Clinical, sociodemographic and environmental factors impact post-COVID-19 syndrome

Abstract:

Background: Sociodemographic and environmental factors are associated with incidence, severity, and mortality of COVID-19. However, little is known about the role of such factors in persisting symptoms among recovering patients. We designed a cohort study of hospitalized COVID-19 survivors to describe persistent symptoms and identify factors associated with post-COVID-19 syndrome.

Methods: We included patients hospitalized between March to August 2020 who were alive six months after hospitalization. We collected individual and clinical characteristics during hospitalization and at follow-up assessed ten symptoms with standardized scales, 19 yes/no symptoms, a functional status and a quality-of-life scale and performed four clinical tests. We examined individual exposure to greenspace and air pollution and considered neighbourhood´s population density and socioeconomic conditions as contextual factors in multilevel regression analysis.

Results: We included 749 patients with a median follow-up of 200 (IQR = 185-235) days, and 618 (83%) had at least one of the ten symptoms measured with scales. Pain (41%), fatigue (38%) and posttraumatic stress disorder (35%) were the most frequent. COVID-19 severity, comorbidities, BMI, female sex, younger age, and low socioeconomic position were associated with different symptoms. Exposure to ambient air pollution was associated with higher dyspnoea and fatigue scores and lower functional status.

Conclusions: We identified a high frequency of persistent symptoms among COVID-19 survivors that were associated with clinical, sociodemographic, and environmental variables. These findings indicate that most patients recovering from COVID-19 will need post-discharge care, and an additional burden to health care systems, especially in LMICs, should be expected.

Source: Ferreira JC, Moreira TCL, de Araújo AL, Imamura M, Damiano RF, Garcia ML, Sawamura MV, Pinna FR, Guedes BF, Gonçalves FAR, Mancini M, Burdmann EA, da Silva Filho DF, Polizel JL, Bento RF, Rocha V, Nitrini R, de Souza HP, Levin AS, Kallas EG, Forlenza OV, Busatto GF, Batistella LR, de Carvalho CRR, Mauad T, Gouveia N; HCFMUSP COVID-19 Study Group. Clinical, sociodemographic and environmental factors impact post-COVID-19 syndrome. J Glob Health. 2022 Aug 9;12:05029. doi: 10.7189/jogh.12.05029. PMID: 35939273. https://jogh.org/2022/jogh-12-05029 (Full text)

Long COVID Symptomatology After 12 Months and Its Impact on Quality of Life According to Initial Coronavirus Disease 2019 Disease Severity

Abstract:

Background: “Long COVID” is characterized by a variety of symptoms and an important burden for affected people. Our objective was to describe long COVID symptomatology according to initial coronavirus disease 2019 (COVID-19) severity.

Methods: Predi-COVID cohort study participants, recruited at the time of acute COVID-19 infection, completed a detailed 12-month symptom and quality of life questionnaire. Frequencies and co-occurrences of symptoms were assessed.

Results: Among the 289 participants who fully completed the 12-month questionnaire, 59.5% reported at least 1 symptom, with a median of 6 symptoms. Participants with an initial moderate or severe acute illness declared more frequently 1 or more symptoms (82.6% vs 38.6%, P < .001) and had on average 6.8 more symptoms (95% confidence interval, 4.18-9.38) than initially asymptomatic participants who developed symptoms after the acute infection. Overall, 12.5% of the participants could not envisage coping with their symptoms in the long term. Frequently reported symptoms, such as neurological and cardiovascular symptoms, but also less frequent ones such as gastrointestinal symptoms, tended to cluster.

Conclusions: Frequencies and burden of symptoms present 12 months after acute COVID-19 infection increased with the severity of the acute illness. Long COVID likely consists of multiple subcategories rather than a single entity. This work will contribute to the better understanding of long COVID and to the definition of precision health strategies.

Clinical trials registration: NCT04380987.

