Category: Overlapping Illnesses

A prospective cohort study assessing the relationship between long-COVID symptom incidence in COVID-19 patients and COVID-19 vaccination

Abstract:

Current studies about the long-term effects of COVID-19 show a wide range of symptoms. This prospective cohort study aimed to find the incidence of long-COVID symptoms and the associated risk factors.

We followed 669 confirmed COVID-19 patients. Sociodemographic and clinical data were extracted from medical records and collected via semi-structured telephone interviews on days 10, 30, 60, and 90. The incidence of long-COVID symptoms was 41.6% (95% CI 37.8-45.4%). Females [aOR = 1.5 (95% CI 1.1-2.3)], the elderly [aOR = 4.9 (95% CI 2.0-11.3)], and those who required hospitalization [aOR = 5.0 (95% CI 1.3-3.7)] were at a higher risk of developing long-COVID. Patients with dyspnea at day 10 [aOR: 2.4 (95% CI 1.6-3.7] and fatigue at day 60 [aOR: 3.1 (95% CI 1.5-6.3] were also at risk. While non-vaccinated patients were almost seven times more likely to report long-COVID symptoms than vaccinated patients [aOR: 6.9 (95% CI 4.2-11.3)].

In conclusion, long-COVID was common among COVID-19 patients, with higher rates among females, older age groups, hospitalized patients, and those with dyspnea and fatigue, while vaccination provided protection. Interventions should educate health professionals, raise general public awareness about the risks and consequences of Long COVID, and the value of vaccination.

Source: Abu Hamdh B, Nazzal Z. A prospective cohort study assessing the relationship between long-COVID symptom incidence in COVID-19 patients and COVID-19 vaccination. Sci Rep. 2023 Mar 25;13(1):4896. doi: 10.1038/s41598-023-30583-2. PMID: 36966161; PMCID: PMC10039348. https://www.nature.com/articles/s41598-023-30583-2 (Full text)

Treatment of Long COVID symptoms with triple anticoagulant therapy

Abstract:

Background: Fibrin(ogen) amyloid microclots and platelet hyperactivation are key pathological findings in patients with acute COVID-19 infection and also in those with Long COVID/Post-Acute Sequelae of COVID-19 (PASC). These pathologies may represent a suitable target for pharmacological treatment of Long COVID.

Methods: Here we report on the symptoms displayed by a cohort of 91 South African Long COVID patients at baseline and after a clinician-initiated anticoagulant regime was completed. For laboratory analysis, patients provided a blood sample before and after treatment. Fibrinaloid microclot presence was studied by adding thioflavin T to platelet poor plasma (PPP), whilst platelet hyperactivation was studied using two platelet markers- PAC1 and CD62P (P-selectin). The anticoagulant regime included dual antiplatelet therapy (DAPT- Clopidogrel 75mg + Aspirin 75mg) once a day, and a direct oral anticoagulant (DOAC- Apixaban) 5mg twice a day. A proton pump inhibitor (PPI) pantoprazole 40 mg/day was also prescribed for gastric protection. Each of the treated cases reported their main Long COVID symptoms, and whether their symptoms resolved following treatment or not.

Results: In our cohort a most participants did not report any comorbidities before acute COVID-19 infection. Hypertension and dyslipidaemia were the commonest underlying illnesses, whilst the most commonly reported Long COVID symptoms included fatigue, cognitive dysfunction, shortness of breath, and joint and muscle pains. Following completion of treatment, each of the different symptoms resolved in the majority of patients. This was also reflected in the laboratory analysis, where a decrease in the severity of fibrin amyloid microclotting and the degree of platelet pathology was noted. No serious adverse bleeding events were reported.

Conclusions: Fibrin amyloid microclots, platelet hyperactivation/ aggregation, and  widespread endothelialitis inhibit the transport of oxygen at a capillary/cellular level. This provides a ready explanation for the symptoms of Long COVID. By normalizing the failed clotting physiology and reversal of the endothelialitis, triple anticoagulant therapy represents a promising treatment option that appears to be highly efficacious, and warrants controlled clinical studies. We caution that such a regime must only be followed under expert medical supervision in view of the risk of  bleeding.

