Emerging COVID-19 reinfection four months after primary SARS-CoV-2 infection

letter to the editor Wien Med Wochenschr https://doi.org/10.1007/s10354-021-00813-1 Emerging COVID-19 reinfection four months after primary SARS-CoV-2 infection Helmut J. F. Salzer Received: 4 November 2020 / Accepted: 7 January 2021 © The Author(s) 2021 To the editor In the last few months, several cases of ominous coronavirus disease 2019 (COVID-19) reinfections have been reported (Table 1). However, there is a scientific controversy whether reinfections can occur just a few months after the first infection and if so, what it means for the fight against the COVID-19 pandemic. On October 27, 2020, a 95-year-old man was re-admitted from his retirement home to Kepler University Hospital in Linz, Austria with new onset dyspnea and fever. Four months before, he had been discharged after 2 weeks of hospitalization due to mild COVID-19 characterized by fever and leukopenia, but absence of viral pneumonia and hypoxia. For virological confirmation a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) was performed showing positive test results on June 27 with a cycle threshold (Ct) value of 32.2 and on July 2, 2020 with a Ct value of 37.7 (cobas 6800 SARSCoV-2 test, Roche, Molecular Systems, Branchburg, NJ, USA). Thereafter, the patient tested negative for SARS-CoV-2 on several occasions including at discharge from hospitalization on July 6 and 7 as well as on September 25 and on October 1, 2020. The patient had a medical history of dementia, arterial hypertension and total thyroidectomy. Referring to local COVID-19 infection precaution regulation the patient was directly isolated in the emergency room and he was again tested for SARSCoV-2 on October 27, 2020. Meanwhile vital parameters were taken showing a reduced oxygen saturation H. J. F. Salzer, MD, MPH () Department of Pulmonology, Kepler University Hospital, Linz, Austria K of 89% on room air and an elevated body temperature of 38.4 °C. Auscultation of the lung revealed no pathological abnormalities, while laboratory test results showed mild leukopenia with 3.18 G/L (reference value 3.9–8.8 G/L) with a decreased lymphocyte count of 0.64 G/L (reference value 1.00–4.00 G/L) and a thrombocytopenia with 126 G/L (reference value 151–400 G/L), respectively. Other laboratory values and urine test results were unremarkable. Two hours later the patient was again tested positive for SARS-CoV-2 with a Ct value of 12.8 in the RT-PCR (Cepheid Xpert Xpress SARS-CoV-2 point-ofcare test, Sunnyvale, CA, USA). Another oropharyngeal swab was taken confirming the positive SARSCoV-2 RT-PCR test result with a Ct value of 14.5 using a different platform (cobas 6800 SARS-CoV-2 test, Roche, Molecular Systems, Branchburg, NJ, USA). Despite primary SARS-CoV-2 infection the patient this time required additional oxygen and had viral pneumonia on chest X-ray. Furthermore, the patient received low molecular weight heparin with enoxaparin 4000 I.E. subcutaneously once daily for prophylaxis of venous thromboembolism and paracetamol 1000 mg intravenously as antipyretic treatment. Antiviral treatment was not administered due to drug shortage of remdesivir in Upper Austria at this time. We did not give dexamethasone at admission because the patient was not critically ill, he had no laboratory findings of hyperinflammation and was in the early phase of viral infection. Over the next few days the patients’ respiratory condition deteriorated continuously consistent with a severe course of COVID-19. Finally, the patient deceased 6 days after admission. Taken this together a COVID-19 reinfection seems to be plausible in our patient 124 days after primary SARS-CoV-2 infection, although a recently published clinical meta-analysis including 15 single or cumulative case reports did not find any clinical reinfec- Emerging COVID-19 reinfection four months after primary SARS-CoV-2 infection letter to the editor Table 1 Clinical characteristics of symptomatic COVID-19 reinfections having a negative SARS-CoV-2 PCR between the first and the second infection and/or a phylogenetic analysis Country Sex Age (years) Comorbidities 1st infection 2nd infection Interval between Negative SARS-CoV-2 Phylogenetic Reference 1st and 2nd PCR between 1st and analysis infection 2nd infection Israel Female 20 None Milda Asymptomatic 112 days Yes No [5] Ecuador Male 46 N/A Mild Mild 63 days N/A Yes [6] USA Male 82 Severeb Severe 55 days Yes No [7] Hong-Kong Male 33 Parkinson’s disease, diabetes, chronic kidney disease, hypertension N/A Mild Asymptomatic 142 days Yes Yes [4] USA Male 25 None Mild Mild 48 days Yes Yes [8] Belgium Female 51 Asthma (inhaled corticosteroids) Mild Mild 93 days No Yes [9] The Nether- Female lands 89 Waldenström’s macroglobulinemia Mild Moderatec 59 days No Yes [10] USA N/A N/A Emphysema, home oxygen, Moderate Moderate hypertension 144 days Yes Yes [11] USA Male 42 N/A Mild Mild 51 days No Yes [12] Brazil 1 × Female, 2 × Male 40, 67, Asthma, ancylosing 47 spondylitis, obesity, OSAS, none Mild Mild to severe 54, 56, 70 days Yes No [13] Austria Male 95 Mild Severe 124 days No – Dementia, hypertension, total thyroidectomy Yes COVID-19 coronavirus disease 2019, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2, PCR polymerase chain reaction, N/A not available, OSAS obstructive sleep apnea syndrome a Symptomatic with absence of hypoxia bCritical ill requiring non-invasive or invasive ventilation and/or death related to COVID-19 c Symptomatic requiring additional oxygen tion after a 70-day period following first infection [1]. These findings are supported by animal studies demonstrating protection against reinfection in rhesus macaques after primary exposure to SARS-CoV-2 [2, 3]. Nevertheless, the first and the second COVID-19 episode in our patient were characterized by clinical symptoms, typical laboratory findings including leukopenia and thrombocytopenia as well as repeated virological confirmation of SARS-CoV-2 infection, while he had no symptoms and he tested negative on several occasions in between. To KK-W et al. also reported a reinfection in a 33-year-old man 142 days after first infection. Whole genome sequencing confirmed that both COVID-19 episodes were caused by phylogenetically diverse SARS-CoV-2 strains, which supports our clinical observation of reinfection instead of persistent viral shedding [4]. Questions remain, for example, why this patient acquired a COVID-19 reinfection, while immunity against the virus is probable, at least in the short term, since SARS-CoV-2 reinfections are only reported occasionally despite the high COVID-19 prevalence worldwide. Explanations could be an infection with a different SARS-CoV-2 strain or an age-related impaired immune response. Unfortunately we were not able to perform a comparison of whole genome sequencing data du (...truncated)