Recurrence or Relapse of COVID-19 in Older Patients: A Description of Three Cases

Ludovic Lafaie, MD; Thomas Célarier, MD, MS; Luc Goethals, MsD; Bruno Pozzetto, MD, PhD; Sylvain Grange, MD; Etienne Ojardias, MD; Cédric Annweiler, MD, PhD; Elisabeth Botelho-Nevers, MD, PhD


J Am Geriatr Soc. 2020;68(10):2179-2183. 

In This Article


We reported here three geriatric cases with two episodes of COVID-19 separated by a symptom-free interval of weeks.

This sequential picture may be explained by either the persistence of nonviable RNA of SARS-CoV-2 after the first COVID-19 episode, by SARS-CoV-2 reinfection, or by COVID-19 relapse.[9] In fact, viral replication was found during the second episode in all three cases, which makes the first hypothesis unlikely. The second wave of respiratory disease could have been caused by something other than SARS-CoV-2, but all virological and bacteriological infectious samples were negative, except for COVID-19. Also, the three women were placed in isolation rooms in hospital units dedicated to COVID-19, with caregivers trained and equipped to comply with the isolation measures. In addition, the symptom-free interval was relatively short. Thus, the hypothesis of reinfection with a new strain is also unlikely.

A relapse of COVID-19 seems to be the preferred hypothesis that would yet need comparisons of strains with sequencing to be affirmed. However, the absence of antibodies presented at readmission for two of the three patients, 22 and 41 days after the first episode, is in favor of a possible reactivation.[10] For the two patients with initially negative serology, a common seroconversion to clinical severity should be noted. This immune reaction may be the cause of clinical deterioration.[11,12] One hypothesis would be that these episodes are linked to the persistence of the virus in a reservoir (sanctuary site), as previously suggested for other viral infections.[13] Immunosenescence would have a role in the observed clinical pictures, with a possible nonresponse at the time of the first COVID-19 episode. Seroconversion monitoring appears important in the management of the disease. Differential causative diagnoses were excluded for the second episode corresponding to a pneumonia in all cases. This series of three geriatric cases with COVID-19 diagnosed two times apart for several weeks questions the possibility of reinfection with SARS-CoV-2. This raises questions in clinical practice about the value of testing for SARS-CoV-2 infection again in the event of symptomatic reoccurrence.

The three cases we present here did not received diagnostic tests, supposedly negative, during the transient improvement in clinical signs.[14] Prolonged infections[15–17] and reactivations have already been described previously.[18–20] If the risk of recurrence is confirmed, it will be crucial to analyze the risk factors (comorbidities, undernutrition, lymphopenia, and weak immune reaction with a low or even negative serology) but also their severity. The inclusion of these patients in therapeutic trials is complex.[21] It can be assumed that the cytokine storm could be greater than during the first contamination, leading to more serious and more frequently lethal forms. In the three cases reported here, the second episode was fatal in each patient. In the case of the second wave, special attention should be paid to older patients who were affected by COVID-19 during the first wave.