Tag: long Covid

Differences in clinical presentation with long covid following community and hospital infection, and associations with all-cause mortality: English sentinel network database study

Abstract:

Background: Most studies of long covid (symptoms of COVID-19 beyond 4 weeks) have focused on people hospitalised in their initial illness. Long covid is thought to be under-recorded in UK primary care electronic records.

Objective: We sought to determine which symptoms people present to primary care following COVID-19, and whether presentation differs in people who were not hospitalised, and post-long covid mortality.

Methods: We used routine data from the nationally representative Primary Care Sentinel Cohort of the Oxford-Royal College of General Practitioners Research and Surveillance Centre (N=7.4million), applying a pre-defined long covid phenotype and grouped by whether the illness index was in hospital or community. We included COVID-19 cases between 1st-March-2020 and 1st-April-2021. We conducted a before and after analysis of pre-specified long covid symptoms identified by the Office of National Statistics, comparing symptoms presented between one and six months after their index infection matched with the same months one year previously. We conducted logistic regression analysis, quoting odds ratios with 95% confidence intervals, reporting differences between those with an index community infection compared to those who had been hospitalised, and separately associations with all-cause mortality.

Results: 5.6% (416,505/7,396,702) and 1.8% (7,623/416,505) of patients respectively had a coded diagnosis of COVID-19 and diagnosis or referral for long covid. People coded as having long covid were significantly more likely to have presented the pre-specified symptoms after vs before COVID-19 infection (odds ratios 2.66 [2.46-2.88] for those with index community infection and 2.42 [2.03-2.89] for those hospitalised). Following an index community infection, patients were more likely to present with non-specific symptoms (odds ratio 3.44 [3.00-3.95], P<.001) than following a hospital admission (odds ratio 2.09 [1.56-2.80], P<.001). Mental health sequelae were more commonly associated with hospital admission index infections (odds ratio 2.21 [1.64-2.96]) compared to community (odds ratio 1.36 [1.21-1.53], P<.001). People presenting to primary care following hospital infection were more likely to be male (odds ratio 1.43 [1.25-1.64], P<.001), more socioeconomically deprived (odds ratio 1.42 [1.24-1.63], P<.001); and to have multi-morbidity (odds ratio 1.41 [1.26-1.57], P<.001) than those presenting after an index community infection. All-cause mortality in people with long covid was associated with increasing age; male gender (odds ratio 3.32 [1.34-9.24], P<.01) and higher multi-morbidity score (odds ratio 2.11 [1.34-3.29], P<.001). One or more vaccine doses was associated with reduced odds of mortality (odds ratio 0.10 [0.03-0.35], P<.001).

Conclusions: The low percentage of people recorded as having long covid following COVID-19 reflects either low prevalence or under-recording. The characteristics and comorbidities of those presenting with long covid following a community infection are different from those who were hospitalised with their index infection. This study provides insights into the presentation of long covid in primary care and implications for workload.

Source: Meza-Torres B, Delanerolle G, Okusi C, Mayer N, Anand S, McCartney J, Gatenby P, Glampson B, Chapman M, Curcin V, Mayer E, Joy M, Greenhalgh T, Delaney B, de Lusignan S. Differences in clinical presentation with long covid following community and hospital infection, and associations with all-cause mortality: English sentinel network database study. JMIR Public Health Surveill. 2022 May 17. doi: 10.2196/37668. Epub ahead of print. PMID: 35605170.  https://preprints.jmir.org/preprint/37668/accepted (Full text)

Symptoms and signs of long COVID: A rapid review and meta-analysis

Abstract:

Background: Long COVID is defined as symptoms and signs related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that are present at least four weeks following acute infection. These symptoms and signs are poorly characterised but may be associated with significant morbidity. We sought to synthesise the evidence on their incidence to guide future research, policy and practice.

Methods: We searched Medline and Embase for longitudinal cohort studies from January 2020 to July 2021 that investigated adults with long COVID at least four weeks after acute infection. Risk of bias was assessed using the Joanna Briggs Institute checklist for cohort studies. Random-effects meta-analyses were performed with subgroup analysis by follow-up time (4-12 vs more than 12 weeks).

