Covid-19: Middle aged women face greater risk of debilitating long term symptoms

Middle aged women have a higher risk of experiencing a range of debilitating ongoing symptoms, such as fatigue, breathlessness, muscle pain, anxiety, depression, and “brain fog” after hospital treatment for covid-19, suggest the findings of two unpublished studies available as preprints.

Seven in 10 patients admitted to hospital with covid-19 reported “long covid” symptoms an average of five months after discharge in the larger PHOSP-COVID study, and symptoms were more prevalent in women aged 40-60.1 White ethnicity, two or more comorbidities at admission, and receiving invasive ventilation while in hospital increased the risk, but severity of acute covid-19 disease did not seem to affect the likelihood of experiencing long covid symptoms.

Only 29% of the 1077 patients studied felt fully recovered when followed up, on average five months after discharge. Over a quarter had clinically significant symptoms of anxiety and depression, 12% had symptoms of post-traumatic stress disorder, 17% had at least mild cognitive impairment, 46% had lower physical performance than age and sex matched controls, and 20% had a new disability.

Before hospital admission 68% of patients had worked full time, but 18% of these had not returned to work and 19% had had to change their way of working because of longlasting effects.

The researchers grouped patients into four clusters according to the severity of their physical and mental symptoms post-covid: very severe (17% of patients), severe (21%), moderate with cognitive impairment (17%), and mild (46%).

Rachael Evans, National Institute for Health Research clinical scientist at the University of Leicester and a study author, said, “The symptoms are very real, but they don’t have a straightforward relationship with heart and lung damage, or certainly heart and lung damage can’t explain all the symptoms.”

Immune response

A smaller second study, from the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC), found that women under 50 were five times less likely to report feeling recovered, twice as likely to report worse fatigue, seven times more likely to become more breathless, and more likely to have greater disability than men of the same age who had been admitted to hospital with covid-19.2 Disability usually affected memory, mobility, communication, vision, or hearing. More than half of the 327 patients assessed in this study did not feel fully recovered when followed up on average seven months later, and persistent symptoms were reported by 93.3%, with fatigue and breathlessness the most common.

Chris Brightling, professor of respiratory medicine at the University of Leicester and a PHOSP-COVID study researcher, speculated that sex based differences in the immune response may be responsible for the higher prevalence of long covid symptoms in women, noting that autoimmune diseases were more prevalent in women than in men at age 40-60.

“Maybe there’s a difference in the immune response acutely, such that men are more likely to have a more severe condition at the time of the infection,” he told a press conference at the Science Media Centre on 24 March. “It may be that the immune response is different in women, so you then have a continued inflammatory reaction that then leads to a higher likelihood of having long covid.”

Higher levels of C reactive protein, a marker of systemic inflammation, were seen in patients in the most severe long covid symptoms. Brightling said that a number of immune and chronic inflammatory conditions can also cause elevated C reactive protein.

About 450 000 people have been admitted to hospital with covid-19 in the UK, so a “very large” proportion of these would potentially be affected by long covid, he said, adding, “Clearly there’s an even larger number of people that have had covid in the community, and a portion of those will also have long covid.”

Source: Torjesen ICovid-19: Middle aged women face greater risk of debilitating long term symptoms doi:10.1136/bmj.n829 https://www.bmj.com/content/372/bmj.n829 (Full text)

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)

Polio Vaccination and Chronic Fatigue Syndrome

Abstract:

Background: Previous research has suggested that enteroviruses may be implicated in the development and persistence of Chronic Fatigue Syndrome (CFS). One method of investigating this topic has been to use a polio vaccination challenge, and a previous study showed that CFS patients had more shedding than healthy controls. There was no effect of the vaccination on the clinical condition or wellbeing of the CFS patients.

Methods: In the previous study, the control group were more likely to have had a recent booster vaccination. This was controlled in the present study, where 18 CFS patients were randomly assigned to vaccination or placebo conditions. Nine healthy volunteers were also given the polio vaccination.

Results: The results confirmed that vaccination had no negative effects on the CFS group. Although there was more virus shedding in the CFS polio group than in the control polio group, this difference was not significant.

Conclusion: This study confirms that polio vaccination is not contraindicated in CFS patients but could not confirm that they are more susceptible to enterovirus infection.

Source: Smith AP and Thomas M. Polio Vaccination and Chronic Fatigue Syndrome. Asian Journal of Research in Infectious Diseases 8(4): 43-49. https://orca.cardiff.ac.uk/146095/1/poliocfs.pdf (Full text)

Severity of COVID-19: Causes and Consequences — From Obesity to Chronic Fatigue Syndrome

Introduction:

In circumstances of COVID-19 epidemiological uncertainty, the causes and consequences of the disease remain important issues.

