Objective
To systematically describe central (CNS) and peripheral (PNS) nervous system complications in hospitalized COVID-19 patients.
Methods
We conducted a prospective, consecutive, observational ...study of adult patients from a tertiary referral center with confirmed COVID-19. All patients were screened daily for neurological and neuropsychiatric symptoms during admission and discharge. Three-month follow-up data were collected using electronic health records. We classified complications as caused by SARS-CoV-2 neurotropism, immune-mediated or critical illness-related.
Results
From April to September 2020, we enrolled 61 consecutively admitted COVID-19 patients, 35 (57%) of whom required intensive care (ICU) management for respiratory failure. Forty-one CNS/PNS complications were identified in 28 of 61 (45.9%) patients and were more frequent in ICU compared to non-ICU patients. The most common CNS complication was encephalopathy (
n
= 19, 31.1%), which was severe in 13 patients (GCS ≤ 12), including 8 with akinetic mutism. Length of ICU admission was independently associated with encephalopathy (OR = 1.22). Other CNS complications included ischemic stroke, a biopsy-proven acute necrotizing encephalitis, and transverse myelitis. The most common PNS complication was critical illness polyneuromyopathy (13.1%), with prolonged ICU stay as independent predictor (OR = 1.14). Treatment-related PNS complications included meralgia paresthetica. Of 41 complications in total, 3 were para/post-infectious, 34 were secondary to critical illness or other causes, and 4 remained unresolved. Cerebrospinal fluid was negative for SARS-CoV-2 RNA in all 5 patients investigated.
Conclusion
CNS and PNS complications were common in hospitalized COVID-19 patients, particularly in the ICU, and often attributable to critical illness. When COVID-19 was the primary cause for neurological disease, no signs of viral neurotropism were detected, but laboratory changes suggested autoimmune-mediated mechanisms.
Abstract
The antiviral drug remdesivir has been shown clinically effective for treatment of COVID-19. We here demonstrate suppressive but not curative effect of remdesivir in an immunocompromised ...patient. A man in his fifties treated with chemoimmunotherapy for chronic lymphocytic leukemia experienced a 9-week course of COVID-19 with high fever and severe viral pneumonia. During two 10-day courses of remdesivir starting 24 and 45 days after fever onset, pneumonia and spiking fevers remitted, but relapsed after discontinuation. Kinetics of temperature, C-reactive protein, and lymphocyte counts mirrored the remitting/relapsing SARS-CoV-2 infection. Combination therapy or longer treatment duration may be needed in immunocompromised patients.
Background and purpose
Currently there is an unmet need for a highly standardized blood biomarker test to monitor treatment response in Lyme neuroborreliosis (LNB). Differentiating between active or ...past infection is challenged by the relatively high frequency of persistent symptoms after the end of antibiotic treatment (estimated 15%–20%), the variable clinical course and the long‐lasting Borrelia burgdorferi antibodies. The aim was therefore to evaluate plasma neurofilament light chain (pNfL) as a marker for disease activity in LNB.
Methods
This was a prospective cohort of definite LNB (N = 36) with blood samples and clinical evaluation including Glasgow Outcome Score at treatment initiation and 3 and 6 months’ follow‐up. Consecutive plasma was retrospectively analysed for the content of neurofilament light chain by Quanterix® kits (Simoa® NF‐light Kit).
Results
Plasma neurofilament light chain significantly decreased between treatment initiation and the 3‐month follow‐up (median 83 pg/ml vs. median 14 pg/ml (25 pairs), p < 0.0001). No significant change was observed between 3 and 6 months’ follow‐up (median 14 pg/ml vs. median 12 pg/ml (21 pairs), p = 0.33). At treatment initiation 90% had pNfL above the age‐defined reference compared to only 23% and 7% respectively at 3 and 6 months’ follow‐up. Decreases in pNfL were mirrored by increasing Glasgow Outcome Score. Reporting persistent symptoms at the 6‐month follow‐up was not associated with pNfL (relative change from reference or actual values) at baseline or at 6 months’ follow‐up.
Conclusion
Plasma neurofilament light chain decreases following antibiotic treatment in LNB and is not associated with reporting persistent symptoms. It was therefore speculated that it may prove useful as a treatment response biomarker in LNB.
Background
Neoehrlichia mikurensis (N. mikurensis) is a newly discovered tick‐borne pathogen that can inflict life‐threatening illness in immunocompromised patients. N. mikurensis infection is only ...detectable by polymerase chain reaction (PCR)‐based methodologies. We describe three distinct clinical manifestations of N. mikurensis infection (neoehrlichiosis) in Danish patients receiving B‐lymphocyte‐depleting therapy, rituximab, for underlying hematological, rheumatological, or neurological disorders. All three patients went through a protracted pre‐diagnostic period.
