Category: Overlapping Illnesses

Long COVID: The latest manifestations, mechanisms, and potential therapeutic interventions

Abstract:

COVID-19 caused by SARS-CoV-2 infection affects humans not only during the acute phase of the infection, but also several weeks to 2 years after the recovery. SARS-CoV-2 infects a variety of cells in the human body, including lung cells, intestinal cells, vascular endothelial cells, olfactory epithelial cells, etc. The damages caused by the infections of these cells and enduring immune response are the basis of long COVID. Notably, the changes in gene expression caused by viral infection can also indirectly contribute to long COVID.

We summarized the occurrences of both common and uncommon long COVID, including damages to lung and respiratory system, olfactory and taste deficiency, damages to myocardial, renal, muscle, and enduring inflammation. Moreover, we provided potential treatments for long COVID symptoms manifested in different organs and systems, which were based on the pathogenesis and the associations between symptoms in different organs.

Importantly, we compared the differences in symptoms and frequency of long COVID caused by breakthrough infection after vaccination and infection with different variants of concern, in order to provide a comprehensive understanding of the characteristics of long COVID and propose improvement for tackling COVID-19.

Source: He ST, Wu K, Cheng Z, He M, Hu R, Fan N, Shen L, Li Q, Fan H, Tong Y. Long COVID: The latest manifestations, mechanisms, and potential therapeutic interventions. MedComm (2020). 2022 Dec 8;3(4):e196. doi: 10.1002/mco2.196. PMID: 36514781; PMCID: PMC9732402. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9732402/ (Full text)

Long COVID and older people

Abstract:

Long COVID is a poorly understood condition, with a wide spectrum of effects on multiple body systems and variable presentation in different individuals. Long COVID is of particular concern among older people (ie, aged 65 years or older), who are at greater risk than younger people of persisting symptoms associated with COVID-19. In addition, COVID-19 might trigger or exacerbate chronic conditions that occur commonly in older people, such as cardiovascular diseases, respiratory diseases, neurodegenerative conditions, and functional decline.

In addition, the disruptive effects of COVID-19 for older people should not be underestimated; lockdowns and other restrictions might have reduced the social interactions of older people, and they are also likely to have lost a spouse or loved one during the pandemic, which can contribute to mental and physical decline.

COVID-19 vaccination appears to reduce the effects of long COVID, and older people, especially those living in aged care facilities, should remain up-to-date with their COVID-19 vaccinations. Health-care staff should also consider long COVID in the differential diagnosis of relevant symptoms in older people, rather than assume increasing frailty, and should pursue early multidisciplinary assessment and management of persisting symptoms. Addressing physical, psychological, and functional sequelae will mitigate the effect of long COVID and improve the health and quality of life of older people.

Source: Mansell V, Hall Dykgraaf S, Kidd M, Goodyear-Smith F. Long COVID and older people. Lancet Healthy Longev. 2022 Dec;3(12):e849-e854. doi: 10.1016/S2666-7568(22)00245-8. PMID: 36480981. https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(22)00245-8/fulltext (Full study)

Musculoskeletal complications in long COVID-19: A systematic review

Abstract:

Background: Coronavirus disease 2019 (COVID-19) has crippled humanity since early 2020. Various sequelae of COVID-19 have been reported in different body systems. Musculoskeletal symptoms are widely reported during COVID-19 infection, but musculoskeletal complications in long COVID-19 are underreported. However, post-COVID-19 survivors have reported complaints of persisting or new-onset fatigue, myalgia, arthralgia, arthritis, muscle weakness, etc in clinical practice. The well-known detrimental effects of steroids on the musculoskeletal system coupled with their over-the-counter availability can also be anticipated since they were the cornerstone of life-saving management in this pandemic.

Aim: To determine the musculoskeletal complications in long COVID.

Methods: We performed a systematic review of ‘systematic reviews and meta-analyses’.

Results: Of the 63 articles screened, 24 articles were included. Two articles specifically discussed children and adolescents. One article discussed rehabilitation intervention. No article addressed rehabilitation of musculoskeletal issues in long COVID-19 in particular. Fatigue was the most common musculoskeletal complication.

Conclusion: Fatigue is found to be very common along with myalgia and arthralgia. There were no studies on rehabilitation intervention in musculoskeletal complications specifically. Considering the lacuna in literature and the needs of the current situation, further studies are warranted to standardize effective rehabilitation interventions in musculoskeletal complications. More homogenous studies are needed. Studies on functional impairment due to musculoskeletal involvement are essential.

Source: Swarnakar R, Jenifa S, Wadhwa S. Musculoskeletal complications in long COVID-19: A systematic review. World J Virol. 2022 Nov 25;11(6):485-495. doi: 10.5501/wjv.v11.i6.485. PMID: 36483107; PMCID: PMC9724204. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9724204/ (Full text)

Persistent symptoms after COVID-19 during the first wave are not associated with differential immunity to SARS-CoV-2

Abstract:

Among the unknowns in decoding the pathogenesis of SARS-CoV-2 persistent symptoms in Long Covid is whether there is a contributory role of abnormal immunity during acute infection – some have proposed that Long Covid may be a consequence of either an excessive or inadequate initial response. We analysed SARS-CoV-2 humoral and cellular immunity in healthcare workers infected during the first wave.

