A systematic review of Vaccine Breakthrough Infections by SARS-CoV-2 Delta Variant

Abstract

Vaccines are proving to be highly effective in controlling hospitalization and deaths associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as shown by clinical trials and real-world evidence. However, a deadly second wave of coronavirus disease 2019 (COVID-19), infected by SARS-CoV-2 variants, especially the Delta (B.1.617.2) variant, with an increased number of post-vaccination breakthrough infections were reported in the world recently. Actually, Delta variant not only resulted in a severe surge of vaccine breakthrough infections which was accompanied with high viral load and transmissibility, but also challenged the development of effective vaccines. Therefore, the biological characteristics and epidemiological profile of Delta variant, the current status of Delta variant vaccine breakthrough infections and the mechanism of vaccine breakthrough infections were discussed in this article. In addition, the significant role of the Delta variant spike (S) protein in the mechanism of immune escape of SARS-CoV-2 was highlighted in this article. In particular, we further discussed key points on the future SARS-CoV-2 vaccine research and development, hoping to make a contribution to the early, accurate and rapid control of the COVID-19 epidemic.

Keywords: Breakthrough infection; COVID-19; Delta variant; S protein; SARS-CoV-2; Vaccine.

Figure 1

A timeline depicting the origin of SARS-CoV-2 VOC (Variant of Concern) and SARS-CoV-2 VOI (Variant of Interest), as well as when SARS-CoV-2 vaccines are authorized to be added to the EUL (emergency use listing) of WHO and the SARS-CoV-2 vaccine breakthrough infection countries.

Figure 2

Organs affected by SARS-CoV-2 and corresponding systemic symptoms and diseases. ARDS: Acute respiratory distress syndrome; DIC: Disseminated intravascular coagulation.

Figure 3

COVID-19 vaccine platforms. A schematic of the targets, production process and immune mechanism of the underlying five types of COVID-19 vaccines currently available in the clinic. APC: antigen presenting cell. ChAdOx1, Ad26, and Ad5 are among the 100 serotypes of adenovirus, and these three have been used as non-replicating adenovirus vectors in clinical practice for vaccination.

Figure 4

(A) The basic structure of SARS-CoV-2 and the position of some significant mutation in the S protein. (B) A schematic diagram of the SARS-CoV-2 S protein anchoring to the virus envelope to interpret the structural characteristics of S protein from three perspectives. The first diagram depicts the basic components of S protein. The second schematic suggests a model for S protein trimer and the binding principle for membrane fusion. The third is a linear ordering of structural domains located at different positions on the S protein. (C) A schematic of SARS-CoV-2 binding to ACE2 under the catalysis of TMPRSS2 and entering the host cell, forming syncytia and producing an immune response.

Figure 5

(A) An investigation of the severity of breakthrough infections from India showed that most breakthrough infections were mild diseases and only 10.2% of patients were hospitalized or died. (B) The pie chart presents data from a study on the types of variants infected by positive patients in India from April to June 2021.

Figure 6

(A) Vaccination or antigen induces the activation of the antigen-presenting cells (APCs) and vaccine-elicited immune responses lead to the clearance of infection in body. (B) Through evolution, the mutation of Delta variant causes immune evasion, the high expression of certain mutations in the lungs causes an increase in virus entering host cells, resulting in severe lung damage.