Left ventricular global longitudinal strain as a parameter of mild myocardial dysfunction in athletes after COVID-19 (preprint)

Background Whether impaired left ventricular (LV) function contributes to persistent cardiopulmonary symptoms or decreased exercise capacity after COVID-19 remains unclear. The aim of this prospective study was to determine differences in LV global longitudinal strain (GLS) between athletes who did not have a history of LV dysfunction but had a positive COVID-19 test (PCAt) and healthy control (CON) athletes and relate them to symptoms during COVID-19. Methods We performed 151 transthoracic echocardiographies in our high-performance laboratory. GLS was determined in four-, two-, and three-chamber views and assessed offline by a blinded investigator in 88 PCAt (35% women) at a median of two months after COVID-19 who trained at least three times per week with more than 20 MET per week and 52 CONs from the German national squad (38% women). Results GLS was significantly lower (GLS -18.53 {+/-}1.94% vs. -19.94{+/-}1.42%, p<0.001) and diastolic function significantly reduced (E/A 1.54{+/-}0.52 vs. 1.66{+/-}0.43, p=0.020; E`l 0.15{+/-}0.04 vs. 0.17{+/-}0.04, p=0.009; E/E'l 5.74{+/-}1.74 vs. 5.22{+/-}1.36, p=0.024) in PCAt. There was no association between GLS and acute symptoms like resting dyspnea, exertional dyspnea during or after COVID-19, palpitations, chest pain or increased resting heart rate. However, there was a trend toward lower GLS in PCAt with subjectively perceived performance limitation (p=0.054). Conclusions In a cohort of athletes at a median two months after COVID-19, significantly lower GLS and diastolic function were observed, suggesting mild myocardial dysfunction. GLS could be used as a screening element during return-to-sport examinations.

Treatment of Long COVID symptoms with triple anticoagulant therapy (preprint)

Background: Fibrin(ogen) amyloid microclots and platelet hyperactivation are key pathological findings in patients with acute COVID-19 infection and also in those with Long COVID/Post-Acute Sequelae of COVID-19 (PASC). These pathologies may represent a suitable target for pharmacological treatment of Long COVID.  Methods: Here we report on the symptoms displayed by a cohort of 91 South African Long COVID patients at baseline and after a clinician-initiated anticoagulant regime was completed. For laboratory analysis, patients provided a blood sample before and after treatment. Fibrinaloid microclot presence was studied by adding thioflavin T to platelet poor plasma (PPP), whilst platelet hyperactivation was studied using two platelet markers- PAC1 and CD62P (P-selectin). The anticoagulant regime included dual antiplatelet therapy (DAPT- Clopidogrel 75mg + Aspirin 75mg) once a day, and a direct oral anticoagulant (DOAC- Apixaban) 5mg twice a day. A proton pump inhibitor (PPI) pantoprazole 40 mg/day was also prescribed for gastric protection. Each of the treated cases reported their main Long COVID symptoms, and whether their symptoms resolved following treatment or not.  Results: In our cohort a most participants did not report any comorbidities before acute COVID-19 infection. Hypertension and dyslipidaemia were the commonest underlying illnesses, whilst the most commonly reported Long COVID symptoms included fatigue, cognitive dysfunction, shortness of breath, and joint and muscle pains. Following completion of treatment, each of the different symptoms resolved in the majority of patients. This was also reflected in the laboratory analysis, where a decrease in the severity of fibrin amyloid microclotting and the degree of platelet pathology was noted. No serious adverse bleeding events were reported.  Conclusions: Fibrin amyloid microclots, platelet hyperactivation/ aggregation, and  widespread endothelialitis inhibit the transport of oxygen at a capillary/cellular level. This provides a ready explanation for the symptoms of Long COVID. By normalizing the failed clotting physiology and reversal of the endothelialitis, triple anticoagulant therapy represents a promising treatment option that appears to be highly efficacious, and warrants controlled clinical studies. We caution that such a regime must only be followed under expert medical supervision in view of the risk of  bleeding.

Pulmonary sequelae at six months in children with SARS-CoV-2 infection: A Single-Centre Study (preprint)

Objective: Pulmonary sequelae post SARS - CoV-2 infection have been reported in adults; however, there is scant literature regarding pulmonary dysfunction following SARS-CoV-2 infection in children. We studied the long term pulmonary sequelae in children who had SARS-CoV-2 infection. Methods: This single center descriptive study conducted in a public sector tertiary care hospital in Northern India, from June, 2020 to October, 2021. We enrolled children aged 7-18 years admitted with SARS-CoV-2 infection and followed them up for 6 months. A detailed interval history was taken and pulmonary function tests were performed after 6 months, using a spirometer. A convenience sample of 40 children was enrolled. There were 21 males and the median (IQR) age was 13 (10.75, 17) years. Results: Thirty percent of children (n=12) had pulmonary function abnormalities, which was of restrictive pattern in all. Children who were underweight had higher odds of developing pulmonary dysfunction following SARS-CoV-2 infection [OR (95% CI) 5.13 (1.19, 22.11); P=0.028]. There were no significant association with age, sex, severity of initial infection and oxygen requirement during the initial infection. Three children had persistence of dyspnea during follow up. Conclusion: This study is the one of the first Indian studies regarding the pulmonary sequelae in children. A possibility of long term sequelae should be considered in children with history of SARS-CoV-2, presenting with suggestive complaints.