Symptom questionnaires allowed stratification into those with persistent symptoms and those without for comparison. During the period up to 18-weeks post-infection, we observed no difference in antibody responses to spike, RBD or nucleoprotein, virus neutralisation, or T cell responses. Also, there was no difference in the profile of antibody waning.

Analysis at 1-year, after two vaccine doses, comparing those with persistent symptoms to those without, again showed similar SARS-CoV-2 immunity. Thus, quantitative differences in SARS-CoV-2 adaptive immunity during acute infection are unlikely to contribute to Long Covid causality.

Source: Altmann D, Reynolds C, Joy G, et al. Persistent symptoms after COVID-19 during the first wave are not associated with differential immunity to SARS-CoV-2. Research Square; 2022. DOI: 10.21203/rs.3.rs-2324777/v1. https://www.researchsquare.com/article/rs-2324777/v1 (Full text)

Stellate Ganglion Block for Long COVID Symptom Management: A Case Report

Abstract:

Stellate ganglion block (SGB) is gaining increasing acceptance as a treatment modality for various medical conditions. It works by blocking neuronal transmissions which in turn alleviates sympathetically-driven disease processes. Many of the prolonged sequelae of long COVID are thought to be mediated by dysregulation of the autonomic nervous system, and SGB is being investigated as a potential option for symptomatic management of long COVID. This case report demonstrates the efficacy of SGB in a previously healthy patient for the management of long COVID symptoms including fatigue, post-exertional malaise, shortness of breath, and gastrointestinal symptoms.

Source: Khan M H, Kirkpatrick K P, Deng Y, et al. (December 07, 2022) Stellate Ganglion Block for Long COVID Symptom Management: A Case Report. Cureus 14(12): e32295. doi:10.7759/cureus.32295 https://www.cureus.com/articles/127985-stellate-ganglion-block-for-long-covid-symptom-management-a-case-report (Full text)

The bidirectional association between diabetes and long-COVID-19 – A systematic review

Abstract:

Some evidence suggests that diabetes may be a risk factor for the development of post-acute sequelae of COVID-19 (PASC). Recent data also indicate that new-onset diabetes may be a complication of COVID-19. Here, we review the existing evidence.

Following PRISMA guidelines, we conducted a systematic review through August 8, 2022. We included longitudinal studies reporting on the risk of PASC (i.e., sequelae that extend beyond four weeks after initial infection) in people with and without diabetes, and studies reporting on the risk of new-onset diabetes in people with vs without COVID-19 with a minimum of 4-weeks of follow-up. All studies were published in English. Among 5,532 studies screened, 39 were included in the final review.

Among 25 studies reporting on diabetes and PASC, 44 % (n = 11) identified diabetes as a significant risk factor for PASC (increased relative risk ranging from 7 % to 342 %) while 56 % (n = 14) did not. Among 14 studies reporting on new-onset diabetes, 12 (86 %) reported that COVID-19 (vs no COVID) was significantly associated with new-onset diabetes with increased risks ranging from 11 % to 276 %. COVID-19 survivors may be at increased risk for new-onset diabetes, but whether pre-existing diabetes is also a risk factor for PASC remains unclear.

Source: Harding JL, Oviedo SA, Ali MK, Ofotokun I, Gander JC, Patel SA, Magliano DJ, Patzer RE. The bidirectional association between diabetes and long-COVID-19 – A systematic review. Diabetes Res Clin Pract. 2022 Dec 7;195:110202. doi: 10.1016/j.diabres.2022.110202. Epub ahead of print. PMID: 36496030; PMCID: PMC9727969. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727969/ (Full text)

Pharmacological Mechanism of NRICM101 for COVID-19 Treatments by Combined Network Pharmacology and Pharmacodynamics

Abstract:

Symptom treatments for Coronavirus disease 2019 (COVID-19) infection and Long COVID are one of the most critical issues of the pandemic era. In light of the lack of standardized medications for treating COVID-19 symptoms, traditional Chinese medicine (TCM) has emerged as a potentially viable strategy based on numerous studies and clinical manifestations. Taiwan Chingguan Yihau (NRICM101), a TCM designed based on a medicinal formula with a long history of almost 500 years, has demonstrated its antiviral properties through clinical studies, yet the pharmacogenomic knowledge for this formula remains unclear. The molecular mechanism of NRICM101 was systematically analyzed by using exploratory bioinformatics and pharmacodynamics (PD) approaches.

Results showed that there were 434 common interactions found between NRICM101 and COVID-19 related genes/proteins. For the network pharmacology of the NRICM101, the 434 common interacting genes/proteins had the highest associations with the interleukin (IL)-17 signaling pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Moreover, the tumor necrosis factor (TNF) was found to have the highest association with the 30 most frequently curated NRICM101 chemicals.

