Different reports indicate that reactivation or re-infection by SARS-CoV-2 are possible, although the event appears to be unusual . Such “reversal to positivity” after negative molecular tests may be due to methodological issues such as sample storage problems, poorly performed sample collection, etc., pointing towards false-negative results . However, such reactivation also has a biological basis .
In this case, the virus could still replicate in undetectable levels in nasopharynx and maybe in the lower respiratory tract  during convalescence, regaining full replication after some time, probably driven by the host's immune status . On the other hand, a re-infection with a new or maybe the same circulating strain is not unfeasible , given the different profiles of immune response to the virus . In fact, the detection of SARS-Cov-2 RNA with the absence of anti-SARS-CoV-2 antibody response has been previously observed .
Although cases vary in terms of serological data, timing of reactivation and clinics, patients who retested positive to SARS-CoV-2 generally have a mild or asymptomatic course [9-13], which is perhaps the result of some level of immunity, while symptomatic reactivation is rare but may happen . Our patient, on the other hand, presented a more potent form of COVID-19 after more than 40 days from the first mild infection, and with a detectable antibody response only after the second infectious episode. Our hypothesis is that the first mild infection was not sufficient to build up a detectable humoral response , which occurred only after 14 days of a second more severe episode. In addition, the absence of detectable antibodies in the first episode may have allowed for a new infection, rather than a recurrence. However, as we did not investigate viral genetics at different times, such a statement is hypothetical.
A limitation of this study is due to the absence of cell culture assays during the period, which could indicate the presence of infectious particles. Also, a false-positive result in the first RT-qPCR test cannot be ruled out as well, so that the patient only became infected with SARS-CoV-2 afterwards, instead of its “reactivation”. However, given the 1) high specificity of RT-qPCR test; 2) presentation of symptoms coinciding with the positive RT-qPCR; and 3) viral detection in close family members living in the same residence during COVID-19 symptoms (data not shown); such false result is unlikely.
In this paper, we describe a COVID-19 recurrence from a mild to a moderate form after convalescence, with RT-qPCR turning positive and antibody detection after more severe symptoms. These findings, although summarized in a case report, raise questions about the influence of the severity of the infection on the immune response and the host's susceptibility, which can have important epidemiological consequences, and should be better understood.