Investigating the association of physical and psychological problems with the levels of interleukin-1 and -6 in Covid-19 patients (preprint)

Introduction: The Covid-19 virus spreads at a high rate, exerting many physical, mental and psychological effects on patients. Patients with Covid-19 have been reported to have high levels of interleukin 1 and interleukin 6. Therefore, this study was conducted to determine the association of physical, mental, and psychological problems with the levels of interleukin-1 and − 6 in Covid-19 patients. Methodology: This is cross-sectional descriptive-analytical research on 121 Covid-19 patients selected using simple random sampling method. The patients were hospitalized in university hospitals affiliated to Ahvaz Jundishapur University of Medical Sciences and Amir al-Momenin Hospital. Data collection tools included the Depression Anxiety Stress Scale (DASS), a demographic questionnaire, and a checklist of physical problems. Blood sampling was also done to perform an ELISA test and measure the level of interleukin-1 and − 6. Data were analyzed based on independent t-tests, chi-square, regression, and Pearson's correlation coefficient, using SPSS ver. 22. Results: The average age of the 121 patients participating in this study was 53.31 ± 14.09. A direct and statistically significant correlation was observed between body temperature on the first day and interleukin 1 level. A statistically significant negative correlation was observed between blood oxygen saturation level and interleukin-1 and − 6 on the first, third and fifth days. Shortness of breath and coughing had a statistically significant correlation with the level of interleukin 1 on the third and fifth days. A direct and statistically significant correlation was observed between body temperature on the first, third and fifth days and interleukin 6 level. Coughing on the third and fifth days had a statistically significant relationship with interleukin 6 level. No direct and non-significant statistical correlation was found between depression and stress and the serum level of interleukin 1, but a significant correlation was observed between anxiety and serum level of interleukin 1. Finally, the results showed that depression, anxiety and stress had a direct and statistically significant correlation with the serum level of interleukin 6. Conclusion: Given the relationship between interleukin-1 and − 6 and most physical and psychological problems, level of the inflammatory biomarkers interleukin-1 and − 6 can be used to estimate the severity of physical and psychological symptoms in Covid-19 patients.

Perceptions of state measures and media coverage during the COVID-19 pandemic by people with long COVID - A qualitative interview study in Germany (preprint)

Background Since its outbreak, the COVID-19 pandemic has been discussed in various media channels. In Germany, state measures such as contact restrictions have been implemented to contain the incidence of infection. Nevertheless, there are many people who have been infected with the coronavirus and are affected by persistent symptoms such as fatigue, shortness of breath, or pain. How these people perceive pandemic-related coverage and state measures has not yet been adequately researched. Methods To address this gap, we conducted guided qualitative interviews with 25 adults with long COVID. The interviews were transcribed in terms of content-semantics and analyzed using qualitative content analysis. Results were then compared with other scientific findings. Results The interviews indicated a high approval of restrictive interventions to protect the public from the consequences of the COVID-19 pandemic in this sample. About three-quarters of the participants rated the pandemic containment measures as appropriate. However, twelve of the 25 respondents were dissatisfied with the media coverage of the pandemic and protective measures. Besides inconsistent coverage, the discourse on coronavirus vaccination was specifically criticized. Several participants felt that the coverage of this issue was one-sided or noted a lack of government resolve. Furthermore, respondents criticized the repeal of state measures such as the mask obligation in Germany. Conclusions Overall, a need for more consideration of the concerns of people with long COVID in the public discourse on the pandemic becomes apparent. Part of an adapted communication strategy should be: (1) a transparent and target group-related information transfer on the newest findings and regulations during the COVID-19 pandemic, (2) an increased presence of the topic, long COVID, in society through various media. Additionally, the relevant public bodies should expand their engagement in this field. Moreover, the findings ot this study could be used as a starting point for a debate on the long-term implementation of measures to protect vulnerable populations. Trial registration: The study is registered in the German register for clinical trials (DRKS00026007).

