Risk of post-acute sequelae of SARS-CoV-2 infection associated with pre-coronavirus disease obstructive sleep apnea diagnoses: an electronic health record-based analysis from the RECOVER initiative.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) has been associated with more severe acute coronavirus disease-2019 (COVID-19) outcomes. We assessed OSA as a potential risk factor for Post-Acute Sequelae of SARS-CoV-2 (PASC). METHODS: We assessed the impact of preexisting OSA on the risk for probable PASC in adults and children using electronic health record data from multiple research networks. Three research networks within the REsearching COVID to Enhance Recovery initiative (PCORnet Adult, PCORnet Pediatric, and the National COVID Cohort Collaborative [N3C]) employed a harmonized analytic approach to examine the risk of probable PASC in COVID-19-positive patients with and without a diagnosis of OSA prior to pandemic onset. Unadjusted odds ratios (ORs) were calculated as well as ORs adjusted for age group, sex, race/ethnicity, hospitalization status, obesity, and preexisting comorbidities. RESULTS: Across networks, the unadjusted OR for probable PASC associated with a preexisting OSA diagnosis in adults and children ranged from 1.41 to 3.93. Adjusted analyses found an attenuated association that remained significant among adults only. Multiple sensitivity analyses with expanded inclusion criteria and covariates yielded results consistent with the primary analysis. CONCLUSIONS: Adults with preexisting OSA were found to have significantly elevated odds of probable PASC. This finding was consistent across data sources, approaches for identifying COVID-19-positive patients, and definitions of PASC. Patients with OSA may be at elevated risk for PASC after SARS-CoV-2 infection and should be monitored for post-acute sequelae.

Pooled Prevalence of Long COVID-19 Symptoms at 12 Months and Above Follow-Up Period: A Systematic Review and Meta-Analysis.

Current data suggests that coronavirus disease 2019 (COVID-19) survivors experience long-lasting problems. It is not yet understood how long these symptoms last. The goal of this study was to compile all the data that was currently available to evaluate COVID-19's long-term effects at 12 months and above. We looked for studies published by December 15, 2022, in PubMed and Embase that discussed follow-up findings for COVID-19 survivors who had been alive for at least a year. A random-effect model was carried out to determine the combined prevalence of different long-COVID symptoms. The Joanna Briggs Institute tool was used to assess the risk of bias for the included studies, and the I2 statistics were used to evaluate the heterogeneity. After reviewing 3,209 studies, 46 were deemed admissible, with an aggregate COVID-19 population of 17976. At 12 months and above, 57% of patients reported a minimum of one symptom, and the five most prevalent symptoms were: dyspnea on exertion (34%, 95% CI 0.2; 0.94); difficulty in concentration (32%, 95% CI 0.16; 0.52); fatigue (31%, 95% CI 0.22; 0.40); frailty (31%, 95% CI 0.06; 0.78); and arthromyalgia (28%, 95% CI 0.09; 0.6). The findings of the present study showed that at 12 months and beyond, a sizable fraction of COVID-19 survivors still have lasting symptoms that impair several body systems. Long-COVID patients require an urgent understanding of pathophysiological processes and the development of tailored treatments.

Subacute thyroiditis following COVID-19: A systematic review.