Source: Gert J Laubscher, M Asad Khan, Chantelle Venter, Etheresia Pretorius et al. Treatment of Long COVID symptoms with triple anticoagulant therapy, 21 March 2023, PREPRINT (Version 1) available at Research Square https://doi.org/10.21203/rs.3.rs-2697680/v1 (Full text)

The health impact of long COVID: a cross-sectional examination of health-related quality of life, disability, and health status among individuals with self-reported post-acute sequelae of SARS CoV-2 infection at various points of recovery

Abstract:

Objective: The novel Coronavirus (COVID-19) has continued to present a significant burden to global public health efforts. The purpose of this study was to estimate the health-related quality of life, disability, and health status of individuals with self-reported long COVID at various lengths of recovery.

Methods: We conducted a cross-sectional online survey of individuals with self-reported long COVID. Participants were asked to complete the five-item EuroQOL EQ-5D-5L and EQ visual analog scale, the 12-item World Health Organization Disability Assessment Schedule (WHODAS) 2.0 and the 10-item Patient Reported Outcome Measurement Information System (PROMIS) Global Health v1.2 short form. Descriptive and inferential statistics were used to characterize the responses and differences across groups.

Results: Eighty-two participants from 13 countries completed the EQ-5D-5L, 73 completed the WHODAS 2.0 and 80 participants completed the PROMIS. The mean EQ-5D-5L utility score was 0.51. The mean WHODAS score was 49.0. In the previous 30 days, participants reported their symptoms affected them for a mean of 24 days, they were totally unable to carry out usual activities for 15 days, and they cut back or reduced activities for 26 days. The mean PROMIS physical health and mental health scores were 10.7 and 8.6, respectively, corresponding to below-average health. No significant differences were detected across time or according to severity of acute infection.

Conclusions: Long COVID presents a significant chronic health burden to adults in the US and abroad. This health burden may persist for many months post-acute infection.

Source: Tak CR. The health impact of long COVID: a cross-sectional examination of health-related quality of life, disability, and health status among individuals with self-reported post-acute sequelae of SARS CoV-2 infection at various points of recovery. J Patient Rep Outcomes. 2023 Mar 21;7(1):31. doi: 10.1186/s41687-023-00572-0. PMID: 36943643; PMCID: PMC10029785. https://jpro.springeropen.com/articles/10.1186/s41687-023-00572-0 (Full text)

What is the role of brown adipose tissue in metabolic health: lessons learned and future perspectives in the long COVID?

Abstract:

Metabolic physiology plays a key role in maintaining our health and resilience. Metabolic disorders can lead to serious illnesses, including obesity. The pathogenesis of the new long COVID syndrome in individuals with long-term recovery after SARS-Co-2 infection is still incomplete. Thus there is growing attention in the study of adipose tissue activities, especially brown adipose tissue (BAT) and associated resilience which plays a crucial role in different types of obesity as potential targets for pharmacologic and nutritional interventions in the context of obesity and long COVID.

The number of studies examining mechanisms underlying BAT has grown rapidly in the last 10 years despite of role of BAT in individuals with COVID-19 and long COVID is modest. Therefore, this review aims to sum up data examining BAT activities, its resilience in health, obesity, and the possible link to long COVID.

The search was conducted on studies published in English mostly between 2004 and 2022 in adult humans and animal models. Database searches were conducted using PubMed, Scopus, and Google Scholar for key terms including adipose tissue, BAT, adipokinins, obesity, VPF/VEGF, and pathogenesis. From the initial search through the database were identified relevant articles that met inclusion and exclusion criteria and our data regarding adipose tissues were presented in this review.

It will discuss adiposity tissue activities. Current literature suggests that there are BAT integral effects to whitening and browning fat phenomenons which reflect the homeostatic metabolic adaptive ability for environmental demand or survival/adaptive mechanisms. We also review neural and vascular impacts in BAT that play a role in resilience and obesity. Finally, we discuss the role of BAT in the context of long COVID in basic research and clinical research.

Source: Muzyka, I., Revenko, O., Kovalchuk, I. et al. What is the role of brown adipose tissue in metabolic health: lessons learned and future perspectives in the long COVID?. Inflammopharmacol (2023). https://doi.org/10.1007/s10787-023-01195-z (Full text)

Long Covid: clues about causes

Abstract:(Full text

Many patients report persistent symptoms after resolution of acute COVID-19, regardless of SARS-CoV-2 variant and even if the initial illness is mild [1, 2]. A multitude of symptoms have been described under the umbrella term ‘Long COVID’, otherwise known as ‘post-COVID syndrome’ or ‘post-acute sequelae of SARS-CoV-2 (PASC)’; for simplicity we will use the term Long COVID.

