Diverse functional autoantibodies in patients with COVID-19

Abstract:

COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1-6. Although pathological innate immune activation is well-documented in severe disease1, the effect of autoantibodies on disease progression is less well-defined. Here we use a high-throughput autoantibody discovery technique known as rapid extracellular antigen profiling7 to screen a cohort of 194 individuals infected with SARS-CoV-2, comprising 172 patients with COVID-19 and 22 healthcare workers with mild disease or asymptomatic infection, for autoantibodies against 2,770 extracellular and secreted proteins (members of the exoproteome).

We found that patients with COVID-19 exhibit marked increases in autoantibody reactivities as compared to uninfected individuals, and show a high prevalence of autoantibodies against immunomodulatory proteins (including cytokines, chemokines, complement components and cell-surface proteins). We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signalling and by altering peripheral immune cell composition, and found that mouse surrogates of these autoantibodies increase disease severity in a mouse model of SARS-CoV-2 infection. Our analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics. Our findings suggest a pathological role for exoproteome-directed autoantibodies in COVID-19, with diverse effects on immune functionality and associations with clinical outcomes.

Source: Wang EY, Mao T, Klein J, Dai Y, Huck JD, Jaycox JR, Liu F, Zhou T, Israelow B, Wong P, Coppi A, Lucas C, Silva J, Oh JE, Song E, Perotti ES, Zheng NS, Fischer S, Campbell M, Fournier JB, Wyllie AL, Vogels CBF, Ott IM, Kalinich CC, Petrone ME, Watkins AE; Yale IMPACT Team, Dela Cruz C, Farhadian SF, Schulz WL, Ma S, Grubaugh ND, Ko AI, Iwasaki A, Ring AM. Diverse functional autoantibodies in patients with COVID-19. Nature. 2021 Jul;595(7866):283-288. doi: 10.1038/s41586-021-03631-y. Epub 2021 May 19. PMID: 34010947. https://pubmed.ncbi.nlm.nih.gov/34010947/

Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats

Abstract:

Recent studies have reported that plasma levels of tricarboxylic acid (TCA) cycle metabolites and TCA cycle-related metabolite change in patients with chronic fatigue syndrome (CFS) and in healthy humans after exercise. Exogenous dietary citric acid has been reported to alleviate fatigue during daily activities and after exercise. However, it is unknown whether dietary citric acid affects the plasma levels of these metabolites. Therefore, the present study aimed to investigate the effects of exogenously administered citric acid on TCA cycle metabolites and TCA cycle-related metabolites in plasma.

Sprague-Dawley rats were divided into control and citric acid groups. We evaluated the effect of exogenous dietary citric acid on the plasma TCA cycle and TCA cycle-related metabolites by metabolome analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). TCA cycle metabolites, including plasma citrate, cis-aconitate, and isocitrate, were significantly elevated after exogenous administration of citric acid. Anaplerotic amino acids, which are converted to TCA cycle metabolites, such as serine, glycine, tryptophan, lysine, leucine, histidine, glutamine, arginine, isoleucine, methionine, valine, and phenylalanine, also showed significantly elevated levels.

Citric acid administration significantly increased the levels of initial TCA cycle metabolites in the plasma. This increase after administration of citric acid was shown to be opposite to the metabolic changes observed in patients with CFS. These results contribute novel insight into the fatigue alleviation mechanism of citric acid.

Source: Hara Y, Kume S, Kataoka Y, Watanabe N. Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats. Heliyon. 2021 Dec 4;7(12):e08501. doi: 10.1016/j.heliyon.2021.e08501. PMID: 34934832; PMCID: PMC8654791. https://pubmed.ncbi.nlm.nih.gov/34934832/

Review article: Physical and psychological comorbidities associated with irritable bowel syndrome

Abstract:

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders encountered by physicians in primary and secondary care. Patients with IBS commonly present with various extraintestinal complaints, which account for a substantial clinical and economic burden. The common extraintestinal comorbidities associated with IBS include anxiety, depression, somatisation, fibromyalgia, chronic fatigue syndrome, chronic pelvic pain, interstitial cystitis, sexual dysfunction and sleep disturbance. The presence of comorbidity in IBS poses a diagnostic and therapeutic challenge with patients frequently undergoing unnecessary investigations and interventions, including surgery. This review discusses the different physical and psychological comorbidities associated with IBS, the shared pathophysiological mechanisms and potential management strategies

Source: Shiha MG, Aziz I. Review article: Physical and psychological comorbidities associated with irritable bowel syndrome. Aliment Pharmacol Ther. 2021 Dec;54 Suppl 1:S12-S23. doi: 10.1111/apt.16589. PMID: 34927759. https://pubmed.ncbi.nlm.nih.gov/34927759/

Can l-carnitine reduce post-COVID-19 fatigue?