Background: Subacute thyroiditis (SAT) is a self-limiting thyroid inflammatory disease occurring specifically after upper respiratory tract infections. Since COVID-19 is a respiratory disease leading to multi-organ involvements, we aimed to systematically review the literature regarding SAT secondary to COVID-19. Methods: We searched Scopus, PubMed/MEDLINE, Cochrane, Web of Science, ProQuest, and LitCovid databases using the terms "subacute thyroiditis" and "COVID-19" and their synonyms from inception to November 3, 2022. We included the original articles of the patients with SAT secondary to COVID-19. Studies reporting SAT secondary to COVID-19 vaccination or SAT symptoms' manifestation before the COVID-19 infection were not included. Results: Totally, 820 articles were retained. Having removed the duplicates, 250 articles remained, out of which 43 articles (40 case reports and three case series) with a total of 100 patients, were eventually selected. The patients aged 18-85 years (Mean: 42.70, SD: 11.85) and 68 (68%) were women. The time from the onset of COVID-19 to the onset of SAT symptoms varied from zero to 168 days (Mean: 28.31, SD: 36.92). The most common symptoms of SAT were neck pain in 69 patients (69%), fever in 54 (54%), fatigue and weakness in 34 (34%), and persistent palpitations in 31 (31%). The most common ultrasonographic findings were hypoechoic regions in 73 (79%), enlarged thyroid in 46 (50%), and changes in thyroid vascularity in 14 (15%). Thirty-one patients (31%) were hospitalized, and 68 (68%) were treated as outpatients. Corticosteroids were the preferred treatment in both the inpatient and outpatient settings (25 inpatients (81%) and 44 outpatients (65%)). Other preferred treatments were nonsteroidal anti-inflammatory drugs (nine inpatients (29%) and 17 outpatients (25%)) and beta-blockers (four inpatients (13%) and seven outpatients (10%)). After a mean duration of 61.59 days (SD: 67.07), 21 patients (23%) developed hypothyroidism and thus, levothyroxine-based treatment was used in six of these patients and the rest of these patients did not receive levothyroxine. Conclusion: SAT secondary to COVID-19 seems to manifest almost similarly to the conventional SAT. However, except for the case reports and case series, lack of studies has limited the quality of the data at hand.

Determining the time of maximum risk of death and associated factors in patients with COVID-19 in the hospital and after discharge

Due to the rather specific course of COVID-19, the question of what day after the start of hospitalization should be expected to be the maximum risk of death in patients both during hospitalization and after discharge is relevant. Aim. The aim of the study was to determine the time of maximum risk of death during hospitalization of patients with COVID-19 as well as after their discharge from the hospital. Methodology and Research Methods. A total of 2, 410 patients hospitalized with a diagnosis of COVID-19 were retrospectively studied. Inhospital 28-day mortality rate was 131 patients, and 28-day mortality rate after discharge from the hospital was 9. The accelerated failure time model (AFT) was used to determine the time of maximum risk of death in patients with COVID-19 after hospitalization as well as after discharge from the hospital during the period up to 28 days. Results. Without taking into account the influence of pathological values of other risk factors, lethal outcomes in patients occurred on days 9-11 after admission to hospital. Age over 60 years and the elevated levels of D-dimer, glucose, urea, creatinine, AST, and C-reactive protein were the risk factors (p < 0.01) that shortened the time to death, except for total protein, which lengthened this period. The maximum risk of death in patients after discharge from the hospital occurred on days 13-25, and an increase in creatinine and a decrease in INR were associated with a shorter time to death. Conclusion. The periods of maximum risk of death as well as the factors affecting these periods in patients with COVID-19 were determined for both hospital stay (days 9-11) and time after discharge from hospital (days 13-25). © 2022 Tomsk State University. All rights reserved.

Pulmonary Function Test as a Diagnostic Tool for Post-COVID-19 Effects.

COVID-19-infected survivors are reporting persistent anomalies upon hospital discharge. After one year, a sizable percentage of COVID-19 survivors still have persistent symptoms affecting different bodily systems. Evidence suggests that the lungs are the most affected organs by COVID-19. It may also cause corollary and other medical issues. The literature on preceding COVID-19 infections reviews that patients may also experience chronic impairment in breathing characteristics after discharge. The outcome of COVID-19 may remain for weeks to months after the initial recovery. Our goal is to determine the superiority of the restrictive pattern, obstructive pattern, and adjusted diffusion in patients post-COVID-19 contamination and to explain the distinctive opinions of breathing characteristics used with those patients. Therefore, lung function tests were measured post-discharge for three to 12 months. According to estimates, 80% of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-infected patients experienced one or more chronic symptoms. Multidisciplinary teams are required to develop preventive measures, rehabilitation methods, and scientific control plans with a completely patient-centered attitude for long-term COVID-19 care. Clarifying the pathophysiologic mechanisms, creating and testing specific interventions, and treating patients with long-term COVID-19 are urgently needed. The goal of this review is to locate research evaluating COVID-19's long-term effects. A person who has suffered from COVID-19 in the past showed changes in their pulmonary function test. So, we have to notice the changes and recovery from post-COVID-19 effects. COVID-19 survivors were observed in an eventual observational study and continuously examined three, six, and 12 months after having COVID-19 infections. We evaluated the clinical features and concentrations of circulating pulmonary epithelial and endothelial markers in COVID-19 survivors with normal or lower diffusion capacity for carbon monoxide (DLCO) six months after discharge to analyze risk factors and underlying pathophysiology.