Symptoms are diverse but include breathlessness, fatigue and brain fog, reported to affect up to 69% of cases [3]. Long COVID can be debilitating, 45.2% of patients requiring a reduced work schedule [4]. The WHO estimates that 17 million people in Europe have experienced Long COVID during the first two years of the pandemic [5]. SARS-CoV-2 variants continue to circulate and the risk of post-acute complications remains; a recent study of 56 003 UK patients found that even after Omicron infection, 4.5% suffered persistent symptoms [6].

It is therefore likely that Long COVID will provide a substantial medical and economic burden for the foreseeable future. There is an urgent need to understand mechanisms of disease and develop effective treatments based on this understanding.

Source: Liew F, Efstathiou C, Openshaw PJ. Long Covid: clues about causes. Eur Respir J. 2023 Mar 23:2300409. doi: 10.1183/13993003.00409-2023. Epub ahead of print. PMID: 36958743; PMCID: PMC10040855. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040855/ (Full text)

What is the impact of post-COVID-19 syndrome on health-related quality of life and associated factors: a cross-sectional analysis

Abstract:

Background: After the acute phase, symptoms or sequelae related to post-COVID-19 syndrome may persist for months. In a population of patients, previously hospitalized and not, followed up to 12 months after the acute infection, we aim to assess whether and to what extent post-COVID-19 syndrome may have an impact on health-related quality of life (HRQoL) and to investigate influencing factors.

Methods: We present the cross-sectional analysis of a prospective study, including patients referred to the post-COVID-19 service. Questionnaires and scales administered at 3, 6, 12 months were: Short-Form 36-item questionnaire (SF-36); Visual Analogue Scale of the EQ5D (EQ-VAS); in a subgroup, Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II) and Pittsburgh Sleep Quality Index (PSQI). Linear regression models were fitted to identify factors associated with HRQoL.

Results: We considered the first assessment of each participant (n = 572). The mean scores in SF-36 and in EQ-VAS were significantly lower than the Italian normative values and remained stable over time, except the mental components score (MCS) of the SF-36 and EQ-VAS which resulted in lower ratings at the last observations. Female gender, presence of comorbidities, and corticosteroids treatment during acute COVID-19, were associated with lower scores in SF-36 and EQ-VAS; patients previously hospitalized (54%) reported higher MCS. Alterations in BAI, BDI-II, and PSQI (n = 265)were associated with lower ratings in SF-36 and EQ-VAS.

Conclusions: This study provides evidence of a significantly bad perception of health status among persons with post-COVID-19 syndrome, associated with female gender and, indirectly, with disease severity. In case of anxious-depressive symptoms and sleep disorders, a worse HRQoL was also reported. A systematic monitoring of these aspects is recommended to properly manage the post-COVID-19 period.

Source: Mastrorosa I, Del Duca G, Pinnetti C, Lorenzini P, Vergori A, Brita AC, Camici M, Mazzotta V, Baldini F, Chinello P, Mencarini P, Giancola ML, Abdeddaim A, Girardi E, Vaia F, Antinori A. What is the impact of post-COVID-19 syndrome on health-related quality of life and associated factors: a cross-sectional analysis. Health Qual Life Outcomes. 2023 Mar 22;21(1):28. doi: 10.1186/s12955-023-02107-z. PMID: 36949439; PMCID: PMC10031164. https://hqlo.biomedcentral.com/articles/10.1186/s12955-023-02107-z (Full text)

Post-COVID Syndrome

Abstract:

Background: As defined by the WHO, the term post-COVID syndrome (PCS) embraces a group of symptoms that can occur following the acute phase of a SARS-CoV-2 infection and as a consequence thereof. PCS is found mainly in adults, less frequently in children and adolescents. It can develop both in patients who initially had only mild symptoms or none at all and in those who had a severe course of coronavirus disease 2019 (COVID-19).

Methods: The data presented here were derived from a systematic literature review.