The burden of long COVID: a multinational cohort analysis of Spanish and UK data including SARS-CoV-2 infections, reinfections, and matched contemporaneous test negative controls (preprint)

As limited data was available on the effect of persisting COVID-19 symptoms, we characterised long COVID and identified key symptoms associated with persistent disease. Using primary care data from Spain and UK, we estimated incidence rates of long COVID in the population and among COVID-19 patients over time. Subsequently, we investigated which WHO-listed symptoms were particularly differential for long COVID by comparing their frequency in COVID-19 patients vs matched test-negative controls. Lastly, we compared persistent symptoms after first infections vs. reinfections. Fortunately, the proportion of COVID-19 cases resulting in long COVID declined over the study period.  Risk for altered smell/taste, dyspnoea, and fatigue were consistently higher in long COVID patient vs controls [RR between 5.97-1.09]. All persistent symptoms were less common after reinfection than first infection. More research is needed into the definition of long COVID, and the effect of interventions to minimise the risk and impact of persistent symptoms.

Excess burden of respiratory and abdominal conditions following COVID-19 infections during the ancestral and Delta variant periods in the United States: An EHR-based cohort study from the RECOVER Program (preprint)

Importance The frequency and characteristics of post-acute sequelae of SARS-CoV-2 infection (PASC) may vary by SARS-CoV-2 variant. Objective To characterize PASC-related conditions among individuals likely infected by the ancestral strain in 2020 and individuals likely infected by the Delta variant in 2021. Design Retrospective cohort study of electronic medical record data for approximately 27 million patients from March 1, 2020-November 30, 2021. Setting Healthcare facilities in New York and Florida. Participants Patients who were at least 20 years old and had diagnosis codes that included at least one SARS-CoV-2 viral test during the study period. Exposure Laboratory-confirmed COVID-19 infection, classified by the most common variant prevalent in those regions at the time. Main Outcome(s) and Measure(s) Relative risk (estimated by adjusted hazard ratio [aHR]) and absolute risk difference (estimated by adjusted excess burden) of new conditions, defined as new documentation of symptoms or diagnoses, in persons between 31-180 days after a positive COVID-19 test compared to persons with only negative tests during the 31-180 days after the last negative test. Results We analyzed data from 560,752 patients. The median age was 57 years; 60.3% were female, 20.0% non-Hispanic Black, and 19.6% Hispanic. During the study period, 57,616 patients had a positive SARS-CoV-2 test; 503,136 did not. For infections during the ancestral strain period, pulmonary fibrosis, edema (excess fluid), and inflammation had the largest aHR, comparing those with a positive test to those with a negative test, (aHR 2.32 [95% CI 2.09 2.57]), and dyspnea (shortness of breath) carried the largest excess burden (47.6 more cases per 1,000 persons). For infections during the Delta period, pulmonary embolism had the largest aHR comparing those with a positive test to a negative test (aHR 2.18 [95% CI 1.57, 3.01]), and abdominal pain carried the largest excess burden (85.3 more cases per 1,000 persons). Conclusions and Relevance We documented a substantial relative risk of pulmonary embolism and large absolute risk difference of abdomen-related symptoms after SARS-CoV-2 infection during the Delta variant period. As new SARS-CoV-2 variants emerge, researchers and clinicians should monitor patients for changing symptoms and conditions that develop after infection.

Prevalence of smell, taste and chemesthesis disorders among patients with the Omicron Variant of SARS-CoV-2 in China (preprint)

Many studies have confirmed that chemosensory disorder (including smell, taste and chemesthesis) is one of the symptoms of COVID-19 infection. However, new data indicated that the changes of chemosensory sensation caused by COVID-19 may be different among different populations and COVID-19 variants. At present, there are few studies focusing on the influence of Omicron on qualitative changes and quantitative reductions of chemosensory in China. We conducted a cross-sectional study on COVID-19 Omicron variant patients to investigate the prevalence of chemosensory disorders and their chemosensory function before and during infection by online questionnaire. A total of 1245 patients with COVID-19 completed the study. The prevalence of smell, taste and chemesthesis disorder was 69.2%, 67.7% and 31.4% respectively. Sex, age, smoking and COVID-19-related symptoms such as lack of appetite, dyspnea and fatigue may have association with chemosensory disorders during COVID-19. Self-ratings of chemosensory function revealed that patients experienced a decline in the function of smell, taste and chemesthesis generally. Further studies are needed to combine the data using objective assessment and investigate the factors affecting chemosensory in COVID-19 through longitudinal research.

Exercise tolerance, fatigue, mental health, and employment status at 5 and 12 months following COVID-19 illness in a physically trained population.