Leveraging Serologic Testing to Identify Children at Risk For Post-Acute Sequelae of SARS-CoV-2 Infection: An Electronic Health Record-Based Cohort Study from the RECOVER Program.

Using an electronic health record-based algorithm, we identified children with Coronavirus disease 2019 (COVID-19) based exclusively on serologic testing between March 2020 and April 2022. Compared with the 131 537 polymerase chain reaction-positive children, the 2714 serology-positive children were more likely to be inpatients (24% vs 2%), to have a chronic condition (37% vs 24%), and to have a diagnosis of multisystem inflammatory syndrome in children (23% vs <1%). Identification of children who could have been asymptomatic or paucisymptomatic and not tested is critical to define the burden of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection in children.

Cardiac Autonomic Function in Long COVID-19 Using Heart Rate Variability: An Observational Cross-Sectional Study.

BACKGROUND: Heart rate variability is a non-invasive, measurable, and established autonomic nervous system test. Long-term COVID-19 sequelae are unclear; however, acute symptoms have been studied. OBJECTIVES: To determine autonomic cardiac differences between long COVID-19 patients and healthy controls and evaluate associations among symptoms, comorbidities, and laboratory findings. METHODS: This single-center study included long COVID-19 patients and healthy controls. The heart rate variability (HRV), a quantitative marker of autonomic activity, was monitored for 24 h using an ambulatory electrocardiogram system. HRV indices were compared between case and control groups. Symptom frequency and inflammatory markers were evaluated. A significant statistical level of 5% (p-value 0.05) was adopted. RESULTS: A total of 47 long COVID-19 patients were compared to 42 healthy controls. Patients averaged 43.8 (SD14.8) years old, and 60.3% were female. In total, 52.5% of patients had moderate illness. Post-exercise dyspnea was most common (71.6%), and 53.2% lacked comorbidities. CNP, D-dimer, and CRP levels were elevated (p-values of 0.0098, 0.0023, and 0.0015, respectively). The control group had greater SDNN24 and SDANNI (OR = 0.98 (0.97 to 0.99; p = 0.01)). Increased low-frequency (LF) indices in COVID-19 patients (OR = 1.002 (1.0001 to 1.004; p = 0.030)) and high-frequency (HF) indices in the control group (OR = 0.987 (0.98 to 0.995; p = 0.001)) were also associated. CONCLUSIONS: Patients with long COVID-19 had lower HF values than healthy individuals. These variations are associated with increased parasympathetic activity, which may be related to long COVID-19 symptoms and inflammatory laboratory findings.

Diabetes mellitus and the risk of post-acute COVID-19 hospitalizations-a nationwide cohort study.

AIMS: This cohort study, based on Danish health registers, examined the post-acute consequences of hospitalization for COVID-19 in patients with diabetes. METHODS: The study population comprised all Danish citizens (≥18 years old) who had diabetes when the pandemic started. A patient was exposed if he/she had a hospitalization with COVID-19 after 1 March 2020. A patient was unexposed when he/she was not hospitalized with COVID-19 between 1 March 2020 and the end of follow-up (4 January 2022), or the first registered event of interest. The outcomes included post-COVID-19 hospitalizations and death. We used a Cox proportional hazards model with time varying exposure estimating the hazards ratio (HR) to analyze if the hazard for an outcome of interest was impacted by being hospitalized with COVID-19. RESULTS: In patients with type 1 diabetes, 101 were hospitalized with COVID-19, and 25,459 were not. We did not have sufficient statistical power to identify differences in risk for those with type 1 diabetes. In type 2 diabetes, 1515 were hospitalized with COVID-19, and 95,887 were not. The adjusted HRs of post-acute hospitalization for respiratory diseases and infections were 1.71 (95% CI 1.45-2.03) and 1.87 (95% CI 1.61-2.18), respectively. The HR of death was 2.05 (95% CI 1.73-2.43). Patients with uncertain type had results similar to those with type 2 diabetes. CONCLUSIONS/INTERPRETATION: In type 2 diabetes and diabetes of uncertain type, hospitalization with COVID-19 was associated with an increased risk of post-acute hospitalization for respiratory diseases, infections and death.

