Tracing the origin of Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): A systematic review and narrative synthesis

Abstract

The aim of the study was to trace and understand the origin of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through various available literatures and accessible databases. Although the world enters the third year of the coronavirus disease 2019 pandemic, health and socioeconomic impacts continue to mount, the origin and mechanisms of spill-over of the SARS-CoV-2 into humans remain elusive. Therefore, a systematic review of the literature was performed that showcased the integrated information obtained through manual searches, digital databases (PubMed, CINAHL, and MEDLINE) searches, and searches from legitimate publications (1966-2022), followed by meta-analysis. Our systematic analysis data proposed three postulated hypotheses concerning the origin of the SARS-CoV-2, which include zoonotic origin (Z), laboratory origin (L), and obscure origin (O). Despite the fact that the zoonotic origin for SARS-CoV-2 has not been conclusively identified to date, our data suggest a zoonotic origin, in contrast to some alternative concepts, including the probability of a laboratory incident or leak. Our data exhibit that zoonotic origin (Z) has higher evidence-based support as compared to laboratory origin (L). Importantly, based on all the studies included, we generated the forest plot with 95% confidence intervals (CIs) of the risk ratio estimates. Our meta-analysis further supports the zoonotic origin of SARS/SARS-CoV-2 in the included studies.

Keywords: COVID-19; MERS-CoV; SARS-CoV; SARS-CoV-2; laboratory incidence; origin; zoonotic.

Figure 1

Phylogenetic of SARS‐like coronaviruses and SARS‐CoV‐2. Phylogenetic relationship showing that the SARS‐CoV‐2 is closely related to the SARS‐like coronaviruses isolated from the bats. However, SARS‐CoV‐2 has been reported in pangolins. Whereas earlier reported SARS‐CoV has been isolated from humans, bats, and civets. SARS‐CoV‐2, Severe acute respiratory syndrome coronavirus 2.

Figure 2

Theories of SARS‐CoV‐2 origin. SARS‐CoV‐2 shares sequence similarity with intermediate hosts including Bat‐CoV‐RaTG13, a bat coronavirus isolated from Rhinolophus affinis shares 96% whole‐genome sequence identity with SARS‐CoV‐2. SARS‐CoV‐2 has been shown to originate as a spillover from the infected intermediate hosts. Pangolin‐CoV‐2019, a pangolin isolates shared a higher sequence homology of 97.5% with spike glycoprotein. Similarly, SARS‐CoV‐2 might have spillover from infected live wild/domestic animals, including their products. Due to previous leakages of microorganisms from the laboratory, several theories support and contradict the origin of SARS‐CoV‐2 from laboratory leakage. Recent emergence of newer SARS‐CoV‐2 variants, Omicron is imposing serious concern about its origin which might be the result of inter‐species evolution of SARS‐CoV‐2.

Figure 3

Heatmap and similarity matrix of SARS‐CoV‐2 origin. (A) Year‐wise studies (Supporting Information: Table S1) supporting the zoonotic origin (Z) of SARS‐CoV‐2 versus laboratory origin (L) versus obscure origin (O). The rows and columns have been hierarchically clustered using cosine‐distance and average linkage, where studies are clustered in rows. Red/blue cells in the matrix represent positive/negative values in the matrix. (B) Heatmap is showing the row similarity matrix among Z, L, and O. The cells in the matrix represent the similarity between rows, where red/blue represents a positive/negative similarity (measured as 1 − cosine‐distance).

Figure 4

Forest plot of theories showing the hypothesis of SARS‐CoV‐2 origin. The horizontal line represents the risk ratio estimates at 95% confidence intervals (95% CI). The black diamond supports the zoonotic origin (Z) of SARS‐CoV‐2 based on the included studies (Supporting Information: Table S1).