The association between the number of symptoms and the severity of Post-COVID-Fatigue after SARS-CoV-2 infection treated in an outpatient setting.

BACKGROUND: Post-COVID-Fatigue (PCF) is one of the most reported symptoms following SARS-CoV-2 infection. Currently, research on persistent symptoms focuses mainly on severe infections, while outpatients are rarely included in observations. OBJECTIVE: To investigate whether the severity of PCF is related to the number of acute and persistent symptoms due to mild-to-moderate COVID-19 and to compare the most common symptoms during acute infection with the persistent symptoms in PCF patients. METHODS: A total of 425 participants were examined after COVID-19 treated as an outpatient (median 249 days [IQR: 135; 322] after acute disease) at the site of University Hospital Augsburg, Germany. The Fatigue Assessment Scale (FAS) was used to quantify the severity of PCF. The number of symptoms (maximum 41) during acute infection and persistent symptoms (during the last 14 days before examination) were added up to sum scores. Multivariable linear regression models were used to show the association between the number of symptoms and PCF. RESULTS: Of the 425 participants, 37% (n = 157) developed PCF; most were women (70%). The median number of symptoms was significantly higher in the PCF group than in the non-PCF group at both time points. In multivariable linear regression models, both sum scores were associated with PCF (acute symptoms: ß-estimate per additional symptom [95%-CI]: 0.48 [0.39; 0.57], p < 0.0001); persistent symptoms: ß-estimate per additional symptom [95%-CI]: 1.18 [1.02; 1.34], p < 0.0001). The acute symptoms strongest associated with PCF severity were difficulty concentrating, memory problems, dyspnea or shortness of breath on exertion, palpitations, and problems with movement coordination. CONCLUSION: Each additional symptom that occurs in COVID-19 increases the likelihood of suffering a higher severity of PCF. Further research is needed to identify the aetiology of PCF. TRIAL REGISTRATION: Nr. NCT04615026. Date of registration: November 4, 2020.

The prevalence of vascular complications in SARS-CoV-2 infected outpatients.

BACKGROUND: The risk of thromboembolic events is increased for coronavirus disease (COVID)-19 inpatients. For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected outpatients, only few data are available so far. METHODS: In our prospective single-center study, 461 SARS-CoV-2-infected outpatients were screened for the presence of deep vein thrombosis. RESULTS: Two outpatients had suffered a deep vein thrombosis. An association with previously known risk factors, such as preexisting thrombosis in the medical history or cardiovascular risk factors, could not be proven. CONCLUSION: General thromboprophylaxis in SARS-CoV-2-infected outpatients is still not recommended.

Subjective and Objective Cognitive Impairments in Non-Hospitalized Persons 9 Months after SARS-CoV-2 Infection.

Studies on cognitive problems of persons with mild COVID-19 courses are still lacking. This study aimed to determine the frequency and associated factors of subjective and objective cognitive problems after COVID-19 in non-hospitalized persons. Study participants were examined at the University Hospital of Augsburg from 04/11/2020 to 26/05/2021. The Wechsler Adult Intelligence Scale (WAIS) IV digit span, Stroop Color and Word Test (SCWT), Regensburger verbal fluency test (RWT) and, subjective ratings of memory and concentration were applied. Of the 372 participants (mean age 46.8 ± 15.2 years, 54.3% women, median time after infection 9.1 months), 24.9% reported concentration and 21.9% memory problems. Overall, 55.6% of the participants had at least a mild negative alteration in any cognitive test. The strongest impairments were found regarding memory functions (41.1% mild alterations, 6.2% distinct impairments) and verbal fluency (12.4% mild alterations, 5.4% distinct impairments). SCWT showed negative alterations in no more than 3.0% of the participants. Level of school education, age, and depressiveness emerged as significantly related to the cognitive tests. The number of complaints and depressiveness were significantly associated with subjective memory and concentration problems. It is important to identify mild cognitive impairment in non-hospitalized COVID-19 patients early to offer them effective interventions.

Elevated Plasma D-Dimer Concentrations in Adults after an Outpatient-Treated COVID-19 Infection.

