Reinfection and Breakthrough Infection of SARS-CoV-2: An Emerging Challenge That Is Threatening Our World

Abstract

The pandemic of coronavirus disease 2019 has threatened humans for more than one and a half years. In particular, viral mutation like delta strain has led to third- or fourth-wave transmission among the countries in Asia, Europe, and North America. Although large-scale vaccination has been carried out in many countries, the incidence of reinfection and vaccine-past breakthrough infection is becoming an emerging challenge to humans worldwide. The related mechanisms underlying the reinfection and breakthrough infection remain unknown. In this review, we summarized the challenge and related reasons for severe acute respiratory syndrome coronavirus 2 reinfection and breakthrough infection. Simultaneously, we addressed some critical contents of the study in future.

Keywords: Breakthrough infections; Reinfection; SARS-CoV-2; Vaccine.

Figure 1

Severe acute respiratory syndrome coronavirus 2 enters and then firstly infects the mucosa ACE2⁺ cells in the oral cavity, nasopharynx cavity, and upper respiratory tract and replicates in these cells, where viruses cannot be cleared by neutralizing antibodies and specific cellular immunity that fail to reach the anatomical exemptive site in mucosal epithelial cells in the mouth, nose, and upper respiratory tract. ACE2: Angiotensin-converting enzyme 2.

Figure 2

A schematic diagram of immune protection of vaccines. In general, there is no breakthrough infection for the vaccines to hepatitis B virus, Japanese encephalitis virus, and hantavirus. However, the vaccines to highly variable RNA viruses including SARS-CoV-2 (red) and influenza virus (red) that are all respiratory viruses, cannot avoid the vaccination breakthrough infection, due to the immunological anatomical “exemption” sites such as in the upper respiratory tract and the oral-nasal mucosa. SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.