed by the high SARS-CoV-2 titers shortly after reinfection (1012 log to clinical management. M. M. and R. P. coordinated the study, collected copies/mL), which is associated with increased disease severity all clinical and laboratory data, and wrote the manuscript. All authors dis- [23–25]. Second, exposure to oral corticosteroids shortly after cussed the results and approved the manuscript. Patient consent statement. The subject provided written informed con- the initiation of symptoms might have contributed to worsening sent for using retrospective testing results, as well as for the prospective col- the clinical course of the second episode. The Randomised lection of samples. The subject provided consent for personal and clinical Evaluation of COVID-19 Therapy trial [26] demonstrated a details along with any identifying images published in this study. The study was approved by the Hospital Universitari Germans Trias i Pujol Ethics trend toward increased mortality when dexamethasone was pre- Committee Board (King cohort extension, reference number PI-20-217). scribed in subjects not requiring oxygen supplementation. Of Data availability statement. All data generated during this study are note, the second infection happened in the absence of evident included in this published article and the Supplementary Data. All of the humoral or cellular protection and with no neutralizing activity. information on GISAID sequences used in this study can be found in the Supplementary Data. Thus, antibody-mediated enhancement was an unlikely mech- Financial support. This work was partially funded by Grifols, the anism for increased severity of the second infection in this case Departament de Salut of the Generalitat de Catalunya (grant numbers [27]. Finally, a recent study showed that factors associated with DSL0016 to J. B. and DSL015 to J. C.); the Spanish Health Institute Carlos III (grant numbers PI17/01518 and PI18/01332 to J. C. and COV20/00660 severe symptomatic SARS-CoV-2 reinfections did not differ to J. G.-P.); and the crowdfunding initiatives “YoMeCorono” (https://www. from those determining severe primary disease [7]. The subject yomecorono.com), BonPreu/Esclat, and Correos. E. P. was supported by a reported here had several of them, including increased age, obe- doctoral grant from Agencia Nacional de Investigatión y Desarrollo, Chile (grant number 72180406). sity (body mass index ≥30 kg/m2), and asthma. Potential conflicts of interest. J. B. and J. C. report personal fees from Albajuna Therapeutics, outside the submitted work. All other authors re- CONCLUSIONS port no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Clinicians, public health officials, and the general public must be Conflicts of Interest. Conflicts that the editors consider relevant to the con- aware that life-threatening SARS-CoV-2 reinfections can occur. tent of the manuscript have been disclosed. This case report and others suggest that, at least in some patients, immune responses to SARS-CoV-2 might be short-lived or be References too weak to be protective. Symptomatic SARS-CoV-2 reinfec- 1. To KK-W, Hung IF-N, Ip JD, et al. COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing tions have been reported as early as 3 months after the first in- [manuscript published online ahead of print 25 August 2020]. Clin Infect Dis fection [1–6]. Systematic prospective cohort studies addressing 2020. doi:10.1093/cid/ciaa1275. NOVEL ID CASES • ofid • 5 2. Van Elslande J, Vermeersch P, Vandervoort K, et al. Symptomatic SARS-CoV-2 15. Trinité B, Tarrés-Freixas F, Rodon J, et al. 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