Elevated D-dimer plasma concentrations are common in hospitalized COVID-19 patients and are often associated with a worse prognosis, but it is not yet clear whether this also applies to outpatient cases. The present cross-sectional study evaluated D-dimer levels and their association with clinical parameters and inflammation biomarkers after a COVID-19 disease in individuals treated as outpatients. The study included 411 individuals (43.3% men) with an average age of 46.8 years (SD 15.2). Study participants who had acute COVID-19 disease at a median of 235 days (120; 323) ago were examined at the University Hospital Augsburg, Southern Germany, between 11/2020 and 05/2021. Plasma D-dimers were measured by a particle-enhanced immunoturbidimetric assay. Sixty-one subjects (15%) showed increased D-dimer concentrations (≥500 µg/L). Study participants with elevated D-dimer levels in comparison to subjects with levels in the reference range were significantly older, and more frequently reported a history of cardiovascular disease, hypertension, venous thromboembolism, and chronic venous insufficiency. In multivariable logistic regression analysis, CRP levels (OR 5.58 per mg/dL, 95% CI 1.77-17.60) and white blood cell count (OR 1.48 per nL, 95% CI 1.19-1.83) were significantly related to elevated D-dimers even after adjustment for multiple testing. However, acute or persistent symptoms were not significantly associated with increased D-dimers. Elevated D-dimer levels months after an acute COVID-19 disease seems to be associated with markers of inflammation. Further studies are needed to investigate the underlying pathophysiological mechanisms and consequences of prolonged D-dimer elevation in these patients.

Post-COVID-19 Fatigue and SARS-CoV-2 Specific Humoral and T-Cell Responses in Male and Female Outpatients.

Background: Information on the clinical characteristics and pathophysiological mechanisms underlying post-COVID-19 fatigue are scarce. The main objective of this study was to evaluate sex-specific humoral and T-cell responses associated with post-COVID-19 fatigue in a sample of individuals treated as outpatients. Methods: At a median time of 279 (179;325) days after the acute infection, a total of 281 individuals (45.9% men) aged 18-87 years old were included in the analysis. The participants were examined at the University Hospital of Augsburg, Southern Germany. Fatigue was assessed using the Fatigue Assessment Scale (FAS). Levels of anti-SARS-CoV2-spike IgG antibodies were measured by an enzyme-linked immunosorbent assay (ELISA), and for exploration of the SARS-CoV2-specific T-cell response, ex vivo ELISpot/FLUOROspot assays were conducted using an interferon-γ (IFN-γ) and interleukin-2 (IL-2) SARS-CoV-iSpot kit. Results: Women more significantly suffered from post-COVID-19 fatigue in comparison to men (47.4% versus 25.6%, p=0.0002). Females but not males with fatigue showed a significantly lower number of T-cells producing IFN-γ, IL-2 or both IL-2 and IFNγ in comparison with females without fatigue. In both sexes, serum levels of anti-SARS-CoV2-spike IgG antibodies did not differ significantly between participants with or without fatigue. Conclusions: Development of fatigue after acute COVID-19 disease might be associated with SARS-CoV-2-specific T-cell responses in women, but not men after a mild infection course treated outpatient.

Post-COVID-19 Fatigue and SARS-CoV-2 Specific Humoral and T-Cell Responses in Male and Female Outpatients

Background Information on the clinical characteristics and pathophysiological mechanisms underlying post-COVID-19 fatigue are scarce. The main objective of this study was to evaluate sex-specific humoral and T-cell responses associated with post-COVID-19 fatigue in a sample of individuals treated as outpatients. Methods At a median time of 279 (179;325) days after the acute infection, a total of 281 individuals (45.9% men) aged 18-87 years old were included in the analysis. The participants were examined at the University Hospital of Augsburg, Southern Germany. Fatigue was assessed using the Fatigue Assessment Scale (FAS). Levels of anti-SARS-CoV2-spike IgG antibodies were measured by an enzyme-linked immunosorbent assay (ELISA), and for exploration of the SARS-CoV2-specific T-cell response, ex vivo ELISpot/FLUOROspot assays were conducted using an interferon-γ (IFN-γ) and interleukin-2 (IL-2) SARS-CoV-iSpot kit. Results Women more significantly suffered from post-COVID-19 fatigue in comparison to men (47.4% versus 25.6%, p=0.0002). Females but not males with fatigue showed a significantly lower number of T-cells producing IFN-γ, IL-2 or both IL-2 and IFNγ in comparison with females without fatigue. In both sexes, serum levels of anti-SARS-CoV2-spike IgG antibodies did not differ significantly between participants with or without fatigue. Conclusions Development of fatigue after acute COVID-19 disease might be associated with SARS-CoV-2-specific T-cell responses in women, but not men after a mild infection course treated outpatient.

Impact of COVID-19 pandemic lockdown on myocardial infarction care.

