Presence of SARS-CoV-2 RNA in COVID-19 survivors with post-COVID symptoms: a systematic review of the literature.

INTRODUCTION: Viral persistence is one of the main hypotheses explaining the presence of post-COVID symptoms. This systematic review investigated the presence of SARS-CoV-2 RNA in plasma, stool, urine, and nasal/oral swab samples in individuals with post-COVID symptomatology. CONTENT: MEDLINE, CINAHL, PubMed, EMBASE, Web of Science databases, as well as medRxiv/bioRxiv preprint servers were searched up to November 25th, 2023. Articles investigating the persistence of SARS-CoV-2 RNA in plasma, stool, urine or nasal/oral swab samples in patients with post-COVID symptoms were included. Methodological quality was assessed using the Newcastle-Ottawa Scale or Cochrane's Risk of Bias (Rob) tool. SUMMARY: From 322 studies identified, six studies met all inclusion criteria. The sample included 678 COVID-19 survivors (52 % female, aged from 29 to 66 years). The methodological quality was moderate in 88 % of the studies (n=5/6). Three papers investigated the presence of SARS-CoV-2 RNA in plasma, three studies in nasal/oral swabs, two studies in stool samples, one in urine and one in saliva. The follow-up was shorter than two months (<60 days after) in 66 % of the studies (n=4/6). The prevalence of SARS-CoV-2 RNA ranged from 5 to 59 % in patients with post-COVID symptoms the first two months after infection, depending on the sample tested, however, SARS-CoV-2 RNA was also identified in COVID-19 survivors without post-COVID symptoms (one study). OUTLOOK: Available evidence can suggest the presence of persistent SARS-CoV-2 RNA in post-COVID patients in the short term, although the biases within the studies do not permit us to make firm assumptions. The association between post-COVID symptoms and SARS-CoV-2 RNA in the samples tested is also conflicting. The lack of comparative group without post-COVID symptoms limits the generalizability of viral persistence in post-COVID-19 condition.

Is antiviral treatment at the acute phase of COVID-19 effective for decreasing the risk of long-COVID? A systematic review.

PURPOSE: Preliminary evidence suggests a potential effect of antiviral medication used during the acute COVID-19 phase for preventing long-COVID. This review investigates if having received pharmacological treatment during acute SARS-CoV-2 infection may reduce the risk of long-COVID. METHODS: MEDLINE, CINAHL, PubMed, EMBASE, Web of Science databases, as well as medRxiv/bioRxiv preprint servers were searched up to July 15th, 2023. Articles comparing the presence of long-COVID symptoms between individuals who received or not a specific medication, particularly antivirals, during the acute phase of SARS-CoV-2 infection were included. Methodological quality was assessed using the Newcastle-Ottawa Scale or Cochrane's Risk of Bias (Rob) tool. RESULTS: From 517 studies identified, 6 peer-reviewed studies and one preprint met all inclusion criteria. The sample included 2683 (n = 4) hospitalized COVID-19 survivors and 307,409 (n = 3) non-hospitalized patients. The methodological quality was high in 71% of studies (n = 5/7). Two studies investigating the effects of Nirmaltrevir/Ritonavir and three studies the effect of Remdesivir reported conflicting results on effectiveness for preventing long-COVID. Three studies investigating the effects of other medication such as Dexamethasone (n = 2) or Metformin (n = 1) found positive results of these medications for preventing long-COVID. CONCLUSION: Available evidence about the effect of medication treatment with antivirals during acute COVID-19 and reduced risk of developing long-COVID is conflicting. Heterogeneous evidence suggests that Remdesivir or Nirmaltrevir/Ritonavir could have a potential protective effect for long-COVID. A limited number of studies demonstrated a potential benefit of other medications such as Dexamethasone or Metformin, but more studies are needed.

Persistence of post-COVID symptoms in the general population two years after SARS-CoV-2 infection: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis investigated the prevalence of post-COVID symptoms two-years after SARS-CoV-2 infection. METHODS: Electronic literature searches on PubMed, MEDLINE, CINAHL, EMBASE, Web of Science databases, and on medRxiv/bioRxiv preprint servers were conducted up to October 1, 2023. Studies reporting data on post-COVID symptoms at two-years after infection were included. Methodological quality was assessed using the Newcastle-Ottawa Scale. Random-effects models were used for meta-analytical pooled prevalence of each symptom. RESULTS: From 742 studies identified, twelve met inclusion criteria. The sample included 7912 COVID-19 survivors (50.7% female; age: 59.5, SD: 16.3). Post-COVID symptoms were assessed at a follow-up of 722.9 (SD: 51.5) days after. The overall methodological quality of studies was moderate (mean: 6/10, SD: 1.2 points). The most prevalent post-COVID symptoms two-years after SARS-CoV-2 infection were fatigue (28.0%, 95%CI 12.0-47.0), cognitive impairments (27.6%, 95%CI 12.6-45.8), and pain (8.4%, 95%CI 4.9-12.8). Psychological disturbances such as anxiety (13.4%, 95%CI 6.3-22.5) and depressive (18.0%, 95%CI 4.8-36.7) levels as well as sleep problems (20.9%, 95%CI 5.25-43.25) were also prevalent. Pooled data showed high heterogeneity (I2 ≥ 75%). CONCLUSION: This meta-analysis shows the presence of post-COVID symptoms in 30% of patients two-years after COVID-19. Fatigue, cognitive disorders, and pain were the most prevalent post-COVID symptoms. Psychological disturbances as well as sleep problems were still present two-years after COVID-19.

Infusion reactions to adeno-associated virus (AAV)-based gene therapy: Mechanisms, diagnostics, treatment and review of the literature.

The use of adeno-associated virus (AAV) vectors in gene therapy has demonstrated great potential in treating genetic disorders. However, infusion-associated reactions (IARs) pose a significant challenge to the safety and efficacy of AAV-based gene therapy. This review provides a comprehensive summary of the current understanding of IARs to AAV therapy, including their underlying mechanisms, clinical presentation, and treatment options. Toll-like receptor activation and subsequent production of pro-inflammatory cytokines are associated with IARs, stimulating neutralizing antibodies (Nabs) and T-cell responses that interfere with gene therapy. Risk factors for IARs include high titers of pre-existing Nabs, previous exposure to AAV, and specific comorbidities. Clinical presentation ranges from mild flu-like symptoms to severe anaphylaxis and can occur during or after AAV administration. There are no established guidelines for pre- and postadministration tests for AAV therapies, and routine laboratory requests are not standardized. Treatment options include corticosteroids, plasmapheresis, and supportive medications such as antihistamines and acetaminophen, but there is no consensus on the route of administration, dosage, and duration. This review highlights the inadequacy of current treatment regimens for IARs and the need for further research to improve the safety and efficacy of AAV-based gene therapy.