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Clinical Features of Patients who had two COVID-19 Episodes: A European Multicenter Case-series

Our take —

This study looked at a case series of 45 patients in 4 European countries who experienced a second episode of COVID-19 an average of 5.6 months after their first episode. All cases were mild-to-moderate during both episodes, though 3 patients required hospitalization during their first episode, whereas none did during their second. Overall symptom prevalence was similar between both episodes. It is not known whether these represent distinct infection events or recurrences, although reinfection has been known to occur. No information was available regarding the strains of SARS-CoV-2 involved in each infection. Because there were a small number of cases and all were initially mild or moderate, their experiences during a second episode may not be representative.

Study design

Case Series

Study population and setting

This study described clinical features of 45 patients with two distinct episodes of COVID-19 from March 22 to December 27, 2020. Patients with an initial COVID-19 diagnosis (n=2,626), confirmed via either PCR or antibody testing, were recruited from 18 hospitals in Belgium, France, Italy, and Spain. Episodes of COVID-19 were considered distinct if they occurred at least one month apart with full symptom clearance between diagnoses, excepting olfactory/taste dysfunction. COVID-19 severity was defined according to WHO Disease Severity Scoring. Those with missing clinical data for one or both infections were excluded.

Summary of Main Findings

Of the 45 patients with two COVID-19 episodes, 31 (69%) were women, the mean age was 38.5 years, and 8 (18%) were healthcare workers. The mean duration between episodes was 5.6 months (standard deviation: 2.3 months). Serology was available for 35/45 patients, and 10/35 (29%) did not have detectable IgG antibodies to SARS-CoV-2 (at an average of one month after symptom resolution for these 10 patients). One of ten patients with serology available after the second episode tested negative for IgG antibodies (2 months after symptom resolution). Just over half (51%) of the patients had PCR-confirmed SARS-CoV-2 infection during the first episode, while that number rose to 89% for the second episode. Three of the 45 patients required hospitalization with oxygen therapy during their first episode, while the remainder had mild COVID-19 with (12/45) or without (30/45) dyspnea. All of the second episodes of COVID-19 were mild and none required hospitalization. The clinical presentation was broadly similar between first and second episodes, with the most common symptoms being weakness (87%), headache (80%), fever (73%), and anorexia (73%) in the first episode; and headache (93%), weakness (91%), fever (71%), and myalgia (71%) in the second. The mean duration of symptoms was similar comparing the first episode (17.0 days) and the second (15.7 days). While 53% of patients self-reported olfactory dysfunction during the first episode, 62% did so during the second, though the duration of olfactory dysfunction was shorter (16.2 days vs. 11.2 days, p<0.05) during the second episode. Of the 16 patients reporting total loss of smell in the first episode, 5 reported partial and 2 reported total loss of smell in the second episode.

Study Strengths

This is one of the first studies to characterize symptoms among the subset of patients with two episodes of COVID-19.


The sample of patients with a second COVID-19 episode was small, and only included patients with mild or moderate COVID-19, and so results may not be representative. Serology was only available for 35/45 patients after the first episode. Only symptomatic cases were included. The duration between the first and second diagnosis dates was not described in detail. There was no requirement for patients to test negative for SARS-CoV-2 infection via PCR after the initial episode of COVID-19, so some patients may never have cleared the virus. Viral genetic sequence data was not available to determine whether the second episode represented a distinct infection event or a recurrence/reactivation of existing infection. It is unknown whether SARS-CoV-2 variants of concern (e.g., B.1.351) were involved in any of the second COVID-19 episodes.

Value added

This is one of the first case series to date of second COVID-19 episodes in patients.

This review was posted on: 12 March 2021