The aim of this study was to evaluate the impact of the COVID-19 pandemic lockdown on acute myocardial infarction (AMI) care, and to identify underlying stressors in the German model region for complete AMI registration. The analysis was based on data from the population-based KORA Myocardial Infarction Registry located in the region of Augsburg, Germany. All cases of AMI (n = 210) admitted to one of four hospitals in the city of Augsburg or the county of Augsburg from February 10th, 2020, to May 19, 2020, were included. Patients were divided into three groups, namely pre-lockdown, strict lockdown, and attenuated lockdown period. An additional survey was conducted asking the patients for stress and fears in the 4 weeks prior to their AMI. The AMI rate declined by 44% in the strict lockdown period; in the attenuated lockdown period the rate was 17% lower compared to the pre-lockdown period. The downward trend in AMI rates during lockdown was seen in STEMI and NSTEMI patients, and independent of sex and age. The door-to-device time decreased by 70-80% in the lockdown-periods. In the time prior to the infarction, patients felt stressed mainly due to fear of infection with Sars-CoV-2 and less because of the restrictions and consequences of the lockdown. A strict lockdown due to the Covid-19 pandemic had a marked impact on AMI care even in a non-hot-spot region with relatively few cases of COVID-19. Fear of infection with the virus is presumably the main reason for the drop in hospitalizations due to AMI.

COVID-19 risk perceptions, worries and preventive behaviors in patients with previous pulmonary embolism.

INTRODUCTION: The presence of conditions, such as cardiovascular or chronic lung diseases, was reported to be associated with more severe cases of COVID-19. It is, however, so far unclear how patients with a history of pulmonary embolism (PE) perceive their individual COVID-19 risk. Moreover, their worries and preventive behaviors and their associations with risk perception are unknown. MATERIALS AND METHODS: A postal survey was conducted in April 2020, including participants with previous PE from the German "Lungenembolie Augsburg" (LEA) cohort study. The questionnaire contained items on COVID-19 knowledge, risk perception (infection likelihood, susceptibility, dangerousness), information sources and satisfaction with information, individual assignment to a high risk group due to pre-existing conditions, worries, infection likelihood, and implementation of preventive behaviors. RESULTS: From the 185 respondents, 71.7% assigned themselves to a high risk group in terms of developing a severe case of COVID-19. The likelihood of being infected was rated as verylow/low by 82.3% and the susceptability by 37.8%. A considerable percentage of patients expected a very high/high infection risk in a hospital (48.3%) or at a doctor's practice (37.9%). Major sources of information were the patients' general practitioners (48.9%) and the internet (31.5%). Assignment to a high risk group (ß = 1.04) and uncertainty in terms of assignment (ß = 1.26) were significantly (p = 0.01) associated with a higher level of health-related worries. CONCLUSIONS: Most patients with previous PE feel that they belong to a high risk group in terms of severe illness from COVID-19. Support in coping with their individual COVID-19 risk is warranted.

Impact of body composition on COVID-19 susceptibility and severity: A two-sample multivariable Mendelian randomization study.

OBJECTIVES: Recent studies suggested obesity to be a possible risk factor for COVID-19 disease in the wake of the coronavirus (SARS-CoV-2) infection. However, the causality and especially the role of body fat distribution in this context is still unclear. Thus, using a univariable as well as multivariable two-sample Mendelian randomization (MR) approach, we investigated for the first time the causal impact of body composition on the susceptibility and severity of COVID-19. METHODS: As indicators of overall and abdominal obesity we considered the measures body mass index (BMI), waist circumference (WC), and trunk fat ratio (TFR). Summary statistics of genome-wide association studies (GWASs) for these body composition measures were drawn from the GIANT consortium and UK Biobank, while for susceptibility and severity due to COVID-19 disease data from the COVID-19 Host Genetics Initiative was used. For the COVID-19 cohort neither age nor gender was available. Total and direct causal effect estimates were calculated using Single Nucleotide Polymorphisms (SNPs), sensitivity analyses were done applying several robust MR techniques and mediation effects of type 2 diabetes (T2D) and cardiovascular diseases (CVD) were investigated within multivariable MR analyses. RESULTS: Genetically predicted BMI was strongly associated with both, susceptibility (OR = 1.31 per 1 SD increase; 95% CI: 1.15-1.50; P-value = 7.3·10-5) and hospitalization (OR = 1.62 per 1 SD increase; 95% CI: 1.33-1.99; P-value = 2.8·10-6) even after adjustment for genetically predicted visceral obesity traits. These associations were neither mediated substantially by T2D nor by CVD. Finally, total but not direct effects of visceral body fat on outcomes could be detected. CONCLUSIONS: This study provides strong evidence for a causal impact of overall obesity on the susceptibility and severity of COVID-19 disease. The impact of abdominal obesity was weaker and disappeared after adjustment for BMI. Therefore, obese people should be regarded as a high-risk group. Future research is necessary to investigate the underlying mechanisms linking obesity with COVID-19.