Tag: long covid prevention

Assessing the effect of selective serotonin reuptake inhibitors in the prevention of post-acute sequelae of COVID-19

Abstract:

Background: Post-acute sequelae of COVID-19 (PASC) produce significant morbidity, prompting evaluation of interventions that might lower risk. Selective serotonin reuptake inhibitors (SSRIs) potentially could modulate risk of PASC via their central, hypothesized immunomodulatory, and/or antiplatelet properties although clinical trial data are lacking.

Materials and methods: This retrospective study was conducted leveraging real-world clinical data within the National COVID Cohort Collaborative (N3C) to evaluate whether SSRIs with agonist activity at the sigma-1 receptor (S1R) lower the risk of PASC, since agonism at this receptor may serve as a mechanism by which SSRIs attenuate an inflammatory response. Additionally, determine whether the potential benefit could be traced to S1R agonism. Presumed PASC was defined based on a computable PASC phenotype trained on the U09.9 ICD-10 diagnosis code.

Results: Of the 17,908 patients identified, 1521 were exposed at baseline to a S1R agonist SSRI, 1803 to a non-S1R agonist SSRI, and 14,584 to neither. Using inverse probability weighting and Poisson regression, relative risk (RR) of PASC was assessed. A 29% reduction in the RR of PASC (0.704 [95% CI, 0.58-0.85]; P = 4 ×10-4) was seen among patients who received an S1R agonist SSRI compared to SSRI unexposed patients and a 21% reduction in the RR of PASC was seen among those receiving an SSRI without S1R agonist activity (0.79 [95% CI, 0.67 – 0.93]; P = 0.005).Thus, SSRIs with and without reported agonist activity at the S1R were associated with a significant decrease in the risk of PASC.

Source: Sidky H, Hansen KA, Girvin AT, Hotaling N, Michael SG, Gersing K, Sahner DK; N3C consortium. Assessing the effect of selective serotonin reuptake inhibitors in the prevention of post-acute sequelae of COVID-19. Comput Struct Biotechnol J. 2024 Jan 9;24:115-125. doi: 10.1016/j.csbj.2023.12.045. PMID: 38318198; PMCID: PMC10839808. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10839808/ (Full text)

The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and Estonia

Summary:

Background: Although vaccines have proved effective to prevent severe COVID-19, their effect on preventing long-term symptoms is not yet fully understood. We aimed to evaluate the overall effect of vaccination to prevent long COVID symptoms and assess comparative effectiveness of the most used vaccines (ChAdOx1 and BNT162b2).

Methods: We conducted a staggered cohort study using primary care records from the UK (Clinical Practice Research Datalink [CPRD] GOLD and AURUM), Catalonia, Spain (Information System for Research in Primary Care [SIDIAP]), and national health insurance claims from Estonia (CORIVA database). All adults who were registered for at least 180 days as of Jan 4, 2021 (the UK), Feb 20, 2021 (Spain), and Jan 28, 2021 (Estonia) comprised the source population. Vaccination status was used as a time-varying exposure, staggered by vaccine rollout period. Vaccinated people were further classified by vaccine brand according to their first dose received. The primary outcome definition of long COVID was defined as having at least one of 25 WHO-listed symptoms between 90 and 365 days after the date of a PCR-positive test or clinical diagnosis of COVID-19, with no history of that symptom 180 days before SARS-Cov-2 infection. Propensity score overlap weighting was applied separately for each cohort to minimise confounding. Sub-distribution hazard ratios (sHRs) were calculated to estimate vaccine effectiveness against long COVID, and empirically calibrated using negative control outcomes. Random effects meta-analyses across staggered cohorts were conducted to pool overall effect estimates.

