This example of COVID-19 possible recurrence appeals at facing major issues for older patients’ care courses, at the individual and collective level.
In our view, the relapse of symptoms (fever), associated to lymphopenia and turned-positive RT-PCR in the present case, with no sign of other infection, could allow for the diagnosis of possible COVID-19 recurrence in this case.
At the individual level, this case alerts on the possibility of recurrence of symptoms and turned-positive RT-PCR in recovered patients, with positive serology. Some recent reports found positive RT-PCR tests in cases of recovered COVID-19 patients, regardless of symptoms [3–8]. Viral test positivity should be differentiated from clinical recurrence and from persistence of contagiousness. The pathophysiology is not clear and several mechanisms are hypothesized, such as technical issues, viral reactivation, lack of immunological control or reinfection [4–6, 9]. Increasing age, male gender, hypertension and corticosteroid treatment, which we know are highly prevalent in older adults, were recently associated to delay in viral clearance . The protective effect to viral infection in females is partly explained by estrogen and progesterone which could help to increase the innate and adaptive immune responses [10, 11]. This protection was probably impaired in this post-menopausal patient treated with anti-aromatase drug for breast cancer. Moreover, immune senescence, known to impair immune response to infectious diseases in older adults may participate to viral clearance delay . A case of COVID-19 recurrence in a 48-year-old man was recently published . As in the present case, the patient had anti-SARS-CoV-2 IgG, indicating that the acute phase of the disease and immunological reaction occurred, and suggesting that in some cases the presence of IgG antibodies could be not protective , although these suggestions should be taken with caution .
Another issue is that prolonged symptoms such as fever in older patients expose them to prolonged risk of complications, such as falls or delirium. Finally, our patient presented a persistent lymphopenia, with new decrease of lymphocytes count the day of the recurrence (at 0.36 ˟109/L). The correlation between lymphopenia and positive virus detection suggests the link between viral replication and viro-induced lymphocyte destruction. Proposed mechanisms leading to lymphopenia during COVID-19 are possibly multiple, including viral toxicity, inflammatory cytokines dysregulation, and metabolic disorders . A prolonged lymphopenia, occurring in all lymphocyte subsets, including CD8+ and natural killer cells (antiviral function), and B cells (which differentiate into plasma cells able to produce neutralizing antibodies) , has been previously associated to higher mortality in older population and with an increased risk of secondary infections .
At the collective level, even if traces of virus detected by RT-PCR were not necessarily correlated with the contagiousness, this case raises the question of patients’ care courses, since it implies the need for prolonged isolation, if reasonably practicable, until we have more data on such contagiousness. Geriatric patients with COVID-19 cumulate risk factors of prolonged viral shedding and of trans-contaminations at risk, since they are often surrounded by frail older people (older spouse, nursing home etc). There does not currently appear to have been any secondary contamination, but intra-hospital transmission of COVID-19 to frail older adults, in acute units, post-acute unit or long-term care would be dramatic.
There are some limitations in the present case report. The patient had only one negative RT-PCR before the relapse, while two consecutive negative RT-PCR  would have been better to talk about recovery. Moreover, the imputability of COVID-19 in the clinical presentation cannot be guaranteed, even if the association of fever, lymphopenia, turned-positive RT-PCR and the absence sign of other respiratory viruses or bacteria are highly suggestive of a possible COVID-19 recurrence.
In conclusion, geriatricians, who are already well aware of the seriousness of COVID-19, will also have to address the issue of possible recurrence, if it is confirmed. We need more studies, specifically in older patients, to define the risk factors for clinical or virologic recurrence, as well as the potential risk of contagiousness. It seems necessary in order to limit consequences of prolonged symptoms (such as fever) or lymphopenia, and to organize safely and effectively the care of older patients with COVID-19 across the whole geriatric pathway, from acute units to long-term care facilities and nursing homes. As the older patients are already the people most at risk of mortality and complications, the burden of the COVID-19 pandemic could be increasingly significant.