Methods
N. mikurensis DNA was detected and confirmed using two methods. Blood was tested by specific real‐time PCR targeting the groEL gene and by 16S and 18S profiling followed by sequencing. Bone marrow was analyzed by 16S and 18S profiling.
Results
N. mikurensis was detected in blood samples in all three cases and in bone marrow from one of the three. The severity of the symptoms ranged from prolonged fever lasting more than 6 months to life‐threatening hyperinflammation in the form of hemophagocytic lymphohistiocytosis (HLH). Interestingly, all patients presented with splenomegaly and two with hepatomegaly. After starting doxycycline therapy, symptoms were relieved within a few days, and biochemistry and organomegaly quickly normalized.
Conclusion
We present three Danish patients recognized by the same clinician over a period of 6 months, strongly suggesting that many cases are going unrecognized. Second, we describe the first case of N. mikurensis‐induced HLH and emphasize the potential severity of undetected neoehrlichiosis.
Objective
Age‐related comorbidities, polypharmacy and thereby the risk of potential drug–drug interactions (PDDIs) among people living with HIV (PLWH) have increased over the years. We estimated the ...prevalence of comedications, including dietary supplements, and evaluated PDDIs among PLWH receiving antiretroviral therapy (ART) in Denmark in an outpatient setting.
Methods
Information on prescription medication, over‐the‐counter medication and dietary supplements was obtained from adult PLWH receiving ART attending two outpatient clinics in Denmark. The PDDIs were identified using the University of Liverpool's drug interaction database. Associations between PDDIs and relevant variables were compared using logistic regression models.
Results
A total of 337 PLWH receiving ART with a median age of 53 years (interquartile range: 45–61) were included; 77% were male and 96% had a HIV‐RNA viral load < 50 copies/mL. Twenty‐six per cent of participants received five or more comedications and 56% consumed dietary supplements. Co‐administration of drugs requiring dose adjustment or monitoring was identified in the medication lists of 52% of participants, and 4.5% were on drugs that should not be co‐administered. Male sex odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.0–3.4, being on a protease inhibitor (OR = 4.3, 95% CI: 1.9–9.7), receiving five or more comedications (OR = 3.3, 95% CI: 1.5–7.2), taking over‐the‐counter medications (OR = 1.9, 95% CI: 1.1–3.3) and dietary supplements (OR = 2.0, 95% CI: 1.2–3.3) were independent predictors of PDDIs.
Conclusion
Potential drug–drug interactions were common among our study population Our study confirms that polypharmacy and being on a protease inhibitor‐based regimen increase the risk of PDDIs considerably and highlights the importance of questioning PLWH about dietary supplement intake.
Many patients exhibit persistently reduced pulmonary diffusing capacity after coronavirus disease 2019 (COVID‐19). In this study, dual test gas diffusing capacity for carbon monoxide and nitric oxide ...(DL,CO,NO) metrics and their relationship to disease severity and physical performance were examined in patients who previously had COVID‐19. An initial cohort of 148 patients diagnosed with COVID‐19 of all severities between March 2020 and March 2021 had a DL,CO,NO measurement performed using the single‐breath method at 5.7 months follow‐up. All patients with at least one abnormal DL,CO,NO metric (n = 87) were revaluated at 12.5 months follow‐up. The DL,CO,NO was used to provide the pulmonary diffusing capacity for nitric oxide (DL,NO), the pulmonary diffusing capacity for carbon monoxide (DL,CO,5s), the alveolar–capillary membrane diffusing capacity and the pulmonary capillary blood volume. At both 5.7 and 12.5 months, physical performance was assessed using a 30 s sit‐to‐stand test and the 6 min walk test. Approximately 60% of patients exhibited a severity‐dependent decline in at least one DL,CO,NO metric at 5.7 months follow‐up. At 12.5 months, both DL,NO and DL,CO,5s had returned towards normal but still remained abnormal in two‐thirds of the patients. Concurrently, improvements in physical performance were observed, but with no apparent relationship to any DL,CO,NO metric. The severity‐dependent decline in DL,NO and DL,CO observed at 5.7 months after COVID‐19 appears to be reduced consistently at 12.5 months follow‐up in the majority of patients, despite marked improvements in physical performance.
What is the central question of this study?