Findings: A total of 1 618 395 (CPRD GOLD), 5 729 800 (CPRD AURUM), 2 744 821 (SIDIAP), and 77 603 (CORIVA) vaccinated people and 1 640 371 (CPRD GOLD), 5 860 564 (CPRD AURUM), 2 588 518 (SIDIAP), and 302 267 (CORIVA) unvaccinated people were included. Compared with unvaccinated people, overall HRs for long COVID symptoms in people vaccinated with a first dose of any COVID-19 vaccine were 0·54 (95% CI 0·44–0·67) in CPRD GOLD, 0·48 (0·34–0·68) in CPRD AURUM, 0·71 (0·55–0·91) in SIDIAP, and 0·59 (0·40–0·87) in CORIVA. A slightly stronger preventative effect was seen for the first dose of BNT162b2 than for ChAdOx1 (sHR 0·85 [0·60–1·20] in CPRD GOLD and 0·84 [0·74–0·94] in CPRD AURUM).

Interpretation: Vaccination against COVID-19 consistently reduced the risk of long COVID symptoms, which highlights the importance of vaccination to prevent persistent COVID-19 symptoms, particularly in adults.

Source: Martí Català, Núria Mercadé-Besora, Raivo Kolde,Nhung T H Trinh,Elena Roel,Edward Burn, Trishna Rathod-Mistry, Kristin Kostka, Wai Yi Man, Antonella Delmestri, Hedvig M E Nordeng, Anneli Uusküla, Talita Duarte-Salles, Daniel Prieto-Alhambra, Annika M Jödicke. The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and Estonia. The Lancet Respiratory Medicine. Published:January 11, 2024 ,DOI: https://doi.org/10.1016/S2213-2600(23)00414-9  https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(23)00414-9/fulltext (Full text)

Long COVID and possible preventive options

Abstract:

Most of the people who suffered from COVID-19 fully recovered, but approximately 10–20% of them developed a wide variety of symptoms after they recover from their initial illness. Long COVID can develop at any patient; however, several studies suggest that the development of Long Covid syndrome may be linked to severity of acute illness.

Some of the risk factors are hospitalization (with mechanical ventilation), Intensive Care Unit admission, age (over 50 years), gender (female) and comorbidities. Since the precise mechanism of Long COVID has not been clarified, neither the management of Long COVID-19 syndrome has been solved yet.

Promising results have been published with vaccines as they effectively reduced the risk of Long COVID; however, other data suggest that vaccination results only partial protection in the post-acute phase of the disease. Recently, the orally effective antiviral agents (Paxlovid, molnupiravir) are preferred for outpatient management, and they highly reduce the progression of mild-to-moderate COVID-19 to severe one, and consequently, might reduce the development of Long COVID. Finally, recently, several clinical trials are in progress with either dietary supplements or drugs with different mechanisms of action.

Additional information on the precise mechanisms, risk factors of Long COVID may result in successful preventive and therapeutic management of Long Covid 19 syndrome.

Source: Sebők S, Gyires K. Long COVID and possible preventive options. Inflammopharmacology. 2023 Jun 21. doi: 10.1007/s10787-023-01204-1. Epub ahead of print. PMID: 37344737. https://link.springer.com/article/10.1007/s10787-023-01204-1 (Full text)

Do COVID-19 Vaccinations Affect the Most Common Post-COVID Symptoms? Initial Data from the STOP-COVID Register-12-Month Follow-Up

Abstract:

Around the world, various vaccines have been developed to prevent the SARS-CoV-2 virus infection and consequently the COVID-19 disease. However, many patients continue to report persistent symptoms after the acute phase. Since gathering scientific information on long COVID and post-COVID syndrome has become an urgent issue, we decided to investigate them in relation to the vaccination status of patients from the STOP-COVID registry.

In this retrospective study, we analyzed data from the medical visit after contraction of COVID-19 and follow-up visits in the 3rd and 12th month after the disease. In total, 801 patients were included in the analysis. The most frequent complaints after 12 months included deterioration of exercise tolerance (37.5%), fatigue (36.3%), and memory/concentration difficulties (36.3%). In total, 119 patients declared that they had been diagnosed with at least one new chronic disease since the end of isolation, and 10.6% required hospitalization.