Results: PCS occurs in up to 15% of unvaccinated adults infected with SARS-CoV-2. The prevalence has decreased in the most recent phase of the pandemic and is lower after vaccination. The pathogenesis of PCS has not yet been fully elucidated. Virus triggered inflammation, autoimmunity, endothelial damage (to blood vessels), and persistence of virus are thought to be causative. Owing to the broad viral tropism, different organs are involved and the symptoms vary. To date, there are hardly any evidence-based recommendations for definitive diagnosis of PCS or its treatment.

Conclusion: The gaps in our knowledge mean that better documentation of the prevalence of PCS is necessary to compile the data on which early detection, diagnosis, and treatment can be based. To ensure the best possible care of patients with PCS, regional PCS centers and networks embracing existing structures from all healthcare system sectors and providers should be set up and structured diagnosis and treatment algorithms should be established. Given the sometimes serious consequences of PCS for those affected, it seems advisable to keep the number of SARS-CoV-2 infections low by protective measures tailored to the prevailing pandemic situation.

Source: Hallek M, Adorjan K, Behrends U, Ertl G, Suttorp N, Lehmann C. Post-COVID Syndrome. Dtsch Arztebl Int. 2023 Jan 27;120(4):48-55. doi: 10.3238/arztebl.m2022.0409. PMID: 36633452; PMCID: PMC10060997. https://www.aerzteblatt.de/int/archive/article/229208 (Full text)

What is really ‘Long COVID’?

Abstract:

The previous acute respiratory diseases caused by viruses originating from China or the middle east (e.g., SARS, MERS) remained fast developing short diseases without major sequalae or any long-lasting complications. The new COVID-19, on the other hand, not only that it rapidly spread over the world, but some patients never fully recovered or even if they did, a few weeks later started to complain not only of shortness of breath, if any, but general weakness, muscle pains and ‘brain fog’, i.e., fuzzy memories. Thus, these signs and symptoms were eventually labelled ‘long COVID’, for which the most widely used definition is ‘new signs and symptoms occurring 4-8 weeks after recovering from acute stage of COVID-19’.

The other most frequent manifestations associated with long COVID include headache, loss of memory, smell and of hair, nausea, and vomiting. Thus, long COVID is not a simple disease, but complex disorder of several organ systems malfunctioning; hence, it is probably more appropriate to call this a syndrome.

The pathogenesis of long COVID syndrome is poorly understood, but initial and persistent vascular endothelial injury that often triggers the formation of microthrombi that if dislodged as emboli, damage several organs, especially in the brain, heart and kidney, by creating microinfarcts.

The other major contributory mechanistic factor is the persistent cytokine storm that may last longer in long COVID patients than in others, probably triggered by aggregates of SARS-Co-2 discovered recently in the adrenal cortex, kidney and brain.

The prevalence of long COVID is relatively high, e.g., initially varied 3-30%, and recent data indicate that 2.5% of UK population suffers from this syndrome, while in the US 14.7% of acute COVID-19 patients continued to have symptoms longer than 2 months. Thus, the long COVID syndrome deserves to be further investigated, both from clinical and basic research perspectives.

Source: Szabo S, Zayachkivska O, Hussain A, Muller V. What is really ‘Long COVID’? Inflammopharmacology. 2023 Mar 25:1–7. doi: 10.1007/s10787-023-01194-0. Epub ahead of print. PMID: 36964860; PMCID: PMC10039447. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10039447/ (Full text)

Risk Factors Associated With Post−COVID-19 Condition A Systematic Review and Meta-analysis

Abstract:

Importance  Post−COVID-19 condition (PCC) is a complex heterogeneous disorder that has affected the lives of millions of people globally. Identification of potential risk factors to better understand who is at risk of developing PCC is important because it would allow for early and appropriate clinical support.

Objective  To evaluate the demographic characteristics and comorbidities that have been found to be associated with an increased risk of developing PCC.

Data sources  Medline and Embase databases were systematically searched from inception to December 5, 2022.

Study Selection  The meta-analysis included all published studies that investigated the risk factors and/or predictors of PCC in adult (≥18 years) patients.

Data Extraction and Synthesis  Odds ratios (ORs) for each risk factor were pooled from the selected studies. For each potential risk factor, the random-effects model was used to compare the risk of developing PCC between individuals with and without the risk factor. Data analyses were performed from December 5, 2022, to February 10, 2023.

