Reactivations, reinfections

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Seasonal coronavirus protective immunity is not long-lasting (Edridge 2020). There are several reports of patients infected with SARS-CoV-2 who became positive again after negative PCR tests (Lan 2020, Xiao 2020, Yuan 2020). These reports have gained much attention, because this could indicate reactivations as well as reinfections. After closer inspection of these reports, however, there is no good evidence for reactivations or reinfections, and other reasons are much more likely. Methodological problems of PCR always have to be considered; the results can considerably fluctuate (Li 2020). Insufficient material collection or storage are just two examples of many problems with PCR. Even if everything is done correctly, it can be expected that a PCR could fluctuate between positive and negative at times when the values are low and the viral load drops at the end of an infection (Wölfel 2020). The largest study to date found a total of 25 (14,5%) of 172 discharged COVID-19 patients who had a positive test at home after two negative PCR results at hospital (Yuan 2020). On average, the time between the last negative and the first positive test was 7,3 (standard deviation 3,9) days. There were no differences to patients who remained negative. This and the short period of time suggest that in these patients, no reactivations are to be expected. However, in recent months several case reports of true (virologically proven: phylogenetically distinct strains) re-infections have been reported (To 2020, Gupta 2020, Van Elslande 2020). In most cases, the second episode was milder than the first. However, there is at least one case where the second infection was more severe, potentially due to immune enhancement, acquisition of a more pathogenic strain, or perhaps a greater in-oculum of infection as the second exposure was from within household contacts (Larson 2020). Up to now, however, these are anecdotal case reports. Animal studies suggest that re-infection is unlikely (Chandrashekar 2020). Following initial viral clearance and on day 35 following initial viral infection, 9 rhesus macaques were re-challenged with the same doses of virus that were utilized for the primary infection. Very limited viral RNA was observed in BAL on day 1, with no viral RNA detected at subsequent timepoints. These data show that SARS-CoV-2 infection induced protective immunity against reexposure in nonhuman primates. There is growing evidence for a long-lived and robust T cell immunity that is generated following natural SARS-CoV-2 infection (Neidleman 2020). Reactivations as well as rapid new infections would be very unusual, especially for coronaviruses. If a lot of testing is done, you will find a number of such patients who become positive again after repeated negative PCR and clinical