Failure to recover following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may have a profound impact on individuals who participate in high-intensity/volume exercise as part of their occupation/recreation. The aim of this study was to describe the longitudinal cardiopulmonary exercise function, fatigue, and mental health status of military-trained individuals (up to 12-mo postinfection) who feel recovered, and those with persistent symptoms from two acute disease severity groups (hospitalized and community-managed), compared with an age-, sex-, and job role-matched control. Eighty-eight participants underwent cardiopulmonary functional tests at baseline (5 mo following acute illness) and 12 mo; 25 hospitalized with persistent symptoms (hospitalized-symptomatic), 6 hospitalized and recovered (hospitalized-recovered); 28 community-managed with persistent symptoms (community-symptomatic); 12 community-managed, now recovered (community-recovered), and 17 controls. Cardiopulmonary exercise function and mental health status were comparable between the 5 and 12-mo follow-up. At 12 mo, symptoms of fatigue (48% and 46%) and shortness of breath (SoB; 52% and 43%) remain high in hospitalized-symptomatic and community-symptomatic groups, respectively. At 12 mo, COVID-19-exposed participants had a reduced capacity for work at anaerobic threshold and at peak exercise levels of deconditioning persist, with many individuals struggling to return to strenuous activity. The prevalence considered "fully fit" at 12 mo was lowest in symptomatic groups (hospitalized-symptomatic, 4%; hospitalized-recovered, 50%; community-symptomatic, 18%; community-recovered, 82%; control, 82%) and 49% of COVID-19-exposed participants remained medically nondeployable within the British Armed Forces. For hospitalized and symptomatic individuals, cardiopulmonary exercise profiles are consistent with impaired metabolic efficiency and deconditioning at 12 mo postacute illness. The long-term deployability status of COVID-19-exposed military personnel is uncertain.NEW & NOTEWORTHY Subjective exercise limiting symptoms such as fatigue and shortness of breath reduce but remain prevalent in symptomatic groups. At 12 mo, COVID-19-exposed individuals still have a reduced capacity for work at the anaerobic threshold (which best predicts sustainable intensity), despite oxygen uptake comparable to controls. The prevalence of COVID-19-exposed individuals considered "medically non-deployable" remains high at 47%.

Hospitalizations and deaths of children and adolescents with Severe Acute Respiratory Infection due to COVID-19 during the epidemiological year of 2020.

This study aimed to analyze the profile of hospitalizations and factors associated with the deaths of children and adolescents with severe acute respiratory infection (SARI) caused by SARS-CoV-2 nationwide. The study comprised 6,843 children and adolescents hospitalized in 2020 who tested positive for COVID-19, based on data from the Influenza Epidemiological Surveillance Information System. Sociodemographic and clinical profiles, hospitalization frequency, lethality and recovery rates were analyzed. The outcome was recovery or death. The 6,843 children and adolescents comprised 1.9% of SARI hospitalized cases (n = 563,051). Of these, 57.7% developed critical SARI and 90% survived. Comorbidities were present in 40.8%, especially asthma, immunodepression, and neurological and cardiovascular diseases. The main symptoms were fever, cough, dyspnea, respiratory distress, and low oxygen saturation. Among those with critical SARI, 91.4% died. There was a higher frequency of children, especially those under five years of age and of mixed ethnicity. The highest hospitalization frequency occurred in the Southeastern and Northeastern regions, the highest recovery rates in the Southeastern and Southern regions, and the highest lethality rates in the Northern and Northeastern regions. Deaths were associated with ages ranging from 12 to 19 and being under one year of age, living in the Northern and Northeastern regions, progression to critical SARI, and having immunosuppression and cardiovascular disease. In contrast, asthma was associated with lower death rates. The frequency of complications and mortality rates caused by SARS-Cov-2 in the pediatric population are relevant, as well as the severity of the epidemic in the social inequality context and the health services' frailty.

Long COVID in Elderly Patients: An Epidemiologic Exploration Using a Medicare Cohort (preprint)

