Reinfections with SARS-CoV-2 or second COVID-19 episodes?

The article titled “Predictors of severe symptomatic laboratory-confirmed SARS-CoV-2 reinfection” by Murillo-Zamora et al. reports the presence of 258 cases of reinfection with SARS-CoV-2 in Mexico.¹ Methodologically, the authors use clinical criteria to define a recovery which was defined as resolution of fever without the use of antipyretic drugs and self-reported improvement in respiratory symptoms at 7–10 days from symptom appearance. They define a case of reinfection as a person with symptoms plus a positive SARS-CoV-2 laboratory test in the second episode, with reappearance of symptoms at 28 days or more from the first positive episode. In this sense, questions arise regarding the study. Although there is no worldwide consensus on the operational definition of a case of reinfection, the Pan American Health Organization (PAHO) published in October 2020 a provisional definition that considers clinical, laboratory, and time interval criteria (a period ≥90 days after the first infection).² Murillo-Zamora et al. indicate that one of the limitations of their study is that in the absence of mass screening in Mexico, it was not possible to identify second-time asymptomatic cases of SARS-CoV-2 infection;¹ thus, the study is limited to the epidemiological definition of the PAHO as the “period of time during which the individual did not present with symptoms of primary infection by SARS-CoV-2”.² Therefore, based on the definitions considered by the researchers, it is possible that they included in the study individuals with prolonged excretion of the virus, given the absence of the laboratory criterion of a negative result by RT-PCR or rapid antigen test for the first episode. The Mexican guidelines for epidemiological surveillance (published in January 2021, after the manuscript was sent to the journal)³ included the following criteria to define a second episode of COVID-19: “person with a positive SARS-CoV-2 result, who after a period ≥45 days of presenting the first infection, begins showing symptoms and has a positive SARS-CoV-2 test result in this second episode”, which is ultimately what the study provides, plus no documented reinfection. Another scenario to consider is individuals with an interval of less than 45 days between the first event and second event because, despite having presented clinical improvement, they may in actuality be cases of relapse. The European Centre for Disease Prevention and Control published on April 8, 2021, that the minimum and maximum number of days identified for reinfection by SARS-CoV-2 between the first and second infection in Europe were 89 and 201 days, respectively.⁴

Regarding data collection, Murillo-Zamora et al. mention that the patients were defined as recovered by self-report, as the epidemiological surveillance system in Mexico does not consider this process in the follow-up; therefore, there is asymmetry of information about the source and mechanism of data collection for the category of recovered case.

Finally, the findings are revealing and challenging, given that health authorities in Mexico have not officially recognized cases of reinfection by SARS-CoV-2.⁵ In addition, to date, there is still no consensus on an operational definition for cases of reinfection.⁴