Results: 19 studies were included, 13 of which included patients hospitalised with COVID-19. The total sample size was 10 643 and the follow-up time ranged from 30 to 340 days. Risk of bias was assessed as high in one study, moderate in two studies and low in the remaining 16 studies. The most common symptoms and signs seen at any time point in long COVID were fatigue (37%; 95% confidence interval (CI) = 23-55), dyspnoea (21%; 95% CI = 14-30), olfactory dysfunction (17%; 95% CI = 9-29), myalgia (12%; 95% CI = 5-25), cough (11%; 95% CI = 6-20) and gustatory dysfunction (10%; 95% CI = 7-17). High heterogeneity was seen for all meta-analyses and the presence of some funnel plot asymmetry may indicate reporting bias. No effect of follow-up time was found for any symptom or sign included in the subgroup analysis.

Conclusions: We have summarised evidence from longitudinal cohort studies on the most common symptoms and signs associated with long COVID. High heterogeneity seen in the meta-analysis means pooled incidence estimates should be interpreted with caution. This heterogeneity may be attributable to studies including patients from different health care settings and countries.

Source: Healey Q, Sheikh A, Daines L, Vasileiou E. Symptoms and signs of long COVID: A rapid review and meta-analysis. J Glob Health. 2022 May 21;12:05014. doi: 10.7189/jogh.12.05014. PMID: 35596571.https://jogh.org/2022/jogh-12-05014 (Full text)

Autoantibodies against apolipoprotein A-1 after COVID-19 predict symptoms persistence

Abstract:

Background: SARS-CoV-2 infection triggers different auto-antibodies, including anti-apolipoprotein A-1 IgGs (AAA1), which could be of concern as mediators of persistent symptoms. We determined the kinetics of AAA1 response over after COVID-19, and the impact of AAA1 on the inflammatory response and symptoms persistence.

Methods: All serologies were assessed at one, three, six, and twelve months in 193 hospital employees with COVID-19. ROC curve analyses and logistic regression models (LRM) were used to determine the prognostic accuracy of AAA1 and their association with patient-reported COVID-19 symptoms persistence at 12 months. Interferon (IFN)-α and-γ production by AAA1-stimulated human monocyte-derived macrophages (HMDM) was assessed in vitro.

Results: AAA1 seropositivity was 93% at one month and declined to 15% at 12 months after COVID-19. Persistent symptoms at 12 months were observed in 45.1% of participants, with a predominance of neurological (28.5%), followed by general (15%) and respiratory symptoms (9.3%). Over time, strength of correlations between AAA1 and anti-SARS-COV2 serologies decreased, but remained significant. From the 3rd month on, AAA1 levels predicted persistent respiratory symptoms (area under the curves 0.72-0.74; p<0.001), independently of disease severity, age and gender (adjusted odds ratios 4.81-4.94; p=0.02), while anti-SARS-CoV-2 serologies did not. AAA1 increased IFN-α production by HMDMs (p=0.03), without affecting the IFN-γ response.

Conclusion: COVID-19 induces a marked though transient AAA1 response, independently predicting one-year persistence of respiratory symptoms. By increasing IFN-α response, AAA1 may contribute to persistent symptoms. If and how AAA1 levels assessment could be of use for COVID-19 risk stratification remains to be determined

Source: L’Huillier AG, Pagano S, Baggio S, Meyer B, Andrey DO, Nehme M, Guessous I, Eberhardt CS, Huttner A, Posfay-Barbe KM, Yerly S, Siegrist CA, Kaiser L, Vuilleumier N. Autoantibodies against apolipoprotein A-1 after COVID-19 predict symptoms persistence. Eur J Clin Invest. 2022 May 22:e13818. doi: 10.1111/eci.13818. Epub ahead of print. PMID: 35598178.  https://pubmed.ncbi.nlm.nih.gov/35598178/ (Full text available as PDF file)

Are vaccines a potential treatment for long covid?

Vaccines in the covid-19 pandemic have been a game changer in reducing rates of SARS-CoV-2 infection and hospital admission for, and death with, covid-19. They also reduce the chance of developing long covid by about half among people who are vaccinated before they develop covid-19.1 However, the effect of vaccines for people who already have long covid is a contentious area for both patients and healthcare professionals. In a linked paper, Ayoubkhani and colleagues (doi:10.1136/bmj-2021-069676) report findings from the largest published study on this topic to date.2 From a random sample of the UK population, they identified 28 356 adults (18-69 years) who were vaccinated after a positive SARS-CoV-2 test result, of whom 6729 (23.7%) reported long covid symptoms (>12 weeks) of any severity at least once during follow-up. Participants were followed for seven months to determine the relationship between vaccination, long covid, and symptom profiles after the first and second dose of either an adenovirus vector or mRNA vaccine.2

Read the rest of this article HERE.