Physiological discrimination and correlation between olfactory and gustatory dysfunction in long-term COVID-19.

The spread of the SARS-CoV-2 virus produces a new disease termed COVID-19, the underlying physiological mechanisms of which are still being understood. Characteristic of the infection is the compromising of taste and smell. There is a persistent need to discriminate the dysfunctions and correlation between taste and smell, which are probably epiphenomena of other concealed conditions. Anosmic and ageusic long-term COVID-19 patients were re-evaluated after 1 year using a Volabolomic approach with an e-nose recording system coupled with olfactometric and gustometric tests. Here a range of sensory arrangements was found, from normal taste and smell to complete losses. The following patterns of olfactory threshold (OT)-taste threshold-olfactory uni- and cross-modal perception were found anosmia-severe hypogeusia-anosmia; hyposmia-hypogeusia-severe hyposmia; normosmia-ageusia-hyposmia; severe hyposmia -normogeusia-normosmia. There is a strong correlation between OT and olfactory uni- and cross-modal perception, a moderate correlation between olfactory and taste threshold and no correlation between OT and taste threshold. In conclusion, this study provides evidence for the feasibility of testing the chemical senses to directly objectify function in order to discriminate taste from olfactory impairment. Furthermore, it allows to hypothesize a long-term effect of the virus due to neuroinvasion through, probably, the olfactory system with injury in the related multisensory areas of taste and smell.

Post-COVID-19 Syndrome: Involvement and Interactions between Respiratory, Cardiovascular and Nervous Systems.

Though the acute effects of SARS-CoV-2 infection have been extensively reported, the long-term effects are less well described. Specifically, while clinicians endure to battle COVID-19, we also need to develop broad strategies to manage post-COVID-19 symptoms and encourage those affected to seek suitable care. This review addresses the possible involvement of the lung, heart and brain in post-viral syndromes and describes suggested management of post-COVID-19 syndrome. Post-COVID-19 respiratory manifestations comprise coughing and shortness of breath. Furthermore, arrhythmias, palpitations, hypotension, increased heart rate, venous thromboembolic diseases, myocarditis and acute heart failure are usual cardiovascular events. Among neurological manifestations, headache, peripheral neuropathy symptoms, memory issues, lack of concentration and sleep disorders are most commonly observed with varying frequencies. Finally, mental health issues affecting mental abilities and mood fluctuations, namely anxiety and depression, are frequently seen. Finally, long COVID is a complex syndrome with protracted heterogeneous symptoms, and patients who experience post-COVID-19 sequelae require personalized treatment as well as ongoing support.

Assessment of Sequelae of COVID-19 Nearly 1 Year After Diagnosis.

