Tag: long Covid

Large scale phenotyping of long COVID inflammation reveals mechanistic subtypes of disease after COVID-19 hospitalisation

Abstract:

One in ten SARS-CoV-2 infections result in prolonged symptoms termed long COVID, yet disease phenotypes and mechanisms are poorly understood. We studied the blood proteome of 719 previously hospitalised adults with long COVID grouped by symptoms. Elevated markers of myeloid inflammation and complement activation were associated with long COVID; elevated IL1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue, and anxiety/depression, while MATN2 and DPP10 were elevated in gastrointestinal (GI) symptoms, and C1QA in cognitive impairment.
Proteins suggestive of neurodegeneration were elevated in cognitive impairment, whilst SCG3 (indicative of brain-gut axis disturbance) was specific to GI symptoms. Nasal inflammation was apparent after COVID-19 but did not associate with symptoms. Although SARS-CoV-2 specific IgG was elevated with some long COVID symptoms, virus was not detected from sputum. Thus, systemic inflammation is evident in long COVID and could be targeted in therapeutic trials tailored to pathophysiological differences between symptom groups.

Source: Peter Openshaw, Felicity Liew, Claudia Efstathiou et al. Large scale phenotyping of long COVID inflammation reveals mechanistic subtypes of disease after COVID-19 hospitalisation, 04 December 2023, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3427282/v1] https://www.researchsquare.com/article/rs-3427282/v1 (Full text)

COVID-19 mRNA Vaccination Reduces the Occurrence of Post-COVID Conditions in U.S. Children Aged 5-17 Years Following Omicron SARS-CoV-2 Infection, July 2021-September 2022

Abstract:

Background An estimated 1-3% of children with SARS-CoV-2 infection will develop Post-COVID Conditions (PCC). This study evaluates mRNA COVID-19 vaccine impact on likelihood of PCC in children.
Methods A multi-site cohort of children enrolled 7/21/2021-9/1/2022 underwent weekly SARS-CoV-2 screening tests and were surveyed via self- or parental report 12/1/2022-5/31/2023 regarding PCC (defined as ≥1 new or on-going symptoms lasting ≥ 1 month after infection). Multivariable logistic regression was performed to estimate the occurrence of PCC by vaccination status among children aged 5–17 years whose first PCR-confirmed SARS-CoV-2 infection occurred in-study with Omicron variant, who completed the survey >60 days from infection, and who were vaccine age-eligible at time of infection per ACIP recommendations. Vaccination status was categorized as vaccinated (at least primary series completed >14 days before infection) and unvaccinated (no vaccine doses before infection). Vaccination status was verified through vaccine registry and/or medical records.
Results Of 622 participants surveyed, 5% (n=28) had PCC (Table 1) and 67% (n=474) were vaccinated (Table 2). Surveys were completed a median (IQR) of 203.7 days (119.0–293.0) after infection. Children with non-Hispanic Black race/ethnicity and good/fair/poor self-rated baseline health were more likely to report PCC. Children aged 12-18 years, Non-Hispanic Asian and White children, those reporting symptomatic SARS-CoV-2 infection, and those with excellent/very good self-rated baseline health were more likely to report vaccination When comparing children with and without PCC symptoms, COVID-19 mRNA vaccination was associated with a decreased likelihood of >1 PCC symptom (aOR 0.66, 95% CI 0.43-0.99), >2 PCC symptoms (aOR 0.52, 95% 0.32-0.83), and respiratory PCC symptoms (aOR 0.53, 95% CI 0.33-0.87) (Table 3).
Conclusion In this study, mRNA COVID-19 vaccination appeared to be protective against PCC in children following Omicron SARS-CoV-2 infection. The adjusted ORs correspond to an estimated 34%, 48%, and 47% reduced likelihood of >1, >2, and respiratory PCC symptoms among vaccinated children, respectively. These findings support COVID-19 vaccination for children and may encourage increased pediatric vaccine uptake.
Source: Anna R Yousaf, Josephine Mak, Lisa Gwynn, Robin Bloodworth, Ramona Rai, Zuha Jeddy, Lindsay B LeClair, Laura Edwards, Lauren E W Olsho, Gabriella Newes-Adeyi, Alexandra F Dalton, Manjusha Gaglani, Sarang K Yoon, Kurt Hegmann, Katherine Ellingson, Leora R Feldstein, Angela P Campbell, Amadea Britton, Sharon Saydah, 1935. COVID-19 mRNA Vaccination Reduces the Occurrence of Post-COVID Conditions in U.S. Children Aged 5-17 Years Following Omicron SARS-CoV-2 Infection, July 2021-September 2022, Open Forum Infectious Diseases, Volume 10, Issue Supplement_2, December 2023, ofad500.2466, https://doi.org/10.1093/ofid/ofad500.2466 https://academic.oup.com/ofid/article/10/Supplement_2/ofad500.2466/7448254 (Full text available as PDF file)