Source: Fischer A, Zhang L, Elbéji A, Wilmes P, Oustric P, Staub T, Nazarov PV, Ollert M, Fagherazzi G. Long COVID Symptomatology After 12 Months and Its Impact on Quality of Life According to Initial Coronavirus Disease 2019 Disease Severity. Open Forum Infect Dis. 2022 Aug 5;9(8):ofac397. doi: 10.1093/ofid/ofac397. PMID: 35983269; PMCID: PMC9379809. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379809/ (Full text)

A Review of Respiratory Post-Acute Sequelae of COVID-19 (PASC) and the Potential Benefits of Pulmonary Rehabilitation

Abstract:

With the SARS-CoV-2 pandemic continuing into its third year, the number of patients who survive acute COVID-19 infection but go on to develop long-term symptoms is increasing daily. Those individuals who experience one or more of a variety of persistent symptoms post-COVID-19 are now diagnosed with the syndrome called post-acute sequelae of COVID-19 (PASC), often colloquially called “Long COVID.” This article discusses relevant research and current hypotheses regarding the pathophysiology and management of respiratory symptoms of PASC, in order to provide primary care physicians with context for management of this heterogeneous population. We focus on the growing body of research that supports the use of pulmonary rehabilitation for patients with PASC to improve symptoms and quality of life.

Source: Simon M, Simmons JE. A Review of Respiratory Post-Acute Sequelae of COVID-19 (PASC) and the Potential Benefits of Pulmonary Rehabilitation. R I Med J (2013). 2022 Sep 1;105(7):11-15. PMID: 35930484.  https://pubmed.ncbi.nlm.nih.gov/35930484/ http://rimed.org/rimedicaljournal/2022/09/2022-09-11-covid-simon.pdf (Full text available as PDF file)

Cognitive Complications of COVID-19 Infection

Abstract:

SARS-CoV-2 is associated with a post-infectious neurocognitive syndrome characterized by fatigue and deficits in attention, memory, and executive function. As screening cognitive testing generally remains normal, the pathophysiologic basis of these symptoms remains controversial and there is no standardized treatment paradigm.

We present a clinical case demonstrative of typical neurocognitive sequelae of SARS-CoV-2 infection, highlighting medical and social factors that may have contributed to the severity of symptoms. We discuss the pathophysiologic evidence for cognitive “brain fog” following COVID-19 infection as well as lifestyle changes and rehabilitation strategies that may improve recovery. As the benefits of pharmacologic therapy remain unproven, we close with a brief discussion of medication options that might be appropriate targets for future clinical trials in the context of rehabilitative treatment.

Source: Warren S, Drake J, Wu CK. Cognitive Complications of COVID-19 Infection. R I Med J (2013). 2022 Sep 1;105(7):27-30. PMID: 35930487. https://pubmed.ncbi.nlm.nih.gov/35930487/ http://rimed.org/rimedicaljournal/2022/09/2022-09-27-covid-warren.pdf  (Full text available as PDF file)

Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/Post-Acute Sequelae of COVID-19 (PASC)

Abstract:

Background: Fibrin(ogen) amyloid microclots and platelet hyperactivation previously reported as a novel finding in South African patients with the coronavirus 2019 disease (COVID-19) and Long COVID/Post-Acute Sequelae of COVID-19 (PASC), might form a suitable set of foci for the clinical treatment of the symptoms of Long COVID/PASC. A Long COVID/PASC Registry was subsequently established as an online platform where patients can report Long COVID/PASC symptoms and previous comorbidities.

Methods: In this study, we report on the comorbidities and persistent symptoms, using data obtained from 845 South African Long COVID/PASC patients. By using a previously published scoring system for fibrin amyloid microclots and platelet pathology, we also analysed blood samples from 80 patients, and report the presence of significant fibrin amyloid microclots and platelet pathology in all cases.

Results: Hypertension, high cholesterol levels (dyslipidaemia), cardiovascular disease and type 2 diabetes mellitus (T2DM) were found to be the most important comorbidities. The gender balance (70% female) and the most commonly reported Long COVID/PASC symptoms (fatigue, brain fog, loss of concentration and forgetfulness, shortness of breath, as well as joint and muscle pains) were comparable to those reported elsewhere. These findings confirmed that our sample was not atypical. Microclot and platelet pathologies were associated with Long COVID/PASC symptoms that persisted after the recovery from acute COVID-19.

