Tag: post-infectious sequelae

Editorial: Current Insights Into Complex Post-infection Fatigue Syndromes With Unknown Aetiology: The Case of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Beyond

Introduction:

Black plague epidemics in Medieval Europe, the Spanish Flu pandemic during the first world war, and the pandemic of COVID-19 disease are just three devastating examples of the fragile co-existence between human beings and the microbial world. Remarkably, the human immune system with its innate and adaptive arms recognizes and clears the invading pathogens in most cases. However, like a scar after an injury, some people who had suffered from acute infections remain ill long after the clearance of the pathogen itself. These individuals develop complex fatigue-related syndromes whose pathological mechanisms remain poorly understood. A prime example of such syndromes is the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) characterized by persistent fatigue and post-exertional malaise among other symptoms (1). Unfortunately, its diagnosis remains challenging due to the inexistence of objective biomarkers that could identify cases. However, researchers are gathering around multidisciplinary networks, such as the US ME/CFS Clinician Coalition and the European Network on ME/CFS, with the aim of fostering collaboration, standardizing research and clinical practices, while accelerating biomarker discovery (2–5). Less-known fatigue-related syndromes have been recently reported after the outbreaks of Ebola virus, Dengue virus, and Chikungunya virus in the Tropics (6–8). However, it is still unclear whether these syndromes constitute clinical entities beyond ME/CFS itself.

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Source: Westermeier F, Lacerda EM, Scheibenbogen C and Sepúlveda N (2022) Editorial: Current Insights Into Complex Post-infection Fatigue Syndromes With Unknown Aetiology: The Case of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Beyond. Front. Med. 9:862953. doi: 10.3389/fmed.2022.862953  https://www.frontiersin.org/articles/10.3389/fmed.2022.862953/full (Full text)

Association Between SARS-CoV-2 RNAemia and Postacute Sequelae of COVID-19

Abstract:

Determinants of Post-Acute Sequelae of COVID-19 are not known. Here we show that 83.3% of patients with viral RNA in blood (RNAemia) at presentation were symptomatic in the post-acute phase. RNAemia at presentation successfully predicted PASC, independent of patient demographics, worst disease severity, and length of symptoms.

Source: Ram-Mohan N, Kim D, Rogers AJ, Blish CA, Nadeau KC, Blomkalns AL, Yang S. Association Between SARS-CoV-2 RNAemia and Postacute Sequelae of COVID-19. Open Forum Infect Dis. 2021 Dec 25;9(2):ofab646. doi: 10.1093/ofid/ofab646. PMID: 35111870; PMCID: PMC8802799. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8802799/ (Full text)

Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of cognitive symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC)

Introduction:

The emergence of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought with it a plethora of new challenges. In the beginning of the pandemic, efforts were focused on pathogenesis and acute treatment; however, over time, understanding and managing post-COVID sequelae have become the new frontier.1, 2 Generally, the majority of individuals show symptom resolution within 3–4 weeks of COVID-19, but a substantial number of people continue to experience lingering effects and develop protracted illness, regardless of initial symptom severity. Although still being defined, these effects can be collectively referred to as postacute sequelae of SARS-CoV-2 infection (PASC),3 which is the term used in this report. Notably, there are a number of other terms that are found in the literature (eg, long COVID, postacute COVID-19 syndrome, long-haul COVID, chronic COVID). At the time of development, much of the literature focused on patients who were not vaccinated, and the incidence and trajectory of PASC in vaccinated patients with “breakthrough” cases (including but not limited to current and emerging variants of the virus) are evolving. The PASC Collaborative took this into account during the development process and these guidance statements generally apply to individuals who develop PASC regardless of their vaccination status.

This guidance statement has a specific focus on the cognitive-related symptoms of PASC that can occur in people who have been diagnosed with acute COVID-19 infection or presumed to have had the infection and initially experienced mild to severe symptoms. Some patients required hospital acute care, whereas many others were managed in nonhospitalized community settings. This consensus guidance statement is one in a series extending across the breadth of the most prevalent or recognized PASC sequelae. Published and in-process guidance statements from this collaborative include the assessment and management of PASC associated fatigue, breathing and respiratory sequelae, cardiovascular complications, autonomic dysfunction, mental health, and neurologic sequelae. These statements are intended to provide consensus-driven practice guidance to clinicians in the assessment and treatment of individuals presenting with PASC.