Post-Traumatic Stress Disorder and Complex Post-Traumatic Stress Disorder in people with long COVID, ME/CFS, and controls

Abstract:

Background: Prevalences of Post-Traumatic Stress Disorder (PTSD) and Complex Post-Traumatic Stress Disorder (CPTSD) have not previously been compared between individuals with long COVID and individuals with Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS), and healthy age-matched controls. For these reasons, this study aimed to determine the prevalence of PTSD and CPTSD in individuals with long COVID (n=21) and ME/CFS (n=20) and age-matched controls (n=20).

Methods: A case-case-control approach was employed, participants completed the International Trauma Questionnaire (ITQ), a self-report measure of the International Classification of Diseases (ICD-11) of PTSD and CPTSD consisting of 18 items. Scores were calculated for each PTSD and Disturbances in Self-Organization (DSO) symptom cluster and summed to produce PTSD and DSO scores. PTSD was diagnosed if the criteria for PTSD were met but not DSO, and CPTSD was diagnosed if the criteria for PTSD and DSO were met. Moreover, each cluster of PTSD and DSO were compared among individuals with long COVID, ME/CFS and healthy controls.

Results: Individuals with long COVID (PTSD= 5%, CPTSD= 33%) had more prevalence of PTSD and CPTSD than individuals with ME/CFS (PTSD= 0%, CPTSD= 20%) and healthy controls (PTSD= 0%, CPTSD= 0%). PTSD and CPTSD prevalence was greater in individuals with long COVID and ME/CFS than controls. Individuals with long COVID had greater values controls for all PTSD values. Moreover, individuals with long COVID had greater values than controls for all DSO values. Individuals with ME/CFS had greater values than controls for all DSO values. Both long COVID and ME/CFS groups differed in overall symptom scores compared to controls.

Conclusion: Findings of this study demonstrated that individuals with long COVID generally had more cases of PTSD and CPTSD than individuals with ME/CFS and healthy controls.

Source: Sanal-Hayes NEM, Hayes LD, Mclaughlin M, Berry ECJ, Sculthorpe NF. Post-Traumatic Stress Disorder and Complex Post-Traumatic Stress Disorder in people with long COVID, ME/CFS, and controls. Am J Med. 2023 Dec 15:S0002-9343(23)00756-8. doi: 10.1016/j.amjmed.2023.12.006. Epub ahead of print. PMID: 38104642. https://pubmed.ncbi.nlm.nih.gov/38104642/

Differential Cardiopulmonary Hemodynamic Phenotypes in PASC Related Exercise Intolerance

Abstract:

Background Post-acute sequelae of COVID-19 (PASC) affects a significant portion of patients who have previously contracted SARS-CoV-2, with exertional intolerance being a prominent symptom.

Study Objective This study aimed to characterize the invasive hemodynamic abnormalities of PASC-related exertional intolerance using a larger data set from invasive cardiopulmonary exercise testing (iCPET).

Study Design & Intervention Fifty-five patients were recruited from the Yale Post-COVID-19-Recovery-Program, with most experiencing mild acute illness. Supine right heart catheterization (RHC) and iCPET were performed on all participants.