Abstract:

A significant number of patients infected with the new coronavirus suffer from chronic fatigue syndrome after COVID-19, and their symptoms may persist for months after the infection. Nevertheless, no particular treatment for post-disease fatigue has been found. At the same time, many clinical trials have shown the effectiveness of l-carnitine in relieving fatigue caused by the treatment of diseases such as cancer, MS, and many other diseases. Therefore, it can be considered as a potential option to eliminate the effects of fatigue caused by COVID-19, and its consumption is recommended in future clinical trials to evaluate its effectiveness and safety.

Source: Vaziri-Harami R, Delkash P. Can l-carnitine reduce post-COVID-19 fatigue? Ann Med Surg (Lond). 2022 Jan;73:103145. doi: 10.1016/j.amsu.2021.103145. Epub 2021 Dec 13. PMID: 34925826; PMCID: PMC8667465. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8667465/ (Full text)

Stellate ganglion block reduces symptoms of Long COVID: A case series

Abstract:

After recovering from COVID-19, a significant proportion of symptomatic and asymptomatic individuals develop Long COVID. Fatigue, orthostatic intolerance, brain fog, anosmia, and ageusia/dysgeusia in Long COVID resemble “sickness behavior,” the autonomic nervous system response to pro-inflammatory cytokines (Dantzer et al., 2008). Aberrant network adaptation to sympathetic/parasympathetic imbalance is expected to produce long-standing dysautonomia. Cervical sympathetic chain activity can be blocked with local anesthetic, allowing the regional autonomic nervous system to “reboot.” In this case series, we successfully treated two Long COVID patients using stellate ganglion block, implicating dysautonomia in the pathophysiology of Long COVID and suggesting a novel treatment.

Source: Liu LD, Duricka DL. Stellate ganglion block reduces symptoms of Long COVID: A case series. J Neuroimmunol. 2021 Dec 8;362:577784. doi: 10.1016/j.jneuroim.2021.577784. Epub ahead of print. PMID: 34922127. https://www.jni-journal.com/article/S0165-5728(21)00311-8/fulltext (Full text)

Neuro-COVID-19

Abstract:

Neuromuscular manifestations of new coronavirus disease 2019 (COVID-19) infection are frequent, and include dizziness, headache, myopathy, and olfactory and gustatory disturbances. Patients with acute central nervous system disorders, such as delirium, impaired consciousness, stroke and convulsive seizures, have a high mortality rate.

The encephalitis/encephalopathy that causes consciousness disturbance and seizures can be classified into three conditions, including direct infection with the SARS-CoV-2 virus, encephalopathy caused by central nervous system damage secondary to systemic hypercytokinemia (cytokine storm) and autoimmune-mediated encephalitis that occurs after infection.

The sequelae, called post-acute COVID-19 syndrome or long COVID, include neuromuscular manifestations, such as anxiety, depression, sleep disturbance, muscle weakness, brain fog and cognitive impairment. It is desirable to establish diagnostic criteria and treatment for these symptoms. Vaccine-induced thrombotic thrombocytopenia, Guillain-Barré syndrome, bilateral facial paralysis, encephalitis and opsoclonus-myoclonus syndrome have been reported as adverse reactions after the COVID-19 vaccine, although these are rare.

Source: Shimohata T. Neuro-COVID-19. Clin Exp Neuroimmunol. 2021 Sep 29:10.1111/cen3.12676. doi: 10.1111/cen3.12676. Epub ahead of print. PMID: 34899999; PMCID: PMC8652810.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8652810/ (Full text)

Persistence of Symptoms After Discharge of Patients Hospitalized Due to COVID-19

Abstract:

Many patients who had coronavirus disease 2019 (COVID-19) had at least one symptom that persisted after recovery from the acute phase. Our purpose was to review the empirical evidence on symptom prevalence, complications, and management of patients with long COVID. We systematically reviewed the literature on the clinical manifestations of long COVID-19, defined by the persistence of symptoms beyond the acute phase of infection. Bibliographic searches in PubMed and Google Scholar were conducted to retrieve relevant studies on confirmed patients with long COVID that were published prior to August 30, 2021.

The most common persistent symptoms were fatigue, cough, dyspnea, chest pains, chest tightness, joint pain, muscle pain, loss of taste or smell, hair loss, sleep difficulties, anxiety, and depression. Some of the less common persistent symptoms were skin rash, decreased appetite, sweating, inability to concentrate, and memory lapses. In addition to these general symptoms, some patients experienced dysfunctions of specific organs, mainly the lungs, heart, kidneys, and nervous system.