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Source: Fine JS, Ambrose AF, Didehbani N, Fleming TK, Glashan L, Longo M, Merlino A, Ng R, Nora GJ, Rolin S, Silver JK, Terzic CM, Verduzco-Gutierrez M, Sampsel S. Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of cognitive symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC). PM R. 2022 Jan;14(1):96-111. doi: 10.1002/pmrj.12745. Epub 2022 Jan 12. PMID: 34902226. https://onlinelibrary.wiley.com/doi/10.1002/pmrj.12745 (Full text)

Impact of Q-fever on physical and psychosocial functioning until 8 years after Coxiella burnetii infection: An integrative data analysis

Abstract:

Background: This study aimed to determine short- and long-term physical and psychosocial impact of Coxiella burnetii infection in three distinct entities: Q-fever fatigue syndrome (QFS), chronic Q-fever, and patients with past acute Q-fever without QFS or chronic Q-fever.

Methods: Integrative data analysis was performed, combining original data from eight studies measuring quality of life (QoL), fatigue, physical and social functioning with identical validated questionnaires, from three months to eight years after onset infection. Linear trends in each outcome were compared between Q-fever groups using multilevel linear regression analyses to account for repeated measures within patients.

Results: Data included 3947 observations of 2313 individual patients (228 QFS, 135 chronic Q-fever and 1950 patients with past acute Q-fever). In the first years following infection, physical and psychosocial impact was highest among QFS patients, and remained high without significant improvements over time. In chronic Q-fever patients, QoL and physical functioning worsened significantly over time. Levels of fatigue and social participation in patients with past acute Q-fever improved significantly over time.

Conclusion: The impact differs greatly between the three Q-fever groups. It is important that physicians are aware of these differences, in order to provide relevant care for each patient group.

Source: Reukers DFM, van Jaarsveld CHM, Akkermans RP, Keijmel SP, Morroy G, van Dam ASG, Wever PC, Wielders CCH, van der Velden K, van Loenhout JAF, Hautvast JLA. Impact of Q-fever on physical and psychosocial functioning until 8 years after Coxiella burnetii infection: An integrative data analysis. PLoS One. 2022 Feb 2;17(2):e0263239. doi: 10.1371/journal.pone.0263239. PMID: 35108330; PMCID: PMC8809529. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0263239 (Full text)

Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae

Summary:

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms.
We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

Source: : Su, Y., Yuan, D., Chen, D.G., Ng, R.H., Wang, K., Choi, J., Li, S., Hong, S., Zhang, R., Xie, J., Kornilov, S.A., Scherler, K., Pavlovitch-Bedzyk, A.J., Dong, S., Lausted, C., Lee, I., Fallen, S., Dai, C.L., Baloni, P., Smith, B., Duvvuri, V.R., Anderson, K.G., Li, J., Yang, F., Duncombe, C.J., McCulloch, D.J., Rostomily, C., Troisch, P., Zhou, J., Mackay, S., DeGottardi, Q., May, D.H, Taniguchi, R., Gittelman, R.M, Klinger, M., Snyder, T.M, Roper, R., Wojciechowska, G., Murray, K., Edmark, R., Evans, S., Jones, L., Zhou, Y., Rowen, L., Liu, R., Chour, W., Algren, H.A, Berrington, W.R., Wallick, J.A., Cochran, R.A., Micikas, M.E., the ISB-Swedish COVID19 Biobanking Unit, Terri Wrin, Petropoulos, C.J., Cole, H.R., Fischer, T.D., Wei, W., Hoon, D.S.B., Price, N.D., Subramanian, N., Hill, J.A, Hadlock, J., Magis, A.T., Ribas, A., Lanier, L.L., Boyd, S.D., Bluestone, J.A., Chu, H., Hood, L., Gottardo, R., Greenberg, P.D., Davis, M.M., Goldman, J.D., Heath, J.R., Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae, Cell (2022), doi: https://doi.org/10.1016/j.cell.2022.01.014. (Full text)

Relationship Between Myocardial Injury During Index Hospitalization for SARS-CoV-2 Infection and Longer-Term Outcomes

Abstract:

Background: Myocardial injury in patients with COVID-19 is associated with increased mortality during index hospitalization; however, the relationship to long-term sequelae of SARS-CoV-2 is unknown. This study assessed the relationship between myocardial injury (high-sensitivity cardiac troponin T level) during index hospitalization for COVID-19 and longer-term outcomes.