The analysis of individual symptoms revealed that headache (p = 0.001), arthralgia (p = 0.032), and dysregulation of hypertension (p = 0.030) were more common in unvaccinated patients. Considering headache and muscle pain, people vaccinated after the disease manifested these symptoms less frequently. Subsequent research is needed to consider vaccines as a preventive factor for post-COVID syndrome.

Source: Babicki M, Kapusta J, Pieniawska-Śmiech K, Kałuzińska-Kołat Ż, Kołat D, Mastalerz-Migas A, Jankowski P, Chudzik M. Do COVID-19 Vaccinations Affect the Most Common Post-COVID Symptoms? Initial Data from the STOP-COVID Register-12-Month Follow-Up. Viruses. 2023 Jun 13;15(6):1370. doi: 10.3390/v15061370. PMID: 37376668; PMCID: PMC10304551. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10304551/ (Full text)

Nirmatrelvir and the Risk of Post-Acute Sequelae of COVID-19

Abstract:

Long Covid — the disease encompassing the post-acute sequelae of SARS-CoV-2 (PASC) — affects millions of people around the world. Prevention of PASC is an urgent public health priority. In this work, we aimed to examine whether treatment with nirmatrelvir in the acute phase of COVID-19 is associated with reduced risk of post-acute sequelae.

We used the healthcare databases of the US Department of Veterans Affairs to identify users of the health system who had a SARS-CoV-2 positive test between March 01, 2022 and June 30, 2022, were not hospitalized on the day of the positive test, had at least 1 risk factor for progression to severe COVID-19 illness and survived the first 30 days after SARS-CoV-2 diagnosis. We identify those who were treated with oral nirmatrelvir within 5 days after the positive test (n=9217) and those who received no COVID-19 antiviral or antibody treatment during the acute phase of SARS-CoV-2 infection (control group, n= 47,123). Inverse probability weighted survival models were used to estimate the effect of nirmatrelvir (versus control) on a prespecified panel of 12 post-acute COVID-19 outcomes and reported as hazard ratio (HR) and absolute risk reduction (ARR) in percentage at 90 days.

Compared to the control group, treatment with nirmatrelvir was associated with reduced risk of PASC (HR 0.74 95% CI (0.69, 0.81), ARR 2.32 (1.73, 2.91)) including reduced risk of 10 of 12 post-acute sequelae in the cardiovascular system (dysrhythmia and ischemic heart disease), coagulation and hematologic disorders (deep vein thrombosis, and pulmonary embolism), fatigue, liver disease, acute kidney disease, muscle pain, neurocognitive impairment, and shortness of breath. Nirmatrelvir was also associated with reduced risk of post-acute death (HR 0.52 (0.35, 0.77), ARR 0.28 (0.14, 0.41)), and post-acute hospitalization (HR 0.70 (0.61, 0.80), ARR 1.09 (0.72, 1.46)). Nirmatrelvir was associated with reduced risk of PASC in people who were unvaccinated, vaccinated, and boosted, and in people with primary SARS-CoV-2 infection and reinfection.

In sum, our results show that in people with SARS-CoV-2 infection who had at least 1 risk factor for progression to severe COVID-19 illness, treatment with nirmatrelvir within 5 days of a positive SARS-CoV-2 test was associated with reduced risk of PASC regardless of vaccination status and history of prior infection. The totality of findings suggests that treatment with nirmatrelvir during the acute phase of COVID-19 reduces the risk of post-acute adverse health outcomes.

Source: Yan Xie, Taeyoung Choi, Ziyad Al-Aly. Nirmatrelvir and the Risk of Post-Acute Sequelae of COVID-19. medRxiv 2022.11.03.22281783; doi: https://doi.org/10.1101/2022.11.03.22281783 https://www.medrxiv.org/content/10.1101/2022.11.03.22281783v1.full.pdf (Full text)