Background: Incidence of long COVID in the elderly is difficult to estimate and can be under-reported. While long COVID is sometimes considered a novel disease, many viral or bacterial infections have been known to cause prolonged illnesses. We postulate that some influenza patients might develop residual symptoms that would satisfy the diagnostic criteria for long COVID, a condition we call "long Flu". In this study, we estimate the incidence of long COVID and long Flu among Medicare patients using the World Health Organization (WHO) consensus definition. We compare the incidence, symptomatology, and healthcare utilization between long COVID and long Flu patients. Methods and Findings: This is a cohort study of Medicare (the U.S. federal health insurance program) beneficiaries over 65. ICD-10-CM codes were used to capture COVID-19, influenza and residual symptoms. Long COVID was identified by a) the designated long COVID-19 code B94.8 (code-based definition), or b) any of 11 symptoms identified in the WHO definition (symptom-based definition), from one to 3 months post infection. A symptom would be excluded if it occurred in the year prior to infection. Long Flu was identified in influenza patients from the combined 2018 and 2019 Flu seasons by the same symptom-based definition for long COVID. Long COVID and long Flu were compared in four outcome measures: a) hospitalization (any cause), b) hospitalization (for long COVID symptom), c) emergency department (ED) visit (for long COVID symptom), and d) number of outpatient encounters (for long COVID symptom), adjusted for age, sex, race, region, Medicare-Medicaid dual eligibility status, prior-year hospitalization, and chronic comorbidities. Among 2,071,532 COVID-19 patients diagnosed between April 2020 and June 2021, symptom-based definition identified long COVID in 16.6% (246,154/1,479,183) and 29.2% (61,631/210,765) of outpatients and inpatients respectively. The designated code gave much lower estimates (outpatients 0.49% (7,213/1,479,183), inpatients 2.6% (5,521/210,765)). Among 933,877 influenza patients, 17.0% (138,951/817,336) of outpatients and 24.6% (18,824/76,390) of inpatients fit the long Flu definition. Long COVID patients had higher incidence of dyspnea, fatigue, palpitations, loss of taste/smell and neurocognitive symptoms compared to long Flu. Long COVID outpatients were more likely to have any-cause hospitalization (31.9% (74,854/234,688) vs. 26.8% (33,140/123,736), odds ratio 1.06 (95% CI 1.05-1.08, p<0.001)), and more outpatient visits than long Flu outpatients (mean 2.9(SD 3.4) vs. 2.5(SD 2.7) visits, incidence rate ratio 1.09 (95% CI 1.08-1.10, p<0.001)). There were less ED visits in long COVID patients, probably because of reduction in ED usage during the pandemic. The main limitation of our study is that the diagnosis of long COVID in is not independently verified. Conclusions: Relying on specific long COVID diagnostic codes results in significant under-reporting. We observed that about 30% of hospitalized COVID-19 patients developed long COVID. In a similar proportion of patients, long COVID-like symptoms (long Flu) can be observed after influenza, but there are notable differences in symptomatology between long COVID and long Flu. The impact of long COVID on healthcare utilization is higher than long Flu.

Comparative admission rates and infection severity of COVID-19 among unvaccinated and vaccinated patients.

Vaccination efforts have limited the burden of the pandemic caused by the coronavirus disease 2019 (COVID-19) with substantial evidence showing reduced hospitalization rates among vaccinated populations. However, few studies have explored correlations between vaccination status and inpatient COVID-19 outcomes. This observational case-control study involved a retrospective chart review of adult patients hospitalized for COVID-19 infection at a medium-sized hospital in Central Michigan between May 1, 2021 and September 30, 2021. Unadjusted analyses involved t-tests and chi-square tests followed by adjusted analyses using binary logistic and linear regression models. Of the 192 screened patients, 171 subjects met the inclusion criteria. Vaccinated patients were significantly older (71.09 vs 57.45, p < 0.001), more likely to identify as white (89.4% vs 66.9%, p = 0.026), and had a lower baseline 10-year survival rate predicted by the Charlson Comorbidity Index (42% vs 69%, p < 0.001) compared to unvaccinated patients. Common symptoms between both groups included shortness of breath (50%), malaise (23%-37%), cough (28%-32%), and fever or chills (25%). Upon matching, adjusted analysis showed significantly higher rates of remdesivir administration to unvaccinated patients (41.3% vs 13.3%, odds ratio (OR): 4.63, 90% confidence interval (CI): 1.98-11.31). Despite higher intensive care unit admission rates among unvaccinated patients (39.1% vs 23.9%, OR: 1.83, 90% CI: 0.74-4.64), this difference did not reach statistical significance. Accordingly, immunization status strongly correlates with patient demographics and differences in inpatient treatment. Larger studies are needed to further assess the vaccine's impact on inpatient outcomes outside of our community.

Characterising patterns of COVID-19 and long COVID symptoms: evidence from nine UK longitudinal studies.