Methods and Results: This is a prospective cohort of patients who were hospitalized at a single center between March and May 2020 with SARS-CoV-2. Cardiac biomarkers were systematically collected. Outcomes were adjudicated and stratified on the basis of myocardial injury. The study cohort includes 483 patients who had high-sensitivity cardiac troponin T data during their index hospitalization. During index hospitalization, 91 (18.8%) died, 70 (14.4%) had thrombotic complications, and 126 (25.6%) had cardiovascular complications. By 12 months, 107 (22.2%) died. During index hospitalization, 301 (62.3%) had cardiac injury (high-sensitivity cardiac troponin T≧14 ng/L); these patients had 28.6%, 32.2%, and 33.2% mortality during index hospitalization, at 6 months, and at 12 months, respectively, compared with 4.1%, 4.9%, and 4.9% mortality for those with low-level positive troponin and 0%, 0%, and 0% for those with undetectable troponin. Of 392 (81.2%) patients who survived the index hospitalization, 94 (24%) had at least 1 readmission within 12 months, of whom 61 (65%) had myocardial injury during the index hospitalization. Of 377 (96%) patients who were alive and had follow-up after the index hospitalization, 211 (56%) patients had a documented, detailed clinical assessment at 6 months. A total of 78 of 211 (37.0%) had ongoing COVID-19-related symptoms; 34 of 211 (16.1%) had neurocognitive decline, 8 of 211 (3.8%) had increased supplemental oxygen requirements, and 42 of 211 (19.9%) had worsening functional status.

Conclusions: Myocardial injury during index hospitalization for COVID-19 was associated with increased mortality and may predict who are more likely to have postacute sequelae of COVID-19. Among patients who survived their index hospitalization, the incremental mortality through 12 months was low, even among troponin-positive patients.

Source: Weber B, Siddiqi H, Zhou G, Vieira J, Kim A, Rutherford H, Mitre X, Feeley M, Oganezova K, Varshney AS, Bhatt AS, Nauffal V, Atri DS, Blankstein R, Karlson EW, Di Carli M, Baden LR, Bhatt DL, Woolley AE. Relationship Between Myocardial Injury During Index Hospitalization for SARS-CoV-2 Infection and Longer-Term Outcomes. J Am Heart Assoc. 2022 Jan 4;11(1):e022010. doi: 10.1161/JAHA.121.022010. Epub 2021 Dec 31. PMID: 34970914. https://www.ahajournals.org/doi/10.1161/JAHA.121.022010 (Full text)

Impaired systemic oxygen extraction long after mild COVID-19: potential perioperative implications

Editor:

The extraordinary number of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections world-wide has made it inevitable that patients who have recovered from COVID-19 will present for anaesthesia and surgery. Recent data indicate that in the United States alone, roughly one-third of the population had been infected by the end of 20201. With this in mind, we read with interest the recent correspondence by Silvapulle and colleagues2 underscoring the wide range of symptoms that often follow recovery from COVID-19 and the complexity of considering residual physiologic abnormalities when assessing perioperative risk. They note that patients suffering from “long COVID” have been reported to exhibit demonstrable abnormalities in several biomarkers as well as cardiac, neurologic, haematologic, renal, hepatic, and endocrine impairment. Based on current evidence, the authors suggest that patients previously experiencing mild COVID-19 but without clear evidence of these sequelae can be regarded as having minimal additional perioperative risk. In this context, the relatively young person who suffered mild COVID-19 a year earlier, complains of exertional fatigue but admits to being sedentary and unfit, and has no objective evidence of cardiopulmonary disease or other organ dysfunction will likely raise little concern.

While the morbidity and mortality associated with severe COVID-19 has appropriately received considerable attention, most SARS-CoV-2 infections result in relatively mild, self-limited symptoms not requiring hospitalization. Nonetheless, some of these patients subsequently experience persistent fatigue and reduced exercise capacity that is not attributable to cardiopulmonary impairment diagnosed by conventional means3. Several mechanisms have been proposed including anaemia, deconditioning, and red blood cell abnormalities4. However, many of the studies describing these mechanisms were conducted in patients following hospitalization and/or within a few months of recovery.

