Tag: antivirals

Feasibility Study of Developing a Saline-Based Antiviral Nanoformulation Containing Lipid-Soluble EGCG: A Potential Nasal Drug to Treat Long COVID

Abstract:

A recent estimate indicates that up to 23.7 million Americans suffer from long COVID, and approximately one million workers may be out of the workforce each day due to associated symptoms, leading to a USD 50 billion annual loss of salary. Post-COVID (Long COVID) neurologic symptoms are due to the initial robust replication of SARS-CoV-2 in the nasal neuroepithelial cells, leading to inflammation of the olfactory epithelium (OE) and the central nervous system (CNS), and the OE becoming a persistent infection site.

Previously, our group showed that Epigallocatechin-3-gallate-palmitate (EC16) nanoformulations possess strong antiviral activity against human coronavirus, suggesting this green tea-derived compound in nanoparticle formulations could be developed as an intranasally delivered new drug to eliminate the persistent SARS-CoV-2 infection, leading to restored olfactory function and reduced inflammation in the CNS. The objective of the current study was to determine the compatibility of the nanoformulations with human nasal primary epithelial cells (HNpECs).

Methods: Nanoparticle size was measured using the ZetaView Nanoparticle Tracking Analysis (NTA) system; contact antiviral activity was determined by TCID50 assay for cytopathic effect on MRC-5 cells; post-infection inhibition activity was determined in HNpECs; and cytotoxicity for these cells was determined using an MTT assay. The rapid inactivation of OC43 (a β-coronavirus) and 229E (α-coronavirus) viruses was further characterized by transmission electron microscopy.

Results: A saline-based nanoformulation containing 0.1% w/v EC16 was able to inactivate 99.9999% β-coronavirus OC43 on direct contact within 1 min. After a 10-min incubation of infected HNpECs with a formulation containing drug-grade EC16 (EGCG-4′ mono-palmitate or EC16m), OC43 viral replication was inhibited by 99%. In addition, all nanoformulations tested for their effect on cell viability were comparable to normal saline, a regularly used nasal irrigation solution. A 1-min incubation of an EC16 nanoformulation with either OC43 or 229E showed an altered viral structure.

Conclusion: Nanoformulations containing EC16 showed properties compatible with nasal application to rapidly inactivate SARS-CoV-2 residing in the olfactory mucosa and to reduce inflammation in the CNS, pending additional formulation and safety studies.

Source: Frank N, Dickinson D, Garcia W, Liu Y, Yu H, Cai J, Patel S, Yao B, Jiang X, Hsu S. Feasibility Study of Developing a Saline-Based Antiviral Nanoformulation Containing Lipid-Soluble EGCG: A Potential Nasal Drug to Treat Long COVID. Viruses. 2024; 16(2):196. https://doi.org/10.3390/v16020196 https://www.mdpi.com/1999-4915/16/2/196 (Full text)

Effect of Paxlovid Treatment on Long COVID Onset: An EHR-Based Target Trial Emulation from N3C

Abstract:

Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. In this study, we examined whether treatment with Paxlovid in the acute phase of COVID-19 helps prevent the onset of PASC.

We used electronic health records from the National Covid Cohort Collaborative (N3C) to define a cohort of 426,461 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation (TTE) framework to estimate the effect of Paxlovid treatment on PASC incidence.

Our primary outcome measure was a PASC computable phenotype. Secondary outcomes were the onset of novel cognitive, fatigue, and respiratory symptoms in the post-acute period. Paxlovid treatment did not have a significant effect on overall PASC incidence (relative risk [RR] = 0.99, 95% confidence interval [CI] 0.96-1.01). However, its effect varied across the cognitive (RR = 0.85, 95% CI 0.79-0.90), fatigue (RR = 0.93, 95% CI 0.89-0.96), and respiratory (RR = 0.99, 95% CI 0.95-1.02) symptom clusters, suggesting that Paxlovid treatment may help prevent post-acute cognitive and fatigue symptoms more than others.