Main results The majority (75%) of PASC patients exhibited impaired peak systemic oxygen extraction (pEO2) during iCPET in conjunction with supranormal cardiac output (CO) (i.e., PASC alone group), On average, the PASC alone group exhibited a “normal” peak exercise capacity, VO2 (89±18% predicted). Approximately 25% of patients had evidence of central cardiopulmonary pathology (i.e., 12 with resting and exercise HFpEF and 2 with exercise PH). PASC patient with HFpEF (i.e., PASC HFpEF group) exhibited similarly impaired pEO2 with well compensated PH (i.e., peak VO2 and cardiac output >80% respectively) despite aberrant central cardiopulmonary exercise hemodynamics. PASC patients with HFpEF also exhibited increased body mass index of 39±7 kg·m−2. To examine the relative contribution of obesity to exertional impairment in PASC HFpEF, a control group compromising of obese non-PASC group (n=61) derived from historical iCPET cohort was used. The non-PASC obese patients with preserved peak VO2 (>80% predicted) exhibited a normal peak pulmonary artery wedge pressure (17±14 versus 25±6 mmHg; p=0.03) with similar maximal voluntary ventilation (90±12 versus 86±10%predicted; p=0.53) compared to PASC HFpEF patients. Impaired pEO2 was not significantly different between PASC patients who underwent supervised rehabilitation and those who did not (p=0.19).

Conclusions This study highlights the importance of considering impaired pEO2 in PASC patients with persistent exertional intolerance unexplained by conventional investigative testing. Results of current study also highlights the prevalence of a distinct high output failure HFpEF phenotype in PASC with a primary peripheral limitation to exercise.

Source: Peter A. Kahn, Phillip Joseph, Paul M. Heerdt, Inderjit Singh. Differential Cardiopulmonary Hemodynamic Phenotypes in PASC Related Exercise Intolerance. ERJ Open Research Jan 2023, 00714-2023; DOI: 10.1183/23120541.00714-2023 https://openres.ersjournals.com/content/early/2023/12/07/23120541.00714-2023 (Full text available as PDF file)

Microvascular Capillary and Precapillary Cardiovascular Disturbances Strongly Interact to Severely Affect Tissue Perfusion and Mitochondrial Function in ME/CFS Evolving from the Post COVID-19 Syndrome

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent, debilitating and still enigmatic disease. There is a broad overlap in the symptomatology of ME/CFS and the Post-COVID Syndrome (PCS). A fraction of the PCS patients develops the full clinical picture of ME/CFS.
New observations in microvessels and blood from patients suffering from PCS have appeared and include microclots and malformed pathological blood cells. Capillary blood flow is impaired not only by pathological blood components but also by prothrombotic changes in the vascular wall, endothelial dysfunction, and expression of adhesion molecules in the capillaries. These disturbances can finally cause a low capillary flow and even capillary stasis. A low cardiac stroke volume due to hypovolemia and the inability of the capacitance vessels to adequately constrict to deliver the necessary cardiac preload generate an unfavorable low precapillary perfusion pressure.
Furthermore, a predominance of vasoconstrictor over vasodilator influences exists, in which sympathetic hyperactivity and endothelial dysfunction play a strong role, causing constriction of resistance vessels and of precapillary sphincters which leads to a fall in capillary pressure behind the sphincters. The interaction of these two precapillary cardiovascular mechanisms causing a low capillary perfusion pressure is hemodynamically highly unfavorable in the presence of a primary capillary stasis already caused by the pathological blood components and their interaction with the capillary wall, to severely impair organ perfusion.
The detrimental coincidence of the microcirculatory with the precapillary cardiovascular disturbances may constitute the key disturbance of the Post-COVID-19 syndrome and finally lead to ME/CFS in pre-disposed patients because the interaction causes a particular kind of perfusion disturbance – capillary ischemia-reperfusion – which has a high potential of causing mitochondrial dysfunction by inducing sodium- and calcium-overload in skeletal muscles. The latter in turns worsens the vascular situation by the generation of reactive oxygen species to close a vicious cycle from which the patient can hardly escape.
Source: Wirth, K.J.; Löhn, M. Microvascular Capillary and Precapillary Cardiovascular Disturbances Strongly Interact to Severely Affect Tissue Perfusion and Mitochondrial Function in ME/CFS Evolving from the Post COVID-19 Syndrome. Preprints 2023, 2023120791. https://doi.org/10.20944/preprints202312.0791.v1  https://www.preprints.org/manuscript/202312.0791/v1 (Full text available as PDF file)