The aim of this study was to investigate obesity as a potential predisposition and chronic fatigue syndrome (CFS) as a possible consequence of COVID-19.

The study was conducted in two parts: a theoretical part, in which a literature review was performed, and an empirical part, in which COVID-19 patient survey data were analysed. To identify the main findings regarding the relationship between obesity and COVID-19, the literature review was focused on the investigation of systematic reviews and meta-analyses by three databases – Medline(via  PubMed),  Cochrane  COVID-19  Study  Register,  and  PROSPERO  (International prospective register of systematic reviews).

The patient survey was performed to investigate the relationship between obesity and severity of the disease, as well as the presence of CFS symptoms in COVID-19 patients in Latvia.

The main findings of the literature review showed that obesity increases the risk of hospitalisation, disease severity, clinical complications, poor outcomes, and mortality. The results of the patient survey showed that overweight and obesity were more critical factors for men (males) suffering with COVID-19 than for women (females) in Latvia.

The patient group with obesity caused almost half of all hospitalisations. The research data assumed that CFS  patients  were  not  a  high-risk  group  for  COVID-19,  but  COVID-19  caused  CFS-like symptoms in patients and potentially increased the number of undiagnosed patients.

In the context of further epidemiological uncertainty and the possibility of severe post-viral consequences, preventive measures are becoming increasingly important.

Source: Arāja, Diāna, Rovīte, Vita, Murovska, Modra, Terentjeva, Anna, Vaidere, Diāna, Vecvagare, Katrīne and Vīksna, Ludmila. Severity of COVID-19: Causes and Consequences — From Obesity to Chronic Fatigue Syndrome. Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences., vol.75, no.6, 2021, pp.411-416. https://sciendo.com/article/10.2478/prolas-2021-0061 (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/

Small heart and single coronary artery in a young patient with chronic fatigue syndrome: a case report

Abstract:

Aims: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a clinically defined condition reported mostly in adults, characterized by fatigue and unexplained aspecifical symptoms. Patients with CFS/ME frequently have reduced stroke volume with an inverse relation between cardiac output and post-exertional malaise severity. We describe a rare case of a young man affected by CFS/ME, small heart, and anomalous anatomy of left main coronary artery (LMCA).

Methods and results: A 19-year-old Caucasian male referred to our clinic complaining weakness, lack of concentration, and sleepiness. He suffered by CFS/ME, D hypovitaminosis, inflammatory bowel disease, and exocrine pancreas insufficiency.

Blood tests revealed no pathological findings. Faecal exams documented intestinal dysbiosis and low pancreatic elastase.

He was treated with oxygen-ozone rectal insufflations and probiotics. Physical examination was unremarkable.

Electrocardiogram showed normal sinus rhythm. Echocardiogram revealed reduced diameters of the left ventricle (LV), normal aortic root dimensions and, in a five-chamber apical view, a binary structure that seemed to cross the aorta perpendicularly. Cardiac magnetic resonance (CMR) found reduced LV stroke volume (34 ml/m2) and end-diastolic volume (57 ml/m2) together with reduced end-diastolic wall mass (51 g/m2). Right ventricle volumes were reduced too.

In addition, the exam confirmed the anomalous origin of LMCA stemming from the proximal segment of right coronary artery and following a retro-aortic course.

Mechanism of CFS/ME remains unknown, although various factors have been implicated, including immune activation, chronic viral infection, and emotional disorders.

A considerable number of patients affected by CFS has an anatomically small heart. Small heart syndrome, in fact, may contribute to the onset of CFS/ME.

Previous studies hypothesized that clinical manifestations of CMS/ME were caused by reduced venous return, cardiac output, and heart mass, together with decreased arterial oxygen saturation. Single coronary artery is an uncommon congenital anatomic abnormality identified by a single coronary ostium giving rise to all arteries supplying the heart.

Thus, we reported a rare case of a very young man affected by chronic fatigue syndrome and small heart, investigated not only with echocardiogram but also with CMR, not often used in this clinical setting. More, we found an anomalous origin of LMCA. From literature, it’s not reported any cases of a patient including these three rare conditions (CFS/ME, small heart, and single coronary artery).

Conclusions: This case highlights that CFS/ME together with small heart is a condition possible also in young people. More studies and reports could be necessary to better define the association between cardiac congenital anomalies and CFS/ME.

