Several cases of SARS-CoV-2 reinfections have been reported worldwide.
In this review, we summarize the reinfection cases reported along with the humoral responses against SARS-CoV-2, with the aim of developing a better understanding of the causes of reinfection as well as the implications on vaccines. In terms of a SARS-CoV-2-specific antibody (Ab) titer, there is controversy on whether they remain stable or decline over time, although several studies reported high antibody titers that last for at least six months after infection and vaccination. Nevertheless, rare cases of prolonged viral shedding (>1 month) have been reported, including a pregnant woman who remained SARS-CoV-2-positive for 104 days after her initial test. The incidence rates and causes of reinfection remain poorly understood, raising many questions: Is it viral persistence (i.e., prolonged viral shedding) or reinfection? Does primary SARS-CoV-2 infection protect against subsequent infections? How does the SARS-CoV-2 antibody response correlate with reinfection? Based on several studies, SARS-CoV-2 RNA is undetectable one month following symptom onset in the majority of patients. Several reinfection cases have been reported worldwide.
According to the Centers for Disease Control and Prevention (CDC) guidelines, SARS-CoV-2 reinfection is identified and confirmed if: (1) viral RNA is identified at two different time points (2) intervening negative RT-PCR tests are present and (3) viral genetic sequencing data support reinfection. Taken together, due to the high transmissibility of SARS-CoV-2 along with the recent emergence of more infectious variants, the risk of reinfections may elevate. The South African variant has two additional mutations in the RBD of the spike protein, allowing it to escape antibodies from natural infections and vaccination. Both variants contained an N501Y mutation in the receptor-binding domain (RBD) of the spike (S) protein, accounting for the increased transmission and infectiousness (40–70%) of the virus. In December 2020, new SARS-CoV-2 variants (B.1.1.7 in the United Kingdom, B.1.351 in South Africa) emerged and led to an unexpected rise in COVID-19 cases. Overall, findings suggest that infection- and vaccine-induced immunity would protect from severe illness, with the vaccine being effective against most VOCs. Infections after vaccination were also reported on several occasions, but mostly associated with mild or no symptoms. Reinfection was attributed to several viral and/or host factors, including (i) underlying immunological comorbidities (ii) low antibody titers due to the primary infection or vaccination (iii) rapid decline in antibody response after infection or vaccination and (iv) reinfection with a different SARS-CoV-2 variant/lineage. Most reinfected patients were asymptomatic during the second episode of infection. Overall, a limited number of reinfection cases have been reported worldwide, suggesting long protective immunity.
In this review, we discuss SARS-CoV-2 reinfection rates in previously infected and vaccinated individuals in relation to humoral responses. The rapid spread of these new variants has raised concerns about the multiple waves of infections and the effectiveness of available vaccines. This increase was associated with the emergence and spread of the new SARS-CoV-2 variants of concern (VOCs), such as the U.K. Despite the modest decrease in the number of cases during September–November 2020, the number of active cases is on the rise again. The COVID-19 pandemic is still posing a devastating threat to social life and economics.