Disease analyses also revealed that the most relevant diseases with COVID-19 infections were pathology, followed by cancer, digestive system disease, and cardiovascular disease. The 30 most frequently curated human genes and 2 microRNAs identified in this study could also be used as molecular biomarkers or therapeutic options for COVID-19 treatments.

In addition, dose-response profiles of NRICM101 doses and IL-6 or TNF-α expressions in cell cultures of murine alveolar macrophages were constructed to provide pharmacodynamic (PD) information of NRICM101. The prevalent use of NRICM101 for standardized treatments to attenuate common residual syndromes or chronic sequelae of COVID-19 were also revealed for post-pandemic future.

Source: Singh S, Yang YF. Pharmacological Mechanism of NRICM101 for COVID-19 Treatments by Combined Network Pharmacology and Pharmacodynamics. Int J Mol Sci. 2022 Dec 6;23(23):15385. doi: 10.3390/ijms232315385. PMID: 36499711; PMCID: PMC9740625. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740625/ (Full text)

Effect of Vaccination against SARS-CoV-2 on Long COVID-19: A Narrative Review

Abstract:

Vaccines against SARS-CoV-2 have saved millions of lives and played an important role in containing the COVID-19 pandemic. Vaccination against SARS-CoV-2 is also associated with reduced disease severity and, perhaps, with COVID-19 symptom burden.

In this narrative review, we present, in a clinically relevant question-and-answer manner, the evidence regarding the association between vaccination against SARS-CoV-2 and long COVID-19. We discuss how the mechanism of action of vaccines could interplay with the pathophysiology of post-COVID-19 condition.

Furthermore, we describe how specific factors, such as the number of vaccine doses and the type of SARS-CoV-2 variants, may affect post-COVID-19 condition. We also discuss the role of timing for vaccination in relation to the onset of long COVID-19 symptoms, as it seems to affect the frequency and severity of the condition.

Additionally, we describe the potential modifying effect of age, as well as the association of type and level of immune response with long COVID-19. We also describe how system-specific long COVID-19 sequelae, namely neurocognitive-psychologic symptoms and cardiovascular pathology, could be altered by vaccination.

Last, we address the question of whether seasonal influenza vaccination has a meaningful impact on the frequency of long COVID-19.

Source: Tofarides AG, Christaki E, Milionis H, Nikolopoulos GK. Effect of Vaccination against SARS-CoV-2 on Long COVID-19: A Narrative Review. Life (Basel). 2022 Dec 8;12(12):2057. doi: 10.3390/life12122057. PMID: 36556422. https://www.mdpi.com/2075-1729/12/12/2057 (Full text)

The effectiveness of coronavirus disease 2019 (COVID-19) vaccine in the prevention of post-COVID-19 conditions: A systematic literature review and meta-analysis

Abstract:

Background: Although multiple studies have revealed that coronavirus disease 2019 (COVID-19) vaccines can reduce COVID-19-related outcomes, little is known about their impact on post-COVID-19 conditions. We performed a systematic literature review and meta-analysis on the effectiveness of COVID-19 vaccination against post-COVID-19 conditions (ie, long COVID).

Methods: We searched PubMed, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from December 1, 2019, to April 27, 2022, for studies evaluating COVID-19 vaccine effectiveness against post-COVID-19 conditions among individuals who received at least 1 dose of Pfizer/BioNTech, Moderna, AstraZeneca, or Janssen vaccine. A post-COVID-19 condition was defined as any symptom that was present 3 or more weeks after having COVID-19. Editorials, commentaries, reviews, study protocols, and studies in the pediatric population were excluded. We calculated the pooled diagnostic odds ratios (DORs) for post-COVID-19 conditions between vaccinated and unvaccinated individuals. Vaccine effectiveness was estimated as 100% × (1 – DOR).

Results: In total, 10 studies with 1,600,830 individuals evaluated the effect of vaccination on post-COVID-19 conditions, of which 6 studies were included in the meta-analysis. The pooled DOR for post-COVID-19 conditions among individuals vaccinated with at least 1 dose was 0.708 (95% confidence interval (CI), 0.692-0.725) with an estimated vaccine effectiveness of 29.2% (95% CI, 27.5%-30.8%). The vaccine effectiveness was 35.3% (95% CI, 32.3%-38.1%) among those who received the COVID-19 vaccine before having COVID-19, and 27.4% (95% CI, 25.4%-29.3%) among those who received it after having COVID-19.

Conclusions: COVID-19 vaccination both before and after having COVID-19 significantly decreased post-COVID-19 conditions for the circulating variants during the study period although vaccine effectiveness was low.

Source: Marra AR, Kobayashi T, Suzuki H, Alsuhaibani M, Hasegawa S, Tholany J, Perencevich E, Maezato AM, Ricardo VCV, Salinas JL, Edmond MB, Rizzo LV. The effectiveness of coronavirus disease 2019 (COVID-19) vaccine in the prevention of post-COVID-19 conditions: A systematic literature review and meta-analysis. Antimicrob Steward Healthc Epidemiol. 2022 Dec 6;2(1):e192. doi: 10.1017/ash.2022.336. PMID: 36505947; PMCID: PMC9726631. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9726631/ (Full text)