Source: Cristina Poleggi, Silvia Perfetti, Davide Restelli, Alessia Perna, Rocco Donato, Gianluca Di Bella, 770 Small heart and single coronary artery in a young patient with chronic fatigue syndrome: a case report, European Heart Journal Supplements, Volume 23, Issue Supplement_G, December 2021, suab133.018, https://doi.org/10.1093/eurheartj/suab133.018

Long term predictors of breathlessness, exercise intolerance, chronic fatigue and well-being in hospitalized patients with COVID-19: A cohort study with 4 months median follow-up

Abstract:

Background: Post-acute COVID-19 syndrome (PACS) is an emerging healthcare burden. We therefore aimed to determine predictors of different functional outcomes after hospital discharge in patients with COVID-19.

Methods: An ambidirectional cohort study was conducted between May and July 2020, in which PCR-confirmed COVID-19 patients underwent a standardized telephone assessment between 6 weeks and 6 months post discharge. We excluded patients who died, had a mental illness or failed to respond to two follow-up phone calls. The medical research council (MRC) dyspnea scale, metabolic equivalent of task (MET) score for exercise tolerance, chronic fatigability syndrome (CFS) scale and World Health Organization-five well-being index (WHO-5) for mental health were used to evaluate symptoms at follow-up.

Results: 375 patients were contacted and 153 failed to respond. The median timing for the follow-up assessment was 122 days (IQR, 109-158). On multivariate analyses, female gender, pre-existing lung disease, headache at presentation, intensive care unit (ICU) admission, critical COVID-19 and post-discharge ER visit were predictors of higher MRC scores at follow-up. Female gender, older age >67 years, arterial hypertension and emergency room (ER) visit were associated with lower MET exercise tolerance scores. Female gender, pre-existing lung disease, and ER visit were associated with higher risk of CFS. Age, dyslipidemia, hypertension, pre-existing lung disease and duration of symptoms were negatively associated with WHO-5 score.

Conclusions: Several risk factors were associated with an increased risk of PACS. Hospitalized patients with COVID-19 who are at risk for PACS may benefit from a targeted pre-emptive follow-up and rehabilitation programs.

Source: Tleyjeh IM, Saddik B, Ramakrishnan RK, AlSwaidan N, AlAnazi A, Alhazmi D, Aloufi A, AlSumait F, Berbari EF, Halwani R. Long term predictors of breathlessness, exercise intolerance, chronic fatigue and well-being in hospitalized patients with COVID-19: A cohort study with 4 months median follow-up. J Infect Public Health. 2021 Nov 18;15(1):21-28. doi: 10.1016/j.jiph.2021.11.016. Epub ahead of print. PMID: 34861604; PMCID: PMC8600938. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600938/ (Full text)

Risk Factors Associated with Development and Persistence of Long COVID: A Cross-Sectional Study

Abstract:

Background: Long coronavirus disease (COVID) has been a social concern. Though patient characteristics associated with the
development of long COVID are partially known, those associated with its persistence have not been identified.

Methods: We conducted a cross-sectional questionnaire survey of patients after COVID-19 recovery who visited the National
Center for Global Health and Medicine between February 2020 and March 2021. Demographic and clinical data and
data regarding the presence and duration of long COVID were obtained. We identified factors associated with the
development and persistence of long COVID using multivariate logistic and linear regression analysis, respectively.

Results: We analyzed 457 of 526 responses (response rate, 86.9%). The median age was 47 years, and 378 patients (84.4%)
had mild disease in the acute phase. The number of patients with any symptoms after 6 and 12 months after onset or
diagnosis were 120 (26.3%) and 40 (8.8%), respectively. Women were at risk for development of fatigue (odds ratio
[OR]: 2.03, 95% confidence interval [CI]: 1.31-3.14), dysosmia (OR: 1.91, 95% CI: 1.24-2.93), dysgeusia (OR: 1.56, 95% CI:
1.02-2.39), and hair loss (OR: 3.00, 95% CI: 1.77-5.09) and for persistence of any symptoms (coefficient: 38.0, 95% CI:
13.3-62.8). Younger age and low body mass index were risk factors for developing dysosmia (OR: 0.96, 95% CI: 0.94-
0.98 and OR: 0.94, 95% CI: 0.89-0.99, respectively) and dysgeusia (OR: 0.98, 95% CI: 0.96-1.00 and OR: 0.93, 95% CI:
0.88-0.98, respectively).

Conclusion: We identified risk factors for the development and persistence of long COVID. Many patients suffer from long-term
residual symptoms, even in mild cases.