A central focus of perioperative management has always been maintenance of systemic oxygen delivery (DO2) and tissue perfusion. Toward this end, research has defined how the fundamental relationships between DO2, tissue oxygen consumption (VO2), and oxygen extraction (EO2) shift from the intraoperative setting where VO2 tends to be reduced, to the postoperative period when VO2 increases5. Although a range of postoperative complications has been linked to suboptimal tissue DO26,  7, the incidence of these complications appears relatively low in relation to the documented incidence of perioperative hypoxaemia8,  9, particularly when considered in light of potential coincidence with other common factors such as anaemia, hypovolaemia, and transient hypotension. A contributing factor may be that, as with most physiological systems, evolutionary pressure has yielded compensatory mechanisms for reduced DO2 to many organs. Under most circumstances, when DO2 is low, VO2 is maintained by augmented EO2 to prevent tissue hypoxia10. This compensatory EO2 reserve persists until limits that vary among tissue beds are reached and VO2 becomes DO2-dependent. Ultimately, in the perioperative setting where alterations in regional VO2/DO2 balance occur with regularity it is probable that this EO2 reserve is working continuously ‘behind the scenes’ for organ protection.

But what if this seemingly occult protective mechanism is impaired? Clinical experience imparts heightened suspicion of tissue vulnerability in patients with defined end-organ impairment or risk factors for reduced functional reserve such as aging, smoking, diabetes mellitus, or hypertension. But how does this affect that relatively young person who admits to being sedentary and unfit but has no objective evidence of cardiopulmonary disease, and whose only other notable medical history is mild COVID-19 a year earlier? A recent report proposed the existence of a specific “long COVID phenotype” with exertional intolerance and dyspnoea despite normal pulmonary function11, raising the question of whether there is more to this patient than meets the eye.

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Source: Paul M. Heerdt, Ben Shelley, Inderjit Singh. Impaired systemic oxygen extraction long after mild COVID-19: potential perioperative implications. Published: December 27, 2021. DOI:https://doi.org/10.1016/j.bja.2021.12.036

Recovery From COVID-19 in Multiple Sclerosis: A Prospective and Longitudinal Cohort Study of the United Kingdom Multiple Sclerosis Register

Abstract:

Background and objectives: To understand the course of recovery from coronavirus disease 2019 (COVID-19) among patients with multiple sclerosis (MS) and to determine its predictors, including patients’ pre-COVID-19 physical and mental health status.

Methods: This prospective and longitudinal cohort study recruited patients with MS who reported COVID-19 from March 17, 2020, to March 19, 2021, as part of the United Kingdom MS Register (UKMSR) COVID-19 study. Participants used online questionnaires to regularly update their COVID-19 symptoms, recovery status, and duration of symptoms for those who fully recovered. Questionnaires were date stamped for estimation of COVID-19 symptom duration for those who had not recovered at their last follow-up. The UKMSR holds demographic and up-to-date clinical data on participants as well as their web-based Expanded Disability Status Scale (web-EDSS) and Hospital Anxiety and Depression Scale (HADS) scores. The association between these factors and recovery from COVID-19 was assessed using multivariable Cox regression analysis.

Results: Of the 7,977 patients with MS who participated in the UKMSR COVID-19 study, 599 reported COVID-19 and prospectively updated their recovery status. Twenty-eight hospitalized participants were excluded. At least 165 participants (29.7%) had long-standing COVID-19 symptoms for ≥4 weeks and 69 (12.4%) for ≥12 weeks. Participants with pre-COVID-19 web-EDSS scores ≥7, participants with probable anxiety and/or depression (HADS scores ≥11) before COVID-19 onset, and women were less likely to report recovery from COVID-19.

Discussion: Patients with MS are affected by postacute sequelae of COVID-19. Preexisting severe neurologic impairment or mental health problems appear to increase this risk. These findings can have implications in tailoring their post-COVID-19 rehabilitation.