Multiple studies across global populations have established the primary symptoms characterising Coronavirus Disease 2019 (COVID-19) and long COVID. However, as symptoms may also occur in the absence of COVID-19, a lack of appropriate controls has often meant that specificity of symptoms to acute COVID-19 or long COVID, and the extent and length of time for which they are elevated after COVID-19, could not be examined. We analysed individual symptom prevalences and characterised patterns of COVID-19 and long COVID symptoms across nine UK longitudinal studies, totalling over 42,000 participants. Conducting latent class analyses separately in three groups ('no COVID-19', 'COVID-19 in last 12 weeks', 'COVID-19 > 12 weeks ago'), the data did not support the presence of more than two distinct symptom patterns, representing high and low symptom burden, in each group. Comparing the high symptom burden classes between the 'COVID-19 in last 12 weeks' and 'no COVID-19' groups we identified symptoms characteristic of acute COVID-19, including loss of taste and smell, fatigue, cough, shortness of breath and muscle pains or aches. Comparing the high symptom burden classes between the 'COVID-19 > 12 weeks ago' and 'no COVID-19' groups we identified symptoms characteristic of long COVID, including fatigue, shortness of breath, muscle pain or aches, difficulty concentrating and chest tightness. The identified symptom patterns among individuals with COVID-19 > 12 weeks ago were strongly associated with self-reported length of time unable to function as normal due to COVID-19 symptoms, suggesting that the symptom pattern identified corresponds to long COVID. Building the evidence base regarding typical long COVID symptoms will improve diagnosis of this condition and the ability to elicit underlying biological mechanisms, leading to better patient access to treatment and services.

Effects of a home-based pulmonary rehabilitation program with and without telecoaching on health-related outcomes in COVID-19 survivors: a randomized controlled clinical study.

OBJECTIVE: To compare the effects of a home-based pulmonary rehabilitation (PR) program with and without telecoaching on health-related outcomes in COVID-19 survivors. METHODS: A total of 42 COVID-19 patients who completed medical treatment were randomly divided into two groups: the study (telecoaching) group (n = 21) and the control (no telecoaching) group (n = 21). Both groups participated in an 8-week home-based PR program including education, breathing exercises, strength training, and regular walking. The study group received phone calls from a physiotherapist once a week. Both groups of patients were assessed before and after the program by means of the following: pulmonary function tests; the modified Medical Research Council dyspnea scale; the six-minute walk test; extremity muscle strength measurement; the Saint George's Respiratory Questionnaire (to assess disease-related quality of life); the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36, to assess overall quality of life); and the Hospital Anxiety and Depression Scale. RESULTS: In both groups, there were significant improvements in the following: FVC; the six-minute walk distance; right and left deltoid muscle strength; Saint George's Respiratory Questionnaire activity domain, impact domain, and total scores; and SF-36 social functioning, role-physical, role-emotional, and bodily pain domain scores (p < 0.05). Decreases in daily-life dyspnea, exertional dyspnea, and exertional fatigue were significant in the study group (p < 0.05), and the improvement in SF-36 social functioning domain scores was greater in the study group (p < 0.05). CONCLUSIONS: A home-based PR program with telecoaching increases social functioning and decreases daily-life dyspnea, exertional dyspnea, and exertional fatigue in COVID-19 survivors in comparison with a home-based PR program without telecoaching.

The effect of COVID rehabilitation for ongoing symptoms Post HOSPitalisation with COVID-19 (PHOSP-R): protocol for a randomised parallel group controlled trial on behalf of the PHOSP consortium.

INTRODUCTION: Many adults hospitalised with COVID-19 have persistent symptoms such as fatigue, breathlessness and brain fog that limit day-to-day activities. These symptoms can last over 2 years. Whilst there is limited controlled studies on interventions that can support those with ongoing symptoms, there has been some promise in rehabilitation interventions in improving function and symptoms either using face-to-face or digital methods, but evidence remains limited and these studies often lack a control group. METHODS AND ANALYSIS: This is a nested single-blind, parallel group, randomised control trial with embedded qualitative evaluation comparing rehabilitation (face-to-face or digital) to usual care and conducted within the PHOSP-COVID study. The aim of this study is to determine the effectiveness of rehabilitation interventions on exercise capacity, quality of life and symptoms such as breathlessness and fatigue. The primary outcome is the Incremental Shuttle Walking Test following the eight week intervention phase. Secondary outcomes include measures of function, strength and subjective assessment of symptoms. Blood inflammatory markers and muscle biopsies are an exploratory outcome. The interventions last eight weeks and combine symptom-titrated exercise therapy, symptom management and education delivered either in a face-to-face setting or through a digital platform ( www.yourcovidrecovery.nhs.uk ). The proposed sample size is 159 participants, and data will be intention-to-treat analyses comparing rehabilitation (face-to-face or digital) to usual care. ETHICS AND DISSEMINATION: Ethical approval was gained as part of the PHOSP-COVID study by Yorkshire and the Humber Leeds West Research NHS Ethics Committee, and the study was prospectively registered on the ISRCTN trial registry (ISRCTN13293865). Results will be disseminated to stakeholders, including patients and members of the public, and published in appropriate journals. Strengths and limitations of this study • This protocol utilises two interventions to support those with ongoing symptoms of COVID-19 • This is a two-centre parallel-group randomised controlled trial • The protocol has been supported by patient and public involvement groups who identified treatments of symptoms and activity limitation as a top priority.