Source: Alexander Preiss, Abhishek Bhatia, Chengxi Zang, Leyna V. Aragon, John M. Baratta, Monika Baskaran, Frank Blancero, M. Daniel Brannock, Robert F. Chew, Iván Díaz, Megan Fitzgerald, Elizabeth P. Kelly, Andrea Zhou, Mark G. Weiner, Thomas W. Carton, Fei Wang, Rainu Kaushal, Christopher G. Chute, Melissa Haendel, Richard Moffitt, Emily Pfaff. Effect of Paxlovid Treatment on Long COVID Onset: An EHR-Based Target Trial Emulation from N3C. medRxiv 2024.01.20.24301525; doi: https://doi.org/10.1101/2024.01.20.24301525 https://www.medrxiv.org/content/10.1101/2024.01.20.24301525v1.full-text (Full text)

A randomized open-label clinical trial on the effect of Amantadine on post Covid 19 fatigue

Abstract:

Many COVID-19 survivors experience lingering post-COVID-19 symptoms, notably chronic fatigue persisting for months after the acute phase. Despite its prevalence, limited research has explored effective treatments for post-COVID-19 fatigue. This randomized controlled clinical trial assessed the impact of Amantadine on patients with post-COVID-19 fatigue.

The intervention group received Amantadine for two weeks, while the control group received no treatment. Fatigue levels were assessed using the Visual Analog Fatigue Scale (VAFS) and Fatigue Severity Scale (FSS) questionnaires before and after the trial. At the study’s onset, VAFS mean scores were 7.90 ± 0.60 in the intervention group and 7.34 ± 0.58 in the control group (P-value = 0.087). After two weeks, intervention group scores dropped to 3.37 ± 0.44, significantly lower than the control group’s 5.97 ± 0.29 (P-value < 0.001). Similarly, FSS mean scores at the trial’s commencement were 53.10 ± 5.96 in the intervention group and 50.38 ± 4.88 in the control group (P-value = 0.053). At the trial’s end, intervention group scores decreased to 28.40 ± 2.42, markedly lower than the control group’s 42.59 ± 1.50 (P-value < 0.001).

In this study, we report the safety, tolerability, and substantial fatigue-relieving effects of Amantadine in post-COVID-19 fatigue. The intervention demonstrates a statistically significant reduction in fatigue levels, suggesting Amantadine’s potential as an effective treatment for this persistent condition.

Source: Harandi, A.A., Pakdaman, H., Medghalchi, A. et al. A randomized open-label clinical trial on the effect of Amantadine on post Covid 19 fatigue. Sci Rep 14, 1343 (2024). https://doi.org/10.1038/s41598-024-51904-z https://www.nature.com/articles/s41598-024-51904-z (Full text)

Association of nirmatrelvir for acute SARS-CoV-2 infection with subsequent Long COVID symptoms in an observational cohort study

Abstract:

Oral nirmatrelvir/ritonavir is approved as treatment for acute COVID-19, but the effect of treatment during acute infection on risk of Long COVID is unknown. We hypothesized that nirmatrelvir treatment during acute SARS-CoV-2 infection reduces risk of developing Long COVID and rebound after treatment is associated with Long COVID. We conducted an observational cohort study within the Covid Citizen Science (CCS) study, an online cohort study with over 100 000 participants.

We included vaccinated, nonhospitalized, nonpregnant individuals who reported their first SARS-CoV-2 positive test March–August 2022. Oral nirmatrelvir/ritonavir treatment was ascertained during acute SARS-CoV-2 infection. Patient-reported Long COVID symptoms, symptom rebound and test-positivity rebound were asked on subsequent surveys at least 3 months after SARS-CoV-2 infection. A total of 4684 individuals met the eligibility criteria, of whom 988 (21.1%) were treated and 3696 (78.9%) were untreated; 353/988 (35.7%) treated and 1258/3696 (34.0%) untreated responded to the Long COVID survey (n = 1611). Among 1611 participants, median age was 55 years and 66% were female.

At 5.4 ± 1.3 months after infection, nirmatrelvir treatment was not associated with subsequent Long COVID symptoms (odds ratio [OR]: 1.15; 95% confidence interval [CI]: 0.80–1.64; p = 0.45). Among 666 treated who answered rebound questions, rebound symptoms or test positivity were not associated with Long COVID symptoms (OR: 1.34; 95% CI: 0.74–2.41; p = 0.33).

Within this cohort of vaccinated, nonhospitalized individuals, oral nirmatrelvir treatment during acute SARS-CoV-2 infection and rebound after nirmatrelvir treatment were not associated with Long COVID symptoms more than 90 days after infection.