Source: Manoj Sivan. Are vaccines a potential treatment for long covid? Cite this as: BMJ 2022;377:o988. https://www.bmj.com/content/377/bmj.o988.full (Full text)

Pathophysiology and mechanism of long COVID: a comprehensive review

Abstract:

Background: After almost 2 years of fighting against SARS-CoV-2 pandemic, the number of patients enduring persistent symptoms long after acute infection is a matter of concern. This set of symptoms was referred to as “long COVID”, and it was defined more recently as “Post COVID-19 condition” by the World health Organization (WHO). Although studies have revealed that long COVID can manifest whatever the severity of inaugural illness, the underlying pathophysiology is still enigmatic.

Aim: To conduct a comprehensive review to address the putative pathophysiology underlying the persisting symptoms of long COVID.

Method: We searched 11 bibliographic databases (Cochrane Library, JBI EBP Database, Medline, Embase, PsycInfo, CINHAL, Ovid Nursing Database, Journals@Ovid, SciLit, EuropePMC, and CoronaCentral). We selected studies that put forward hypotheses on the pathophysiology, as well as those that encompassed long COVID patients in their research investigation.

Results: A total of 98 articles were included in the systematic review, 54 of which exclusively addressed hypotheses on pathophysiology, while 44 involved COVID patients. Studies that included patients displayed heterogeneity with respect to the severity of initial illness, timing of analysis, or presence of a control group. Although long COVID likely results from long-term organ damage due to acute-phase infection, specific mechanisms following the initial illness could contribute to the later symptoms possibly affecting many organs. As such, autonomic nervous system damage could account for many symptoms without clear evidence of organ damage. Immune dysregulation, auto-immunity, endothelial dysfunction, occult viral persistence, as well as coagulation activation are the main underlying pathophysiological mechanisms so far.

Conclusion: Evidence on why persistent symptoms occur is still limited, and available studies are heterogeneous. Apart from long-term organ damage, many hints suggest that specific mechanisms following acute illness could be involved in long COVID symptoms.

KEY MESSAGES:

  • Long-COVID is a multisystem disease that develops regardless of the initial disease severity. Its clinical spectrum comprises a wide range of symptoms.
  • The mechanisms underlying its pathophysiology are still unclear. Although organ damage from the acute infection phase likely accounts for symptoms, specific long-lasting inflammatory mechanisms have been proposed, as well.
  • Existing studies involving Long-COVID patients are highly heterogeneous, as they include patients with various COVID-19 severity levels and different time frame analysis, as well.

Source: Castanares-Zapatero D, Chalon P, Kohn L, Dauvrin M, Detollenaere J, Maertens de Noordhout C, Primus-de Jong C, Cleemput I, Van den Heede K. Pathophysiology and mechanism of long COVID: a comprehensive review. Ann Med. 2022 Dec;54(1):1473-1487. doi: 10.1080/07853890.2022.2076901. PMID: 35594336; PMCID: PMC9132392. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132392/ (Full text)

Oxytocin, the panacea for long-COVID? a review

Abstract:

Objectives: In this hypothesis paper we explore the underlying mechanisms for long-COVID and how the oxytocinergic neurones could be infected by SARS-CoV-2 leading to a reduction in plasma oxytocin (OXT). Furthermore, we aim to review the relevance of OXT and hypothalamic function in recovery from long-COVID symptoms and pathology, through exploring the pro-health effects of the OXT neuropeptide.

Methods: A review of published literature was surveyed using Google Scholar and PubMed.

Results: Numerous experimental data can be shown to correlate with OXT and long-COVID symptoms and conditions, thus providing strong circumstantial evidence to support our hypothesis. It is postulated that the reduction in plasma OXT due to acute and post-viral damage to the hypothalamus and oxytocinergic neurones contributes to the variable multi-system, remitting and relapsing nature of long-COVID. The intranasal route of OXT application was determined to be most appropriate and clinically relevant for the restoration of oxytocinergic function post COVID-19 infection.

Conclusions: We believe it is imperative to further investigate whether OXT alleviates the prolonged suffering of patients with long-COVID. Succinctly, OXT may be the much-needed post-pandemic panacea.

