Discussion
While our knowledge regarding the risk factors for reinfection and other associated parameters are evolving, data points out the temporary protectivity of anti SARS-CoV-2 antibodies6 and the emergence of viral escape mutants as potential mechanisms for recurrent cases7. Our case developed a reinfection with SARS-CoV-2 after an initial episode of symptomatic disease and a 2-month disease-free interval. The second episode was significantly milder requiring no inpatient medical care but relatively different in presentation from the initial episode. In a surveillance study at the Oxford University Hospitals in the United Kingdom, Lumley et al. measured anti-spike and anti-nucleocapsid IgG antibodies in 12,541 healthcare workers and followed them for a period of 31 weeks6. The authors found that out of 1,265 seropositive cases, 88 had developed seroconversion during the follow-up period. On the other hand, 223 seronegative subjects developed a positive PCR test (1.09 per 10,000 days at risk) of whom 44.84% were asymptomatic and 51.6% were symptomatic. This was significantly different from the only 2 seropositive cases who became PCR-positive during the follow-up period (0.13 per 10,000 days at risk). While in average the anti SARS-CoV-2 antibodies rendered an immunity against reinfection for a duration of 6-month, our case report along with others raise questions about the generalizability of such a short-term protection4,5. However, none of these case reports have monitored the evolution of neutralizing antibodies against SARS-CoV-2 from the initial infection to the time of reinfection.
A genomic analysis of SARS-CoV-2 obtained at two different times from a 25-year-old man from Washoe, Nevada revealed genetically significant differences between the two species4. Unlike our patient’s, the second episode was more severe in terms of clinical symptomatology. Further case reports have also shown a declining antibody titer to coincide with the reinfection of SARS-CoV-22,3,8. The case report from Hong Kong showed that an initially mild infection with SARS-CoV-2 did not produce any effective neutralizing antibody, which 5 months later resulted in reinfection with the virus although completely asymptomatic 2. Another case report from Netherlands showed a more severe presentation of SARS-CoV-2 reinfection compared to the index episode3. Although the latter patient was immunocompromised due to recent B-cell depleting chemotherapy for Waldenström’s macroglobulinemia, an effective innate immune or T-cell response might have acted as a savior. The same path can be imagined for the case report from Hong Kong in whom no effective neutralizing antibody was detected in either of the episodes. Unfortunately, our current laboratory setting did not permit measuring anti SARS-CoV-2 serum antibody titers from the index infection to the recurrence of COVID-19 nor did it allow the genomic analysis of the causative agents in these two different episodes.
The time interval between the initial infection with SARS-CoV-2 and the second episode has been variably reported in the literature3-5,8. While the duration of protectivity rendered by anti-spike or anti-nucleocapsid IgG antibodies has been shown to be a minimum of 6 months, a systematic review of the reported cases of reinfection with SARS-CoV-2 has estimated this interval to be 35.4 days5. The review has also found that younger age and a longer time to become PCR-negative is significantly associated with a higher risk of reinfection with SARS-CoV-2 while a severe disease might play a protective role.
Our case report supports the growing doubt about a lasting herd immunity against SARS-CoV-2. Although our patient presented differently in the second episode from the initial one, the clinical manifestation was less severe clinically. The time from initial infection to the recurrent episode was above the average reported in the literature. However, we could not examine the evolution of neutralizing antibody over this interval as the titer was not measured in our case. While the current endeavors in global vaccination against SARS-CoV-2 is ongoing, clinicians should stay alert about variation in individuals’ response to the infection and the potential risk of reinfection despite receiving the vaccine. This is especially important when we are reading the news about the emerging variants of the virus, which seem to be more contagious9.