A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial

Abstract:

Background: Post-acute COVID-19 syndrome (PACS) affects over 65 million individuals worldwide but treatment options are scarce. We aimed to assess a synbiotic preparation (SIM01) for the alleviation of PACS symptoms.

Methods: In this randomised, double-blind, placebo-controlled trial at a tertiary referral centre in Hong Kong, patients with PACS according to the US Centers for Disease Control and Prevention criteria were randomly assigned (1:1) by random permuted blocks to receive SIM01 (10 billion colony-forming units in sachets twice daily) or placebo orally for 6 months. Inclusion criterion was the presence of at least one of 14 PACS symptoms for 4 weeks or more after confirmed SARS-CoV-2 infection, including fatigue, memory loss, difficulty in concentration, insomnia, mood disturbance, hair loss, shortness of breath, coughing, inability to exercise, chest pain, muscle pain, joint pain, gastrointestinal upset, or general unwellness. Individuals were excluded if they were immunocompromised, were pregnant or breastfeeding, were unable to receive oral fluids, or if they had received gastrointestinal surgery in the 30 days before randomisation. Participants, care providers, and investigators were masked to group assignment. The primary outcome was alleviation of PACS symptoms by 6 months, assessed by an interviewer-administered 14-item questionnaire in the intention-to-treat population. Forward stepwise multivariable logistical regression was performed to identify predictors of symptom alleviation. The trial is registered with ClinicalTrials.gov, NCT04950803.

Findings: Between June 25, 2021, and Aug 12, 2022, 463 patients were randomly assigned to receive SIM01 (n=232) or placebo (n=231). At 6 months, significantly higher proportions of the SIM01 group had alleviation of fatigue (OR 2·273, 95% CI 1·520-3·397, p=0·0001), memory loss (1·967, 1·271-3·044, p=0·0024), difficulty in concentration (2·644, 1·687-4·143, p<0·0001), gastrointestinal upset (1·995, 1·304-3·051, p=0·0014), and general unwellness (2·360, 1·428-3·900, p=0·0008) compared with the placebo group. Adverse event rates were similar between groups during treatment (SIM01 22 [10%] of 232 vs placebo 25 [11%] of 231; p=0·63). Treatment with SIM01, infection with omicron variants, vaccination before COVID-19, and mild acute COVID-19, were predictors of symptom alleviation (p<0·0036).

Interpretation: Treatment with SIM01 alleviates multiple symptoms of PACS. Our findings have implications on the management of PACS through gut microbiome modulation. Further studies are warranted to explore the beneficial effects of SIM01 in other chronic or post-infection conditions.

Source: Lau RI, Su Q, Lau ISF, Ching JYL, Wong MCS, Lau LHS, Tun HM, Mok CKP, Chau SWH, Tse YK, Cheung CP, Li MKT, Yeung GTY, Cheong PK, Chan FKL, Ng SC. A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2023 Dec 7:S1473-3099(23)00685-0. doi: 10.1016/S1473-3099(23)00685-0. Epub ahead of print. PMID: 38071990. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00685-0/fulltext (Full text)

Long-term symptom profiles after COVID-19 vs other acute respiratory infections: a population-based observational study (COVIDENCE UK)

Abstract:

Summary:

Background: Long COVID is a well recognised, if heterogeneous, entity. Acute respiratory infections (ARIs) due to other pathogens may cause long-term symptoms, but few studies compare post-acute sequelae between SARS-CoV-2 and other ARIs. We aimed to compare symptom profiles between people with previous SARS-CoV-2 infection, people with previous non-COVID-19 ARIs, and contemporaneous controls, and to identify clusters of long-term symptoms.