Main Outcomes and Measures  The risk factors for PCC included patient age; sex; body mass index, calculated as weight in kilograms divided by height in meters squared; smoking status; comorbidities, including anxiety and/or depression, asthma, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, immunosuppression, and ischemic heart disease; previous hospitalization or ICU (intensive care unit) admission with COVID-19; and previous vaccination against COVID-19.

Results  The initial search yielded 5334 records of which 255 articles underwent full-text evaluation, which identified 41 articles and a total of 860 783 patients that were included. The findings of the meta-analysis showed that female sex (OR, 1.56; 95% CI, 1.41-1.73), age (OR, 1.21; 95% CI, 1.11-1.33), high BMI (OR, 1.15; 95% CI, 1.08-1.23), and smoking (OR, 1.10; 95% CI, 1.07-1.13) were associated with an increased risk of developing PCC. In addition, the presence of comorbidities and previous hospitalization or ICU admission were found to be associated with high risk of PCC (OR, 2.48; 95% CI, 1.97-3.13 and OR, 2.37; 95% CI, 2.18-2.56, respectively). Patients who had been vaccinated against COVID-19 with 2 doses had a significantly lower risk of developing PCC compared with patients who were not vaccinated (OR, 0.57; 95% CI, 0.43-0.76).

Conclusions and Relevance  This systematic review and meta-analysis demonstrated that certain demographic characteristics (eg, age and sex), comorbidities, and severe COVID-19 were associated with an increased risk of PCC, whereas vaccination had a protective role against developing PCC sequelae. These findings may enable a better understanding of who may develop PCC and provide additional evidence for the benefits of vaccination.

Trial Registration  PROSPERO Identifier: CRD42022381002

Source: Tsampasian V, Elghazaly H, Chattopadhyay R, et al. Risk Factors Associated With Post−COVID-19 Condition: A Systematic Review and Meta-analysis. JAMA Intern Med. Published online March 23, 2023. doi:10.1001/jamainternmed.2023.0750 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2802877 (Full text)

Social support, distress and well-being in individuals experiencing Long-COVID: a cross-sectional survey study

Abstract:

Objectives: Increasingly attention of the COVID-19 pandemic is directed towards its long-term effects, also known as Long-COVID. So far, Long-COVID was examined mainly from a medical perspective, leaving psychosocial effects of Long-COVID understudied. The present study advances the current literature by examining social support in the context of Long-COVID. The study not only examines received support reported by individuals with Long-COVID, but also provided support reported by relatives of individuals with Long-COVID.

Design: Cross-sectional study.

Setting: The study was conducted from June to October 2021 in Austria, Germany and the German-speaking part of Switzerland.

Participants: We examined 256 individuals with Long-COVID (MAge=45.05 years, 90.2% women) and 50 relatives of individuals with Long-COVID (MAge=48.34 years, 66.1% female) in two separate online surveys, assessing social support, well-being and distress.

Primary outcome measures: Primary outcomes were positive and negative affect, anxiety and depressive symptoms and perceived stress.

Results: For individuals with Long-COVID, receiving emotional support was related to higher well-being (positive affect: b=0.29, p<0.01; negative affect: b=-0.31, p<0.05) and less distress (anxiety: b=-1.45, p<0.01; depressive symptoms: b=-1.04, p<0.05; perceived stress: b=-0.21, p<0.05) but no effects emerged for receiving practical support. For relatives of individuals with Long-COVID, providing emotional support was only related to lower depressive symptoms (b=-2.57, p<0.05). Again, provided practical support was unrelated to the outcomes considered.

Conclusions: Emotional support is likely to play an important role in well-being and distress of patients and relatives, whereas practical support does not seem to make a difference. Future research should clarify under what conditions different kinds of support unfold their positive effects on well-being and distress in the context of Long-COVID.

Source: Lüscher J, Scholz U, Bierbauer W. Social support, distress and well-being in individuals experiencing Long-COVID: a cross-sectional survey study. BMJ Open. 2023 Mar 22;13(3):e067166. doi: 10.1136/bmjopen-2022-067166. PMID: 36948566; PMCID: PMC10039976. https://bmjopen.bmj.com/content/13/3/e067166 (Full text)