Recurring SARS-CoV-2 variants: an update on post-pandemic, co-infections and immune response

Abstract

The post-pandemic era following the global spread of the SARS-CoV-2 virus has brought about persistent concerns regarding recurring coinfections. While significant strides in genome mapping, diagnostics, and vaccine development have controlled the pandemic and reduced fatalities, ongoing virus mutations necessitate a deeper exploration of the interplay between SARS-CoV-2 mutations and the host's immune response. Various vaccines, including RNA-based ones like Pfizer and Moderna, viral vector vaccines like Johnson & Johnson and AstraZeneca, and protein subunit vaccines like Novavax, have played critical roles in mitigating the impact of COVID-19. Understanding their strengths and limitations is crucial for tailoring future vaccines to specific variants and individual needs. The intricate relationship between SARS-CoV-2 mutations and the immune response remains a focus of intense research, providing insights into personalized treatment strategies and long-term effects like long-COVID. This article offers an overview of the post-pandemic landscape, highlighting emerging variants, summarizing vaccine platforms, and delving into immunological responses and the phenomenon of long-COVID. By presenting clinical findings, it aims to contribute to the ongoing understanding of COVID-19's progression in the aftermath of the pandemic.

Figure 1

(A) A schematic showing different clinical conditions and their symptoms, amidst to COVID-19 disease; (B) Dermatological manifestation of COVID-19 such as COVID toe, hair loss; Adopted with permission from ref. ; (C) Macroscopic and microscopic aspect of the lung in a 55-year-old male patient with COVID-19; adopted from ref; (D) Masson's trichrome staining of paraffin-embedded lung sections of K18-hACE2 marker and Immunohistochemical staining of B1R (brown) in lung tissue of recovered from mild SARS-CoV-2 infection to analyse the post-COVID neuropsychological disorders in mice models; adopted from ref ; (E) number and types of thrombotic events such as venous thromboembolism, pulmonary embolism, stroke, hyperventilation; adopted from ref ; (F) risk and excess burden of post-acute COVID-19 kidney histomorphological and immunofluorescence features; adopted from ref .

Figure 2

A) Schematic showing the development of variants of concern from the SARS-CoV-2 (D614G variant). The 614G is the earliest spike protein mutant of SARS-CoV-2 which swiftly dominated the 614D (wild type) all over the world. B) Physiology of SARS-CoV-2 variants showing error prone replication. The error prone replication of SARS-CoV-2 helps to produce most suitable variants by spontaneous mutation on the receptor binding domain (RBD) of the spike protein. These mutations change the infectivity index of the variants. In the bottom, the spike protein of the wild type is compared with the spike protein of the triple mutant, wherein 417 LYS has been replaced by 417 ASN; 484 GLU replaced by 484 LYS; and 501 ASN replaced by 501 TYR. All these mutations are at the RBD, and known to alter the electrostatic charge which effect the infectivity index of the variants -.

Figure 3

Mutations and characteristic features of SARS-CoV-2 major variants. In the case of B.1.1.529 (Omicron), mutations listed in blue color already have been reported also in other variants of SARS-CoV-2 virus.

Figure 4

Schematics showing how different mutations near the S1 and S2 furin cleavage site, which virus uses to enter and bind to host cells are contributing in transmissibility and infection rate across different variants of the SARS-CoV-2. (A) E484K and N501Y mutation at the RBD and deletion of H69 and V70 amino acids in Alpha variant, which allows the virus to evade the vaccine and infect both vaccinated and non-vaccinated patients. (B) and (C) K417N mutation in variants, affecting the spike protein to bind with ACE2 receptor. (D) Different other mutations in other variants to invade the host cell.

Figure 5

Schematic comparing the process of vaccine development. A) Development of typical vaccine: The multicolor arrow indicates the timeline and the amount of time it takes to develop a normal vaccine before COVID-19. B) The green arrow indicates how COVID-19 vaccines were developed, and how each phase was overlapped and shortened significantly in comparison to normal vaccine development.

Figure 6

(A) Characterization of vaccine formulations. Different adjuvant systems, cationic liposomes (CAF01), squalene emulsion (SE) and aluminium hydroxide (AH), were tested for compatibility with pre-fusion stabilized (S-2P) spike trimer protein. a) The particle size comparison, polydispersity index (PDI, middle panels) and the Zeta potential (Zp, right panel). b) Adsorption of spike protein to aluminium hydroxide (AH) and the Cryo-TEM micrographs. c) Adsorption of the spike protein determined by measuring protein content recovered in the supernatant after ultracentrifugation; adopted with permission from ref . (B) The strategies used for the development of vaccine for COVID-19. The viral vector and RNA based vaccine are ahead in global outreach, and also available in the form of 3rd and 4th booster shots for SARS-CoV-2 variants; adopted from ref .

Figure 7

(A) The formation of NET by macrophage assisted neutrophil in response to pathogen attack. The reactive oxygen species inside neutrophil activates PAD- 4, and granules release NE which move inside the nucleus to trigger the chromatin decondensation. After decondensation, chromatin expands until it is released from the cell to engulf the pathogen. (B) Scanning electron microscopy of human neutrophils incubated with Salmonella, a bacterium that causes typhoid fever and gastroenteritis; adopted from ref. (C) Transmission electron microscopy (TEM) of a naive human neutrophil; adopted from ref. . Abbreviations: NE: Neutrophil elastase, MYD88: Myeloid differentiation primary response 88, JAK: Janus kinase, STAT: signal transducer and activator of transcription, NF-kB: nuclear transcription factor-kappa B, ISGs: interferon stimulated genes, DAMPS: damage-associated molecular patterns, TLR2/4: toll-like Receptor 2/4, IL6R: interleukin 6 Receptor, LL37: antimicrobial peptide, PAD4: peptidylarginine deiminase 4, NE: neutrophil elastase, MPO: myeloperoxidase enzyme.

Figure 8

Immune responses elicited by SARS-CoV-2 mRNA vaccines. (A) After vaccination, antigen presenting cell activate the CD4+ and CD8+ T cells. CD8+ T cells directly kill the infected cells while CD4+ T cells activate the B cells for the formation of long-lived plasma cells (LLPCs) and memory B Cells (MBCs) inside the germinal center. The macrophages phagocytize and digest the infected cells as well as antigen-antibody complex. (B) The interaction of CD147 and spike was detected by SPR assay, ELISA, immune-electron microscope, and Co-IP assay. The mouse IgG and rabbit IgG were served as negative controls; adopted from ref. (C) SARS-CoV-2 enters the host cells through CD147-mediated endocytosis and the sequential endocytosis of SARS-CoV-2 was observed in Vero E6 cells by electron microscope. And the co-localization of spike protein, CD147, and Rab5 were analysed in BHK-21-CD147 cells and lung tissues; adopted from ref. .

Figure 9

Schematic showing the T cell response after SARS-CoV-2 mRNA vaccines. T lymphocytes attach to antigens presented by dendritic cells and develop into regulatory suppressor, helper, or cytotoxic T lymphocytes. A vital part of the production of Abs and memory B cells, activated helper T cells display receptors on their surface that are unique to vaccine strains.