Methods: COVIDENCE UK is a prospective, population-based UK study of ARIs in adults. We analysed data on 16 potential long COVID symptoms and health-related quality of life (HRQoL), reported in January, 2021, by participants unvaccinated against SARS-CoV-2. We classified participants as having previous SARS-CoV-2 infection or previous non-COVID-19 ARI (≥4 weeks prior) or no reported ARI. We compared symptoms by infection status using logistic and fractional regression, and identified symptom clusters using latent class analysis (LCA).

Findings: We included 10,203 participants (1343 [13.2%] with SARS-CoV-2 infection, 472 [4.6%] with non-COVID-19 ARI). Both types of infection were associated with increased prevalence/severity of most symptoms and decreased HRQoL compared with no infection. Participants with SARS-CoV-2 infection had increased odds of taste/smell problems and hair loss compared with participants with non-COVID-19 ARIs. Separate LCA models identified three symptom severity groups for each infection type. In the most severe groups (including 23% of participants with SARS-CoV-2, and 21% with non-COVID-19 ARI), SARS-CoV-2 infection presented with a higher probability of memory problems, difficulty concentrating, hair loss, and taste/smell problems than non-COVID-19 ARI.

Interpretation: Both SARS-CoV-2 and non-COVID-19 ARIs are associated with a wide range of long-term symptoms. Research on post-acute sequelae of ARIs should extend from SARS-CoV-2 to include other pathogens.

Source: Vivaldi G, Pfeffer PE, Talaei M, et al. Long-term symptom profiles after COVID-19 vs other acute respiratory infections: a population-based observational study (COVIDENCE UK). medRxiv; 2023. DOI: 10.1101/2023.07.06.23292296. https://europepmc.org/article/PPR/ppr687749 (Full text)

Comparison of post-acute sequelae following hospitalization for COVID-19 and influenza

Abstract

Background: Few studies have directly compared the risk and magnitude of post-acute sequelae following COVID-19 and influenza, and most of these studies were conducted before emergence of the Omicron. This study investigated the prevalence of post-COVID conditions and the long-term risk of emergency department (ED) visits, hospitalizations, and deaths in patients with COVID-19 and compared their risk with that of patients with influenza.

Methods: A retrospective study based on the TriNetX databases, a global health research network. We identified patients with COVID-19 and influenza who required hospitalization between January 1, 2022, and January 1, 2023. We compared the risk of developing any post-COVID conditions between the two groups and also analyzed each post-COVID-19 condition and all-cause ED visits, hospitalizations, and deaths in both populations during the follow-up 90-180 days.

Results: Before matching, 7,187 patients with COVID-19 were older (63.9 ± 16.7 vs. 55.4 ± 21.2) and were predominantly male (54.0% vs. 45.4%), and overweight/obese (16.1% vs. 11.2%) than 11,266 individuals with influenza. After propensity score matching, 6,614 patients were identified in each group, resulting in well-balanced baseline characteristics. During follow-up, the COVID-19 group had a higher incidence of any post-COVID-19 condition when compared with the influenza group (17.9% vs. 13.0%), with a hazard ratio (HR) of 1.398 (95% CI, 1.251-1.562). Compared to the influenza group, the COVID-19 group had a significantly higher incidence of abnormal breathing (HR, 1.506; 95% CI, 1.246-1.822), abdominal symptoms (HR, 1.313; HR, 1.034-1.664), fatigue (HR, 1.486; 95% CI, 1.158-1.907), and cognitive symptoms (HR, 1.815; 95% CI, 1.235-2.668). Moreover, the COVID-19 group had a significantly higher risk of the composite outcomes during all-cause ED visits, hospitalizations, and deaths when compared with the influenza group (27.5% vs. 21.7; HR, 1.303; 95% CI, 1.194-1.422).

Conclusions: This study indicates that hospitalized COVID-19 patients are at a higher risk of long-term complications when compared with influenza survivors.