Source: Diep, Phuoc-Tan, Chaudry, Mohammed, Dixon, Adam, Chaudry, Faisal and Kasabri, Violet. “Oxytocin, the panacea for long-COVID? a review” Hormone Molecular Biology and Clinical Investigation, vol. , no. , 2022. https://doi.org/10.1515/hmbci-2021-0034 (Full text)

Trajectory of long covid symptoms after covid-19 vaccination: community based cohort study

Abstract:

Objective: To estimate associations between covid-19 vaccination and long covid symptoms in adults with SARS-CoV-2 infection before vaccination.

Design: Observational cohort study.

Setting: Community dwelling population, UK.

Participants: 28 356 participants in the Office for National Statistics COVID-19 Infection Survey aged 18-69 years who received at least one dose of an adenovirus vector or mRNA covid-19 vaccine after testing positive for SARS-CoV-2 infection.

Main outcome measure: Presence of long covid symptoms at least 12 weeks after infection over the follow-up period 3 February to 5 September 2021.

Results: Mean age of participants was 46 years, 55.6% (n=15 760) were women, and 88.7% (n=25 141) were of white ethnicity. Median follow-up was 141 days from first vaccination (among all participants) and 67 days from second vaccination (83.8% of participants). 6729 participants (23.7%) reported long covid symptoms of any severity at least once during follow-up. A first vaccine dose was associated with an initial 12.8% decrease (95% confidence interval -18.6% to -6.6%, P<0.001) in the odds of long covid, with subsequent data compatible with both increases and decreases in the trajectory (0.3% per week, 95% confidence interval -0.6% to 1.2% per week, P=0.51). A second dose was associated with an initial 8.8% decrease (95% confidence interval -14.1% to -3.1%, P=0.003) in the odds of long covid, with a subsequent decrease by 0.8% per week (-1.2% to -0.4% per week, P<0.001). Heterogeneity was not found in associations between vaccination and long covid by sociodemographic characteristics, health status, hospital admission with acute covid-19, vaccine type (adenovirus vector or mRNA), or duration from SARS-CoV-2 infection to vaccination.

Conclusions: The likelihood of long covid symptoms was observed to decrease after covid-19 vaccination and evidence suggested sustained improvement after a second dose, at least over the median follow-up of 67 days. Vaccination may contribute to a reduction in the population health burden of long covid, although longer follow-up is needed.

Source: Ayoubkhani D, Bermingham C, Pouwels KB, Glickman M, Nafilyan V, Zaccardi F, Khunti K, Alwan NA, Walker AS. Trajectory of long covid symptoms after covid-19 vaccination: community based cohort study. BMJ. 2022 May 18;377:e069676. doi: 10.1136/bmj-2021-069676. PMID: 35584816; PMCID: PMC9115603. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115603/ (Full text)

Epipharyngeal Abrasive Therapy (EAT) Has Potential as a Novel Method for Long COVID Treatment

Abstract:

COVID-19 often causes sequelae after initial recovery, referred to collectively as long COVID. Long COVID is considered to be caused by the persistence of chronic inflammation after acute COVID-19 infection. We found that all long COVID patients had residual inflammation in the epipharynx, an important site of coronavirus replication, and some long COVID symptoms are similar to those associated with chronic epipharyngitis.

Epipharyngeal abrasive therapy (EAT) is a treatment for chronic epipharyngitis in Japan that involves applying zinc chloride as an anti-inflammatory agent to the epipharyngeal mucosa. In this study, we evaluated the efficacy of EAT for the treatment of long COVID. The subjects in this study were 58 patients with long COVID who were treated with EAT in the outpatient department once a week for one month (mean age = 38.4 ± 12.9 years). The intensities of fatigue, headache, and attention disorder, which are reported as frequent symptoms of long COVID, were assessed before and after EAT using the visual analog scale (VAS).

EAT reduced inflammation in the epipharynx and significantly improved the intensity of fatigue, headache, and attention disorder, which may be related to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These results suggest that EAT has potential as a novel method for long COVID treatment.

Source: Imai K, Yamano T, Nishi S, Nishi R, Nishi T, Tanaka H, Tsunoda T, Yoshimoto S, Tanaka A, Hiromatsu K, Shirasawa S, Nakagawa T, Nishi K. Epipharyngeal Abrasive Therapy (EAT) Has Potential as a Novel Method for Long COVID Treatment. Viruses. 2022 Apr 27;14(5):907. doi: 10.3390/v14050907. PMID: 35632649. https://www.mdpi.com/1999-4915/14/5/907/htm (Full text)

The Impact of COVID Vaccination on Symptoms of Long COVID: An International Survey of People with Lived Experience of Long COVID

Abstract:

Long COVID is a multi-system syndrome following SARS-CoV-2 infection with persistent symptoms of at least 4 weeks, and frequently for several months. It has been suggested that there may be an autoimmune component. There has been an understandable caution amongst some people experiencing long COVID that, by boosting their immune response, a COVID vaccine may exacerbate their symptoms. We aimed to survey people living with long COVID, evaluating the impact of their first COVID vaccination on their symptoms.