Source: Garjani A, Middleton RM, Nicholas R, Evangelou N. Recovery From COVID-19 in Multiple Sclerosis: A Prospective and Longitudinal Cohort Study of the United Kingdom Multiple Sclerosis Register. Neurol Neuroimmunol Neuroinflamm. 2021 Nov 30;9(1):e1118. doi: 10.1212/NXI.0000000000001118. PMID: 34848503; PMCID: PMC8631790. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631790/ (Full text)

Spectrum of SARS-CoV-2-Related Clinical Syndromes in Children: A Year in the Life

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a wide pediatric clinical spectrum. Initial reports suggested that children had milder symptoms compared with adults; then diagnosis of multisystem inflammatory syndrome in children (MIS-C) emerged. We performed a retrospective cohort study of hospitalized patients at a children’s hospital over 1 year. Our objectives were to study the demographic and clinical profile of pediatric SARS-CoV-2-associated diagnoses.

Based on the clinical syndrome, patients were classified into coronavirus disease 2019 (COVID-19; non-MIS-C) and MIS-C cohorts. Among those who tested positive, 67% were symptomatic. MIS-C was diagnosed in 24 patients. Both diagnoses were more frequent in Caucasians. Both cohorts had different symptom profiles.

Inflammatory markers were several-fold higher in MIS-C patients. These patients had critical care needs and longer hospital stays. More COVID-19 patients had respiratory complications, while MIS-C cohort saw cardiovascular involvement. Health care awareness of both syndromes is important for early recognition, diagnosis, and prompt treatment.

Source: Khan M, Dang L, Singh H, Dalrymple A, Miller A, Tanios A. Spectrum of SARS-CoV-2-Related Clinical Syndromes in Children: A Year in the Life. Clin Pediatr (Phila). 2021 Dec 3:99228211064655. doi: 10.1177/00099228211064655. Epub ahead of print. PMID: 34859714. https://pubmed.ncbi.nlm.nih.gov/34859714/

Autonomic dysfunction post-acute COVID-19 infection

Introduction:

SARS-CoV-2 infection which causes the disease COVID-19 is most known for its severe respiratory complications. However, a variety of extrapulmonary effects have since been described, with cardiovascular complications being amongst the most common [ 1 ]. Those who recover from the acute phase of COVID-19 may be left with residual symptoms such as chest pain and dyspnea, resulting in a decreased quality of life and a syndrome sometimes described as “long COVID”[ 2 ].

Recent evidence suggests that survivors with some of these chronic symptoms may have autonomic dysfunction with features of postural orthostatic tachycardia syndrome (POTS) and/or inappropriate sinus tachycardia (IST)3 , 4. POTS is characterized by symptoms that occur with standing, an increase in heart rate of ≥30 beats per minute (or heart rate >120 bpm) when moving from a supine to a standing position, and the absence of orthostatic hypotension[ 5 ]. IST is defined as a sinus heart rate >100 beats per minute at rest without an identifiable cause of sinus tachycardia[ 6 ]. Cardiac manifestations of autonomic dysfunction lie on a wide spectrum and can therefore be classified as either POTS, IST, or other unspecified symptoms such as tachycardia and palpitations without a clear, single underlying pathological mechanism.[ 7 ]

The treatment of these arrhythmias includes nonpharmacologic management, such as increasing salt and fluid intake, as well as the use of oral medications. Beta-blockers or off label use of ivabradine have used reported to be used in both syndromes with the goal of controlling heart rate to reduce the symptoms 8 , 9. Other therapies more common in POTS include fludrocortisone, midodrine, pyridostigmine, and alpha-2 agonists[ 8 ].

There is a need to understand the patient characteristics and risk factors for developing AD as a sequela of COVID-19. Furthermore, there is limited management information specific to patients suffering from AD following COVID-19. It is unclear how treatment of these patients and their prognoses may differ from other cases of POTS or IST. In this study, we investigated a small cohort of patients diagnosed with suspected AD post SARS-CoV-2 infection to elucidate possible risk factors and treatment strategies in this population.

Source: Desai AD, Boursiquot BC, Moore CJ, Gopinathannair R, Waase MP, Rubin GA, Wan EY. Autonomic dysfunction post-acute COVID-19 infection. HeartRhythm Case Rep. 2021 Nov 27. doi: 10.1016/j.hrcr.2021.11.019. Epub ahead of print. PMID: 34868880; PMCID: PMC8626157. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626157/ (Full text)