Background: A previous study has shown that 81% of the COVID-19 patients had mild or moderate symptoms. However, most studies on the sequelae in COVID-19 patients focused on severe cases and the long-term follow-up studies on the health consequences in non-severe cases are limited. The current study aimed to assess the sequelae of COVID-19 in patients nearly 1 year after diagnosis with a particular focus on the recovery of patients with non-severe COVID-19. Methods: We enrolled 120 patients infected with SARS-CoV-2 discharged from Wuhan Union hospital west district (designated hospital for COVID-19) and Fangcang shelter hospitals between January 29, 2020 and April 1, 2020. All participants were asked to complete a series of questionnaires to assess their symptoms and quality of life and for psychological evaluation. Also, pulmonary function test, chest CT, 6-min walking test (6MWT), routine blood test, liver and kidney function tests, fasting blood glucose test, lipid test, and immunoglobulin G antibody test were performed to evaluate their health. Results: The mean age of the study population was 51.6 ± 10.8 years. Of the 120 patients, 104 (86.7%) were cases of non-severe COVID-19. The follow-up study was performed between November 23, 2020 and January 11, 2021, and the median time between the diagnosis and the follow-up was 314.5 (IQR, 296-338) days. Sleep difficulties, shortness of breath, fatigue, and joint pain were common symptoms observed during follow-up and nearly one-third of the non-severe cases had these symptoms. A total of 50 (41.7%) and 45 (37.5%) patients reported anxiety and depression, respectively. And 18.3% of the patients showed negative results in the IgG test at the follow-up, which correlated with the severity of the infection (R = 0.203, p = 0.026), and the proportion of IgG negative cases in non-severe COVID-19 patients was higher than that in the severe cases (20.2 vs. 6.3%). Pulmonary diffusion impairment was reported in 30 (26.1%) out of 115 patients, and 24 (24.2%) out of the 99 non-severe cases. The values of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FVC/FEV1, vital capacity (VC), total lung capacity (TLC), and residual volume (RV) were less than the normal range in 1.7, 8.6, 0.9, 11.2, 7.0, and 0.9% of the patients, respectively. A total of 55 (56.7%) out of the 97 patients showed abnormal CT findings, including ground-glass opacities (GGO), bronchiectasis, nodules, lines and bands, and fibrosis. Furthermore, there was a correlation between all the SF-36-domain scores and the duration of hospitalization, pulmonary function, and a 6MWT. Conclusions: At the nearly 1-year follow-up, COVID-19 survivors still had multi-system issues, including those in the respiratory functioning, radiography, quality of life, and anxiety and depression. Moreover, non-severe cases also showed some sequelae and the proportion of IgG negative cases in the non-severe patients was higher than that in severe cases. Therefore, conducting follow-ups and preventing the reinfection of SARS-CoV-2 in this group is necessary.

Post COVID-19 hospitalizations in patients with chronic inflammatory diseases - A nationwide cohort study.

OBJECTIVE: To study long term consequences of hospitalization for COVID-19 in patients with chronic inflammatory diseases. We studied the risk of subsequent hospitalizations in patients with chronic inflammatory diseases, who survived a hospitalization for COVID-19, compared to other patients who had been hospitalized for COVID-19. DESIGN AND SETTING: Population based cohort study based on Danish nationwide health registers. The study population included all adult patients in Denmark who had been discharged alive after a hospitalization with COVID-19 from March 1, 2020 to July 31, 2021. POPULATION: From the study population, the exposed cohort constituted patients who had inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), spondyloarthropathy (SpA), or psoriatic arthritis (PsA) prior to hospitalization for COVID-19, and the unexposed cohort constituted those without these diseases. MAIN OUTCOME MEASURES: We estimated the adjusted Hazard Rate (aHR) for the following outcomes: overall risk of hospitalization, cardiovascular diseases, respiratory diseases, blood and blood-forming organs, nervous system diseases, infections, sequelae of COVID-19, and death. RESULTS: A total of 417 patients with IBD/RA/SpA/PsA were discharged alive after COVID-19, and 9,248 patients without these diseases. Across the different outcomes examined, the median length of follow up was 6.50 months in the exposed cohort (25-75% percentiles: 4.38-8.12), and among the unexposed the median time of follow up was 6.59 months (25-75% percentiles: 4.17-8.49). Across different analyses, we consistently found a significantly increased risk of hospitalizations due to respiratory diseases (aHR 1.27 (95% CI 1.02-1.58)) and infections (aHR 1.55 (95% CI 1.26-1.92)). In sensitivity analyses, the overall risk of hospitalization was aHR 1.15 (95% CI 0.96-1.38) and the risk of hospitalization due to cardiovascular diagnoses was aHR 1.14 (95% CI 0.91-1.42). During the time of follow up, the risk of nervous system diagnoses or death was not increased in patients with IBD/RA/SpA/PsA. CONCLUSIONS: After hospitalization with COVID-19, patients with IBD/RA/SpA/PsA had an increased risk of subsequent hospitalizations for a number of categories of diseases, compared to other patients who have been hospitalized with COVID-19. These results are disturbing and need to be examined further. The implication of our results is that clinicians should be particularly alert for post COVID-19 symptoms from several organ systems in patients with IBD/RA/SpA/PsA.

Myofascial pain syndrome and SARS-CoV-2: a case series.