A comprehensive understanding of the persistent clinical manifestations of COVID-19 can improve and facilitate patient management and referrals. Prompt rehabilitative care and targeted interventions of these patients may improve their recovery from physical, immune, and mental health symptoms.

Source: Wu L, Wu Y, Xiong H, Mei B, You T. Persistence of Symptoms After Discharge of Patients Hospitalized Due to COVID-19. Front Med (Lausanne). 2021 Nov 22;8:761314. doi: 10.3389/fmed.2021.761314. PMID: 34881263; PMCID: PMC8645792. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645792/ (Full text)

Incidence and risk factors of long COVID in the UK: a single-centre observational study

Abstract:

Background: Studies to evaluate long COVID symptoms and their risk factors are limited. We evaluated the presence of long COVID and its risk factors in patients discharged from a hospital with COVID-19 illness.

Methods: This observational study included 271 COVID-19 patients admitted between February and July 2020 in a hospital in the UK. The primary outcome measure was to assess the duration and severity of long COVID and its predictors at 3, 6 and 9 months. Logistic regression was performed to assess the potential risk factors for long COVID.

Results: Out of 89 patients interviewed, 55 (62%) had long COVID for 3 months, 46 (52%) for 6 months and 37 of the 75 patients admitted to the hospital with acute COVID-19 had long COVID for 9 months (49%). The most common long COVID symptoms were fatigue and breathlessness.

Conclusion: Nearly two-thirds of patients at 3 months and a half at 9 months had long COVID. COVID-19 pneumonia was the strongest predictor of long COVID in Caucasians at 3 months.

Source: Nune A, Durkowski V, Titman A, Gupta L, Hadzhiivanov M, Ahmed A, Musat C, Sapkota HR. Incidence and risk factors of long COVID in the UK: a single-centre observational study. J R Coll Physicians Edinb. 2021 Dec;51(4):338-343. doi: 10.4997/JRCPE.2021.405. PMID: 34882130. https://pubmed.ncbi.nlm.nih.gov/34882130/

Long COVID-The New “Invisible” Illness: How School Nurses Can Support the Nursing and Educational Teams for Student Success

Abstract:

School-age children are not immune to COVID-19 or the pronounced and persistent symptoms associated with a long-COVID diagnosis. Students may present with a variety of symptoms affecting their physical, cognitive, and mental health. The school community should be educated on the school-based interventions and recommendations for creating an individualized safe and successful return to school plan. As we await approval for vaccinations in school-age children younger than 12 years and continue to reposition ourselves to the waves of this pandemic and new variants of the virus, understanding the medical and educational long-term effects on our students may be a long-term need.

Source: Roesler M, Fato P, Obst B. Long COVID-The New “Invisible” Illness: How School Nurses Can Support the Nursing and Educational Teams for Student Success. NASN Sch Nurse. 2021 Dec 10:1942602X211059427. doi: 10.1177/1942602X211059427. Epub ahead of print. PMID: 34889154. https://pubmed.ncbi.nlm.nih.gov/34889154/

Proposed subtypes of post-COVID-19 syndrome (or long-COVID) and their respective potential therapies

Abstract:

The effects of coronavirus disease 2019 (COVID-19), a highly transmissible infectious respiratory disease that has initiated an ongoing pandemic since early 2020, do not always end in the acute phase. Depending on the study referred, about 10%-30% (or more) of COVID-19 survivors may develop long-COVID or post-COVID-19 syndrome (PCS), characterised by persistent symptoms (most commonly fatigue, dyspnoea, and cognitive impairments) lasting for 3 months or more after acute COVID-19. While the pathophysiological mechanisms of PCS have been extensively described elsewhere, the subtypes of PCS have not.

Owing to its highly multifaceted nature, this review proposes and characterises six subtypes of PCS based on the existing literature. The subtypes are non-severe COVID-19 multi-organ sequelae (NSC-MOS), pulmonary fibrosis sequelae (PFS), myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), post-intensive care syndrome (PICS) and medical or clinical sequelae (MCS). Original studies supporting each of these subtypes are documented in this review, as well as their respective symptoms and potential interventions. Ultimately, the subtyping proposed herein aims to provide better clarity on the current understanding of PCS.

Source: Yong SJ, Liu S. Proposed subtypes of post-COVID-19 syndrome (or long-COVID) and their respective potential therapies. Rev Med Virol. 2021 Dec 9:e2315. doi: 10.1002/rmv.2315. Epub ahead of print. PMID: 34888989. https://pubmed.ncbi.nlm.nih.gov/34888989/  https://onlinelibrary.wiley.com/doi/pdf/10.1002/rmv.2315 (Full text)