Prevalence of persistent SARS-CoV-2 in a large community surveillance study

Abstract:

Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks1-5, give rise to highly divergent lineages6-8 and contribute to cases with post-acute COVID-19 sequelae (long COVID)9,10. However, the population prevalence of persistent infections, their viral load kinetics and evolutionary dynamics over the course of infections remain largely unknown.

Here, using viral sequence data collected as part of a national infection survey, we identified 381 individuals with SARS-CoV-2 RNA at high titre persisting for at least 30 days, of which 54 had viral RNA persisting at least 60 days. We refer to these as ‘persistent infections’ as available evidence suggests that they represent ongoing viral replication, although the persistence of non-replicating RNA cannot be ruled out in all.

Individuals with persistent infection had more than 50% higher odds of self-reporting long COVID than individuals with non-persistent infection. We estimate that 0.1-0.5% of infections may become persistent with typically rebounding high viral loads and last for at least 60 days. In some individuals, we identified many viral amino acid substitutions, indicating periods of strong positive selection, whereas others had no consensus change in the sequences for prolonged periods, consistent with weak selection. Substitutions included mutations that are lineage defining for SARS-CoV-2 variants, at target sites for monoclonal antibodies and/or are commonly found in immunocompromised people11-14. This work has profound implications for understanding and characterizing SARS-CoV-2 infection, epidemiology and evolution.

Source: Ghafari M, Hall M, Golubchik T, Ayoubkhani D, House T, MacIntyre-Cockett G, Fryer HR, Thomson L, Nurtay A, Kemp SA, Ferretti L, Buck D, Green A, Trebes A, Piazza P, Lonie LJ, Studley R, Rourke E, Smith DL, Bashton M, Nelson A, Crown M, McCann C, Young GR, Santos RAND, Richards Z, Tariq MA, Cahuantzi R; Wellcome Sanger Institute COVID-19 Surveillance Team; COVID-19 Infection Survey Group; COVID-19 Genomics UK (COG-UK) Consortium; Barrett J, Fraser C, Bonsall D, Walker AS, Lythgoe K. Prevalence of persistent SARS-CoV-2 in a large community surveillance study. Nature. 2024 Feb 21. doi: 10.1038/s41586-024-07029-4. Epub ahead of print. PMID: 38383783. https://www.nature.com/articles/s41586-024-07029-4 (Full text)

Post-acute sequelae of COVID-19 in solid organ transplant recipients

Abstract:

Background: Post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC), defined as prolonged symptoms following an episode of COVID-19, is not well-characterized in solid organ transplant recipients (SOTR). In this study, we aimed to assess the prevalence of PASC in SOTR, its descriptive characteristics, and associated risk factors.

Methods: We retrospectively identified SOTRs with acute COVID-19 between June 1, 2020 and April 15, 2022, and abstracted demographic and medical history, characteristics of acute COVID-19 illness, and COVID-19 vaccination status. We defined PASC as ongoing/new symptoms present at 6 weeks or longer following acute COVID-19 diagnosis.

Results: Among 208 SOTRs with acute COVID-19, 72 (35%) developed PASC. Common symptoms were respiratory symptoms (67%), headache (40%), and difficulty concentrating (10%). Severe acute COVID-19 disease and presence of respiratory symptoms were associated with higher odds of PASC in multivariable analyses, while receipt of at least one COVID-19 vaccination prior to transplantation was protective.

Conclusion: We found that PASC occurs in about a third of SOTRs with acute COVID-19 and has similar symptoms as described previously in immunocompetent hosts. Pre-transplant vaccination may be protective. Further prospective multicenter studies are needed.

Source: Sigler R, Covarrubias K, Chen B, Rubarth RB, Torosian K, Sanchez CR, Bharti A, DeGruttola V, Aslam S. Post-acute sequelae of COVID-19 in solid organ transplant recipients. Transpl Infect Dis. 2023 Nov 3:e14167. doi: 10.1111/tid.14167. Epub ahead of print. PMID: 37922371. https://onlinelibrary.wiley.com/doi/10.1111/tid.14167 (Full text available as PDF file)

Long-COVID in immunocompromised children

Abstract:

Coronavirus disease 2019 (COVID-19) can lead to an illness characterized by persistent symptoms which affect various organs and systems, known as long-COVID. This study aimed to assess the prevalence and clinical characteristics of long-COVID in children with immunodeficiency, in comparison to those without. A self-constructed questionnaire was created, which included questions regarding the child’s general health, the course of their COVID-19, their symptoms of long-COVID and its impact on their daily functioning, the diagnosis of multisystem inflammatory syndrome (MIS-C), and vaccination status. The questionnaire was completed by parents of 147 children – 70 children with a diagnosis of immunodeficiency (47.6%) and 77 who were immunocompetent (52.4%).

Immunocompetent children were more significantly affected by long-COVID than those immunocompromised. Its prevalence in the first 12-week post-infection was 60.0% and 35.7% in these groups, respectively. Beyond this period, these percentages had dropped to 34.6% and 11.43%, respectively. Children who were immunocompetent reported more often symptoms of fatigue, reduced exercise tolerance, and difficulty concentrating. Meanwhile, there was a slight increase in complaints of gastrointestinal symptoms in immunocompromised patients. The risk of developing long-COVID increased with age and COVID-19 severity in both groups. Furthermore, the daily activities of immunocompetent children were limited more frequently (41.8%) than for those who were immunocompromised (25%).

Conclusions: Although immunocompromised children experienced long-COVID, its prevalence and impact on daily functioning were significantly lower than among immunocompetent children. However, as the pathomechanisms of long-COVID are not yet fully understood, it is not currently possible to fully explain these findings.

What is known: • Long COVID is characterized by persistent symptoms following COVID-19, which can affect various tissues and organs, as well as mental health. • Due to the similar course of COVID-19 – mainly mild or asymptomatic – among children with and without immunodeficiency, the question arises, over whether the prevalence and severity of long-COVID is also similar in both groups.

What is new: • Immunocompromised children also suffer from long-COVID, but the prevalence is significantly lower than in the immunocompetent group of children. • The potential causes of less frequent and milder long-COVID in this group may be the milder course of COVID-19 and the state of reduced immunity protecting against neuroinflammation.

Source: Kuczborska K, Buda P, Książyk J. Long-COVID in immunocompromised children. Eur J Pediatr. 2022 Jul 14:1–9. doi: 10.1007/s00431-022-04561-1. Epub ahead of print. PMID: 35834042; PMCID: PMC9281224.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281224/ (Full text)