Source: Durstenfeld MS, Peluso MJ, Lin F, et al. Association of nirmatrelvir for acute SARS-CoV-2 infection with subsequent Long COVID symptoms in an observational cohort study. J Med Virol. 2024; 96:e29333. doi:10.1002/jmv.29333 https://onlinelibrary.wiley.com/doi/10.1002/jmv.29333 (Full text)

Effectiveness of Antiviral Therapy on Long COVID: A Systematic Review and Meta-Analysis

Abstract:

Antiviral treatment reduces the severity and mortality of SARS-CoV-2 infection; however, its effectiveness against long COVID-19 is unclear. This study aimed to evaluate the effectiveness of antiviral drugs in preventing long COVID and related hospitalizations/deaths. Scientific and medical databases were searched from 1 January 2020 to 30 June 2023. We included observational cohort studies comparing individuals receiving early antiviral therapy for COVID-19 and those receiving supportive treatment.
A fixed-effects model was used to merge the effects reported in two or more studies. The risk of post-acute sequelae of COVID-19 (PASC) was combined as an odds ratio (OR). Six studies were selected, including a total of 3,352,235 participants. The occurrence of PASC was 27.5% lower in patients who received antiviral drugs during the early stages of SARS-CoV-2 infection (OR = 0.725; 95% confidence interval [CI] = 0.409–0.747) than in the supportive treatment group. Moreover, the risk of PASC-associated hospitalization and mortality was 29.7% lower in patients receiving early antiviral therapy than in the supportive treatment group (OR = 0.721; 95% CI = 0.697–0.794).
Early antiviral therapy was associated with a reduced risk of PASC and related hospitalization or death. Thus, early antiviral therapy is recommended for at-risk individuals.
Source: Choi YJ, Seo YB, Seo J-W, Lee J, Nham E, Seong H, Yoon JG, Noh JY, Cheong HJ, Kim WJ, et al. Effectiveness of Antiviral Therapy on Long COVID: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine. 2023; 12(23):7375. https://doi.org/10.3390/jcm12237375 https://www.mdpi.com/2077-0383/12/23/7375 (Full text)

Nirmatrelvir/ritonavir and risk of long COVID symptoms: a retrospective cohort study

Abstract:

We conducted a retrospective cohort study to assess whether treatment with nirmatrelvir/ritonavir was associated with a reduced risk of long COVID. We enrolled 500 adults with confirmed SARS-CoV-2 who were eligible for nirmatrelvir/ritonavir; 250 who took nirmatrelvir/ritonavir and 250 who did not. The primary outcome was the development of one or more of eleven prespecified long COVID symptoms, assessed through a structured telephone interview four months after the positive SARS-CoV-2 test. Multivariable logistic regression models controlled for age, sex, race/ethnicity, chronic conditions, and COVID-19 vaccination status.

We found that participants who took nirmatrelvir/ritonavir were no less likely to develop long COVID symptoms, compared to those who did not take the medication (44% vs. 49.6%, p = 0.21). Taking nirmatrelvir/ritonavir was associated with a lower odds of two of the eleven long COVID symptoms, brain fog (OR 0.58, 95% CI 0.38-0.88) and chest pain/tightness (OR 0.51, 95% CI 0.28-0.91). Our finding that treatment with nirmatrelvir/ritonavir was not associated with a lower risk of developing long COVID is different from prior studies that obtained data only from electronic medical records.

Source: Congdon S, Narrowe Z, Yone N, Gunn J, Deng Y, Nori P, Cowman K, Islam M, Rikin S, Starrels J. Nirmatrelvir/ritonavir and risk of long COVID symptoms: a retrospective cohort study. Sci Rep. 2023 Nov 11;13(1):19688. doi: 10.1038/s41598-023-46912-4. PMID: 37951998; PMCID: PMC10640584. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10640584/ (Full text)

Long COVID-19 Symptoms Remedied by Anti-Viral Treatment in Neurosurgical Patients

Abstract:

The pandemic of COVID-19 is the largest in this century. Aside from the acute infection, some of the patients have been challenged with a complication that is known as long COVID-19. The symptoms of long COVID-19 are extensive and diverse. Long COVID-19 continues to plague many patients post-COVID-19 infection. No universal treatment has been found.

This study presents four patients who suffered from long COVID-19. Each patient presented with a different and diverse symptom of long COVID-19. Each of the patient’s symptoms resolved or greatly improved upon taking the anti-viral drug acyclovir. Acyclovir has been in use since 1981 and is generally considered safe. A novel theory as to the pathophysiology of long COVID-19 symptoms and the result of a new treatment is presented. The purpose of this study is to provide a foundation for much bigger studies and useful resources for further testing to halt long COVID-19.