Conclusions: Fibrin amyloid microclots that block capillaries and inhibit the transport of O2 to tissues, accompanied by platelet hyperactivation, provide a ready explanation for the symptoms of Long COVID/PASC. Removal and reversal of these underlying endotheliopathies provide an important treatment option that urgently warrants controlled clinical studies to determine efficacy in patients with a diversity of comorbidities impacting on SARS-CoV-2 infection and COVID-19 severity. We suggest that our platelet and clotting grading system provides a simple and cost-effective diagnostic method for early detection of Long COVID/PASC as a major determinant of effective treatment, including those focusing on reducing clot burden and platelet hyperactivation.

Source: Pretorius E, Venter C, Laubscher GJ, Kotze MJ, Oladejo SO, Watson LR, Rajaratnam K, Watson BW, Kell DB. Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/Post-Acute Sequelae of COVID-19 (PASC). Cardiovasc Diabetol. 2022 Aug 6;21(1):148. doi: 10.1186/s12933-022-01579-5. PMID: 35933347; PMCID: PMC9356426. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356426/ (Full text)

Long COVID: which symptoms can be attributed to SARS-CoV-2 infection?

Comment:

Mortality rates following SARS-CoV-2 infection have decreased as a consequence of public health policies, vaccination, and acute antiviral and anti-inflammatory theBrightling CE, Evans RA. Long COVID: which symptoms can be attributed to SARS-CoV-2 infection? Lancet. 2022 Aug 6;400(10350):411-413. doi: 10.1016/S0140-6736(22)01385-X. PMID: 35933996; PMCID: PMC9352303.rapies. However, in the wake of the pandemic, post-acute sequelae of COVID-19, or long COVID, has emerged: a chronic illness in people who have ongoing multidimensional symptomatology and disability weeks to years after the initial infection. Early reports of long COVID prevalence, summarised in a systematic review examining the frequency and variety of persistent symptoms after COVID-19, found that the median proportion of people who had at least one persistent symptom 60 days or more after diagnosis or at least 30 days after recovery from COVID-19 infection was 73%. However, the estimated prevalence depends on the duration, population, and symptoms used to define long COVID. More recently, community-based studies have suggested a lower prevalence of persistent symptoms; whereas among people who were hospitalised following COVID-19 infection, a high proportion do not fully recover (50–70%).

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Source: Brightling CE, Evans RA. Long COVID: which symptoms can be attributed to SARS-CoV-2 infection? Lancet. 2022 Aug 6;400(10350):411-413. doi: 10.1016/S0140-6736(22)01385-X. PMID: 35933996; PMCID: PMC9352303. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352303/ (Full text)

Herpesvirus and neurological manifestations in patients with severe coronavirus disease

Abstract:

Background: Certain clinical manifestations of coronavirus disease (COVID-19) mimic those associated with human herpesvirus (HHV) infection. In this study, we estimated the prevalence of herpesvirus in patients with COVID-19 and determined if coinfection is associated with poorer outcomes and neurological symptoms.

Methods: We analyzed samples of 53 patients diagnosed with COVID-19. The samples were evaluated for the presence of alphaherpesviruses, betaherpesviruses, and gammaherpesviruses, and the viral loads were quantified using quantitative polymerase chain reaction (qPCR) method.

Results: Among the patients, in 79.2% had detection at least one type of herpesvirus. HHV-6 (47.2%), cytomegalovirus (43.3%), and HHV-7 (39.6%) showed the highest detection rates. Patients with a high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) load were more likely to show herpes simplex virus 1 detection (p = 0.037). Among patients coinfected with SARS-CoV-2 and HHVs, 26.4% showed central nervous system-associated neurological symptoms and herpetic manifestations. A statistically significant association was observed between neurological changes and HHV-6 detection (p = 0.034).

Conclusions: The findings showed a high prevalence of herpesvirus in patients with COVID-19. Furthermore, even though SARS-CoV-2 and HHV coinfection was not associated with poorer outcomes, the findings demonstrated the association between neurological symptoms and HHV-6 detection.

