#17,863
While there are often dozens of diverse COVID variants co-circulating at any given time, the history has been that when new, hugely dominant variants emerge they quickly supplant older variants.
- The original Wuhan variant quickly gave way to the European variant (D614G) which appeared in early 2020.
- The next major shift began in November 2020 in the UK (see CDC Update On New COVID Variant In The UK') and would be dubbed the `Alpha Variant'.
- By the summer of 2021, the Delta variant would become dominant throughout most of the world (see UK PHE Technical Briefing On COVID Variant B.1.617.2 (Delta).
- And in November of 2021, a new - highly divergent - Omicron variant emerged, quickly dethroning Delta, causing the biggest wave of the pandemic.
The pre-Omicron variants (Alpha, Delta, D614G, etc.) are all now virtually extinct, with the last reported Delta case in the United Stares in March of 2022. Alpha has been a no-show since late 2021.
But there have been a few exceptions.
In early 2022 we looked at a report from researchers at the University of Pennsylvania which found evidence of "deer-derived alpha variants" that "diverged significantly from those in humans" still circulating in wild deer (see Preprint: Evolutionary Trajectories of SARS-CoV-2 Alpha and Delta Variants in White-Tailed Deer in Pennsylvania).
The authors wrote:
Our findings of alpha persistence in deer after replacement of alpha by delta in humans, and the divergence seen between our deer and human alpha genomes, are all consistent with long-term persistence and spread of the alpha variant in deer.
In August of 2022, in EID: Highly Divergent SARS-CoV-2 Alpha Variant in Chronically Infected Immunocompromised Person, we saw a report from Erasmus Medical Center on an immunocompromised patient who appears to have carried the Alpha variant for 42 weeks, testing positive for it long after the virus had been supplanted by Delta.
All of which brings us to a new report, published today in BMC Genomics, which describes waste-water-treatment plant (WWTP) testing in Michigan over > 2 year period which continued to pick up evidence of the Alpha Variant well into 2023.
The authors hypothesize that a chronically infected individual not only shed the Alpha virus for 24-28 months, but over that time the virus accrued numerous mutations in the Spike RBD and NTD.
Although we've seen prolonged shedding of the virus - particularly in immunocompromised individuals - this is easily the longest duration to date.
In addition to showing the value of WWTP monitoring, this study reminds us that COVID is still able to surprise us. Due to its length, I've only posted some excerpts. Follow the link to read it in its entirety.
Chronic shedding of a SARS-CoV-2 Alpha variant in wastewater
Michael J. Conway, Hannah Yang, Lauren A. Revord, Michael P. Novay, Rachel J. Lee, Avery S. Ward, Jackson D. Abel, Maggie R. Williams, Rebecca L. Uzarski & Elizabeth W. Alm
BMC Genomics volume 25, Article number: 59 (2024) Cite this article
Abstract
Background
Central Michigan University (CMU) participated in a state-wide SARS-CoV-2 wastewater monitoring program since 2021. Wastewater samples were collected from on-campus sites and nine off-campus wastewater treatment plants servicing small metropolitan and rural communities. SARS-CoV-2 genome copies were quantified using droplet digital PCR and results were reported to the health department.
Results
One rural, off-campus site consistently produced higher concentrations of SARS-CoV-2 genome copies. Samples from this site were sequenced and contained predominately a derivative of Alpha variant lineage B.1.1.7, detected from fall 2021 through summer 2023. Mutational analysis of reconstructed genes revealed divergence from the Alpha variant lineage sequence over time, including numerous mutations in the Spike RBD and NTD.
Conclusions
We discuss the possibility that a chronic SARS-CoV-2 infection accumulated adaptive mutations that promoted long-term infection. This study reveals that small wastewater treatment plants can enhance resolution of rare events and facilitate reconstruction of viral genomes due to the relative lack of contaminating sequences.(SNIP)
Sampling began in July 2021, which was at least seven months after emergence of the Alpha variant (B.1.1.7). The Alpha variant first appeared in North America in late November 2020 and became the predominant SARS-CoV-2 variant by the end of March 2021. The Alpha variant diverged into multiple lineages, including B.1.1.7-derivatives like Q.3. The Q.3 lineage is present in 5,422 clinical sequences worldwide that were uploaded to the NCBI database, and a positive sample was first collected on 7-11-20 (The dates used to describe samples are formatted using the American system (MM-DD-YY)). The Q.3 lineage was detected in clinical samples from Michigan 16 times between 2-18-21 and 7-9-21.
It became clear that our smallest WWTP (estimated population served: 851) consistently produced higher concentrations of SARS-CoV-2 genome copies. Samples taken from this site from 2021 to 2023 were sequenced and many contained sequences that corresponded to an Alpha variant lineage. These sequences also accumulated novel mutations over time, including previously described mutations found only in cryptic lineages derived from wastewater and not in circulating clinical samples [13, 14]. In this manuscript, a cryptic mutation is a mutation previously identified in cryptic lineages, which were previously identified in wastewater but not clinical samples. It’s important to highlight that many of the mutations previously identified in cryptic lineages have since been identified in clinical samples.We hypothesize that an individual was chronically infected with an Alpha variant lineage for 20–28 months. During this time, the virus adapted by accumulating novel mutations, which included previously described cryptic mutations [13, 14]. Importantly, we found that the earliest sample corresponded to Alpha variant lineage Q.3, which closely aligned with clinical sequences reported in summer and fall 2021; however, the sequence diverged over time and accumulated novel mutations.
These data reveal that wastewater surveillance in small metropolitan and rural communities provide an opportunity to identify novel isolates and reconstruct genes due to lower contamination with unrelated sequences. These data also suggest that humans and other animals can chronically shed SARS-CoV-2 over many months, which is associated with accumulation of adaptive mutations. Mutations associated with chronic infection may be useful to identify individuals who are chronically infected and to drive selection of appropriate therapeutics.(SNIP)In summary, these data support that an individual can be chronically infected with SARS-CoV-2 over many months and possibly a few years. During this time, SARS-CoV-2 can accumulate many mutations in the Spike gene, which concentrate in the RBD and NTD. Further research is needed to determine if these mutations are predictive of chronic infection and if they can be used as a biomarker in individuals with Long COVID and leveraged to tailor selection or development of pharmaceutical therapies. Additionally, this study shows that small WWTPs can enhance the resolution of rare biological events and allow for total reconstruction of viral genes and their corresponding proteins