Methods: Patients with long COVID were invited to complete a web-based questionnaire through postings on social media and direct mailing from support groups. Basic demographics, range and severity of long COVID symptoms, before and after their vaccine, were surveyed.

Results: 900 people participated in the questionnaire, of whom 45 had pre-existing myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) but no evidence of COVID infection, and a further 43 did not complete the survey in full. The demographics and symptomology of the remaining 812 people were similar to those recorded by the UK Office of National Statistics. Following vaccination, 57.9% of participants reported improvements in symptoms, 17.9% reported deterioration and the remainder no change. There was considerable individual variation in responses. Larger improvements in symptom severity scores were seen in those receiving the mRNA vaccines compared to adenoviral vector vaccines.

Conclusions: Our survey suggests COVID-19 vaccination may improve long COVID patients, on average. The observational nature of the survey limits drawing direct causal inference, but requires validation with a randomised controlled trial.

Source: Strain WD, Sherwood O, Banerjee A, Van der Togt V, Hishmeh L, Rossman J. The Impact of COVID Vaccination on Symptoms of Long COVID: An International Survey of People with Lived Experience of Long COVID. Vaccines (Basel). 2022 Apr 21;10(5):652. doi: 10.3390/vaccines10050652. PMID: 35632408. https://www.mdpi.com/2076-393X/10/5/652  (Full text)

LOng COvid Multidisciplinary consortium Optimising Treatments and servIces acrOss the NHS (LOCOMOTION): protocol for a mixed-methods study in the UK

Abstract:

Introduction: Long COVID, a new condition whose origins and natural history are not yet fully established, currently affects 1.5 million people in the UK. Most do not have access to specialist long COVID services. We seek to optimise long COVID care both within and outside specialist clinics, including improving access, reducing inequalities, helping self-management and providing guidance and decision support for primary care. We aim to establish a ‘gold standard’ of care by systematically analysing current practices, iteratively improving pathways and systems of care.

Methods and analysis: This mixed-methods, multisite study is informed by the principles of applied health services research, quality improvement, co-design, outcome measurement and learning health systems. It was developed in close partnership with patients (whose stated priorities are prompt clinical assessment; evidence-based advice and treatment and help with returning to work and other roles) and with front-line clinicians. Workstreams and tasks to optimise assessment, treatment and monitoring are based in three contrasting settings: workstream 1 (qualitative research, up to 100 participants), specialist management in 10 long COVID clinics across the UK, via a quality improvement collaborative, experience-based co-design and targeted efforts to reduce inequalities of access, return to work and peer support; workstream 2 (quantitative research, up to 5000 participants), patient self-management at home, technology-supported monitoring and validation of condition-specific outcome measures and workstream 3 (quantitative research, up to 5000 participants), generalist management in primary care, harnessing electronic record data to study population phenotypes and develop evidence-based decision support, referral pathways and analysis of costs. Study governance includes an active patient advisory group.

Ethics and dissemination: LOng COvid Multidisciplinary consortium Optimising Treatments and servIces acrOss the NHS study is sponsored by the University of Leeds and approved by Yorkshire & The Humber-Bradford Leeds Research Ethics Committee (ref: 21/YH/0276). Participants will provide informed consent. Dissemination plans include academic and lay publications, and partnerships with national and regional policymakers.

Source: Sivan M, Greenhalgh T, Darbyshire JL, Mir G, O’Connor RJ, Dawes H, Greenwood D, O’Connor D, Horton M, Petrou S, de Lusignan S, Curcin V, Mayer E, Casson A, Milne R, Rayner C, Smith N, Parkin A, Preston N, Delaney B; LOCOMOTION consortium. LOng COvid Multidisciplinary consortium Optimising Treatments and servIces acrOss the NHS (LOCOMOTION): protocol for a mixed-methods study in the UK. BMJ Open. 2022 May 17;12(5):e063505. doi: 10.1136/bmjopen-2022-063505. PMID: 35580970; PMCID: PMC9114312. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114312/ (Full text)