Source: Carneiro VCS, Alves-Leon SV, Sarmento DJS, Coelho WLDCNP, Moreira ODC, Salvio AL, Ramos CHF, Ramos Filho CHF, Marques CAB, da Costa Gonçalves JP, Leon LAA, de Paula VS. Herpesvirus and neurological manifestations in patients with severe coronavirus disease. Virol J. 2022 Jun 8;19(1):101. doi: 10.1186/s12985-022-01828-9. PMID: 35676707; PMCID: PMC9174631. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174631/  (Full text)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is common in post-acute sequelae of SARS-CoV-2 infection (PASC): Results from a post-COVID-19 multidisciplinary clinic

Summary:

Background The global prevalence of PASC is estimated to be present in 0·43 and based on the WHO estimation of 470 million worldwide COVID-19 infections, corresponds to around 200 million people experiencing long COVID symptoms. Despite this, its clinical features are not well defined.

Methods We collected retrospective data from 140 patients with PASC in a post-COVID-19 clinic on demographics, risk factors, illness severity (graded as one-mild to five-severe), functional status, and 29 symptoms and principal component symptoms cluster analysis. The Institute of Medicine (IOM) 2015 criteria were used to determine the ME/CFS phenotype.

Findings The median age was 47 years, 59·0% were female; 49·3% White, 17·2% Hispanic, 14·9% Asian, and 6·7% Black. Only 12·7% required hospitalization. Seventy-two (53·5%) patients had no known comorbid conditions. Forty-five (33·9%) were significantly debilitated. The median duration of symptoms was 285·5 days, and the number of symptoms was 12. The most common symptoms were fatigue (86·5%), post-exertional malaise (82·8%), brain fog (81·2%), unrefreshing sleep (76·7%), and lethargy (74·6%). Forty-three percent fit the criteria for ME/CFS.

Interpretations Most PASC patients evaluated at our clinic had no comorbid condition and were not hospitalized for acute COVID-19. One-third of patients experienced a severe decline in their functional status. About 43% had the ME/CFS subtype.

Source:  H Bonilla, TC Quach, A Tiwari, AE Bonilla, M Miglis, P Yang, L Eggert, H Sharifi, A Horomanski, A Subramanian, L Smirnoff, N Simpson, H Halawi, O Sum-Ping, A Kalinowski, Z Patel, R Shafer, L. Geng. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is common in post-acute sequelae of SARS-CoV-2 infection (PASC): Results from a post-COVID-19 multidisciplinary clinic. medRxiv 2022.08.03.22278363; doi: https://doi.org/10.1101/2022.08.03.22278363

Post-acute COVID-19 syndrome and gut dysbiosis linger beyond 1 year after SARS-CoV-2 clearance

We recently published in Gut to show that gut dysbiosis persisted for at least 6 months in patients with post-acute COVID-19 syndrome (PACS).1 Murine and human studies have also reported microbial alterations associated with different PACS symptoms.2 3 With the pandemic entering its third year, PACS could potentially affect recovered individuals for over 1 year.4 It remains unknown whether PACS-associated gut dysbiosis would also linger for such a long time.

Here, we conducted a prospective study to determine long-term alterations in the gut microbiome of patients with COVID-19 using shotgun metagenomic sequencing (online supplemental materials). A total of 155 patients with COVID-19 in Hong Kong were followed up for an average of 14 months after SARS-CoV-2 viral clearance, and 155 age-matched, sex-matched and body mass index-matched subjects without COVID-19 were recruited as controls. Patients with COVID-19 were infected with the original or earlier variants of SARS-CoV-2 from January 2020 to February 2021. Consistent with previous finding that 76.4% of patients had PACS 6 months after recovery from acute COVID-19,1 we found that the prevalence of PACS was 78.7% at an average of 14-month (IQR 11–18 months) follow-up. The three most common symptoms were fatigue (50.9%), memory problems (44.5%) and difficulty in sleeping (35.5%, figure 1A). Gut dysbiosis in these patients did not fully recover. Both bacteria diversity (p=0.0036, figure 1B) and richness (p=0.00032, figure 1C) of patients with COVID-19 were still significantly lower than that of controls. Principal coordinates analysis of beta diversity also showed distinct separation of patients with COVID-19 from controls (F=8.3822, p<0.001, figure 1D). These observations suggest persistent gut dysbiosis beyond 1 year in patients with PACS