To what extent do changes in pulmonary diffusing capacity observed 6 months after coronavirus disease 2019 (COVID‐19) persist after a year?
What is the main finding and its importance?
In patients who have had COVID‐19, the changes in pulmonary diffusing capacity for carbon monoxide and nitric oxide, the alveolar–capillary membrane diffusing capacity and pulmonary capillary blood volume observed at approximately 6 months follow‐up largely persist 1 year after the acute disease, despite a marked improvement in physical performance.
In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. ...Various immunological and inflammatory biomarkers have been associated with cancer, including soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin‐3, mannose‐binding lectin, ficolin‐1, ficolin‐2 and ficolin‐3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer in patients with NSSC. Patients were included from the DOC, Department of Infectious Diseases, Copenhagen University Hospital Hvidovre. Patients were given a final diagnosis based on the combined results from scans, blood work and physical examination. Weight loss, Charlson score and previous cancer were registered on admission, and plasma concentrations of biomarkers were measured. The primary outcome was incident cancer within 1 year. Out of 197 patients included, 39 patients (19.8%) were diagnosed with cancer. Patients with cancer were significantly older and had a higher burden of comorbidities and previous cancer diagnoses compared to patients who were not diagnosed with cancer. Previous cancer, C‐reactive protein (CRP) and suPAR were significantly associated with newly diagnosed cancer during follow‐up in multiple logistic regression analyses adjusted for age, sex and CRP. Neither any of the PRRs investigated nor self‐reported weight loss was associated with cancer. In this study, previous cancer, CRP and suPAR were significantly associated with cancer diagnosis in patients with NSSC. Ficolin‐1‐3, MBL and pentraxin‐3 were not associated with cancer.
What's new?
In Denmark, patients with serious non‐specific symptoms and signs of cancer are referred to an accelerated cancer diagnostic program. But screening and diagnosis is challenging as patients form a heterogeneous group. Possible advances in the diagnostic strategy must be studied to improve accuracy and safety. This study found that the novel inflammatory biomarker suPAR and the routinely evaluated inflammatory biomarker CRP were independently associated with incident cancer diagnoses, while the innate immune markers, pentraxin‐3, mannose‐binding lectin and ficolin‐1‐3, were not. Addition of suPAR to the existing blood samples may improve diagnosis and prognostication of cancer in this heterogeneous patient group.
For a given body mass index, human immunodeficiency virus (HIV) infection was associated with an excess risk of abdominal obesity, which was exacerbated by age. People living with HIV also had higher ...risk of elevated low-density lipoprotein cholesterol and hypertriglyceridemia.
Abstract
Background
People living with human immunodeficiency virus (PLWH) are characterized by excess risk of cardiovascular diseases (CVD) and CVD risk factors compared to uninfected individuals. We investigated the association between HIV infection and abdominal obesity, elevated low-density lipoprotein cholesterol (LDL-C), hypertriglyceridemia, and hypertension in a large cohort of predominantly well-treated PLWH and matched controls.
Methods
1099 PLWH from the Copenhagen Co-morbidity in HIV Infection Study and 12 161 age- and sex-matched uninfected controls from the Copenhagen General Population Study were included and underwent blood pressure, waist, hip, weight, and height measurements and nonfasting blood samples. We assessed whether HIV was independently associated with abdominal obesity, elevated LDL-C, hypertriglyceridemia, and hypertension using logistic regression models adjusted for known risk factors.
Results
HIV infection was associated with higher risk of abdominal obesity (adjusted odds ratio aOR, 1.92 1.60-2.30) for a given body mass index, elevated LDL-C (aOR, 1.32 1.09-1.59), hypertriglyceridemia (aOR, 1.76 1.49-2.08), and lower risk of hypertension (aOR, 0.63 0.54-0.74). The excess odds of abdominal obesity in PLWH was stronger with older age (p interaction, 0.001). Abdominal obesity was associated with elevated LDL-C (aOR, 1.44 1.23-1.69), hypertension (aOR, 1.32 1.16-1.49), and hypertriglyceridemia (aOR, 2.12 1.86-2.41).
Conclusions
Abdominal obesity was associated with proaterogenic metabolic factors including elevated LDL-C, hypertension, and hypertriglyceridemia and remains a distinct HIV-related phenotype, particularly among older PLWH. Effective interventions to reduce the apparent detrimental impact on cardiovascular risk from this phenotype are needed.
Prolonged neuropsychiatric and cognitive symptoms are increasingly reported in patients after COVID-19, but studies with well-matched controls are lacking.