Correlates of symptomatic remission among individuals with post-COVID-19 condition (preprint)

Importance: Post-COVID-19 condition (PCC), or long COVID, has become prevalent. The course of this syndrome, and likelihood of remission, has not been characterized. Objective: To quantify the rates of remission of PCC, and the sociodemographic features associated with remission. Design: 16 waves of a 50-state U.S. non-probability internet survey conducted between August 2020 and November 2022 Setting: Population-based Participants: Survey respondents age 18 and older Main Outcome and Measure: PCC remission, defined as reporting full recovery from COVID-19 symptoms among individuals who on a prior survey wave reported experiencing continued COVID-19 symptoms beyond 2 months after the initial month of symptoms. Results: Among 423 survey respondents reporting continued symptoms more than 2 months after acute test-confirmed COVID-19 illness, who then completed at least 1 subsequent survey, mean age was 53.7 (SD 13.6) years; 293 (69%) identified as women, and 130 (31%) as men; 9 (2%) identified as Asian, 29 (7%) as Black, 13 (3%) as Hispanic, 15 (4%) as another category including Native American or Pacific Islander, and the remaining 357 (84%) as White. Overall, 131/423 (31%) of those who completed a subsequent survey reported no longer being symptomatic. In Cox regression models, male gender, younger age, lesser impact of PCC symptoms at initial visit, and infection when the Omicron strain predominated were all statistically significantly associated with greater likelihood of remission; presence of brain fog or shortness of breath were associated with lesser likelihood of remission. Conclusions and Relevance: A minority of individuals reported remission of PCC symptoms, highlighting the importance of efforts to identify treatments for this syndrome or means of preventing it.

Clinical manifestations of COVID-19 versus other upper respiratory tract infections in pediatric patients.

OBJECTIVES: To explore the differences between COVID-19 and upper respiratory tract infections (URTI) in the pediatric population, emphasizing smell and taste disturbances. METHODS: A case-control study included 468 patients, 234 with COVID-19 (cases) and 234 with URTI (controls) at a tertiary hospital, Riyadh, Saudi Arabia, from 2020-2021. Patients with bacterial URTI, lower tract respiratory infections, and speech or developmental delays were excluded. Statistical analysis was carried out using Statistical Analysis System, 9.2 version. A p-value of ≤0.05 was considered significant. RESULTS: The male-to-female ratio was almost equal, with a mean age of 9.90±2.34. Multivariable logistic regression analysis showed that a change in taste significantly increases the probability of COVID-19 by 21.98 times. On the other hand, sore throat (81.5%), dyspnea (63.5%), nasal obstruction (72.7%), and otalgia significantly (74.8%) decrease the likelihood of COVID-19. CONCLUSION: Taste disturbances increase the probability of COVID-19 infections, whereas sore throat, dyspnea, nasal obstruction, and otalgia increase the likelihood of other URTIs. The described differences might aid physicians in their differential diagnosis and treatment during the pandemic.

Evaluation of long-term sequelae by cardiopulmonary exercise testing 12 months after hospitalization for severe COVID-19.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is an important clinical tool that provides a global assessment of the respiratory, circulatory and metabolic responses to exercise which are not adequately reflected through the measurement of individual organ system function at rest. In the context of critical COVID-19, CPET is an ideal approach for assessing long term sequelae. METHODS: In this prospective single-center study, we performed CPET 12 months after symptom onset in 60 patients that had required intensive care unit treatment for a severe COVID-19 infection. Lung function at rest and chest computed tomography (CT) scan were also performed. RESULTS: Twelve months after severe COVID-19 pneumonia, dyspnea was the most frequently reported symptom although only a minority of patients had impaired respiratory function at rest. Mild ground-glass opacities, reticulations and bronchiectasis were the most common CT scan abnormalities. The majority of the patients (80%) had a peak O2 uptake (V'O2) considered within normal limits (median peak predicted O2 uptake (V'O2) of 98% [87.2-106.3]). Length of ICU stay remained an independent predictor of V'O2. More than half of the patients with a normal peak predicted V'O2 showed ventilatory inefficiency during exercise with an abnormal increase of physiological dead space ventilation (VD/Vt) (median VD/VT of 0.27 [0.21-0.32] at anaerobic threshold (AT) and 0.29 [0.25-0.34] at peak) and a widened median peak alveolar-arterial gradient for O2 (35.2 mmHg [31.2-44.8]. Peak PetCO2 was significantly lower in subjects with an abnormal increase of VD/Vt (p = 0.001). Impairments were more pronounced in patients with dyspnea. Peak VD/Vt values were positively correlated with peak D-Dimer plasma concentrations from blood samples collected during ICU stay (r2 = 0.12; p = 0.02) and to predicted diffusion capacity of the lung for carbon monoxide (DLCO) (r2 = - 0.15; p = 0.01). CONCLUSIONS: Twelve months after severe COVID-19 pneumonia, most of the patients had a peak V'O2 considered within normal limits but showed ventilatory inefficiency during exercise with increased dead space ventilation that was more pronounced in patients with persistent dyspnea. TRIAL REGISTRATION: NCT04519320 (19/08/2020).

Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study.

OBJECTIVES: To determine the clinical sequelae of long covid for a year after infection in patients with mild disease and to evaluate its association with age, sex, SARS-CoV-2 variants, and vaccination status. DESIGN: Retrospective nationwide cohort study. SETTING: Electronic medical records from an Israeli nationwide healthcare organisation. POPULATION: 1 913 234 Maccabi Healthcare Services members of all ages who did a polymerase chain reaction test for SARS-CoV-2 between 1 March 2020 and 1 October 2021. MAIN OUTCOME MEASURES: Risk of an evidence based list of 70 reported long covid outcomes in unvaccinated patients infected with SARS-CoV-2 matched to uninfected people, adjusted for age and sex and stratified by SARS-CoV-2 variants, and risk in patients with a breakthrough SARS-CoV-2 infection compared with unvaccinated infected controls. Risks were compared using hazard ratios and risk differences per 10 000 patients measured during the early (30-180 days) and late (180-360 days) time periods after infection. RESULTS: Covid-19 infection was significantly associated with increased risks in early and late periods for anosmia and dysgeusia (hazard ratio 4.59 (95% confidence interval 3.63 to 5.80), risk difference 19.6 (95% confidence interval 16.9 to 22.4) in early period; 2.96 (2.29 to 3.82), 11.0 (8.5 to 13.6) in late period), cognitive impairment (1.85 (1.58 to 2.17), 12.8, (9.6 to 16.1); 1.69 (1.45 to 1.96), 13.3 (9.4 to 17.3)), dyspnoea (1.79 (1.68 to 1.90), 85.7 (76.9 to 94.5); 1.30 (1.22 to 1.38), 35.4 (26.3 to 44.6)), weakness (1.78 (1.69 to 1.88), 108.5, 98.4 to 118.6; 1.30 (1.22 to 1.37), 50.2 (39.4 to 61.1)), and palpitations (1.49 (1.35 to 1.64), 22.1 (16.8 to 27.4); 1.16 (1.05 to 1.27), 8.3 (2.4 to 14.1)) and with significant but lower excess risk for streptococcal tonsillitis and dizziness. Hair loss, chest pain, cough, myalgia, and respiratory disorders were significantly increased only during the early phase. Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period. Findings remained consistent across SARS-CoV-2 variants. Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnoea and similar risk for other outcomes compared with unvaccinated infected patients. CONCLUSIONS: This nationwide study suggests that patients with mild covid-19 are at risk for a small number of health outcomes, most of which are resolved within a year from diagnosis.

Clinical and chest computed tomography features associated with severe Chlamydia psittaci pneumonia diagnosed by metagenomic next-generation sequencing: A multicenter, retrospective, observational study.

Chlamydia psittaci pneumonia is a rare disease with varying clinical presentations. Here, we aimed to investigate the clinical and chest computed tomography (CT) features of severe psittacosis pneumonia. Clinical data of 35 patients diagnosed with psittacosis pneumonia were retrospectively analyzed using metagenomic next-generation sequencing. The patients were classified into severe (n = 20) and non-severe (n = 15) groups. The median age of patients was 54 years, and 27 patients (77.1%) had a definite history of bird contact. Severe patients had more underlying comorbidities and were more prone to dyspnea and consciousness disorders than non-severe patients. The neutrophil count and D-dimer, lactate dehydrogenase, interleukin (IL)-2, IL-6, and IL-10 levels were higher, whereas the lymphocyte, CD3 + T cell, and CD4 + T cell counts, CD4+/CD8 + T cell ratio, and albumin level were substantially lower in severe patients than in non-severe patients. Chest CT findings of severe patients revealed large areas of pulmonary consolidation, and ground-glass opacities were observed in some patients, with a higher risk of involving multiple lobes of the lungs and pleural effusion. One patient died of multiple organ failure, whereas the condition of the other 34 patients improved, and they were discharged from the hospital. Patients with severe psittacosis pneumonia often have underlying comorbidities and are prone to developing dyspnea, consciousness disorder, and lesions in both lungs. Serum D-dimer, IL-2, IL-6, and IL-10 levels and lymphocyte, CD3 + T cell, and CD4 + T cell counts are associated with disease severity.