Source: Beatty, R. M. (2023). Long COVID-19 Symptoms Remedied by Anti-Viral Treatment in Neurosurgical Patients. American Journal of Infectious Diseases, 19(3), 39-44. https://doi.org/10.3844/ajidsp.2023.39.44 https://thescipub.com/abstract/ajidsp.2023.39.44 (Full text available as PDF file)

Long COVID treated successfully with antivirals in a rituximab-treated follicular lymphoma patient with persistent negative-antibodies to SARS-CoV2

Abstract:

Long COVID is a well-known complication to COVID-19 that affect millions of people worldwide and causes wide range of symptoms. We present a rare case of a previously diagnosed follicular lymphoma patient, who had a long COVID with persistent negative SARS-CoV-2 antibodies and required an aggressive antiviral treatment.

Source: Tayar E, Isber R, Isber N. Long COVID treated successfully with antivirals in a rituximab-treated follicular lymphoma patient with persistent negative-antibodies to SARS-CoV2. Heliyon. 2023 Jun;9(6):e17149. doi: 10.1016/j.heliyon.2023.e17149. Epub 2023 Jun 21. PMID: 37378376; PMCID: PMC10284434. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284434/ (Full text)

Long COVID: Is There a Role for Antidepressants?

Abstract:

Two years into this historic pandemic, the scientific and healthcare communities continue to learn a great deal regarding COVID-19. The most urgent and immediate focus has been on vaccine development for disease prevention/mitigation and on identification of effective therapeutic interventions for acute phase of illness. However, attention is increasingly being placed on formulating treatment strategies for individuals who are post-COVID-19 and experiencing a syndrome of persistent symptoms that is being referred to as long COVID.

One strategy is to repurpose drugs which have been approved for other conditions and subsequently assess their safety and efficacy when applied to COVID-19. In this light, antidepressant medications have garnered attention amidst evidence supporting anti-inflammatory and anti-viral properties.

In this article, we present purported anti-inflammatory mechanisms of antidepressants, review studies appearing in the literature to date regarding antidepressants and acute COVID-19, and discuss the utility of antidepressants as a potential therapeutic resource for long COVID.

Source: Rivas-Vázquez R, Carrazana EJ, Blais MA, Rey GJ, RivasVázquez E, Quintana AA. Long COVID: Is There a Role for Antidepressants? Neurol Curr Res. 2022;2(3):1019. https://www.medtextpublications.com/open-access/long-covid-is-there-a-role-for-antidepressants-1249.pdf (Full text)

Paxlovid accelerates cartilage degeneration and senescence through activating endoplasmic reticulum stress and interfering redox homeostasis

Abstract:

Background: The COVID-19 pandemic has become a huge threat to human health, infecting millions of people worldwide and causing enormous economic losses. Many novel small molecule drugs have been developed to treat patients with COVID-19, including Paxlovid, which block the synthesis of virus-related proteins and replication of viral RNA, respectively. Despite satisfactory clinical trial results, attention is now being paid to the long-term side effects of these antiviral drugs on the musculoskeletal system. To date, no study has reported the possible side effects, such as osteoarthritis, of Paxlovid. This study explored the effects of antiviral drug, Paxlovid, on chondrocyte proliferation and differentiation.

Methods: In this study, both in vitro and in vivo studies were performed to determine the effect of Paxlovid on chondrocyte degeneration and senescence. Furthermore, we explored the possible mechanism behind Paxlovid-induced acceleration of cartilage degeneration using transcriptome sequencing and related inhibitors were adopted to verify the downstream pathways behind such phenomenon.

Results: Paxlovid significantly inhibited chondrocyte extracellular matrix protein secretion. Additionally, Paxlovid significantly induced endoplasmic reticulum stress, oxidative stress, and downstream ferroptosis, thus accelerating the senescence and degeneration of chondrocytes. In vivo experiments showed that intraperitoneal injection of Paxlovid for 1 week exacerbated cartilage abrasion and accelerated the development of osteoarthritis in a mouse model.

Conclusions: Paxlovid accelerated cartilage degeneration and osteoarthritis development, potentially by inducing endoplasmic reticulum stress and oxidative stress. Long-term follow-up is needed with special attention to the occurrence and development of osteoarthritis in patients treated with Paxlovid.

Source: Kong K, Chang Y, Qiao H, Zhao C, Chen X, Rong K, Zhang P, Jin M, Zhang J, Li H, Zhai Z. Paxlovid accelerates cartilage degeneration and senescence through activating endoplasmic reticulum stress and interfering redox homeostasis. J Transl Med. 2022 Nov 26;20(1):549. doi: 10.1186/s12967-022-03770-4. PMID: 36435786; PMCID: PMC9701426. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9701426/ (Full text)