Source: Yusuke Miyazato, Shinya Tsuzuki, Shinichiro Morioka, Mari Terda, Satoshi Kutsuna, Sho Saito, Yumiko Shimanishi, Kozue Takahashi, Mio Sanada, Masako Akashi, Chika Kuge, Yasuyo Osanai, Keiko Tanaka, Michiyo Suzuki, Kayoko Hayakawa, Norio Ohmagari. Risk Factors Associated with Development and Persistence of Long COVID: A Cross-Sectional Study.
doi: https://doi.org/10.1101/2021.09.22.21263998 https://www.medrxiv.org/content/10.1101/2021.09.22.21263998v1.full-text (Full text)

Risk Factors for Severe ME/CFS

Abstract:

ME/CFS is a serious illness affecting several hundred thousand British people. Some 25% of people with ME/CFS may be severely ill (housebound or bedbound), sometimes for decades. This observational, questionnaire-based study was designed to identify risk factors for severe disease. Exposure to potential risk factors, including familial risks, personality, and early management of the illness, was compared in 124 people with severe disease and 619 mildly ill controls. Severity was determined by self-report and the Barthel (activities of daily living) Index.

Premorbid personality was assessed using the Neuroticism and Conscientiousness domains of the IPIP scale. Analysis was by tests of association and logistic regression. Early management of the illness appeared the most important determinant of severity. Having a mother with ME/CFS was also important. Smoking and personality were not risk factors, neurotic traits being more frequent among the less severely ill. Conscientiousness overall was not related to severity.

Source: Derek Pheby, Lisa Saffron. Risk Factors for Severe ME/CFS. Biology and Medicine, Vol 1 (4): 50-74, 2009. https://meassociation.org.uk/wp-content/uploads/2013/04/Biology-and-Medicine_Published-paper_vol1_4_50-74.pdf  (Full text)

Evolving phenotypes of non-hospitalized patients that indicate long COVID

Abstract:

Background: For some SARS-CoV-2 survivors, recovery from the acute phase of the infection has been grueling with lingering effects. Many of the symptoms characterized as the post-acute sequelae of COVID-19 (PASC) could have multiple causes or are similarly seen in non-COVID patients. Accurate identification of PASC phenotypes will be important to guide future research and help the healthcare system focus its efforts and resources on adequately controlled age- and gender-specific sequelae of a COVID-19 infection.

Methods: In this retrospective electronic health record (EHR) cohort study, we applied a computational framework for knowledge discovery from clinical data, MLHO, to identify phenotypes that positively associate with a past positive reverse transcription-polymerase chain reaction (RT-PCR) test for COVID-19. We evaluated the post-test phenotypes in two temporal windows at 3-6 and 6-9 months after the test and by age and gender. Data from longitudinal diagnosis records stored in EHRs from Mass General Brigham in the Boston Metropolitan Area was used for the analyses. Statistical analyses were performed on data from March 2020 to June 2021. Study participants included over 96 thousand patients who had tested positive or negative for COVID-19 and were not hospitalized.

Results: We identified 33 phenotypes among different age/gender cohorts or time windows that were positively associated with past SARS-CoV-2 infection. All identified phenotypes were newly recorded in patients’ medical records 2 months or longer after a COVID-19 RT-PCR test in non-hospitalized patients regardless of the test result. Among these phenotypes, a new diagnosis record for anosmia and dysgeusia (OR 2.60, 95% CI [1.94-3.46]), alopecia (OR 3.09, 95% CI [2.53-3.76]), chest pain (OR 1.27, 95% CI [1.09-1.48]), chronic fatigue syndrome (OR 2.60, 95% CI [1.22-2.10]), shortness of breath (OR 1.41, 95% CI [1.22-1.64]), pneumonia (OR 1.66, 95% CI [1.28-2.16]), and type 2 diabetes mellitus (OR 1.41, 95% CI [1.22-1.64]) is one of the most significant indicators of a past COVID-19 infection. Additionally, more new phenotypes were found with increased confidence among the cohorts who were younger than 65.

Conclusions: The findings of this study confirm many of the post-COVID-19 symptoms and suggest that a variety of new diagnoses, including new diabetes mellitus and neurological disorder diagnoses, are more common among those with a history of COVID-19 than those without the infection. Additionally, more than 63% of PASC phenotypes were observed in patients under 65 years of age, pointing out the importance of vaccination to minimize the risk of debilitating post-acute sequelae of COVID-19 among younger adults.

Source: Estiri H, Strasser ZH, Brat GA, Semenov YR; Consortium for Characterization of COVID-19 by EHR (4CE), Patel CJ, Murphy SN. Evolving phenotypes of non-hospitalized patients that indicate long COVID. BMC Med. 2021 Sep 27;19(1):249. doi: 10.1186/s12916-021-02115-0. PMID: 34565368. https://pubmed.ncbi.nlm.nih.gov/34565368/