SARS-CoV-2 is a novel virus that has caused a plethora of dysfunctions and changes in the human body. Our goal in this case study series was to demonstrate the relationship that coronavirus has had in newly diagnosing patients with myofascial pain syndrome (MFPS). Medical records were obtained from a pain clinic that demonstrated the effects of this virus on patients who developed MFPS between March 2020 and December 2020. Chart reviews were performed and demonstrated patients who had a history of chronic pain had subsequent episodes of worsening exacerbations of pain, more specifically trigger points, after being diagnosed with coronavirus. MFPS and SARS-CoV-2 are proposed to be correlated amongst chronic pain patients. Potential pathological mechanisms include coronavirus-induced hypoxic muscle dysfunctions as well as psychological stress triggering pain receptors, leading to myofascial pain syndrome.

COVID-19, the disease caused by the SARS-CoV-2 virus, may cause many problems and changes in the human body. In this case series, we propose a relationship between COVID-19 and myofascial pain syndrome (MFPS), a kind of chronic muscle pain affecting connective tissue in the muscles. Medical records of people who developed MFPS after a diagnosis of COVID-19 between March 2020 and December 2020 were obtained from a pain clinic. Chart reviews demonstrated that the three people with chronic pain included in this case series had episodes of worsening pain, more specifically in focal points, after being diagnosed with COVID-19. COVID-19 is suggested to have affected the development of MFPS in these chronic pain patients. Potential mechanisms of this relationship include different types of stress leading to MFPS.

Electrophysiological and olfactometric evaluation of long-term COVID-19.

COVID-19 is a public health emergency with cases increasing globally. Its clinical manifestations range from asymptomatic and acute respiratory disease to multiple organ dysfunction syndromes and effects of COVID-19 in the long term. Interestingly, regardless of variant, all COVID-19 share impairment of the sense of smell and taste. We would like to report, as far as we know, the first comprehensive neurophysiological evaluation of the long-term effects of SARS-CoV-2 on the olfactory system with potential-related neurological damage. The case report concerns a military doctor, with a monitored health history, infected in April 2020 by the first wave of the epidemic expansion while on military duty in Codogno (Milan). In this subject, we find the electrophysiological signal in the periphery, while its correlate is absent in the olfactory bulb region than in whole brain recordings. In agreement with this result is the lack of metabolic signs of brain activation under olfactory stimulation. Consequently, quantitative and qualitative diagnoses of anosmia were made by means of olfactometric tests. We strongly suggest a comprehensive series of olfactometric tests from the first sign of COVID-19 and subsequent patient assessments. In conclusion, electrophysiological and metabolic tests of olfactory function have made it possible to study the long-term effects and the establishment of neurological consequences.

Myopathic changes in patients with long-term fatigue after COVID-19.

OBJECTIVE: To investigate the peripheral nerve and muscle function electrophysiologically in patients with persistent neuromuscular symptoms following Coronavirus disease 2019 (COVID-19). METHODS: Twenty consecutive patients from a Long-term COVID-19 Clinic referred to electrophysiological examination with the suspicion of mono- or polyneuropathy were included. Examinations were performed from 77 to 255 (median: 216) days after acute COVID-19. None of the patients had received treatment at the intensive care unit. Of these, 10 patients were not even hospitalized. Conventional nerve conduction studies (NCS) and quantitative electromyography (qEMG) findings from three muscles were compared with 20 age- and sex-matched healthy controls. RESULTS: qEMG showed myopathic changes in one or more muscles in 11 patients (55%). Motor unit potential duration was shorter in patients compared to healthy controls in biceps brachii (10.02 ± 0.28 vs 11.75 ± 0.21), vastus medialis (10.86 ± 0.37 vs 12.52 ± 0.19) and anterior tibial (11.76 ± 0.31 vs 13.26 ± 0.21) muscles. All patients with myopathic qEMG reported about physical fatigue and 8 patients about myalgia while 3 patients without myopathic changes complained about physical fatigue. CONCLUSIONS: Long-term COVID-19 does not cause large fibre neuropathy, but myopathic changes are seen. SIGNIFICANCE: Myopathy may be an important cause of physical fatigue in long-term COVID-19 even in non-hospitalized patients.