To investigate cognitive impairment, ...neuropsychiatric diagnoses, and symptoms in survivors of COVID-19 compared with patients hospitalized for non-COVID-19 illness.
This prospective case-control study from a tertiary referral hospital in Copenhagen, Denmark, conducted between July 2020 and July 2021, followed up hospitalized COVID-19 survivors and control patients hospitalized for non-COVID-19 illness, matched for age, sex, and intensive care unit (ICU) status 6 months after symptom onset.
Hospitalization for COVID-19.
Participants were investigated with the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semi-structured interview for subjective symptoms. Primary outcomes were total MoCA score and new onset of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses, subjective symptoms, and neurologic examination results. All outcomes were adjusted for age, sex, ICU admission, admission length, and days of follow-up. Secondary outcomes were adjusted for multiple testing.
A total of 85 COVID-19 survivors (36 42% women; mean SD age 56.8 14 years) after hospitalization and 61 matched control patients with non-COVID-19 illness (27 44% women, mean age 59.4 years SD, 13) were enrolled. Cognitive status measured by total geometric mean MoCA scores at 6-month follow-up was lower (P = .01) among COVID-19 survivors (26.7; 95% CI, 26.2-27.1) than control patients (27.5; 95% CI, 27.0-27.9). The cognitive status improved substantially (P = .004), from 19.2 (95% CI, 15.2-23.2) at discharge to 26.1 (95% CI, 23.1-29.1) for 15 patients with COVID-19 with MoCA evaluations from hospital discharge. A total of 16 of 85 patients with COVID-19 (19%) and 12 of 61 control patients (20%) had a new-onset psychiatric diagnosis at 6-month follow-up, which was not significantly different (odds ratio, 0.93; 95% CI, 0.39-2.27; P = .87). In fully adjusted models, secondary outcomes were not significantly different, except anosmia, which was more common after COVID-19 (odds ratio, 4.56; 95% CI, 1.52-17.42; P = .006); but no longer when adjusting for multiple testing.
In this prospective case-control study, cognitive status at 6 months was worse among survivors of COVID-19, but the overall burden of neuropsychiatric and neurologic signs and symptoms among survivors of COVID-19 requiring hospitalization was comparable with the burden observed among matched survivors hospitalized for non-COVID-19 causes.
We compared characteristics and outcomes of individuals who in the cerebrospinal fluid (CSF) were positive for herpes simplex virus (HSV) or varicella-zoster virus (VZV)-intrathecal antibody index ...test (AI-positive) vs. individuals who were PCR-positive for HSV type 1 (HSV1), type 2 (HSV2), and for VZV.
Nationwide cohort study of all Danish residents with positive CSF-AI or -PCR for HSV or VZV (1995–2021). We calculated short- and long-term risks as age-, sex-, and comorbidity-adjusted odds ratios (aOR), adjusted hazard ratios (aHR), and absolute risk differences with 95% CIs.
Compared with individuals with positive PCR for HSV1 (n = 321), HSV2 (n = 497), and VZV (n = 1054), individuals with a positive AI for HSV (n = 177) and VZV (n = 219) had CSF pleocytosis less frequently (leucocyte count >10/μL: HSV-AI: 39%, VZV-AI: 52%, HSV1-PCR: 81%, HSV2-PCR: 92%, VZV-PCR: 83%), and were less frequently diagnosed with central nervous system infection (aOR {95%CI}: HSV-AI vs. HSV1-PCR: 0.1 {0.1, 0.2}, HSV-AI vs. HSV2-PCR: 0.1 {0.0, 0.1}, VZV-AI vs. VZV-PCR: 0.2 {0.2, 0.3}). Individuals with a positive HSV-AI or VZV-AI had increased risk of demyelinating disease (aOR {95%CI}; aHR {95%CI}: HSV-AI vs. HSV1-PCR: 4.6 {0.9, 24.5}; aHR not applicable, HSV-AI vs. HSV2-PCR: 10.4 {2.3, 45.9}; 12.4 {2.3, 66.0}, VZV-AI vs. VZV-PCR: aOR not applicable; 10.3 {1.8, 58.8}). Disability pension was less frequent among HSV-AI than HSV1-PCR cohort members (5-year risk difference: −23.6%, 95%CI: −35.2, −11.8), and more frequent among VZV-AI than VZV-PCR cohort members (5-year risk difference: 16.8%, 95%CI: 5.0, 28.7).
AI-positive individuals differ from PCR-positive individuals in several aspects. AI appears unspecific for current central nervous system infections.
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