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Source: Su Q, Lau RI, Liu Q, Chan FKL, Ng SC. Post-acute COVID-19 syndrome and gut dysbiosis linger beyond 1 year after SARS-CoV-2 clearance. Gut. 2022 Aug 8:gutjnl-2022-328319. doi: 10.1136/gutjnl-2022-328319. Epub ahead of print. PMID: 35940857. https://gut.bmj.com/content/early/2022/08/08/gutjnl-2022-328319 (Full text)

Persistence of somatic symptoms after COVID-19 in the Netherlands: an observational cohort study

Abstract:

Background: Patients often report various symptoms after recovery from acute COVID-19. Previous studies on post-COVID-19 condition have not corrected for the prevalence and severity of these common symptoms before COVID-19 and in populations without SARS-CoV-2 infection. We aimed to analyse the nature, prevalence, and severity of long-term symptoms related to COVID-19, while correcting for symptoms present before SARS-CoV-2 infection and controlling for the symptom dynamics in the population without infection.

Methods: This study is based on data collected within Lifelines, a multidisciplinary, prospective, population-based, observational cohort study examining the health and health-related behaviours of people living in the north of the Netherlands. All Lifelines participants aged 18 years or older received invitations to digital COVID-19 questionnaires. Longitudinal dynamics of 23 somatic symptoms surrounding COVID-19 diagnoses (due to SARS-CoV-2 alpha [B.1.1.7] variant or previous variants) were assessed using 24 repeated measurements between March 31, 2020, and Aug 2, 2021. Participants with COVID-19 (a positive SARS-CoV-2 test or a physician’s diagnosis of COVID-19) were matched by age, sex, and time to COVID-19-negative controls. We recorded symptom severity before and after COVID-19 in participants with COVID-19 and compared that with matched controls.

Findings: 76 422 participants (mean age 53·7 years [SD 12·9], 46 329 [60·8%] were female) completed a total of 883 973 questionnaires. Of these, 4231 (5·5%) participants had COVID-19 and were matched to 8462 controls. Persistent symptoms in COVID-19-positive participants at 90-150 days after COVID-19 compared with before COVID-19 and compared with matched controls included chest pain, difficulties with breathing, pain when breathing, painful muscles, ageusia or anosmia, tingling extremities, lump in throat, feeling hot and cold alternately, heavy arms or legs, and general tiredness. In 12·7% of patients, these symptoms could be attributed to COVID-19, as 381 (21·4%) of 1782 COVID-19-positive participants versus 361 (8·7%) of 4130 COVID-19-negative controls had at least one of these core symptoms substantially increased to at least moderate severity at 90-150 days after COVID-19 diagnosis or matched timepoint.

Interpretation: To our knowledge, this is the first study to report the nature and prevalence of post-COVID-19 condition, while correcting for individual symptoms present before COVID-19 and the symptom dynamics in the population without SARS-CoV-2 infection during the pandemic. Further research that distinguishes potential mechanisms driving post-COVID-19-related symptomatology is required.

Funding: ZonMw; Dutch Ministry of Health, Welfare, and Sport; Dutch Ministry of Economic Affairs; University Medical Center Groningen, University of Groningen; Provinces of Drenthe, Friesland, and Groningen.

Source: Ballering AV, van Zon SKR, Olde Hartman TC, Rosmalen JGM; Lifelines Corona Research Initiative. Persistence of somatic symptoms after COVID-19 in the Netherlands: an observational cohort study. Lancet. 2022 Aug 6;400(10350):452-461. doi: 10.1016/S0140-6736(22)01214-4. PMID: 35934007. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01214-4/fulltext (Full text)