Source: Liu TH, Huang PY, Wu JY, Chuang MH, Hsu WH, Tsai YW, Lai CC. Comparison of post-acute sequelae following hospitalization for COVID-19 and influenza. BMC Med. 2023 Dec 5;21(1):480. doi: 10.1186/s12916-023-03200-2. PMID: 38049876; PMCID: PMC10696681. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10696681/ (Full text)

Incidence of long-term post-acute sequelae of SARS-CoV-2 infection related to pain and other symptoms: A systematic review and meta-analysis

Abstract:

Background: Persistent symptoms are reported in patients who survive the initial stage of COVID-19, often referred to as “long COVID” or “post-acute sequelae of SARS-CoV-2 infection” (PASC); however, evidence on their incidence is still lacking, and symptoms relevant to pain are yet to be assessed.

Methods: A literature search was performed using the electronic databases PubMed, EMBASE, Scopus, and CHINAL and preprint servers MedRχiv and BioRχiv through January 15, 2021. The primary outcome was pain-related symptoms such as headache or myalgia. Secondary outcomes were symptoms relevant to pain (depression or muscle weakness) and symptoms frequently reported (anosmia and dyspnea). Incidence rates of symptoms were pooled using inverse variance methods with a DerSimonian-Laird random-effects model. The source of heterogeneity was explored using meta-regression, with follow-up period, age and sex as covariates.

Results: In total, 38 studies including 19,460 patients were eligible. Eight pain-related symptoms and 26 other symptoms were identified. The highest pooled incidence among pain-related symptoms was chest pain (17%, 95% confidence interval [CI], 11%-24%), followed by headache (16%, 95% CI, 9%-27%), arthralgia (13%, 95% CI, 7%-24%), neuralgia (12%, 95% CI, 3%-38%) and abdominal pain (11%, 95% CI, 7%-16%). The highest pooled incidence among other symptoms was fatigue (44%, 95% CI, 32%-57%), followed by insomnia (27%, 95% CI, 10%-55%), dyspnea (26%, 95% CI, 17%-38%), weakness (25%, 95% CI, 8%-56%) and anosmia (19%, 95% CI, 13%-27%). Substantial heterogeneity was identified (I2, 50-100%). Meta-regression analyses partially accounted for the source of heterogeneity, and yet, 53% of the symptoms remained unexplained.

Conclusions: The current meta-analysis may provide a complete picture of incidence in PASC. It remains unclear, however, whether post-COVID symptoms progress or regress over time or to what extent PASC are associated with age or sex.

Source: Hoshijima H, Mihara T, Seki H, Hyuga S, Kuratani N, Shiga T. Incidence of long-term post-acute sequelae of SARS-CoV-2 infection related to pain and other symptoms: A systematic review and meta-analysis. PLoS One. 2023 Nov 29;18(11):e0250909. doi: 10.1371/journal.pone.0250909. PMID: 38019841; PMCID: PMC10686440. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686440/ (Full text)

Molecular Mechanisms Involved in the Occurrence and Progression of Long COVID and Associated Analysis Techniques

Abstract:

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged as a significant health concern following the COVID-19 pandemic. Molecular mechanisms underlying the occurrence and progression of long COVID include viral persistence, immune dysregulation, endothelial dysfunction, and neurological involvement, and highlight the need for further research to develop targeted therapies for this condition.
While a clearer picture of the clinical symptomatology is shaping, many molecular mechanisms are yet to be unraveled, given their complexity and high level of interaction with other metabolic pathways. This review summarizes some of the most important symptoms and associated molecular mechanisms that occur in long COVID, as well as the most relevant molecular techniques that can be used in understanding the viral pathogen, its affinity towards the host and the possible outcomes of host-pathogen interaction.
Source: Constantinescu-Bercu, A.; Lobiuc, A.; Caliman Sturdza, O.A.; Oita, R.; Iavorschi, M.; Paval, N.; Soldanescu, I.; Dimian, M.; Covasa, M. Molecular Mechanisms Involved in the Occurrence and Progression of Long COVID and Associated Analysis Techniques. Preprints 2023, 2023111865. https://doi.org/10.20944/preprints202311.1865.v1 https://www.preprints.org/manuscript/202311.1865/v1 (Full text available as PDF file)